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Sample records for investigating multi-cancer biomarkers

  1. Using Metabolomics to Investigate Biomarkers of Drug Addiction.

    Science.gov (United States)

    Ghanbari, Reza; Sumner, Susan

    2018-02-01

    Drug addiction has been associated with an increased risk for cancer, psychological complications, heart, liver, and lung disease, as well as infection. While genes have been identified that can mark individuals at risk for substance abuse, the initiation step of addiction is attributed to persistent metabolic disruptions occurring following the first instance of narcotic drug use. Advances in analytical technologies can enable the detection of thousands of signals in body fluids and excreta that can be used to define biochemical profiles of addiction. Today, these approaches hold promise for determining how exposure to drugs, in the absence or presence of other environmentally relevant factors, can impact human metabolism. We posit that these can lead to candidate biomarkers of drug dependence, treatment, withdrawal, or relapse. Copyright © 2017. Published by Elsevier Ltd.

  2. 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.

  3. Urinary biomarker investigation in children with Fabry disease using tandem mass spectrometry.

    Science.gov (United States)

    Auray-Blais, Christiane; Blais, Catherine-Marie; Ramaswami, Uma; Boutin, Michel; Germain, Dominique P; Dyack, Sarah; Bodamer, Olaf; Pintos-Morell, Guillem; Clarke, Joe T R; Bichet, Daniel G; Warnock, David G; Echevarria, Lucia; West, Michael L; Lavoie, Pamela

    2015-01-01

    Fabry disease is an X-linked lysosomal storage disorder affecting both males and females with tremendous genotypic/phenotypic variability. Concentrations of globotriaosylceramide (Gb3), globotriaosylsphingosine (lyso-Gb3)/related analogues were investigated in pediatric and adult Fabry cohorts. The aims of this study were to transfer and validate an HPLC-MS/MS methodology on a UPLC-MS/MS new generation platform, using an HPLC column, for urine analysis of treated and untreated pediatric and adult Fabry patients, to establish correlations between the excretion of Fabry biomarkers with gender, treatment, types of mutations, and to evaluate the biomarker reliability for early detection of pediatric Fabry patients. A UPLC-MS/MS was used for biomarker analysis. Reference values are presented for all biomarkers. Results show that gender strongly influences the excretion of each biomarker in the pediatric Fabry cohort, with females having lower urinary levels of all biomarkers. Urinary distribution of lyso-Gb3/related analogues in treated Fabry males was similar to the untreated and treated Fabry female groups in both children and adult cohorts. Children with the late-onset p.N215S mutation had normal urinary levels of Gb3, and lyso-Gb3 but abnormal levels of related analogues. In this study, Fabry males and most Fabry females would have been diagnosed using the urinary lyso-Gb3/related analogue profile. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. An MEG Investigation of Neural Biomarkers and Language in Nonverbal Children with Autism Spectrum Disorders

    Science.gov (United States)

    2014-09-01

    1.Lord C, Risi S, Pickles A. Trajectory of language development in autistic spectrum disorders . In: Rice M, Warren S, eds. Developmental Language...Nonverbal Children with Autism Spectrum Disorders PRINCIPAL INVESTIGATOR: Kristina McFadden CONTRACTING ORGANIZATION: University of...SUBTITLE 5a. CONTRACT NUMBER An MEG Investigation of Neural Biomarkers and Language in Nonverbal Children with Autism Spectrum Disorders 5b

  5. Novel Biomarkers of Physical Activity Maintenance in Midlife Women: Preliminary Investigation

    Directory of Open Access Journals (Sweden)

    Kelly A. Bosak

    2018-04-01

    Full Text Available The precision health initiative is leading the discovery of novel biomarkers as important indicators of biological processes or responses to behavior, such as physical activity. Neural biomarkers identified by magnetic resonance imaging (MRI hold promise to inform future research, and ultimately, for transfer to the clinical setting to optimize health outcomes. This study investigated resting-state and functional brain biomarkers between midlife women who were maintaining physical activity in accordance with the current national guidelines and previously acquired age-matched sedentary controls. Approval was obtained from the Human Subjects Committee. Participants included nondiabetic, healthy weight to overweight (body mass index 19–29.9 kg/m2 women (n = 12 aged 40–64 years. Control group data were used from participants enrolled in our previous functional MRI study and baseline resting-state MRI data from a subset of sedentary (<500 kcal of physical activity per week midlife women who were enrolled in a 9-month exercise intervention conducted in our imaging center. Differential activation of the inferior frontal gyrus (IFG and greater connectivity with the dorsolateral prefrontal cortex (dlPFC was identified between physically active women and sedentary controls. After correcting for multiple comparisons, these differences in biomarkers of physical activity maintenance did not reach statistical significance. Preliminary evidence in this small sample suggests that neural biomarkers of physical activity maintenance involve activations in the brain region associated with areas involved in implementing goal-directed behavior. Specifically, activation of the IFG and connectivity with the dlPFC is identified as a neural biomarker to explain and predict long-term physical activity maintenance for healthy aging. Future studies should evaluate these biomarker links with relevant clinical correlations.

  6. Relationship between Investigative Biomarkers and Radiographic Grading in Patients with Knee Osteoarthritis

    Science.gov (United States)

    Anitua, Eduardo; Sánchez, Mikel; de la Fuente, Maria; Azofra, Juan; Zalduendo, Mar; Aguirre, Jose J.; Andía, Isabel

    2009-01-01

    Objective. To examine new investigative biomarkers and their relevance for radiographic severity in knee osteoarthritis. Methods. The group comprised 63 patients with 73 knees examined. Patients were divided according to radiographic severity to allow for comparison of biomarker levels. Hyaluronic acid (HA), matrix metalloproteases (MMP-1, MMP-3 and MMP-13), tissue inhibitors of metalloproteases (TIMP-1 and TIMP-2), platelet-derived growth factor (PDGF-AB), transformed growth factor (TGF-β), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and insulin-like growth factor (IGF-I) were measured on synovial fluid and in plasma releasate at a single time point. Principal component analysis (PCA) followed by analysis of covariance were applied to evaluate data. Results. Four different groups of biomarker were identified in plasma releasates. The first (platelet number, PDGF-AB and TGF-β) and second groups (HA and IGF-I) were related to radiographic severity, P = .005 and P = .022, respectively. The third (MMP-1 and TIMP-2) and fourth groups (MMP-3 and TIMP-1) represented the catabolic balance, but were not associated to radiographic grading. Three different clusters of biomarkers were found in synovial fluid but did not show any significant association to radiographic grading. Conclusions. New imaging approaches to assess structural deterioration and correlation with biomarker levels are warranted to advance in OA research. PMID:20130801

  7. Relationship between Investigative Biomarkers and Radiographic Grading in Patients with Knee Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Eduardo Anitua

    2009-01-01

    Full Text Available Objective. To examine new investigative biomarkers and their relevance for radiographic severity in knee osteoarthritis. Methods. The group comprised 63 patients with 73 knees examined. Patients were divided according to radiographic severity to allow for comparison of biomarker levels. Hyaluronic acid (HA, matrix metalloproteases (MMP-1, MMP-3 and MMP-13, tissue inhibitors of metalloproteases (TIMP-1 and TIMP-2, platelet-derived growth factor (PDGF-AB, transformed growth factor (TGF-β, vascular endothelial growth factor (VEGF, hepatocyte growth factor (HGF and insulin-like growth factor (IGF-I were measured on synovial fluid and in plasma releasate at a single time point. Principal component analysis (PCA followed by analysis of covariance were applied to evaluate data. Results. Four different groups of biomarker were identified in plasma releasates. The first (platelet number, PDGF-AB and TGF-β and second groups (HA and IGF-I were related to radiographic severity, P=.005 and P=.022, respectively. The third (MMP-1 and TIMP-2 and fourth groups (MMP-3 and TIMP-1 represented the catabolic balance, but were not associated to radiographic grading. Three different clusters of biomarkers were found in synovial fluid but did not show any significant association to radiographic grading. Conclusions. New imaging approaches to assess structural deterioration and correlation with biomarker levels are warranted to advance in OA research.

  8. Investigating the biomarker potential of glycoproteins using comparative glycoprofiling - application to tissue inhibitor of metalloproteinases-1

    DEFF Research Database (Denmark)

    Thaysen-Andersen, Morten; Thøgersen, Ida; Lademann, Ulrik Axel

    2008-01-01

    Cancer-induced alterations of protein glycosylations are well-known phenomena. Hence, the glycoprofile of certain glycoproteins can potentially be used as biomarkers for early diagnosis. However, there are a substantial number of candidates and the techniques for measuring their biomarker potential...

  9. Clinical investigation of TROP-2 as an independent biomarker and potential therapeutic target in colon cancer.

    Science.gov (United States)

    Zhao, Peng; Yu, Hai-Zheng; Cai, Jian-Hui

    2015-09-01

    Colon cancer is associated with a severe demographic and economic burden worldwide. The pathogenesis of colon cancer is highly complex and involves sequential genetic and epigenetic mechanisms. Despite extensive investigation, the pathogenesis of colon cancer remains to be elucidated. As the third most common type of cancer worldwide, the treatment options for colon cancer are currently limited. Human trophoblast cell‑surface marker (TROP‑2), is a cell‑surface transmembrane glycoprotein overexpressed by several types of epithelial carcinoma. In addition, TROP‑2 has been demonstrated to be associated with tumorigenesis and invasiveness in solid types of tumor. The aim of the present study was to investigate the protein expression of TROP‑2 in colon cancer tissues, and further explore the association between the expression of TROP‑2 and clinicopathological features of patients with colon cancer. The expression and localization of the TROP‑2 protein was examined using western blot analysis and immunofluorescence staining. Finally, the expression of TROP‑2 expression was correlated to conventional clinicopathological features of colon cancer using a χ2 test. The results revealed that TROP‑2 protein was expressed at high levels in the colon cancer tissues, which was associated with the development and pathological process of colon cancer. Therefore, TROP‑2 may be used as a biomarker to determine the clinical prognosis, and as a potential therapeutic target in colon cancer.

  10. Neuroimaging to Investigate Multisystem Involvement and Provide Biomarkers in Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Pradat, Pierre-François; El Mendili, Mohamed-Mounir

    2014-01-01

    Neuroimaging allows investigating the extent of neurological systems degeneration in amyotrophic lateral sclerosis (ALS). Advanced MRI methods can detect changes related to the degeneration of upper motor neurons but have also demonstrated the participation of other systems such as the sensory system or basal ganglia, demonstrating in vivo that ALS is a multisystem disorder. Structural and functional imaging also allows studying dysfunction of brain areas associated with cognitive signs. From a biomarker perspective, numerous studies using diffusion tensor imaging showed a decrease of fractional anisotropy in the intracranial portion of the corticospinal tract but its diagnostic value at the individual level remains limited. A multiparametric approach will be required to use MRI in the diagnostic workup of ALS. A promising avenue is the new methodological developments of spinal cord imaging that has the advantage to investigate the two motor system components that are involved in ALS, that is, the lower and upper motor neuron. For all neuroimaging modalities, due to the intrinsic heterogeneity of ALS, larger pooled banks of images with standardized image acquisition and analysis procedures are needed. In this paper, we will review the main findings obtained with MRI, PET, SPECT, and nuclear magnetic resonance spectroscopy in ALS. PMID:24949452

  11. Explorative investigation of biomarkers of brain damage and coagulation system activation in clinical stroke differentiation

    DEFF Research Database (Denmark)

    Undén, Johan; Strandberg, Karin; Malm, Jan

    2009-01-01

    INTRODUCTION: A simple and accurate method of differentiating ischemic stroke and intracerebral hemorrhage (ICH) is potentially useful to facilitate acute therapeutic management. Blood measurements of biomarkers of brain damage and activation of the coagulation system may potentially serve as nov...

  12. Investigation of volatile organic biomarkers derived from Plasmodium falciparum in vitro

    Directory of Open Access Journals (Sweden)

    Wong Rina PM

    2012-09-01

    Full Text Available Abstract Background There remains a need for techniques that improve the sensitive detection of viable Plasmodium falciparum as part of diagnosis and therapeutic monitoring in clinical studies and usual-care management of malaria infections. A non-invasive breath test based on P. falciparum-associated specific volatile organic compounds (VOCs could fill this gap and provide insights into parasite metabolism and pathogenicity. The aim of this study was to determine whether VOCs are present in the headspace above in vitro P. falciparum cultures. Methods A novel, custom-designed apparatus was developed to enable efficient headspace sampling of infected and non-infected cultures. Conditions were optimized to support cultures of high parasitaemia (>20% to improve the potential detection of parasite-specific VOCs. A number of techniques for VOC analysis were investigated including solid phase micro-extraction using two different polarity fibres, and purge and trap/thermal desorption, each coupled to gas chromatography–mass spectrometry. Each experiment and analysis method was performed at least on two occasions. VOCs were identified by comparing their mass spectra against commercial mass spectral libraries. Results No unique malarial-specific VOCs could be detected relative to those in the control red blood cell cultures. This could reflect sequestration of VOCs into cell membranes and/or culture media but solvent extractions of supernatants and cell lysates using hexane, dichloromethane and ethyl acetate also showed no obvious difference compared to control non-parasitized cultures. Conclusions Future in vivo studies analysing the breath of patients with severe malaria who are harbouring a parasite biomass that is significantly greater than achievable in vitro may yet reveal specific clinically-useful volatile chemical biomarkers.

  13. Pilot Study on the Investigation of Tear Fluid Biomarkers as an Indicator of Ocular, Neurological, and Immunological Health in Astronauts

    Science.gov (United States)

    Morton, Stephen; Crucian, Brian; Hagan, Suzanne; Satyamitra, Merriline; Daily, Anna

    2018-01-01

    The purpose of this pilot study is to investigate the collection, preparation, and analysis of tear biomarkers as a means of assessing ocular, neurological, and immunological health. At present, no published data exists on the cytokine profiles of tears from astronauts exposed to long periods of microgravity and space irradiations. In addition, no published data exist on cytokine (biomarker) profiles of tears that have been collected from irradiated non-human biological systems (primates and other animal models). A goal for the proposed pilot study is to discover novel tear biomarkers which can help inform researchers, clinicians, epidemiologist and healthcare providers about the health status of a living biological system, as well as informing them when a disease state is triggered. This would be done via analysis of the onset of expression of pro-inflammatory cytokines, leading up to the full progression of a disease (i.e. cancer, loss of vision, radiation-induced oxidative stress, cardiovascular disorders, fibrosis in major organs, bone loss). Another goal of this pilot study is to investigate the state of disease against proposed medical countermeasures, in order to determine whether the countermeasures are efficacious in preventing or mitigating these injuries. An example of an up and coming tear biomarker technology, Ascendant Dx, a clinical stage diagnostic company, is developing a screening test to detect breast cancer using proteins from tears. The team utilized Liquid Chromatography -Mass Spectrometry with Mass analysis (LC MS/MS) as a discovery platform followed by validation with ELISA to come up with a panel of protein biomarkers that can differentiate breast cancer samples from control ("cancer free") samples with results far surpassing the results of imaging techniques in use today. Continued research into additional proteins is underway to increase the sensitivity and specificity of the test and development efforts are on the way to transfer the

  14. Investigation of polycyclic aromatic hydrocarbons (PAHs) and cyclic terpenoid biomarkers in the sediments of fishing harbors in Taiwan

    International Nuclear Information System (INIS)

    Kao, Nien-Hsin; Su, Ming-Chien; Fan, Jheng-Rong; Yen, Chih-Chun

    2015-01-01

    Highlights: • Biomarkers in three fishing harbors were investigated and identified. • 17 terpanes, 10 steranes and 10 bicyclic sesquiterpanes were quantified. • Marine diesel and the three kinds of lubricants were studied. • The study can be applied to other harbors to identify oil products in sediments. - Abstract: Three fishing harbors were investigated to study the polycyclic aromatic hydrocarbons in the sediments and trace possible anthropogenic sources by identification of cyclic terpenoid biomarkers. Seventeen terpanes, 10 steranes and 10 bicyclic sesquiterpanes in the marine diesel and the three kinds of lubricants that are mainly used by fishing boats were identified and quantified. Eighteen biomarker diagnostic ratios are suggested and the correlation coefficients among the lubricants and sediment samples have the R 2 value greater than 0.73. Analyzed 16 PAHs in the sediment shows non-normal distributions and the Kruskal Wallis Test shows the significant differences (p value smaller than 0.05) with the greatest variability in benzo[g,h,i]perylene which more than 84% of the effective size (E.S.) is accounted. X-ray Photoelectron Spectroscopy (XPS) analysis was applied and the Kruskal Wallis Test shows a significant difference (p value smaller than 0.05) among certain atoms with the effective size greater than 60%

  15. Paleoenvironmental implications from biomarker and stable isotope investigations on the Pliocene Velenje lignite seam (Slovenia)

    Energy Technology Data Exchange (ETDEWEB)

    Bechtel, A.; Sachsenhofer, R.F.; Markic, M.; Gratzer, R.; Lucke, A.; Puttmann, W. [Montan University of Leoben, Leoben (Austria)

    2003-07-01

    A Pliocene lignite seam up to 160 m thick occurs in the Velenje basin (Slovenia). The seam originated in a topogenous mire and evolved within a non-marine, transgressive setting. Differences in soluble organic matter yield and hydrocarbon content of borehole samples from the lignite are related to differences in the composition of free lipids of microbial origin and/or hydrocarbons derived from the biogeochemical degradation of plant tissue. Variations of the redox conditions within the mire are reflected by pristane/phytane ratios. The abundance of terpenoid biomarkers indicates the predominance of gymnosperms over angiosperms, which is consistent with palynomorphic spectra dominated by pollen of the Sequoia-Taxodium-Metasequoia plant community rather than by angiosperms. Evidence is also provided that the content of land plant derived biomarkers and the preservation of plant tissue is controlled by the input of resin-rich, decay-resistant conifers.

  16. Investigation of serum biomarkers in primary gout patients using iTRAQ-based screening.

    Science.gov (United States)

    Ying, Ying; Chen, Yong; Zhang, Shun; Huang, Haiyan; Zou, Rouxin; Li, Xiaoke; Chu, Zanbo; Huang, Xianqian; Peng, Yong; Gan, Minzhi; Geng, Baoqing; Zhu, Mengya; Ying, Yinyan; Huang, Zuoan

    2018-03-21

    Primary gout is a major disease that affects human health; however, its pathogenesis is not well known. The purpose of this study was to identify biomarkers to explore the underlying mechanisms of primary gout. We used the isobaric tags for relative and absolute quantitation (iTRAQ) technique combined with liquid chromatography-tandem mass spectrometry to screen differentially expressed proteins between gout patients and controls. We also identified proteins potentially involved in gout pathogenesis by analysing biological processes, cellular components, molecular functions, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and protein-protein interactions. We further verified some samples using enzyme-linked immunosorbent assay (ELISA). Statistical analyses were carried out using SPSS v. 20.0 and ROC (receiver operating characterstic) curve analyses were carried out using Medcalc software. Two-sided p-values gout than in controls (p=0.023). iTRAQ technology was useful in the selection of differentially expressed proteins from proteomes, and provides a strong theoretical basis for the study of biomarkers and mechanisms in primary gout. In addition, TBB4A protein may be associated with primary gout.

  17. New Biomarker Approaches for Investigating Export Productivity in the Post-K/Pg Living Ocean

    Science.gov (United States)

    Pancost, R.; Taylor, K. W.; Hollis, C. J.

    2012-12-01

    The long-term consequences of the Cretaceous-Paleogene (K/Pg) boundary event on the Earth system have been the subject of much scrutiny. Postulated climate events include a brief period of global cooling induced by sulphate aerosols (the so-called 'impact winter') and an interval of gradual warming caused by impact-induced CO2 release, as well as longer-term climatic oscillations during the subsequent 1 to 3Myr, including periods of sustained cooling. Associated with these were putative changes in the biogeochemical cycle, including suggestions that export production was much reduced and brought about a decrease in the deep to shallow water carbon isotope gradient. In this study we develop new biomarker-based climate and biogeochemical records for the mid-Waipara River section, NZ. We have used these to confirm hypotheses that: a) the post-K/Pg interval was characterised by a negative carbon isotope excursion, documented by both algal and higher plant biomarkers; b) that dramatic fluctuations in ocean temperature followed the K/Pg in the SW Pacific but that there was an overall cooling compared to the Late Cretaceous; c) that the terrestrial biosphere was affected bringing about decreased higher plant inputs to marginal marine sediments; and d) that the biological pump was less efficient during the first ca. 1 to 3 Myr of the Danian. Here we focus on the final aspect, proposing that the distribution of glycerol dialkyl glycerol tetraethers (GDGT) can be used not only as an ocean temperature proxy but to evaluate export production dynamics. We have shown that the ratio of GDGT-2/GDGT-3 (where numerals denote number of cyclopentyl moieties) increases with water column depth in modern and ancient oceans. In Waipara sediments spanning nearly 25 million years, 2/3 ratios are uniformly low (2-3); the only exception is the interval following the K/Pg boundary, during which they markedly increase to values of 6 to 10. We argue that this is evidence for a less efficient

  18. Investigation of p16(INK4a) as a prognostic biomarker in oral epithelial dysplasia.

    Science.gov (United States)

    Nankivell, Paul; Williams, Hazel; Webster, Keith; Pearson, David; High, Alec; MacLennan, Kenneth; Senguven, Burcu; McConkey, Christopher; Rabbitts, Pamela; Mehanna, Hisham

    2014-04-01

    Human papilloma virus is a risk factor for oropharyngeal cancer. Evidence for a similar aetiological role in the development of oral dysplasia or its transformation to oral cancer is not as clear. Meta-analyses estimate the prevalence of high-risk human papilloma virus (HPV) serotypes to be three times higher in pre-malignant lesions and cancer than in normal oral mucosa. However, this does not imply a causal relationship. Conflicting results are reported from the few studies examining the prognostic significance of HPV positivity in the development of oral cancer. We aimed to examine the ability of p16(INK4a) protein expression, a surrogate marker of HPV infection, to predict malignant progression in a large cohort of oral dysplasia patients. One hundred forty eight oral dysplasia cases underwent immunohistochemical analysis using a monoclonal antibody against p16(INK4a) . Clinical factors were also collated on each case. Slides were double scored independently by two trained observers. Univariate analyses using both logistic and Cox regression models were performed. Thirty nine of 148 cases progressed to cancer. Ten of 148 cases (7%) were p16(INK4a) positive. High grade of dysplasia (P = 0.0002) and lesion morphology (P = 0.03) were found to be prognostic of malignant progression. p16(INK4a) score was not prognostic in this cohort (P = 0.29). This did not change with a time to event analysis (P = 0.24). Few studies have assessed the aetiological role of HPV in cancer development from dysplastic lesions. Our study, using one of the largest cohorts of oral dysplasia, demonstrated a low rate of p16(INK4a) positivity and was unable to confirm a prognostic ability for this biomarker. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. An Investigation of Modifying Effects of Metallothionein Single-Nucleotide Polymorphisms on the Association between Mercury Exposure and Biomarker Levels

    Science.gov (United States)

    Wang, Yi; Goodrich, Jaclyn M.; Gillespie, Brenda; Werner, Robert; Basu, Niladri

    2012-01-01

    Background: Recent studies have suggested that several genes that mediate mercury metabolism are polymorphic in humans. Objective: We hypothesized that single-nucleotide polymorphisms (SNPs) in metallothionein (MT) genes may underlie interindividual differences in mercury biomarker levels. We studied the potential modifying effects of MT SNPs on mercury exposure–biomarker relationships. Methods: We measured total mercury in urine and hair samples of 515 dental professionals. We also surveyed occupational and personal exposures to dental amalgam and dietary fish consumption, from which daily methylmercury (MeHg) intake was estimated. Log-transformed urine and hair levels were modeled in multivariable linear regression separately against respective exposure surrogates, and the effect modification of 13 MT SNPs on exposure was investigated. Results: The mean mercury levels in urine (1.06 μg/L) and hair (0.51 μg/g) were not significantly different from the U.S. general population (0.95 μg/L and 0.47 μg/g, respectively). The mean estimated daily MeHg intake was 0.084 μg/kg/day (range, 0–0.98 μg/kg/day), with 25% of study population intakes exceeding the current U.S. Environmental Protection Agency reference dose of 0.1 μg/kg/day. Multivariate regression analysis showed that subjects with the MT1M (rs2270837) AA genotype (n = 10) or the MT2A (rs10636) CC genotype (n = 42) had lower urinary mercury levels than did those with the MT1M or MT2A GG genotype (n = 329 and 251, respectively) after controlling for exposure and potential confounders. After controlling for MeHg intake, subjects with MT1A (rs8052394) GA and GG genotypes (n = 24) or the MT1M (rs9936741) TT genotype (n = 459) had lower hair mercury levels than did subjects with MT1A AA (n = 113) or MT1M TC and CC genotypes (n = 15), respectively. Conclusion: Our findings suggest that some MT genetic polymorphisms may influence mercury biomarker concentrations at levels of exposure relevant to the general

  20. Different Statistical Approaches to Investigate Porcine Muscle Metabolome Profiles to Highlight New Biomarkers for Pork Quality Assessment

    Science.gov (United States)

    Welzenbach, Julia; Neuhoff, Christiane; Looft, Christian; Schellander, Karl; Tholen, Ernst; Große-Brinkhaus, Christine

    2016-01-01

    The aim of this study was to elucidate the underlying biochemical processes to identify potential key molecules of meat quality traits drip loss, pH of meat 1 h post-mortem (pH1), pH in meat 24 h post-mortem (pH24) and meat color. An untargeted metabolomics approach detected the profiles of 393 annotated and 1,600 unknown metabolites in 97 Duroc × Pietrain pigs. Despite obvious differences regarding the statistical approaches, the four applied methods, namely correlation analysis, principal component analysis, weighted network analysis (WNA) and random forest regression (RFR), revealed mainly concordant results. Our findings lead to the conclusion that meat quality traits pH1, pH24 and color are strongly influenced by processes of post-mortem energy metabolism like glycolysis and pentose phosphate pathway, whereas drip loss is significantly associated with metabolites of lipid metabolism. In case of drip loss, RFR was the most suitable method to identify reliable biomarkers and to predict the phenotype based on metabolites. On the other hand, WNA provides the best parameters to investigate the metabolite interactions and to clarify the complex molecular background of meat quality traits. In summary, it was possible to attain findings on the interaction of meat quality traits and their underlying biochemical processes. The detected key metabolites might be better indicators of meat quality especially of drip loss than the measured phenotype itself and potentially might be used as bio indicators. PMID:26919205

  1. Cardiac biomarkers in Neonatology

    OpenAIRE

    Vijlbrief, D.C.

    2015-01-01

    In this thesis, the role for cardiac biomarkers in neonatology was investigated. Several clinically relevant results were reported. In term and preterm infants, hypoxia and subsequent adaptation play an important role in cardiac biomarker elevation. The elevated natriuretic peptides are indicative of abnormal function; elevated troponins are suggestive for cardiomyocyte damage. This methodology makes these biomarkers of additional value in the treatment of newborn infants, separate or as a co...

  2. Preliminary investigation of a sensitive biomarker of organotin pollution in Chinese coastal aquatic environment and marine organisms

    International Nuclear Information System (INIS)

    Zhou Qunfang; Li Zhongyang; Jiang Guibin; Yang Ruiqiang

    2003-01-01

    A new sensitive biomarker can be potentially used to indicate the pollution status of organotin in oceanic environment. - In nine batches of sea bivalves collected from Chinese coastal cities during the year of 2000 to 2002, a special sample named Mya arenaria was found to have strong ability of butyltin accumulation compared with the other sampled bivalves in the corresponding batches. Tributyltin compound was the predominant pollutant with the detection rate high up to 100%. Special high levels of μg Sn/g were detected in some Mya arenaria samples. The results obtained showed that Mya arenaria was potentially a biomarker to indicate organotin pollution in coastal aquatic environment

  3. Investigation of cannabis biomarkers and transformation products in waters by liquid chromatography coupled to time of flight and triple quadrupole mass spectrometry

    OpenAIRE

    Boix Sales, Clara; Ibáñez Martínez, María; Bijlsma, Lubertus; Sancho Llopis, Juan Vicente; Hernández Hernández, Félix

    2014-01-01

    11-Nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) is commonly selected as biomarker for the investigation of cannabis consumption through wastewater analysis. The removal efficiency of THC-COOH in wastewater treatment plants (WWTPs) has been reported to vary between 31% and 98%. Accordingly, possible transformation products (TPs) of this metabolite might be formed during treatment processes or in receiving surface water under environmental conditions. In this work, surface water was spiked ...

  4. Investigating the emerging role of comparative proteomics in the search for new biomarkers of metal contamination under varying abiotic conditions

    Energy Technology Data Exchange (ETDEWEB)

    Vellinger, Céline, E-mail: celine.vellinger@gmail.com [Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), CNRS UMR 7360, Université de Lorraine – Metz (France); Sohm, Bénédicte, E-mail: benedicte.sohm@univ-lorraine.fr [Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), CNRS UMR 7360, Université de Lorraine – Metz (France); Parant, Marc, E-mail: marc.parant@univ-lorraine.fr [Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), CNRS UMR 7360, Université de Lorraine – Metz (France); Immel, Françoise, E-mail: Francoise.Immel@u-bourgogne.fr [Biogéosciences, CNRS UMR 6282, Université de Bourgogne – Dijon (France); Usseglio-Polatera, Philippe, E-mail: philippe.usseglio-polatera@univ-lorraine.fr [Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), CNRS UMR 7360, Université de Lorraine – Metz (France)

    2016-08-15

    This study aims at investigating the potential use of comparative proteomics as a multi-marker approach of metal contamination, taking into account the potential confounding effect of water temperature. The major objective was to identify combinations of proteins specifically responding to a given metal, even if included in a metal mixture. The diagnostic approach was performed via the comparative analysis of protein expression on spot mapping provided by adult males of Gammarus pulex (Amphipoda, Crustacea) respectively exposed to arsenate (As), cadmium (Cd) or a binary mixture of these metals (AsCd) at three realistic temperatures (5, 10 and 15 °C). Proteomic expression analysis was performed by Differential in-Gel Electrophoresis (2D-DiGE), and completed by an adapted inferential statistical approach. Combinations of under/over-expressed protein spots discriminated the metal identity. However, none of these spots discriminated both the individual metal effect (As or Cd) and its effect in metal mixture (AsCd) whatever the tested temperature. Some limits of the two-dimensional analysis of protein spot maps in G. pulex have been highlighted: (i) the presence of contaminating peptides and/or abundant “déja-vu” proteins which can mask the responses of other proteins of interest or (ii) the presence of post-translational modifications. An optimization of the experimental design (especially during the sample preparation) has been described for future investigations. This study has also highlighted (i) the importance of precisely identifying the protein spots of interest to avoid erroneous interpretations in terms of action mechanisms of chemicals and (ii) the importance of working under controlled laboratory conditions with a temperature close to 10 °C. In such conditions, we have demonstrated a higher impact of As than Cd on the energetic metabolism of Gammarus. This As impact is reduced in AsCd mixture confirming the antagonistic interaction of this binary

  5. Investigating the emerging role of comparative proteomics in the search for new biomarkers of metal contamination under varying abiotic conditions

    International Nuclear Information System (INIS)

    Vellinger, Céline; Sohm, Bénédicte; Parant, Marc; Immel, Françoise; Usseglio-Polatera, Philippe

    2016-01-01

    This study aims at investigating the potential use of comparative proteomics as a multi-marker approach of metal contamination, taking into account the potential confounding effect of water temperature. The major objective was to identify combinations of proteins specifically responding to a given metal, even if included in a metal mixture. The diagnostic approach was performed via the comparative analysis of protein expression on spot mapping provided by adult males of Gammarus pulex (Amphipoda, Crustacea) respectively exposed to arsenate (As), cadmium (Cd) or a binary mixture of these metals (AsCd) at three realistic temperatures (5, 10 and 15 °C). Proteomic expression analysis was performed by Differential in-Gel Electrophoresis (2D-DiGE), and completed by an adapted inferential statistical approach. Combinations of under/over-expressed protein spots discriminated the metal identity. However, none of these spots discriminated both the individual metal effect (As or Cd) and its effect in metal mixture (AsCd) whatever the tested temperature. Some limits of the two-dimensional analysis of protein spot maps in G. pulex have been highlighted: (i) the presence of contaminating peptides and/or abundant “déja-vu” proteins which can mask the responses of other proteins of interest or (ii) the presence of post-translational modifications. An optimization of the experimental design (especially during the sample preparation) has been described for future investigations. This study has also highlighted (i) the importance of precisely identifying the protein spots of interest to avoid erroneous interpretations in terms of action mechanisms of chemicals and (ii) the importance of working under controlled laboratory conditions with a temperature close to 10 °C. In such conditions, we have demonstrated a higher impact of As than Cd on the energetic metabolism of Gammarus. This As impact is reduced in AsCd mixture confirming the antagonistic interaction of this binary

  6. Adiposity, mediating biomarkers and risk of colon cancer in the european prospective investigation into cancer and nutrition study

    NARCIS (Netherlands)

    Aleksandrova, K.; Drogan, D.; Boeing, H.; Jenab, M.; Bueno de Mesquita, H.B.; Duijnhoven, van F.J.B.

    2014-01-01

    Adiposity is a risk factor for colon cancer, but underlying mechanisms are not well understood. We evaluated the extent to which 11 biomarkers with inflammatory and metabolic actions mediate the association of adiposity measures, waist circumference (WC) and body mass index (BMI), with colon cancer

  7. Evaluation of miR-122 as a Serum Biomarker for Hepatotoxicity in Investigative Rat Toxicology Studies.

    Science.gov (United States)

    Sharapova, T; Devanarayan, V; LeRoy, B; Liguori, M J; Blomme, E; Buck, W; Maher, J

    2016-01-01

    MicroRNAs are short noncoding RNAs involved in regulation of gene expression. Certain microRNAs, including miR-122, seem to have ideal properties as biomarkers due to good stability, high tissue specificity, and ease of detection across multiple species. Recent reports have indicated that miR-122 is a highly liver-specific marker detectable in serum after liver injury. The purpose of the current study was to assess the performance of miR-122 as a serum biomarker for hepatotoxicity in short-term (5-28 days) repeat-dose rat toxicology studies when benchmarked against routine clinical chemistry and histopathology. A total of 23 studies with multiple dose levels of experimental compounds were examined, and they included animals with or without liver injury and with various hepatic histopathologic changes. Serum miR-122 levels were quantified by reverse transcription quantitative polymerase chain reaction. Increases in circulating miR-122 levels highly correlated with serum elevations of liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH). Statistical analysis showed that miR-122 outperformed ALT as a biomarker for histopathologically confirmed liver toxicity and was equivalent in performance to AST and GLDH. Additionally, an increase of 4% in predictive accuracy was obtained using a multiparameter approach incorporating miR-122 with ALT, AST, and GLDH. In conclusion, serum miR-122 levels can be utilized as a biomarker of hepatotoxicity in acute and subacute rat toxicology studies, and its performance can rival or exceed those of standard enzyme biomarkers such as the liver transaminases. © The Author(s) 2015.

  8. Investigation of cytokines, oxidative stress, metabolic, and inflammatory biomarkers after orange juice consumption by normal and overweight subjects

    Directory of Open Access Journals (Sweden)

    Grace K. Z. S. Dourado

    2015-10-01

    Full Text Available Background: Abdominal adiposity has been linked to metabolic abnormalities, including dyslipidemia, oxidative stress, and low-grade inflammation. Objective: To test the hypothesis that consumption of 100% orange juice (OJ would improve metabolic, oxidative, and inflammatory biomarkers and cytokine levels in normal and overweight subjects with increased waist circumference. Design: Subjects were divided into two groups in accordance with their body mass index: normal and overweight. Both groups of individuals consumed 750 mL of OJ daily for 8 weeks. Body composition (weight, height, percentage of fat mass, and waist circumference; metabolic biomarkers (total cholesterol, low-density lipoprotein-cholesterol [LDL-C], high-density lipoprotein-cholesterol [HDL-C], triglycerides, glucose, insulin, HOMA-IR, and glycated hemoglobin; oxidative biomarkers (malondialdehyde and DPPH•; inflammatory biomarkers (high-sensitivity C-reactive protein [hsCRP]; cytokines (IL-4, IL-10, IL-12, TNF-α, and IFN-γ; and diet were evaluated before and after consumption of OJ for 8 weeks. Results: The major findings of this study were: 1 no alteration in body composition in either group; 2 improvement of the lipid profile, evidenced by a reduction in total cholesterol and LDL-C; 3 a potential stimulation of the immune response due to increase in IL-12; 4 anti-inflammatory effect as a result of a marked reduction in hsCRP; and 5 antioxidant action by the enhancement of total antioxidant capacity and the reduction of lipid peroxidation, in both normal and overweight subjects. Conclusions: OJ consumption has a positive effect on important biomarkers of health status in normal and overweight subjects, thereby supporting evidence that OJ acts as functional food and could be consumed as part of a healthy diet to prevent metabolic and chronic diseases.

  9. Investigation of HOXA9 promoter methylation as a biomarker to distinguish oral cancer patients at low risk of neck metastasis

    International Nuclear Information System (INIS)

    Uchida, Kenichiro; Veeramachaneni, Ratna; Huey, Bing; Bhattacharya, Aditi; Schmidt, Brian L; Albertson, Donna G

    2014-01-01

    Metastasis to the cervical (neck) lymph nodes is one of the most significant clinical factors responsible for death from oral squamous cell carcinoma (SCC). Therefore, the lymph nodes are frequently removed when the tumor is excised (neck dissection), even though the majority of patients will not benefit from the extra surgery. Two subtypes of oral SCC distinguished by the presence of tumor genomic aberrations +3q, -8p, +8q and/or +20 differ in risk for metastasis – high for the 3q8pq20 subtype, harboring one or more of the aberrations and low for the non-3q8pq20 subtype, lacking these alterations. A prior analysis of the literature suggested genes differentially methylated in the two subtypes. Therefore, the goal of this study was to further investigate the methylation status of candidate biomarkers of the non-3q8pq20 subtype, and evaluate their utility for identifying patients at low risk for metastasis. Methylation status of genes in a cohort of 52 oral SCC patients with at least five year follow up was determined by pyrosequencing. Gene expression levels were determined by quantitative RT-PCR. Growth following re-expression of HOXA9 in cultured oral SCC cells was assessed by proliferation and colony formation assays. A pilot study evaluating methylation levels of HOXA9, MT1A and HOXA11 promoters in DNA from 12 tumors (six each of the 3q8pq20 and non-3q8pq20 subtypes) revealed that only HOXA9 was differentially methylated. Significant differences in methylation levels of HOXA9 were observed amongst the 52 oral SCCs with respect to genomic subtype and nodal status (p = 0.014, and p = 0.024, respectively, Wilcoxon rank sum test). High levels of HOXA9 methylation and low levels of expression in oral SCC cell lines were observed compared to HaCaT, a non-tumorigenic keratinocyte cell line. Re-expression of HOXA9 in the SCC4 oral cancer cell line resulted in diminished proliferation and colony formation. HOXA9 methylation is frequent in oral cancers and levels are

  10. Investigation of nuclear nano-morphology marker as a biomarker for cancer risk assessment using a mouse model

    Science.gov (United States)

    Bista, Rajan K.; Uttam, Shikhar; Hartman, Douglas J.; Qiu, Wei; Yu, Jian; Zhang, Lin; Brand, Randall E.; Liu, Yang

    2012-06-01

    The development of accurate and clinically applicable tools to assess cancer risk is essential to define candidates to undergo screening for early-stage cancers at a curable stage or provide a novel method to monitor chemoprevention treatments. With the use of our recently developed optical technology--spatial-domain low-coherence quantitative phase microscopy (SL-QPM), we have derived a novel optical biomarker characterized by structure-derived optical path length (OPL) properties from the cell nucleus on the standard histology and cytology specimens, which quantifies the nano-structural alterations within the cell nucleus at the nanoscale sensitivity, referred to as nano-morphology marker. The aim of this study is to evaluate the feasibility of the nuclear nano-morphology marker from histologically normal cells, extracted directly from the standard histology specimens, to detect early-stage carcinogenesis, assess cancer risk, and monitor the effect of chemopreventive treatment. We used a well-established mouse model of spontaneous carcinogenesis--ApcMin mice, which develop multiple intestinal adenomas (Min) due to a germline mutation in the adenomatous polyposis coli (Apc) gene. We found that the nuclear nano-morphology marker quantified by OPL detects the development of carcinogenesis from histologically normal intestinal epithelial cells, even at an early pre-adenomatous stage (six weeks). It also exhibits a good temporal correlation with the small intestine that parallels the development of carcinogenesis and cancer risk. To further assess its ability to monitor the efficacy of chemopreventive agents, we used an established chemopreventive agent, sulindac. The nuclear nano-morphology marker is reversed toward normal after a prolonged treatment. Therefore, our proof-of-concept study establishes the feasibility of the SL-QPM derived nuclear nano-morphology marker OPL as a promising, simple and clinically applicable biomarker for cancer risk assessment and

  11. An investigation of the anti-inflammatory effects and a potential biomarker of PI3Kδ inhibition in COPD T cells.

    Science.gov (United States)

    Khan, Abid; Southworth, Thomas; Worsley, Sally; Sriskantharajah, Srividya; Amour, Augustin; Hessel, Edith M; Singh, Dave

    2017-09-01

    Lymphocyte numbers are increased in the lungs of chronic obstructive pulmonary disease (COPD) patients. Phosphatidylinositol-3-kinase delta (PI3Kδ) is involved in lymphocyte activation. We investigated the effect of PI3Kδ inhibition on cytokine release from COPD lymphocytes. We also evaluated phosphorylated ribosomal S6 protein (rS6) as a potential biomarker of PI3Kδ activation. Peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage (BAL) cells isolated from healthy never smokers (HNS), smokers (S) and COPD patients were stimulated to induce a T cell receptor response. The effects of a PI3Kδ specific inhibitor (GSK045) on cytokine release and rS6 phosphorylation were measured by Luminex and flow cytometry respectively. The effects of GSK045 on cytokine production from PHA stimulated chopped lung samples were investigated. GSK045 reduced cytokine release from PBMCs, BAL cells and chopped lung. Inhibition was greatest in the chopped lung model, with approximately 80% inhibition of interferon (IFN) γ, interleukin (IL)-2, IL-17 and IL-10. PI3Kδ inhibition suppressed rS6 phosphorylation in unstimulated airway T-lymphocytes by up to 60%. Inhibition of PI3Kδ suppressed T cell cytokine production in COPD patients. rS6 phosphorylation shows potential as a biomarker to assess PI3Kδ activity. © 2017 John Wiley & Sons Australia, Ltd.

  12. 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.

  13. Investigation of potential biomarkers for the early diagnosis of cellular stability after the exposure of agricultural workers to pesticides

    Directory of Open Access Journals (Sweden)

    JODEL S. ALVES

    2016-03-01

    Full Text Available ABSTRACT Agricultural workers involved in the harvest of tobacco crops are regularly exposed to large quantities of pesticides. In order to determine how this exposure to pesticides induces genetic alterations in these workers, blood samples were obtained from 77 exposed individuals, as well as from 60 unexposed subjects. DNA damage was analyzed by the Comet assay and by the micronucleus (MN test. The antioxidant profile was evaluated by activity of superoxide dismutase (SOD, and the polymorphism of gene PON1 was used as a susceptibility biomarker. The content of inorganic elements in the blood samples was determined by PIXE analysis. Our results demonstrated that the damage frequency, damage index, the MN frequency, and the SOD activity were significantly elevated in the exposed relative to the unexposed group. A modulation of the MN results for the PON1 gene was observed in the exposed group. The concentrations of inorganic elements in the exposed group were higher compared to those of the unexposed group. In this study, we observed that genetic damage, and change in oxidative balance were induced by the exposure of workers to complex mixtures of pesticides in the presence of inorganic compounds, whereby an influence of the genotype was evident.

  14. Investigation of acetone, butanol and carbon dioxide as new breath biomarkers for convenient and noninvasive diagnosis of obstructive sleep apnea syndrome.

    Science.gov (United States)

    Bayrakli, Ismail; Öztürk, Önder; Akman, Hatice

    2016-12-01

    The objective of the present study was to investigate whether analysis of carbon dioxide, acetone and/or butanol present in human breath can be used as a simple and noninvasive diagnosis method for obstructive sleep apnea syndrome (OSAS). For this purpose, overnight changes in the concentrations of these breath molecules were measured before and after sleep in 10 patients who underwent polysomnography and were diagnosed with OSAS, and were compared with the levels of these biomarkers determined after sleep in 10 healthy subjects. The concentrations of exhaled carbon dioxide were measured using external cavity laser-based off-axis cavity enhanced absorption spectroscopy, whereas the levels of exhaled acetone and butanol were determined using thermal desorption gas chromatography mass spectrometry. We observed no significant changes in the levels of exhaled acetone and carbon dioxide in OSAS patients after sleep compared with pre-sleep values and compared with those in healthy control subjects. However, for the first time, to our knowledge, analyses of expired air showed an increased concentration of butanol after sleep compared with that before sleep and compared with that in healthy subjects. These results suggest that butanol can be established as a potential biomarker to enable the convenient and noninvasive diagnosis of OSAS in the future. Copyright © 2016 John Wiley & Sons, Ltd.

  15. Sperm quality biomarkers complement reproductive and endocrine parameters in investigating environmental contaminants in common carp (Cyprinus carpio) from the Lake Mead National Recreation Area

    Science.gov (United States)

    Jenkins, Jill A.; Rosen, Michael R.; Dale, Rassa O.; Echols, Kathy R.; Torres, Leticia; Wieser, Carla M.; Kersten, Constance A.; Goodbred, Steven L.

    2018-01-01

    Lake Mead National Recreational Area (LMNRA) serves as critical habitat for several federally listed species and supplies water for municipal, domestic, and agricultural use in the Southwestern U.S. Contaminant sources and concentrations vary among the sub-basins within LMNRA. To investigate whether exposure to environmental contaminants is associated with alterations in male common carp (Cyprinus carpio) gamete quality and endocrine- and reproductive parameters, data were collected among sub-basins over 7 years (1999–2006). Endpoints included sperm quality parameters of motility, viability, mitochondrial membrane potential, count, morphology, and DNA fragmentation; plasma components were vitellogenin (VTG), 17ß-estradiol, 11-keto-testosterone, triiodothyronine, and thyroxine. Fish condition factor, gonadosomatic index, and gonadal histology parameters were also measured. Diminished biomarker effects were noted in 2006, and sub-basin differences were indicated by the irregular occurrences of contaminants and by several associations between chemicals (e.g., polychlorinated biphenyls, hexachlorobenzene, galaxolide, and methyl triclosan) and biomarkers (e.g., plasma thyroxine, sperm motility and DNA fragmentation). By 2006, sex steroid hormone and VTG levels decreased with subsequent reduced endocrine disrupting effects. The sperm quality bioassays developed and applied with carp complemented endocrine and reproductive data, and can be adapted for use with other species.

  16. Extracellular miRNA-21 as a novel biomarker in glioma: evidence from meta-analysis, clinical validation and experimental investigations

    Science.gov (United States)

    Liu, Tian; Wang, Zhixin; Tai, Minghui; Meng, Fandi; Zhang, Jingyao; Wan, Yong; Mao, Ping; Dong, Xiaoqun; Liu, Chang; Niu, Wenquan; Dong, Shunbin

    2016-01-01

    Evidence is accumulating highlighting the importance of extracellular miRNA as a novel biomarker for diagnosing various kinds of malignancies. MiR-21 is one of the most studied miRNAs and is over-expressed in cancer tissues. To explore the clinical implications and secretory mechanisms of extracellular miR-21, we firstly meta-analyzed the diagnostic efficiency of extracellular miR-21 in different cancer types. Eighty-one studies based on 59 articles were finally included. In our study, extracellular miR-21 was observed to exhibit an outstanding diagnostic accuracy in detecting brain cancer (area under the summary receiver operating characteristic curve or AUC = 0.94), and this accuracy was more obvious in glioma diagnosis (AUC = 0.95). Our validation study (n = 45) further confirmed the diagnostic and prognostic role of miR-21 in cerebrospinal fluid (CSF) for glioma. These findings inspired us to explore the biological function of miR-21. We next conducted mechanistic investigations to explain the secretory mechanisms of extracellular miR-21 in glioma. TGF-β/Smad3 signaling was identified to participate in mediating the release of miR-21 from glioma cells. Further targeting TGF-β/Smad3 signaling using galunisertib, an inhibitor of the TGF-β type I receptor kinase, can attenuate the secretion of miR-21 from glioma cells. Taken together, CSF-based miR-21 might serve as a potential biomarker for diagnosing brain cancer, especially for patients with glioma. Moreover, extracellular levels of miR-21 were affected by exogenous TGF-β activity and galunisertib treatment. PMID:27166186

  17. Investigating the Effects of Robot-Assisted Therapy among Children with Autism Spectrum Disorder using Bio-markers

    Science.gov (United States)

    Bharatharaj, Jaishankar; Huang, Loulin; Al-Jumaily, Ahmed; Elara, Mohan Rajesh; Krägeloh, Chris

    2017-09-01

    Therapeutic pet robots designed to help humans with various medical conditions could play a vital role in physiological, psychological and social-interaction interventions for children with autism spectrum disorder (ASD). In this paper, we report our findings from a robot-assisted therapeutic study conducted over seven weeks to investigate the changes in stress levels of children with ASD. For this study, we used the parrot-inspired therapeutic robot, KiliRo, we developed and investigated urinary and salivary samples of participating children to report changes in stress levels before and after interacting with the robot. This is a pioneering human-robot interaction study to investigate the effects of robot-assisted therapy using salivary samples. The results show that the bio-inspired robot-assisted therapy can significantly help reduce the stress levels of children with ASD.

  18. Investigation of autoantibody profiles for cerebrospinal fluid biomarker discovery in patients with relapsing-remitting multiple sclerosis

    DEFF Research Database (Denmark)

    Beyer, Natascha Helena; Lueking, Angelika; Kowald, Axel

    2012-01-01

    Using the UNIarray® marker technology platform, cerebrospinal fluid immunoglobulin G reactivities of 15 controls and 17 RRMS patients against human recombinant proteins were investigated. Patient cerebrospinal fluids were oligoclonal band positive and reactivities were compared to that of sex...

  19. Forensic Interviews for Child Sexual Abuse Allegations: An Investigation into the Effects of Animal-Assisted Intervention on Stress Biomarkers.

    Science.gov (United States)

    Krause-Parello, Cheryl A; Gulick, Elsie E

    2015-01-01

    The use of therapy animals during forensic interviews for child sexual abuse allegations is a recommendation by the Therapy Animals Supporting Kids Program to help ease children's discomfort during the forensic interview process. Based on this recommendation, this study incorporated a certified therapy canine into the forensic interview process for child sexual abuse allegations. This study investigated changes in salivary cortisol, immunoglobulin A, blood pressure, and heart rate as a result of forensic interview phenomenon (e.g., outcry) incorporating animal-assisted intervention versus a control condition in children (N = 42) interviewed for alleged child sexual abuse. The results supported significantly greater heart rate values for the control group (n = 23) who experienced sexual contact and/or indecency than the experience of aggravated sexual assault compared to no difference in HR for the intervention group (n = 19). The results suggest that the presence of the canine in the forensic interview may have acted as a buffer or safeguard for the children when disclosing details of sexual abuse. In the intervention group, children's HR was lower at the start of the forensic interview compared to the control group. Finding an effect of having a certified handler-canine team available during the forensic interview on physiological measures of stress has real-world value for children, child welfare personnel, and clinical therapists. It is suggested that animal-assisted intervention be expanded to children facing other types of trauma and to treatment programs for child survivors of sexual abuse.

  20. Investigation of cannabis biomarkers and transformation products in waters by liquid chromatography coupled to time of flight and triple quadrupole mass spectrometry.

    Science.gov (United States)

    Boix, Clara; Ibáñez, María; Bijlsma, Lubertus; Sancho, Juan V; Hernández, Félix

    2014-03-01

    11-Nor-9-carboxy-Δ(9)-tetrahydrocannabinol (THC-COOH) is commonly selected as biomarker for the investigation of cannabis consumption through wastewater analysis. The removal efficiency of THC-COOH in wastewater treatment plants (WWTPs) has been reported to vary between 31% and 98%. Accordingly, possible transformation products (TPs) of this metabolite might be formed during treatment processes or in receiving surface water under environmental conditions. In this work, surface water was spiked with THC-COOH and subjected to hydrolysis, chlorination and photo-degradation (both ultraviolet and simulated sunlight) experiments under laboratory-controlled conditions. One hydrolysis, eight chlorination, three ultraviolet photo-degradation and seven sunlight photo-degradation TPs were tentatively identified by liquid chromatography coupled to quadrupole time-of-flight mass spectrometer (LC-QTOF MS). In a subsequent step, THC-COOH and the identified TPs were searched in wastewater samples using LC coupled to tandem mass spectrometry (LC-MS/MS) with triple quadrupole. THC-COOH was found in all influent and effluent wastewater samples analyzed, although at significant lower concentrations in the effluent samples. The removal efficiency of WWTP under study was approximately 86%. Furthermore, THC-COOH was also investigated in several surface waters, and it was detected in 50% of the samples analyzed. Regarding TPs, none were found in influent wastewater, while one hydrolysis and five photo-degradation (simulated sunlight) TPs were detected in effluent and surface waters. The most detected compound, resulting from sunlight photo-degradation, was found in 60% of surface waters analyzed. This fact illustrates the importance of investigating these TPs in the aquatic environment. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. The first investigation of Wilms' tumour atomic structure-nitrogen and carbon isotopic composition as a novel biomarker for the most individual approach in cancer disease

    Science.gov (United States)

    Taran, Katarzyna; Frączek, Tomasz; Sikora-Szubert, Anita; Sitkiewicz, Anna; Młynarski, Wojciech; Kobos, Józef; Paneth, Piotr

    2016-01-01

    The paper describes a novel approach to investigating Wilms' tumour (nephroblastoma) biology at the atomic level. Isotope Ratio Mass Spectrometry (IRMS) was used to directly assess the isotope ratios of nitrogen and carbon in 84 Wilms' tumour tissue samples from 28 cases representing the histological spectrum of nephroblastoma. Marked differences in nitrogen and carbon isotope ratios were found between nephroblastoma histological types and along the course of cancer disease, with a breakout in isotope ratio of the examined elements in tumour tissue found between stages 2 and 3. Different isotopic compositions with regard to nitrogen and carbon content were observed in blastemal Wilms' tumour, with and without focal anaplasia, and in poorly- and well-differentiated epithelial nephroblastoma. This first assessment of nitrogen and carbon isotope ratio reveals the previously unknown part of Wilms' tumour biology and represents a potential novel biomarker, allowing for a highly individual approach to treating cancer. Furthermore, this method of estimating isotopic composition appears to be the most sensitive tool yet for cancer tissue evaluation, and a valuable complement to established cancer study methods with prospective clinical impact. PMID:27732932

  2. Non-invasively collected amniotic fluid as a source of possible biomarkers for premature rupture of membranes investigated by proteomic approach.

    Science.gov (United States)

    Consonni, Sara; Mainini, Veronica; Pizzardi, Agnese; Gianazza, Erica; Chinello, Clizia; Locatelli, Anna; Magni, Fulvio

    2014-02-01

    Preterm delivery is one of the main causes of perinatal morbidity and mortality and it accounts for 75 % of perinatal mortality and more than half of the long-term morbidity. We applied a proteomic approach based on mass spectrometry (MS) for biomarkers discovery of preterm premature rupture of membranes (pPROM) by investigating amniotic fluid (AF) invasively and non-invasively collected. Amniotic fluid was obtained from vagina of women with pPROM (group 1), PROM at term (group 2) and by genetic amniocentesis (group 3). Pre-fractionated AF proteome was analyzed through matrix assisted laser desorption ionization-time of flight (MALDI-TOF) MS. The characterization of proteins/peptides of interest was obtained by high performance liquid chromatography-electrospray tandem MS. Three peptides overexpressed in pPROM and able to discriminate the groups 1 and 2 were detected. One peptide was identified as the fragment Gly452LAVPDGPLGLPPKPro466 of the protein KIAA1522, expressed by fetal brain and liver. This peptide was overexpressed in a patient of the group 3, completely asymptomatic at the time of the amniocentesis, who later developed pPROM. Amniotic fluid invasively and non-invasively collected can be analyzed by MALDI-TOF MS to obtain proteomic profiles. Proteomic analysis identified a peptide with promising diagnostic capability for pPROM.

  3. Implementation of proteomic biomarkers: making it work.

    Science.gov (United States)

    Mischak, Harald; Ioannidis, John P A; Argiles, Angel; Attwood, Teresa K; Bongcam-Rudloff, Erik; Broenstrup, Mark; Charonis, Aristidis; Chrousos, George P; Delles, Christian; Dominiczak, Anna; Dylag, Tomasz; Ehrich, Jochen; Egido, Jesus; Findeisen, Peter; Jankowski, Joachim; Johnson, Robert W; Julien, Bruce A; Lankisch, Tim; Leung, Hing Y; Maahs, David; Magni, Fulvio; Manns, Michael P; Manolis, Efthymios; Mayer, Gert; Navis, Gerjan; Novak, Jan; Ortiz, Alberto; Persson, Frederik; Peter, Karlheinz; Riese, Hans H; Rossing, Peter; Sattar, Naveed; Spasovski, Goce; Thongboonkerd, Visith; Vanholder, Raymond; Schanstra, Joost P; Vlahou, Antonia

    2012-09-01

    While large numbers of proteomic biomarkers have been described, they are generally not implemented in medical practice. We have investigated the reasons for this shortcoming, focusing on hurdles downstream of biomarker verification, and describe major obstacles and possible solutions to ease valid biomarker implementation. Some of the problems lie in suboptimal biomarker discovery and validation, especially lack of validated platforms with well-described performance characteristics to support biomarker qualification. These issues have been acknowledged and are being addressed, raising the hope that valid biomarkers may start accumulating in the foreseeable future. However, successful biomarker discovery and qualification alone does not suffice for successful implementation. Additional challenges include, among others, limited access to appropriate specimens and insufficient funding, the need to validate new biomarker utility in interventional trials, and large communication gaps between the parties involved in implementation. To address this problem, we propose an implementation roadmap. The implementation effort needs to involve a wide variety of stakeholders (clinicians, statisticians, health economists, and representatives of patient groups, health insurance, pharmaceutical companies, biobanks, and regulatory agencies). Knowledgeable panels with adequate representation of all these stakeholders may facilitate biomarker evaluation and guide implementation for the specific context of use. This approach may avoid unwarranted delays or failure to implement potentially useful biomarkers, and may expedite meaningful contributions of the biomarker community to healthcare. © 2012 The Authors. European Journal of Clinical Investigation © 2012 Stichting European Society for Clinical Investigation Journal Foundation.

  4. Biomarkers of PTSD: military applications and considerations

    Directory of Open Access Journals (Sweden)

    Amy Lehrner

    2014-08-01

    Full Text Available Background: Although there are no established biomarkers for posttraumatic stress disorder (PTSD as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk for PTSD following trauma exposure, and predict or identify recovery. While there has been much interest in PTSD biomarkers, there has been less discussion of their potential clinical applications, and of the social, legal, and ethical implications of such biomarkers. Objective: This article will discuss possible applications of PTSD biomarkers, including the social, legal, and ethical implications of such biomarkers, with an emphasis on military applications. Method: Literature on applications of PTSD biomarkers and on potential ethical and legal implications will be reviewed. Results: Biologically informed research findings hold promise for prevention, assessment, treatment planning, and the development of prophylactic and treatment interventions. As with any biological indicator of disorder, there are potentially positive and negative clinical, social, legal, and ethical consequences of using such biomarkers. Conclusions: Potential clinical applications of PTSD biomarkers hold promise for clinicians, patients, and employers. The search for biomarkers of PTSD should occur in tandem with an interdisciplinary discussion regarding the potential implications of applying biological findings in clinical and employment settings.

  5. Biomarkers of PTSD: military applications and considerations.

    Science.gov (United States)

    Lehrner, Amy; Yehuda, Rachel

    2014-01-01

    Although there are no established biomarkers for posttraumatic stress disorder (PTSD) as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk for PTSD following trauma exposure, and predict or identify recovery. While there has been much interest in PTSD biomarkers, there has been less discussion of their potential clinical applications, and of the social, legal, and ethical implications of such biomarkers. This article will discuss possible applications of PTSD biomarkers, including the social, legal, and ethical implications of such biomarkers, with an emphasis on military applications. Literature on applications of PTSD biomarkers and on potential ethical and legal implications will be reviewed. Biologically informed research findings hold promise for prevention, assessment, treatment planning, and the development of prophylactic and treatment interventions. As with any biological indicator of disorder, there are potentially positive and negative clinical, social, legal, and ethical consequences of using such biomarkers. Potential clinical applications of PTSD biomarkers hold promise for clinicians, patients, and employers. The search for biomarkers of PTSD should occur in tandem with an interdisciplinary discussion regarding the potential implications of applying biological findings in clinical and employment settings.

  6. Biomarkers of PTSD: military applications and considerations

    OpenAIRE

    Amy Lehrner; Rachel Yehuda

    2014-01-01

    Background: Although there are no established biomarkers for posttraumatic stress disorder (PTSD) as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk fo...

  7. Multiple Sclerosis Cerebrospinal Fluid Biomarkers

    Directory of Open Access Journals (Sweden)

    Gavin Giovannoni

    2006-01-01

    Full Text Available Cerebrospinal fluid (CSF is the body fluid closest to the pathology of multiple sclerosis (MS. For many candidate biomarkers CSF is the only fluid that can be investigated. Several factors need to be standardized when sampling CSF for biomarker research: time/volume of CSF collection, sample processing/storage, and the temporal relationship of sampling to clinical or MRI markers of disease activity. Assays used for biomarker detection must be validated so as to optimize the power of the studies. A formal method for establishing whether or not a particular biomarker can be used as a surrogate end-point needs to be adopted. This process is similar to that used in clinical trials, where the reporting of studies has to be done in a standardized way with sufficient detail to permit a critical review of the study and to enable others to reproduce the study design. A commitment must be made to report negative studies so as to prevent publication bias. Pre-defined consensus criteria need to be developed for MS-related prognostic biomarkers. Currently no candidate biomarker is suitable as a surrogate end-point. Bulk biomarkers of the neurodegenerative process such as glial fibrillary acidic protein (GFAP and neurofilaments (NF have advantages over intermittent inflammatory markers.

  8. Implementation of proteomic biomarkers: making it work

    Science.gov (United States)

    Mischak, Harald; Ioannidis, John PA; Argiles, Angel; Attwood, Teresa K; Bongcam-Rudloff, Erik; Broenstrup, Mark; Charonis, Aristidis; Chrousos, George P; Delles, Christian; Dominiczak, Anna; Dylag, Tomasz; Ehrich, Jochen; Egido, Jesus; Findeisen, Peter; Jankowski, Joachim; Johnson, Robert W; Julien, Bruce A; Lankisch, Tim; Leung, Hing Y; Maahs, David; Magni, Fulvio; Manns, Michael P; Manolis, Efthymios; Mayer, Gert; Navis, Gerjan; Novak, Jan; Ortiz, Alberto; Persson, Frederik; Peter, Karlheinz; Riese, Hans H; Rossing, Peter; Sattar, Naveed; Spasovski, Goce; Thongboonkerd, Visith; Vanholder, Raymond; Schanstra, Joost P; Vlahou, Antonia

    2012-01-01

    While large numbers of proteomic biomarkers have been described, they are generally not implemented in medical practice. We have investigated the reasons for this shortcoming, focusing on hurdles downstream of biomarker verification, and describe major obstacles and possible solutions to ease valid biomarker implementation. Some of the problems lie in suboptimal biomarker discovery and validation, especially lack of validated platforms with well-described performance characteristics to support biomarker qualification. These issues have been acknowledged and are being addressed, raising the hope that valid biomarkers may start accumulating in the foreseeable future. However, successful biomarker discovery and qualification alone does not suffice for successful implementation. Additional challenges include, among others, limited access to appropriate specimens and insufficient funding, the need to validate new biomarker utility in interventional trials, and large communication gaps between the parties involved in implementation. To address this problem, we propose an implementation roadmap. The implementation effort needs to involve a wide variety of stakeholders (clinicians, statisticians, health economists, and representatives of patient groups, health insurance, pharmaceutical companies, biobanks, and regulatory agencies). Knowledgeable panels with adequate representation of all these stakeholders may facilitate biomarker evaluation and guide implementation for the specific context of use. This approach may avoid unwarranted delays or failure to implement potentially useful biomarkers, and may expedite meaningful contributions of the biomarker community to healthcare. PMID:22519700

  9. Carbon isotopes and lipid biomarker investigation of sources, transport and degradation of terrestrial organic matter in the Buor-Khaya Bay, SE Laptev Sea

    Directory of Open Access Journals (Sweden)

    E. S. Karlsson

    2011-07-01

    Full Text Available The world's largest continental shelf, the East Siberian Shelf Sea, receives substantial input of terrestrial organic carbon (terr-OC from both large rivers and erosion of its coastline. Degradation of organic matter from thawing permafrost in the Arctic is likely to increase, potentially creating a positive feedback mechanism to climate warming. This study focuses on the Buor-Khaya Bay (SE Laptev Sea, an area with strong terr-OC input from both coastal erosion and the Lena river. To better understand the fate of this terr-OC, molecular (acyl lipid biomarkers and isotopic tools (stable carbon and radiocarbon isotopes have been applied to both particulate organic carbon (POC in surface water and sedimentary organic carbon (SOC collected from the underlying surface sediments.

    Clear gradients in both extent of degradation and differences in source contributions were observed both between surface water POC and surface sediment SOC as well as over the 100 s km investigation scale (about 20 stations. Depleted δ13C-OC and high HMW/LMW n-alkane ratios signaled that terr-OC was dominating over marine/planktonic sources.

    Despite a shallow water column (10–40 m, the isotopic shift between SOC and POC varied systematically from +2 to +5 per mil for δ13C and from +300 to +450 for Δ14C from the Lena prodelta to the Buor-Khaya Cape. At the same time, the ratio of HMW n-alkanoic acids to HMW n-alkanes as well as HMW n-alkane CPI, both indicative of degradation, were 5–6 times greater in SOC than in POC. This suggests that terr-OC was substantially older yet less degraded in the surface sediment than in the surface waters. This unusual vertical degradation trend was only recently found also for the central East Siberian Sea.

    Numerical modeling (Monte Carlo simulations with δ13C and Δ14C in both POC and SOC was applied to deduce the relative

  10. Implementation of proteomic biomarkers : Making it work

    NARCIS (Netherlands)

    Mischak, Harald; Ioannidis, John P. A.; Argiles, Angel; Attwood, Teresa K.; Bongcam-Rudloff, Erik; Broenstrup, Mark; Charonis, Aristidis; Chrousos, George P.; Delles, Christian; Dominiczak, Anna; Dylag, Tomasz; Ehrich, Jochen; Egido, Jesus; Findeisen, Peter; Jankowski, Joachim; Johnson, Robert W.; Julien, Bruce A.; Lankisch, Tim; Leung, Hing Y.; Maahs, David; Magni, Fulvio; Manns, Michael P.; Manolis, Efthymios; Mayer, Gert; Navis, Gerarda; Novak, Jan; Ortiz, Alberto; Persson, Frederik; Peter, Karlheinz; Riese, Hans H.; Rossing, Peter; Sattar, Naveed; Spasovski, Goce; Thongboonkerd, Visith; Vanholder, Raymond; Schanstra, Joost P.; Vlahou, Antonia

    Eur J Clin Invest 2012; 42 (9): 10271036 Abstract While large numbers of proteomic biomarkers have been described, they are generally not implemented in medical practice. We have investigated the reasons for this shortcoming, focusing on hurdles downstream of biomarker verification, and describe

  11. 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....

  12. Investigation of human cationic antimicrobial protein-18 (hCAP-18), lactoferrin and CD163 as potential biomarkers for ovarian cancer

    DEFF Research Database (Denmark)

    Lim, Ratana; Lappas, Martha; Riley, Clyde

    2013-01-01

    controls, including 28 women with benign pelvic masses; 91 cancer, including 21 women with borderline tumours). Localisation of each antigen within the ovary was assessed by immunohistochemistry and serum concentrations determined by ELISA assays. RESULTS: Immunoreactive (ir) hCAP-18 and lactoferrin were......BACKGROUND: Epithelial ovarian cancer is one of the leading causes of gynaecological cancer morbidity and mortality in women. Early stage ovarian cancer is usually asymptomatic, therefore, is often first diagnosed when it is widely disseminated. Currently available diagnostics lack the requisite...... and plasma concentrations of three putative ovarian cancer biomarkers: human cationic antimicrobial protein-18 (hCAP-18); lactoferrin; and CD163 in normal healthy women and women with ovarian cancer. METHODS: In this case-control cohort study, ovarian tissue and blood samples were obtained from 164 women (73...

  13. Chiral Biomarkers in Meteorites

    Science.gov (United States)

    Hoover, Richard B.

    2010-01-01

    The chirality of organic molecules with the asymmetric location of group radicals was discovered in 1848 by Louis Pasteur during his investigations of the rotation of the plane of polarization of light by crystals of sodium ammonium paratartrate. It is well established that the amino acids in proteins are exclusively Levorotary (L-aminos) and the sugars in DNA and RNA are Dextrorotary (D-sugars). This phenomenon of homochirality of biological polymers is a fundamental property of all life known on Earth. Furthermore, abiotic production mechanisms typically yield recemic mixtures (i.e. equal amounts of the two enantiomers). When amino acids were first detected in carbonaceous meteorites, it was concluded that they were racemates. This conclusion was taken as evidence that they were extraterrestrial and produced by abiologically. Subsequent studies by numerous researchers have revealed that many of the amino acids in carbonaceous meteorites exhibit a significant L-excess. The observed chirality is much greater than that produced by any currently known abiotic processes (e.g. Linearly polarized light from neutron stars; Circularly polarized ultraviolet light from faint stars; optically active quartz powders; inclusion polymerization in clay minerals; Vester-Ulbricht hypothesis of parity violations, etc.). This paper compares the measured chirality detected in the amino acids of carbonaceous meteorites with the effect of these diverse abiotic processes. IT is concluded that the levels observed are inconsistent with post-arrival biological contamination or with any of the currently known abiotic production mechanisms. However, they are consistent with ancient biological processes on the meteorite parent body. This paper will consider these chiral biomarkers in view of the detection of possible microfossils found in the Orgueil and Murchison carbonaceous meteorites. Energy dispersive x-ray spectroscopy (EDS) data obtained on these morphological biomarkers will be

  14. Functional activity of plasmid DNA after entry into the atmosphere of earth investigated by a new biomarker stability assay for ballistic spaceflight experiments.

    Directory of Open Access Journals (Sweden)

    Cora S Thiel

    Full Text Available Sounding rockets represent an excellent platform for testing the influence of space conditions during the passage of Earth's atmosphere and re-entry on biological, physical and chemical experiments for astrobiological purposes. We designed a robust functionality biomarker assay to analyze the biological effects of suborbital spaceflights prevailing during ballistic rocket flights. During the TEXUS-49 rocket mission in March 2011, artificial plasmid DNA carrying a fluorescent marker (enhanced green fluorescent protein: EGFP and an antibiotic resistance cassette (kanamycin/neomycin was attached on different positions of rocket exterior; (i circular every 90 degree on the outer surface concentrical of the payload, (ii in the grooves of screw heads located in between the surface application sites, and (iii on the surface of the bottom side of the payload. Temperature measurements showed two major peaks at 118 and 130 °C during the 780 seconds lasting flight on the inside of the recovery module, while outer gas temperatures of more than 1000 °C were estimated on the sample application locations. Directly after retrieval and return transport of the payload, the plasmid DNA samples were recovered. Subsequent analyses showed that DNA could be recovered from all application sites with a maximum of 53% in the grooves of the screw heads. We could further show that up to 35% of DNA retained its full biological function, i.e., mediating antibiotic resistance in bacteria and fluorescent marker expression in eukaryotic cells. These experiments show that our plasmid DNA biomarker assay is suitable to characterize the environmental conditions affecting DNA during an atmospheric transit and the re-entry and constitute the first report of the stability of DNA during hypervelocity atmospheric transit indicating that sounding rocket flights can be used to model the high-speed atmospheric entry of organics-laden artificial meteorites.

  15. Study protocol of the B-CAST study: a multicenter, prospective cohort study investigating the tumor biomarkers in adjuvant chemotherapy for stage III colon cancer

    International Nuclear Information System (INIS)

    Ishiguro, Megumi; Mori, Masaki; Kakeji, Yoshihiro; Kanazawa, Akiyoshi; Kobayashi, Michiya; Okajima, Masazumi; Hyodo, Ichinosuke; Miyakoda, Keiko; Sugihara, Kenichi; Kotake, Kenjiro; Nishimura, Genichi; Tomita, Naohiro; Ichikawa, Wataru; Takahashi, Keiichi; Watanabe, Toshiaki; Furuhata, Tomohisa; Kondo, Ken

    2013-01-01

    Adjuvant chemotherapy for stage III colon cancer is internationally accepted as standard treatment with established efficacy. Several oral fluorouracil (5-FU) derivatives with different properties are available in Japan, but which drug is the most appropriate for each patient has not been established. Although efficacy prediction of 5-FU derivatives using expression of 5-FU activation/metabolism enzymes in tumors has been studied, it has not been clinically applied. The B-CAST study is a multicenter, prospective cohort study aimed to identify the patients who benefit from adjuvant chemotherapy with each 5-FU regimen, through evaluating the relationship between tumor biomarker expression and treatment outcome. The frozen tumor specimens of patients with stage III colon cancer who receives postoperative adjuvant chemotherapy are examined. Protein expression of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) are evaluated using enzyme-linked immunosorbent assay (ELISA). mRNA expression of TP, DPD, thymidylate synthase (TS) and orotate phosphoribosyl transferase (OPRT) are evaluated using reverse transcription polymerase chain reaction (RT-PCR). The patients’ clinical data reviewed are as follow: demographic and pathological characteristics, regimen, drug doses and treatment duration of adjuvant therapy, types and severity of adverse events, disease free survival, relapse free survival and overall survival. Then, relationships among the protein/mRNA expression, clinicopathological characteristics and the treatment outcomes are analyzed for each 5-FU derivative. A total of 2,128 patients from the 217 institutions were enrolled between April 2009 and March 2012. The B-CAST study demonstrated that large-scale, multicenter translational research using frozen samples was feasible when the sample shipment and Web-based data collection were well organized. The results

  16. 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.

  17. 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

  18. Evaluating biomarkers for prognostic enrichment of clinical trials.

    Science.gov (United States)

    Kerr, Kathleen F; Roth, Jeremy; Zhu, Kehao; Thiessen-Philbrook, Heather; Meisner, Allison; Wilson, Francis Perry; Coca, Steven; Parikh, Chirag R

    2017-12-01

    A potential use of biomarkers is to assist in prognostic enrichment of clinical trials, where only patients at relatively higher risk for an outcome of interest are eligible for the trial. We investigated methods for evaluating biomarkers for prognostic enrichment. We identified five key considerations when considering a biomarker and a screening threshold for prognostic enrichment: (1) clinical trial sample size, (2) calendar time to enroll the trial, (3) total patient screening costs and the total per-patient trial costs, (4) generalizability of trial results, and (5) ethical evaluation of trial eligibility criteria. Items (1)-(3) are amenable to quantitative analysis. We developed the Biomarker Prognostic Enrichment Tool for evaluating biomarkers for prognostic enrichment at varying levels of screening stringency. We demonstrate that both modestly prognostic and strongly prognostic biomarkers can improve trial metrics using Biomarker Prognostic Enrichment Tool. Biomarker Prognostic Enrichment Tool is available as a webtool at http://prognosticenrichment.com and as a package for the R statistical computing platform. In some clinical settings, even biomarkers with modest prognostic performance can be useful for prognostic enrichment. In addition to the quantitative analysis provided by Biomarker Prognostic Enrichment Tool, investigators must consider the generalizability of trial results and evaluate the ethics of trial eligibility criteria.

  19. Biomarkers in Airway Diseases

    Directory of Open Access Journals (Sweden)

    Janice M Leung

    2013-01-01

    Full Text Available The inherent limitations of spirometry and clinical history have prompted clinicians and scientists to search for surrogate markers of airway diseases. Although few biomarkers have been widely accepted into the clinical armamentarium, the authors explore three sources of biomarkers that have shown promise as indicators of disease severity and treatment response. In asthma, exhaled nitric oxide measurements can predict steroid responsiveness and sputum eosinophil counts have been used to titrate anti-inflammatory therapies. In chronic obstructive pulmonary disease, inflammatory plasma biomarkers, such as fibrinogen, club cell secretory protein-16 and surfactant protein D, can denote greater severity and predict the risk of exacerbations. While the multitude of disease phenotypes in respiratory medicine make biomarker development especially challenging, these three may soon play key roles in the diagnosis and management of airway diseases.

  20. amphibian_biomarker_data

    Data.gov (United States)

    U.S. Environmental Protection Agency — Amphibian metabolite data used in Snyder, M.N., Henderson, W.M., Glinski, D.G., Purucker, S. T., 2017. Biomarker analysis of american toad (Anaxyrus americanus) and...

  1. 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...

  2. 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.

  3. Biomarkers in T cell therapy clinical trials

    Directory of Open Access Journals (Sweden)

    Kalos Michael

    2011-08-01

    Full Text Available Abstract T cell therapy represents an emerging and promising modality for the treatment of both infectious disease and cancer. Data from recent clinical trials have highlighted the potential for this therapeutic modality to effect potent anti-tumor activity. Biomarkers, operationally defined as biological parameters measured from patients that provide information about treatment impact, play a central role in the development of novel therapeutic agents. In the absence of information about primary clinical endpoints, biomarkers can provide critical insights that allow investigators to guide the clinical development of the candidate product. In the context of cell therapy trials, the definition of biomarkers can be extended to include a description of parameters of the cell product that are important for product bioactivity. This review will focus on biomarker studies as they relate to T cell therapy trials, and more specifically: i. An overview and description of categories and classes of biomarkers that are specifically relevant to T cell therapy trials, and ii. Insights into future directions and challenges for the appropriate development of biomarkers to evaluate both product bioactivity and treatment efficacy of T cell therapy trials.

  4. Current investigations into the genotoxicity of zinc oxide and silica nanoparticles in mammalian models in vitro and in vivo: carcinogenic/genotoxic potential, relevant mechanisms and biomarkers, artifacts, and limitations

    Directory of Open Access Journals (Sweden)

    Kwon JY

    2014-12-01

    Full Text Available Jee Young Kwon,1,* Preeyaporn Koedrith,2,* Young Rok Seo1 1Department of Life Science, Institute of Environmental Medicine, Dongguk University, Seoul, Republic of Korea; 2Faculty of Environment and Resource Studies, Mahidol University, Phuttamonthon District, NakhonPathom, Thailand *These authors contributed equally to this work and should be considered as co-first authors Abstract: Engineered nanoparticles (NPs are widely used in many sectors, such as food, medicine, military, and sport, but their unique characteristics may cause deleterious health effects. Close attention is being paid to metal NP genotoxicity; however, NP genotoxic/carcinogenic effects and the underlying mechanisms remain to be elucidated. In this review, we address some metal and metal oxide NPs of interest and current genotoxicity tests in vitro and in vivo. Metal NPs can cause DNA damage such as chromosomal aberrations, DNA strand breaks, oxidative DNA damage, and mutations. We also discuss several parameters that may affect genotoxic response, including physicochemical properties, widely used assays/end point tests, and experimental conditions. Although potential biomarkers of nanogenotoxicity or carcinogenicity are suggested, inconsistent findings in the literature render results inconclusive due to a variety of factors. Advantages and limitations related to different methods for investigating genotoxicity are described, and future directions and recommendations for better understanding genotoxic potential are addressed. Keywords: carcinogenicity, exposure assessment, genotoxicity, nanoparticles, risk evaluation

  5. The Wide and Complex Field of NAFLD Biomarker Research: Trends.

    Science.gov (United States)

    Wichro, Erika; Macheiner, Tanja; Schmid, Jasmin; Kavsek, Barbara; Sargsyan, Karine

    2014-01-01

    Background. Nonalcoholic fatty liver disease is now acknowledged as a complex public health issue linked to sedentary lifestyle, obesity, and related disorders like type 2 diabetes and metabolic syndrome. Aims. We aimed to retrieve its trends out of the huge amount of published data. Therefore, we conducted an extensive literature search to identify possible biomarker and/or biomarker combinations by retrospectively assessing and evaluating common and novel biomarkers to predict progression and prognosis of obesity related liver diseases. Methodology. We analyzed finally 62 articles accounting for 157 cohorts and 45,288 subjects. Results. Despite the various approaches, most cohorts were considerably small and rarely comparable. Also, we found that the same standard parameters were measured rather than novel biomarkers. Diagnostics approaches appeared incomparable. Conclusions. Further collaborative investigations on harmonizing ways of data acquisition and identifying such biomarkers for clinical use are necessary to yield sufficient significant results of potential biomarkers.

  6. Biomarkers of sepsis

    Science.gov (United States)

    2013-01-01

    Sepsis is an unusual systemic reaction to what is sometimes an otherwise ordinary infection, and it probably represents a pattern of response by the immune system to injury. A hyper-inflammatory response is followed by an immunosuppressive phase during which multiple organ dysfunction is present and the patient is susceptible to nosocomial infection. Biomarkers to diagnose sepsis may allow early intervention which, although primarily supportive, can reduce the risk of death. Although lactate is currently the most commonly used biomarker to identify sepsis, other biomarkers may help to enhance lactate’s effectiveness; these include markers of the hyper-inflammatory phase of sepsis, such as pro-inflammatory cytokines and chemokines; proteins such as C-reactive protein and procalcitonin which are synthesized in response to infection and inflammation; and markers of neutrophil and monocyte activation. Recently, markers of the immunosuppressive phase of sepsis, such as anti-inflammatory cytokines, and alterations of the cell surface markers of monocytes and lymphocytes have been examined. Combinations of pro- and anti-inflammatory biomarkers in a multi-marker panel may help identify patients who are developing severe sepsis before organ dysfunction has advanced too far. Combined with innovative approaches to treatment that target the immunosuppressive phase, these biomarkers may help to reduce the mortality rate associated with severe sepsis which, despite advances in supportive measures, remains high. PMID:23480440

  7. 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.

  8. Biomarkers of the Dementia

    Directory of Open Access Journals (Sweden)

    Mikio Shoji

    2011-01-01

    Full Text Available Recent advances in biomarker studies on dementia are summarized here. CSF Aβ40, Aβ42, total tau, and phosphorylated tau are the most sensitive biomarkers for diagnosis of Alzheimer's disease (AD and prediction of onset of AD from mild cognitive impairment (MCI. Based on this progress, new diagnostic criteria for AD, MCI, and preclinical AD were proposed by National Institute of Aging (NIA and Alzheimer's Association in August 2010. In these new criteria, progress in biomarker identification and amyloid imaging studies in the past 10 years have added critical information. Huge contributions of basic and clinical studies have established clinical evidence supporting these markers. Based on this progress, essential therapy for cure of AD is urgently expected.

  9. Inflammatory biomarkers and cancer

    DEFF Research Database (Denmark)

    Rasmussen, Line Jee Hartmann; Schultz, Martin; Gaardsting, Anne

    2017-01-01

    and previous cancer diagnoses compared to patients who were not diagnosed with cancer. Previous cancer, C-reactive protein (CRP) and suPAR were significantly associated with newly diagnosed cancer during follow-up in multiple logistic regression analyses adjusted for age, sex and CRP. Neither any of the PRRs......In Denmark, patients with serious nonspecific symptoms and signs of cancer (NSSC) are referred to the diagnostic outpatient clinics (DOCs) where an accelerated cancer diagnostic program is initiated. Various immunological and inflammatory biomarkers have been associated with cancer, including...... soluble urokinase plasminogen activator receptor (suPAR) and the pattern recognition receptors (PRRs) pentraxin-3, mannose-binding lectin, ficolin-1, ficolin-2 and ficolin-3. We aimed to evaluate these biomarkers and compare their diagnostic ability to classical biomarkers for diagnosing cancer...

  10. The economics of cardiac biomarker testing in suspected myocardial infarction.

    Science.gov (United States)

    Goodacre, Steve; Thokala, Praveen

    2015-03-01

    Suspected myocardial infarction (MI) is a common reason for emergency hospital attendance and admission. Cardiac biomarker measurement is an essential element of diagnostic assessment of suspected MI. Although the cost of a routinely available biomarker may be small, the large patient population and consequences in terms of hospital admission and investigation mean that the economic impact of cardiac biomarker testing is substantial. Economic evaluation involves comparing the estimated costs and effectiveness (outcomes) of two or more interventions or care alternatives. This process creates some difficulties with respect to cardiac biomarkers. Estimating the effectiveness of cardiac biomarkers involves identifying how they help to improve health and how we can measure this improvement. Comparison to an appropriate alternative is also problematic. New biomarkers may be promoted on the basis of reducing hospital admission or length of stay, but hospital admission for low risk patients may incur significant costs while providing very little benefit, making it an inappropriate comparator. Finally, economic evaluation may conclude that a more sensitive biomarker strategy is more effective but, by detecting and treating more cases, is also more expensive. In these circumstances it is unclear whether we should use the more effective or the cheaper option. This article provides an introduction to health economics and addresses the specific issues relevant to cardiac biomarkers. It describes the key concepts relevant to economic evaluation of cardiac biomarkers in suspected MI and highlights key areas of uncertainty and controversy. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  11. Addressing small sample size bias in multiple-biomarker trials: Inclusion of biomarker-negative patients and Firth correction.

    Science.gov (United States)

    Habermehl, Christina; Benner, Axel; Kopp-Schneider, Annette

    2018-03-01

    In recent years, numerous approaches for biomarker-based clinical trials have been developed. One of these developments are multiple-biomarker trials, which aim to investigate multiple biomarkers simultaneously in independent subtrials. For low-prevalence biomarkers, small sample sizes within the subtrials have to be expected, as well as many biomarker-negative patients at the screening stage. The small sample sizes may make it unfeasible to analyze the subtrials individually. This imposes the need to develop new approaches for the analysis of such trials. With an expected large group of biomarker-negative patients, it seems reasonable to explore options to benefit from including them in such trials. We consider advantages and disadvantages of the inclusion of biomarker-negative patients in a multiple-biomarker trial with a survival endpoint. We discuss design options that include biomarker-negative patients in the study and address the issue of small sample size bias in such trials. We carry out a simulation study for a design where biomarker-negative patients are kept in the study and are treated with standard of care. We compare three different analysis approaches based on the Cox model to examine if the inclusion of biomarker-negative patients can provide a benefit with respect to bias and variance of the treatment effect estimates. We apply the Firth correction to reduce the small sample size bias. The results of the simulation study suggest that for small sample situations, the Firth correction should be applied to adjust for the small sample size bias. Additional to the Firth penalty, the inclusion of biomarker-negative patients in the analysis can lead to further but small improvements in bias and standard deviation of the estimates. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Biomarkers for anorexia nervosa

    DEFF Research Database (Denmark)

    Sjøgren, Jan Magnus

    2017-01-01

    Biomarkers for anorexia nervosa (AN) which reflect the pathophysiology and relate to the aetiology of the disease, are warranted and could bring us one step closer to targeted treatment of AN. Some leads may be found in the biochemistry which often is found disturbed in AN, although normalization...

  13. 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.

  14. Biomarkers of Pediatric Brain Tumors

    Directory of Open Access Journals (Sweden)

    Mark D Russell

    2013-03-01

    Full Text Available Background and Need for Novel Biomarkers: Brain tumors are the leading cause of death by solid tumors in children. Although improvements have been made in their radiological detection and treatment, our capacity to promptly diagnose pediatric brain tumors in their early stages remains limited. This contrasts several other cancers where serum biomarkers such as CA 19-9 and CA 125 facilitate early diagnosis and treatment. Aim: The aim of this article is to review the latest literature and highlight biomarkers which may be of clinical use in the common types of primary pediatric brain tumor. Methods: A PubMed search was performed to identify studies reporting biomarkers in the bodily fluids of pediatric patients with brain tumors. Details regarding the sample type (serum, cerebrospinal fluid or urine, biomarkers analyzed, methodology, tumor type and statistical significance were recorded. Results: A total of 12 manuscripts reporting 19 biomarkers in 367 patients vs. 397 controls were identified in the literature. Of the 19 biomarkers identified, 12 were isolated from cerebrospinal fluid, 2 from serum, 3 from urine, and 2 from multiple bodily fluids. All but one study reported statistically significant differences in biomarker expression between patient and control groups.Conclusions: This review identifies a panel of novel biomarkers for pediatric brain tumors. It provides a platform for the further studies necessary to validate these biomarkers and, in addition, highlights several techniques through which new biomarkers can be discovered.

  15. Anxiety, Family Functioning and Neuroendocrine Biomarkers in Obese Children

    Directory of Open Access Journals (Sweden)

    Inês Pinto

    2017-04-01

    Conclusion: These results highlight the importance of taking into account family functioning, parental mental state and gender, when investigating neuroendocrine biomarkers in obese children associated with symptoms of anxiety and depression.

  16. Can Biomarkers Help the Early Diagnosis of Parkinson's Disease?

    Institute of Scientific and Technical Information of China (English)

    Weidong Le; Jie Dong; Song Li; Amos D.Korczyn

    2017-01-01

    Parkinson's disease (PD) is a complex neurodegenerative disease with progressive loss of dopamine neurons.PD patients usually manifest a series of motor and non-motor symptoms.In order to provide better early diagnosis and subsequent disease-modifying therapies for PD patients,there is an urgent need to identify sensitive and specific biomarkers.Biomarkers can be divided into four categories:clinical,imaging,biochemical,and genetic.Ideal biomarkers not only improve our understanding of PD pathogenesis and progression,but also provide benefits for early risk evaluation and clinical diagnosis of PD.Although many efforts have been made and several biomarkers have been extensively investigated,few if any have been found useful for early diagnosis.Here,we summarize recent developments in the discovered biomarkers of PD and discuss their merits and limitations for the early diagnosis of PD.

  17. Novel biomarkers for sepsis

    DEFF Research Database (Denmark)

    Larsen, Frederik Fruergaard; Petersen, J Asger

    2017-01-01

    BACKGROUND: Sepsis is a prevalent condition among hospitalized patients that carries a high risk of morbidity and mortality. Rapid recognition of sepsis as the cause of deterioration is desirable, so effective treatment can be initiated rapidly. Traditionally, diagnosis was based on presence of two...... or more positive SIRS criteria due to infection. However, recently published sepsis-3 criteria put more emphasis on organ dysfunction caused by infection in the definition of sepsis. Regardless of this, no gold standard for diagnosis exist, and clinicians still rely on a number of traditional and novel...... biomarkers to discriminate between patients with and without infection, as the cause of deterioration. METHOD: Narrative review of current literature. RESULTS: A number of the most promising biomarkers for diagnoses and prognostication of sepsis are presented. CONCLUSION: Procalcitonin, presepsin, CD64, su...

  18. 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.

  19. Imperfect Gold Standards for Kidney Injury Biomarker Evaluation

    Science.gov (United States)

    Betensky, Rebecca A.; Emerson, Sarah C.; Bonventre, Joseph V.

    2012-01-01

    Clinicians have used serum creatinine in diagnostic testing for acute kidney injury for decades, despite its imperfect sensitivity and specificity. Novel tubular injury biomarkers may revolutionize the diagnosis of acute kidney injury; however, even if a novel tubular injury biomarker is 100% sensitive and 100% specific, it may appear inaccurate when using serum creatinine as the gold standard. Acute kidney injury, as defined by serum creatinine, may not reflect tubular injury, and the absence of changes in serum creatinine does not assure the absence of tubular injury. In general, the apparent diagnostic performance of a biomarker depends not only on its ability to detect injury, but also on disease prevalence and the sensitivity and specificity of the imperfect gold standard. Assuming that, at a certain cutoff value, serum creatinine is 80% sensitive and 90% specific and disease prevalence is 10%, a new perfect biomarker with a true 100% sensitivity may seem to have only 47% sensitivity compared with serum creatinine as the gold standard. Minimizing misclassification by using more strict criteria to diagnose acute kidney injury will reduce the error when evaluating the performance of a biomarker under investigation. Apparent diagnostic errors using a new biomarker may be a reflection of errors in the imperfect gold standard itself, rather than poor performance of the biomarker. The results of this study suggest that small changes in serum creatinine alone should not be used to define acute kidney injury in biomarker or interventional studies. PMID:22021710

  20. [Biomarkers of Alzheimer disease].

    Science.gov (United States)

    Rachel, Wojciech; Grela, Agatha; Zyss, Tomasz; Zieba, Andrzej; Piekoszewski, Wojciech

    2014-01-01

    Cognitive impairment is one of the most abundant age-related psychiatric disorders. The outcome of cognitive impairment in Alzheimer's disease has both individual (the patients and their families) and socio-economic effects. The prevalence of Alzheimer's disease doubles after the age of 65 years, every 4.5 years. An etiologically heterogenic group of disorders related to aging as well as genetic and environmental interactions probably underlie the impairment in Alzheimer's disease. Those factors cause the degeneration of brain tissue which leads to significant cognitive dysfunction. There are two main hypotheses that are linked to the process of neurodegeneration: (i) amyloid cascade and (ii) the role of secretases and dysfunction of mitochondria. From the therapeutic standpoint it is crucial to get an early diagnosis and start with an adequate treatment. The undeniable progress in the field of biomarker research should lead to a better understanding of the early stages of the disorder. So far, the best recognised and described biomarkers of Alzheimer's disease, which can be detected in both cerebrospinal fluid and blood, are: beta-amyloid, tau-protein and phosphorylated tau-protein (phospho-tau). The article discusses the usefulness of the known biomarkers of Alzheimer's disease in early diagnosis.

  1. 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

  2. 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

  3. Predictive Biomarkers for Asthma Therapy.

    Science.gov (United States)

    Medrek, Sarah K; Parulekar, Amit D; Hanania, Nicola A

    2017-09-19

    Asthma is a heterogeneous disease characterized by multiple phenotypes. Treatment of patients with severe disease can be challenging. Predictive biomarkers are measurable characteristics that reflect the underlying pathophysiology of asthma and can identify patients that are likely to respond to a given therapy. This review discusses current knowledge regarding predictive biomarkers in asthma. Recent trials evaluating biologic therapies targeting IgE, IL-5, IL-13, and IL-4 have utilized predictive biomarkers to identify patients who might benefit from treatment. Other work has suggested that using composite biomarkers may offer enhanced predictive capabilities in tailoring asthma therapy. Multiple biomarkers including sputum eosinophil count, blood eosinophil count, fractional concentration of nitric oxide in exhaled breath (FeNO), and serum periostin have been used to identify which patients will respond to targeted asthma medications. Further work is needed to integrate predictive biomarkers into clinical practice.

  4. 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.

  5. 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.)

  6. Biomarkers for predicting complete debulking in ovarian cancer

    DEFF Research Database (Denmark)

    Fagö-Olsen, Carsten Lindberg; Ottesen, Bent; Christensen, Ib Jarle

    2014-01-01

    AIM: We aimed to construct and validate a model based on biomarkers to predict complete primary debulking surgery for ovarian cancer patients. PATIENTS AND METHODS: The study consisted of three parts: Part I: Biomarker data obtained from mass spectrometry, baseline data and, surgical outcome were...... used to construct predictive indices for complete tumour resection; Part II: sera from randomly selected patients from part I were analyzed using enzyme-linked immunosorbent assay (ELISA) to investigate the correlation to mass spectrometry; Part III: the indices from part I were validated in a new.......64. CONCLUSION: Our validated model based on biomarkers was unable to predict surgical outcome for patients with ovarian cancer....

  7. Biomarkers in Prostate Cancer Epidemiology

    Directory of Open Access Journals (Sweden)

    Mudit Verma

    2011-09-01

    Full Text Available Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high risk for developing prostate cancer. In cancer epidemiology, epigenetic biomarkers offer advantages over other types of biomarkers because they are expressed against a person’s genetic background and environmental exposure, and because abnormal events occur early in cancer development, which includes several epigenetic alterations in cancer cells. This article describes different biomarkers that have potential use in studying the epidemiology of prostate cancer. We also discuss the characteristics of an ideal biomarker for prostate cancer, and technologies utilized for biomarker assays. Among epigenetic biomarkers, most reports indicate GSTP1 hypermethylation as the diagnostic marker for prostate cancer; however, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS, and NSE1 also have been reported to be regulated by methylation mechanisms in prostate cancer. Current challenges in utilization of biomarkers in prostate cancer diagnosis and epidemiologic studies and potential solutions also are discussed.

  8. 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.

  9. Hepcidin- A Burgeoning Biomarker

    Directory of Open Access Journals (Sweden)

    Hemkant Manikrao Deshmukh

    2017-10-01

    Full Text Available The discovery of hepcidin has triggered a virtual ignition of studies on iron metabolism and related disorders. The peptide hormone hepcidin is a key homeostatic regulator of iron metabolism. The synthesis of hepcidin is induced by systemic iron levels and by inflammatory stimuli. Several human diseases are associated with variations in hepcidin concentrations. The evaluation of hepcidin in biological fluids is therefore a promising device in the diagnosis and management of medical situations in which iron metabolism is affected. Thus, it made us to recapitulate role of hepcidin as biomarker.

  10. Towards Improved Biomarker Research

    DEFF Research Database (Denmark)

    Kjeldahl, Karin

    This thesis takes a look at the data analytical challenges associated with the search for biomarkers in large-scale biological data such as transcriptomics, proteomics and metabolomics data. These studies aim to identify genes, proteins or metabolites which can be associated with e.g. a diet...... with very specific competencies. In order to optimize the basis of a sound and fruitful data analysis, suggestions are givenwhich focus on (1) collection of good data, (2) preparation of data for the data analysis and (3) a sound data analysis. If these steps are optimized, PLS is a also a very goodmethod...

  11. Metabolomics approach for discovering disease biomarkers and understanding metabolic pathway

    Directory of Open Access Journals (Sweden)

    Jeeyoun Jung

    2011-12-01

    Full Text Available Metabolomics, the multi-targeted analysis of endogenous metabolites from biological samples, can be efficiently applied to screen disease biomarkers and investigate pathophysiological processes. Metabolites change rapidly in response to physiological perturbations, making them the closest link to disease phenotypes. This study explored the role of metabolomics in gaining mechanistic insight into disease processes and in searching for novel biomarkers of human diseases

  12. Biomarkers for Ectopic Pregnancy and Pregnancy of Unknown Location

    OpenAIRE

    Senapati, Suneeta; Barnhart, Kurt T.

    2013-01-01

    Early pregnancy failure is the most common complication of pregnancy, and 1–2% of all pregnancies will be ectopic. As one of the leading causes of maternal morbidity and mortality, diagnosing ectopic pregnancy and determining the fate of a pregnancy of unknown location are of great clinical concern. Several serum and plasma biomarkers for ectopic pregnancy have been investigated independently and in combination. The following is a review of the state of biomarker discovery and development for...

  13. Biomarkers in Vasculitis

    Science.gov (United States)

    Monach, Paul A.

    2014-01-01

    Purpose of review Better biomarkers are needed for guiding management of patients with vasculitis. Large cohorts and technological advances had led to an increase in pre-clinical studies of potential biomarkers. Recent findings The most interesting markers described recently include a gene expression signature in CD8+ T cells that predicts tendency to relapse or remain relapse-free in ANCA-associated vasculitis, and a pair of urinary proteins that are elevated in Kawasaki disease but not other febrile illnesses. Both of these studies used “omics” technologies to generate and then test hypotheses. More conventional hypothesis-based studies have indicated that the following circulating proteins have potential to improve upon clinically available tests: pentraxin-3 in giant cell arteritis and Takayasu’s arteritis; von Willebrand factor antigen in childhood central nervous system vasculitis; eotaxin-3 and other markers related to eosinophils or Th2 immune responses in eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome); and MMP-3, TIMP-1, and CXCL13 in ANCA-associated vasculitis. Summary New markers testable in blood and urine have the potential to assist with diagnosis, staging, assessment of current disease activity, and prognosis. However, the standards for clinical usefulness, in particular the demonstration of either very high sensitivity or very high specificity, have yet to be met for clinically relevant outcomes. PMID:24257367

  14. Tracking Biocultural Pathways to Health Disparities: The Value of Biomarkers

    Science.gov (United States)

    Worthman, Carol M.; Costello, E. Jane

    2009-01-01

    Background Cultural factors and biomarkers are emerging emphases in social epidemiology that readily ally with human biology and anthropology. Persistent health challenges and disparities have established biocultural roots, and environment plays an integral role in physical development and function that form the bases of population health. Biomarkers have proven to be valuable tools for investigating biocultural bases of health disparities. Aims We apply recent insights from biology to consider how culture gets under the skin and evaluate the construct of embodiment. We analyze contrasting biomarker models and applications, and propose an integrated model for biomarkers. Three examples from the Great Smoky Mountains Study (GSMS) illustrate these points. Subjects and methods The longitudinal developmental epidemiological GSMS comprises a population-based sample of 1420 children with repeated measures including mental and physical health, life events, household conditions, and biomarkers for pubertal development and allostatic load. Results Analyses using biomarkers resolved competing explanations for links between puberty and depression, identified gender differences in stress at puberty, and revealed interactive effects of birthweight and postnatal adversity on risk for depression at puberty in girls. Conclusion An integrated biomarker model can both enrich epidemiology and illuminate biocultural pathways in population health. PMID:19381986

  15. Biomarkers of general stress in mussels as common indicators for marine biomonitoring programmes in Europe: The ICON experience

    NARCIS (Netherlands)

    Martínez-Gómez, C.; Robinson, C.D.; Burgeot, T.; Gubbins, M.J.; Halldórsson, H.P.; Albentosa, M.; Bignell, J.P.; Hylland, K.; Vethaak, A.D.

    2017-01-01

    This study investigated whether general stress biomarkers in mussels can be applied as common first-tier biomarkers in regional biomonitoring programmes in the North Sea (including Iceland) and western Mediterranean Sea. Stress on Stress (SoS) and lysosomal membrane stability (LMS) biomarkers were

  16. Biomarkers for the Diagnosis of Cholangiocarcinoma: A Systematic Review.

    Science.gov (United States)

    Tshering, Gyem; Dorji, Palden Wangyel; Chaijaroenkul, Wanna; Na-Bangchang, Kesara

    2018-06-01

    Cholangiocarcinoma (CCA), a malignant tumor of the bile duct, is a major public health problem in many Southeast Asian countries, particularly Thailand. The slow progression makes it difficult for early diagnosis and most patients are detected in advanced stages. This study aimed to review all relevant articles related to the biomarkers for the diagnosis of CCA and point out potential biomarkers. A thorough search was performed in PubMed and ScienceDirect for CCA biomarker articles. Required data were extracted. A total of 46 articles that fulfilled the inclusion and had none of the exclusion criteria were included in the analysis (17, 22, 3, 4, and 1 articles on blood, tissue, bile, both blood and tissue, and urine biomarkers, respectively). Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA), either alone or in combination with other biomarkers, are the most commonly studied biomarkers in the serum. Their sensitivity and specificity ranged from 47.2% to 98.2% and 89.7% to 100%, respectively. However, in the tissue, gene methylations and DNA-related markers were the most studied CCA biomarkers. Their sensitivity and specificity ranged from 58% to 87% and 98% to 100%, respectively. Some articles investigated biomarkers both in blood and tissues, particularly CA19-9 and CEA, with sensitivity and specificity ranging from 33% to 100% and 50% to 97.7%, respectively. Although quite a number of biomarkers with a potential role in the early detection of CCA have been established, it is difficult to single out any particular marker that could be used in the routine clinical settings.

  17. [Autoantibodies as biomarkers].

    Science.gov (United States)

    Tron, François

    2014-01-01

    Activation and differentiation of autoreactive B-lymphocytes lead to the production of autoantibodies, which are thus the direct consequence of the autoimmune process. They often constitute biomarkers of autoimmune diseases and are measured by tests displaying various diagnosis sensitivity and specificity. Autoantibody titers can be correlated to the disease activity and certain autoantibody populations associated with particular clinical manifestations or tissue lesions. The demonstration that autoantibodies appear years before the onset of autoimmune diseases indicates that their presence in healthy individuals may be a predictive marker of the occurrence of disease. Certain autoantibodies could also be predictive markers of a therapeutic response to biologics and of the occurrence of side effects as well. Thus, autoantibodies are useful tools in the diagnosis and the management of patients with organ specific or non-organ specific autoimmune diseases at different steps of the autoimmune process. Copyright © 2013. Published by Elsevier Masson SAS.

  18. Biomarkers of adverse drug reactions.

    Science.gov (United States)

    Carr, Daniel F; Pirmohamed, Munir

    2018-02-01

    Adverse drug reactions can be caused by a wide range of therapeutics. Adverse drug reactions affect many bodily organ systems and vary widely in severity. Milder adverse drug reactions often resolve quickly following withdrawal of the casual drug or sometimes after dose reduction. Some adverse drug reactions are severe and lead to significant organ/tissue injury which can be fatal. Adverse drug reactions also represent a financial burden to both healthcare providers and the pharmaceutical industry. Thus, a number of stakeholders would benefit from development of new, robust biomarkers for the prediction, diagnosis, and prognostication of adverse drug reactions. There has been significant recent progress in identifying predictive genomic biomarkers with the potential to be used in clinical settings to reduce the burden of adverse drug reactions. These have included biomarkers that can be used to alter drug dose (for example, Thiopurine methyltransferase (TPMT) and azathioprine dose) and drug choice. The latter have in particular included human leukocyte antigen (HLA) biomarkers which identify susceptibility to immune-mediated injuries to major organs such as skin, liver, and bone marrow from a variety of drugs. This review covers both the current state of the art with regard to genomic adverse drug reaction biomarkers. We also review circulating biomarkers that have the potential to be used for both diagnosis and prognosis, and have the added advantage of providing mechanistic information. In the future, we will not be relying on single biomarkers (genomic/non-genomic), but on multiple biomarker panels, integrated through the application of different omics technologies, which will provide information on predisposition, early diagnosis, prognosis, and mechanisms. Impact statement • Genetic and circulating biomarkers present significant opportunities to personalize patient therapy to minimize the risk of adverse drug reactions. ADRs are a significant heath issue

  19. New biomarkers for sepsis

    Directory of Open Access Journals (Sweden)

    Li-xin XIE

    2013-01-01

    Full Text Available There is a higher sepsis rate in the intensive care unit (ICU patients, which is one of the most important causes for patient death, but the sepsis lacks specific clinical manifestations. Exploring sensitive and specific molecular markers for infection that accurately reflect infection severity and prognosis is very clinically important. In this article, based on our previous study, we introduce some new biomarkers with high sensitivity and specificity for the diagnosis and predicting the prognosis and severity of sepsis. Increase of serum soluble(s triggering receptor expressed on myeloid cells-1 (sTREM-1 suggests a poor prognosis of septic patients, and changes of locus rs2234237 of sTREM-1 may be the one of important mechanisms. Additionally, urine sTREM-1 can provide an early warning of possible secondary acute kidney injury (AKI in sepsis patients. Serum sCD163 level was found to be a more important factor than procalcitonin (PCT and C-reactive protein (CRP in prognosis of sepsis, especially severe sepsis. Moreover, urine sCD163 also shows excellent performance in the diagnosis of sepsis and sepsis-associated AKI. Circulating microRNAs, such as miR-150, miR-297, miR-574-5p, miR -146a , miR-223, miR -15a and miR-16, also play important roles in the evaluation of status of septic patients. In the foreseeable future, newly-emerging technologies, including proteomics, metabonomics and trans-omics, may exert profound effects on the discovery of valuable biomarkers for sepsis.

  20. Serum adipokines as biomarkers of beta-cell function in patients with type 1 diabetes

    DEFF Research Database (Denmark)

    Pham, Minh Nguyet; Kolb, Hubert; Mandrup-Poulsen, Thomas

    2013-01-01

    We investigated the adipokines adiponectin, leptin and resistin as serum biomarkers of beta-cell function in patients with type 1 diabetes.......We investigated the adipokines adiponectin, leptin and resistin as serum biomarkers of beta-cell function in patients with type 1 diabetes....

  1. Selected CSF biomarkers indicate no evidence of early neuroinflammation in Huntington disease

    DEFF Research Database (Denmark)

    Vinther-Jensen, Tua; Börnsen, Lars Svend; Budtz-Jorgensen, Esben

    2016-01-01

    Objective: To investigate CSF biomarkers of neuroinflammation and neurodegeneration in Huntington disease (HD) gene-expansion carriers compared to controls and to investigate these biomarkers in association with clinical HD rating scales and disease burden score. Methods: We collected CSF from 32...

  2. A biomarker profile for predicting efficacy of cisplatin-vinorelbine therapy in malignant pleural mesothelioma

    DEFF Research Database (Denmark)

    Zimling, Zarah Glad; Sørensen, Jens Benn; Gerds, Thomas Alexander

    2012-01-01

    Malignant pleural mesothelioma (MPM) has a dismal prognosis. Treatment results may be improved by biomarker-directed therapy. We investigated the baseline expression and impact on outcome of predictive biomarkers ERCC1, BRCA1, and class III β-tubulin in a cohort of MPM patients treated with cispl......Malignant pleural mesothelioma (MPM) has a dismal prognosis. Treatment results may be improved by biomarker-directed therapy. We investigated the baseline expression and impact on outcome of predictive biomarkers ERCC1, BRCA1, and class III β-tubulin in a cohort of MPM patients treated...

  3. 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

  4. Biomarkers for Detecting Mitochondrial Disorders

    Directory of Open Access Journals (Sweden)

    Josef Finsterer

    2018-01-01

    Full Text Available (1 Objectives: Mitochondrial disorders (MIDs are a genetically and phenotypically heterogeneous group of slowly or rapidly progressive disorders with onset from birth to senescence. Because of their variegated clinical presentation, MIDs are difficult to diagnose and are frequently missed in their early and late stages. This is why there is a need to provide biomarkers, which can be easily obtained in the case of suspecting a MID to initiate the further diagnostic work-up. (2 Methods: Literature review. (3 Results: Biomarkers for diagnostic purposes are used to confirm a suspected diagnosis and to facilitate and speed up the diagnostic work-up. For diagnosing MIDs, a number of dry and wet biomarkers have been proposed. Dry biomarkers for MIDs include the history and clinical neurological exam and structural and functional imaging studies of the brain, muscle, or myocardium by ultrasound, computed tomography (CT, magnetic resonance imaging (MRI, MR-spectroscopy (MRS, positron emission tomography (PET, or functional MRI. Wet biomarkers from blood, urine, saliva, or cerebrospinal fluid (CSF for diagnosing MIDs include lactate, creatine-kinase, pyruvate, organic acids, amino acids, carnitines, oxidative stress markers, and circulating cytokines. The role of microRNAs, cutaneous respirometry, biopsy, exercise tests, and small molecule reporters as possible biomarkers is unsolved. (4 Conclusions: The disadvantages of most putative biomarkers for MIDs are that they hardly meet the criteria for being acceptable as a biomarker (missing longitudinal studies, not validated, not easily feasible, not cheap, not ubiquitously available and that not all MIDs manifest in the brain, muscle, or myocardium. There is currently a lack of validated biomarkers for diagnosing MIDs.

  5. HCC Biomarkers in China and Taiwan

    Directory of Open Access Journals (Sweden)

    Regina M. Santella

    2007-02-01

    those who went on to develop HCC. Biologic response markers include measurement of specific mutations in the p53 gene. These studies have demonstrated dramatic differences in mutational spectra of HCC depending on the geographic location. Other early response markers measure tumor DNA released into the blood stream. This DNA has been shown to carry the same genetic and epigenetic changes as does the tumor. In particular, detection of mutations in p53 and methylation of a number of tumor suppressor genes including p16, RASSF1A, MGMT, etc have been analyzed. While not yet applied to HCC cases, the area of proteomic and metabolomics may also lead to useful biomarkers of HCC. In terms of genetic susceptibility, a number of investigators are determining whether single nucleotide polymorphisms are related to HCC risk. The genes investigated to date have included those in the carcinogen metabolism, oxidative stress and DNA repair pathways. While definitive studies are still lacking, the data suggest that, in combination with environmental exposures, genetic factors may also be important in HCC risk.

    The ultimate goal of these biomarker studies is the early identification of high risk individuals so that they can be targeted for enhanced screening or chemopreventive strategies.

  6. 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.

  7. Biomarkers of latent TB infection

    DEFF Research Database (Denmark)

    Ruhwald, Morten; Ravn, Pernille

    2009-01-01

    For the last 100 years, the tuberculin skin test (TST) has been the only diagnostic tool available for latent TB infection (LTBI) and no biomarker per se is available to diagnose the presence of LTBI. With the introduction of M. tuberculosis-specific IFN-gamma release assays (IGRAs), a new area...... of in vitro immunodiagnostic tests for LTBI based on biomarker readout has become a reality. In this review, we discuss existing evidence on the clinical usefulness of IGRAs and the indefinite number of potential new biomarkers that can be used to improve diagnosis of latent TB infection. We also present...... early data suggesting that the monocyte-derived chemokine inducible protein-10 may be useful as a novel biomarker for the immunodiagnosis of latent TB infection....

  8. Breath biomarkers in toxicology.

    Science.gov (United States)

    Pleil, Joachim D

    2016-11-01

    Exhaled breath has joined blood and urine as a valuable resource for sampling and analyzing biomarkers in human media for assessing exposure, uptake metabolism, and elimination of toxic chemicals. This article focuses current use of exhaled gas, aerosols, and vapor in human breath, the methods for collection, and ultimately the use of the resulting data. Some advantages of breath are the noninvasive and self-administered nature of collection, the essentially inexhaustible supply, and that breath sampling does not produce potentially infectious waste such as needles, wipes, bandages, and glassware. In contrast to blood and urine, breath samples can be collected on demand in rapid succession and so allow toxicokinetic observations of uptake and elimination in any time frame. Furthermore, new technologies now allow capturing condensed breath vapor directly, or just the aerosol fraction alone, to gain access to inorganic species, lung pH, proteins and protein fragments, cellular DNA, and whole microorganisms from the pulmonary microbiome. Future applications are discussed, especially the use of isotopically labeled probes, non-targeted (discovery) analysis, cellular level toxicity testing, and ultimately assessing "crowd breath" of groups of people and the relation to dose of airborne and other environmental chemicals at the population level.

  9. 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

  10. Urine Metabonomics Reveals Early Biomarkers in Diabetic Cognitive Dysfunction.

    Science.gov (United States)

    Song, Lili; Zhuang, Pengwei; Lin, Mengya; Kang, Mingqin; Liu, Hongyue; Zhang, Yuping; Yang, Zhen; Chen, Yunlong; Zhang, Yanjun

    2017-09-01

    Recently, increasing attention has been paid to diabetic encephalopathy, which is a frequent diabetic complication and affects nearly 30% of diabetics. Because cognitive dysfunction from diabetic encephalopathy might develop into irreversible dementia, early diagnosis and detection of this disease is of great significance for its prevention and treatment. This study is to investigate the early specific metabolites biomarkers in urine prior to the onset of diabetic cognitive dysfunction (DCD) by using metabolomics technology. An ultra-high performance liquid-chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-Q/TOF-MS) platform was used to analyze the urine samples from diabetic mice that were associated with mild cognitive impairment (MCI) and nonassociated with MCI in the stage of diabetes (prior to the onset of DCD). We then screened and validated the early biomarkers using OPLS-DA model and support vector machine (SVM) method. Following multivariate statistical and integration analysis, we found that seven metabolites could be accepted as early biomarkers of DCD, and the SVM results showed that the prediction accuracy is as high as 91.66%. The identities of four biomarkers were determined by mass spectrometry. The identified biomarkers were largely involved in nicotinate and nicotinamide metabolism, glutathione metabolism, tryptophan metabolism, and sphingolipid metabolism. The present study first revealed reliable biomarkers for early diagnosis of DCD. It provides new insight and strategy for the early diagnosis and treatment of DCD.

  11. Biomarkers of Tumour Radiosensitivity and Predicting Benefit from Radiotherapy.

    Science.gov (United States)

    Forker, L J; Choudhury, A; Kiltie, A E

    2015-10-01

    Radiotherapy is an essential component of treatment for more than half of newly diagnosed cancer patients. The response to radiotherapy varies widely between individuals and although advances in technology have allowed the adaptation of radiotherapy fields to tumour anatomy, it is still not possible to tailor radiotherapy based on tumour biology. A biomarker of intrinsic radiosensitivity would be extremely valuable for individual dosing, aiding decision making between radical treatment options and avoiding toxicity of neoadjuvant or adjuvant radiotherapy in those unlikely to benefit. This systematic review summarises the current evidence for biomarkers under investigation as predictors of radiotherapy benefit. Only 10 biomarkers were identified as having been evaluated for their radiotherapy-specific predictive value in over 100 patients in a clinical setting, highlighting that despite a rich literature there were few high-quality studies for inclusion. The most extensively studied radiotherapy predictive biomarkers were the radiosensitivity index and MRE11; however, neither has been evaluated in a randomised controlled trial. Although these biomarkers show promise, there is not enough evidence to justify their use in routine practice. Further validation is needed before biomarkers can fulfil their potential and predict treatment outcomes for large numbers of patients. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  12. Novel ageing-biomarker discovery using data-intensive technologies.

    Science.gov (United States)

    Griffiths, H R; Augustyniak, E M; Bennett, S J; Debacq-Chainiaux, F; Dunston, C R; Kristensen, P; Melchjorsen, C J; Navarrete, Santos A; Simm, A; Toussaint, O

    2015-11-01

    Ageing is accompanied by many visible characteristics. Other biological and physiological markers are also well-described e.g. loss of circulating sex hormones and increased inflammatory cytokines. Biomarkers for healthy ageing studies are presently predicated on existing knowledge of ageing traits. The increasing availability of data-intensive methods enables deep-analysis of biological samples for novel biomarkers. We have adopted two discrete approaches in MARK-AGE Work Package 7 for biomarker discovery; (1) microarray analyses and/or proteomics in cell systems e.g. endothelial progenitor cells or T cell ageing including a stress model; and (2) investigation of cellular material and plasma directly from tightly-defined proband subsets of different ages using proteomic, transcriptomic and miR array. The first approach provided longitudinal insight into endothelial progenitor and T cell ageing. This review describes the strategy and use of hypothesis-free, data-intensive approaches to explore cellular proteins, miR, mRNA and plasma proteins as healthy ageing biomarkers, using ageing models and directly within samples from adults of different ages. It considers the challenges associated with integrating multiple models and pilot studies as rational biomarkers for a large cohort study. From this approach, a number of high-throughput methods were developed to evaluate novel, putative biomarkers of ageing in the MARK-AGE cohort. Crown Copyright © 2015. Published by Elsevier Ireland Ltd. All rights reserved.

  13. 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.

  14. Analysis of biomarker data a practical guide

    CERN Document Server

    Looney, Stephen W

    2015-01-01

    A "how to" guide for applying statistical methods to biomarker data analysis Presenting a solid foundation for the statistical methods that are used to analyze biomarker data, Analysis of Biomarker Data: A Practical Guide features preferred techniques for biomarker validation. The authors provide descriptions of select elementary statistical methods that are traditionally used to analyze biomarker data with a focus on the proper application of each method, including necessary assumptions, software recommendations, and proper interpretation of computer output. In addition, the book discusses

  15. A Preliminary ToF-SIMS Assessment of Preservation Potential of Organic Biomarkers in Modern Siliceous Sinter and Core, Yellowstone National Park, Wyoming

    Science.gov (United States)

    Guidry, S. A.; Chafetz, H. S.; Steele, A.; Toporski, J. K. W.

    2000-01-01

    Until recently, most biomarker work has focused on morphological body fossils. As a complement to this, three suites of siliceous precipitates were chosen for ToF-SIMS investigation in order to elucidate potential organic biomarkers.

  16. Biomarkers in cancer screening: a public health perspective.

    Science.gov (United States)

    Srivastava, Sudhir; Gopal-Srivastava, Rashmi

    2002-08-01

    definitive technology, such as CT scan. The National Cancer Institute's Early Detection Research Network (EDRN) has begun an innovative, investigator-initiated project to improve methods for detecting the biomarkers of cancer cells. The EDRN is a consortium of more than 32 institutions to link discovery of biomarkers to the next steps in the process of developing early detection tests. These discoveries will lead to early clinical validation of tests with improved accuracy and reliability.

  17. Resting-State Functional Connectivity-Based Biomarkers and Functional MRI-Based Neurofeedback for Psychiatric Disorders: A Challenge for Developing Theranostic Biomarkers.

    Science.gov (United States)

    Yamada, Takashi; Hashimoto, Ryu-Ichiro; Yahata, Noriaki; Ichikawa, Naho; Yoshihara, Yujiro; Okamoto, Yasumasa; Kato, Nobumasa; Takahashi, Hidehiko; Kawato, Mitsuo

    2017-10-01

    Psychiatric research has been hampered by an explanatory gap between psychiatric symptoms and their neural underpinnings, which has resulted in poor treatment outcomes. This situation has prompted us to shift from symptom-based diagnosis to data-driven diagnosis, aiming to redefine psychiatric disorders as disorders of neural circuitry. Promising candidates for data-driven diagnosis include resting-state functional connectivity MRI (rs-fcMRI)-based biomarkers. Although biomarkers have been developed with the aim of diagnosing patients and predicting the efficacy of therapy, the focus has shifted to the identification of biomarkers that represent therapeutic targets, which would allow for more personalized treatment approaches. This type of biomarker (i.e., "theranostic biomarker") is expected to elucidate the disease mechanism of psychiatric conditions and to offer an individualized neural circuit-based therapeutic target based on the neural cause of a condition. To this end, researchers have developed rs-fcMRI-based biomarkers and investigated a causal relationship between potential biomarkers and disease-specific behavior using functional MRI (fMRI)-based neurofeedback on functional connectivity. In this review, we introduce a recent approach for creating a theranostic biomarker, which consists mainly of 2 parts: (1) developing an rs-fcMRI-based biomarker that can predict diagnosis and/or symptoms with high accuracy, and (2) the introduction of a proof-of-concept study investigating the relationship between normalizing the biomarker and symptom changes using fMRI-based neurofeedback. In parallel with the introduction of recent studies, we review rs-fcMRI-based biomarker and fMRI-based neurofeedback, focusing on the technological improvements and limitations associated with clinical use. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  18. 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.

  19. 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.

  20. Circulating miRNAs as biomarkers for oral squamous cell carcinoma recurrence in operated patients

    DEFF Research Database (Denmark)

    Yan, Yan; Wang, Xuan; Venø, Morten Trillingsgaard

    2017-01-01

    MicroRNAs (miRNAs) are small regulatory non-coding RNAs for which altered expression in cancers can serve as potential biomarkers for diseases. We here investigated whether circulating miRNAs can serve as biomarkers for predicting post-operational recurrence of oral squamous cell carcinoma (OSCC...

  1. Cognitive Reserve and Alzheimer's Disease Biomarkers Are Independent Determinants of Cognition

    Science.gov (United States)

    Vemuri, Prashanthi; Weigand, Stephen D.; Przybelski, Scott A.; Knopman, David S.; Smith, Glenn E.; Trojanowski, John Q.; Shaw, Leslie M.; Decarli, Charlie S.; Carmichael, Owen; Bernstein, Matt A.; Aisen, Paul S.; Weiner, Michael; Petersen, Ronald C.; Jack, Clifford R., Jr.

    2011-01-01

    The objective of this study was to investigate how a measure of educational and occupational attainment, a component of cognitive reserve, modifies the relationship between biomarkers of pathology and cognition in Alzheimer's disease. The biomarkers evaluated quantified neurodegeneration via atrophy on magnetic resonance images, neuronal injury…

  2. Biomarkers for atopic dermatitis : a systematic review and meta-analysis

    NARCIS (Netherlands)

    Thijs, Judith; Krastev, Todor; Weidinger, Stephan; Buckens, Constantinus F; de Bruin-Weller, Marjolein; Bruijnzeel-Koomen, Carla; Flohr, Carsten; Hijnen, DirkJan

    2015-01-01

    PURPOSE OF REVIEW: A large number of studies investigating the correlation between severity of atopic dermatitis and various biomarkers have been published over the past decades. The aim of this review was to identify, evaluate and synthesize the evidence examining the correlation of biomarkers with

  3. 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.

  4. Biomarkers in acute heart failure.

    Science.gov (United States)

    Mallick, Aditi; Januzzi, James L

    2015-06-01

    The care of patients with acutely decompensated heart failure is being reshaped by the availability and understanding of several novel and emerging heart failure biomarkers. The gold standard biomarkers in heart failure are B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide, which play an important role in the diagnosis, prognosis, and management of acute decompensated heart failure. Novel biomarkers that are increasingly involved in the processes of myocardial injury, neurohormonal activation, and ventricular remodeling are showing promise in improving diagnosis and prognosis among patients with acute decompensated heart failure. These include midregional proatrial natriuretic peptide, soluble ST2, galectin-3, highly-sensitive troponin, and midregional proadrenomedullin. There has also been an emergence of biomarkers for evaluation of acute decompensated heart failure that assist in the differential diagnosis of dyspnea, such as procalcitonin (for identification of acute pneumonia), as well as markers that predict complications of acute decompensated heart failure, such as renal injury markers. In this article, we will review the pathophysiology and usefulness of established and emerging biomarkers for the clinical diagnosis, prognosis, and management of acute decompensated heart failure. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  5. The Procalcitonin And Survival Study (PASS) - a randomised multi-center investigator-initiated trial to investigate whether daily measurements biomarker Procalcitonin and pro-active diagnostic and therapeutic responses to abnormal Procalcitonin levels, can improve survival in intensive care unit patients. Calculated sample size (target population): 1000 patients

    DEFF Research Database (Denmark)

    Jensen, Jens-Ulrik; Lundgren, Bettina; Hein, Lars

    2008-01-01

    . Complies with, "Good Clinical Practice" (ICH-GCP Guideline (CPMP/ICH/135/95, Directive 2001/20/EC)). Inclusion: 1) Age > or = 18 years of age, 2) Admitted to the participating intensive care units, 3) Signed written informed consent.Exclusion: 1) Known hyper-bilirubinaemia. or hypertriglyceridaemia, 2...... daily Procalcitonin measurements and immediate diagnostic and therapeutic response on day-to-day changes in procalcitonin can reduce the mortality of critically ill patients. DISCUSSION: For the first time ever, a mortality-endpoint, large scale randomized controlled trial with a biomarker......-guided strategy compared to the best standard of care, is conducted in an Intensive care setting. Results will, with a high statistical power answer the question: Can the survival of critically ill patients be improved by actively using biomarker procalcitonin in the treatment of infections? 700 critically ill...

  6. Biomarkers in inflammatory bowel diseases

    DEFF Research Database (Denmark)

    Bennike, Tue; Birkelund, Svend; Stensballe, Allan

    2014-01-01

    Unambiguous diagnosis of the two main forms of inflammatory bowel diseases (IBD): Ulcerative colitis (UC) and Crohn's disease (CD), represents a challenge in the early stages of the diseases. The diagnosis may be established several years after the debut of symptoms. Hence, protein biomarkers...... for early and accurate diagnostic could help clinicians improve treatment of the individual patients. Moreover, the biomarkers could aid physicians to predict disease courses and in this way, identify patients in need of intensive treatment. Patients with low risk of disease flares may avoid treatment...... with medications with the concomitant risk of adverse events. In addition, identification of disease and course specific biomarker profiles can be used to identify biological pathways involved in the disease development and treatment. Knowledge of disease mechanisms in general can lead to improved future...

  7. Biomarkers of replicative senescence revisited

    DEFF Research Database (Denmark)

    Nehlin, Jan

    2016-01-01

    Biomarkers of replicative senescence can be defined as those ultrastructural and physiological variations as well as molecules whose changes in expression, activity or function correlate with aging, as a result of the gradual exhaustion of replicative potential and a state of permanent cell cycle...... arrest. The biomarkers that characterize the path to an irreversible state of cell cycle arrest due to proliferative exhaustion may also be shared by other forms of senescence-inducing mechanisms. Validation of senescence markers is crucial in circumstances where quiescence or temporary growth arrest may...... be triggered or is thought to be induced. Pre-senescence biomarkers are also important to consider as their presence indicate that induction of aging processes is taking place. The bona fide pathway leading to replicative senescence that has been extensively characterized is a consequence of gradual reduction...

  8. 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.

  9. Biomarkers in scleroderma: Current status

    Directory of Open Access Journals (Sweden)

    Latika Gupta

    2017-01-01

    Full Text Available Scleroderma is an autoimmune disease characterized by indolent obliterative vasculopathy and widespread fibrosis. The two main morphological manifestations of the disease overlap and may make it difficult to separate activity from damage. Many patients, especially those with the limited subset of the disease, have an indolent course without clear-cut inflammatory manifestations. There is a felt need for validated biomarkers, which can differentiate activity from damage, and yet be sensitive to change with therapy. Multiplex arrays of biomarkers have ushered an era of targeted or personalized medicine based on phenotypic characteristics in an individual.

  10. Molecular Elucidation of Disease Biomarkers at the Interface of Chemistry and Biology.

    Science.gov (United States)

    Zhang, Liqin; Wan, Shuo; Jiang, Ying; Wang, Yanyue; Fu, Ting; Liu, Qiaoling; Cao, Zhijuan; Qiu, Liping; Tan, Weihong

    2017-02-22

    Disease-related biomarkers are objectively measurable molecular signatures of physiological status that can serve as disease indicators or drug targets in clinical diagnosis and therapy, thus acting as a tool in support of personalized medicine. For example, the prostate-specific antigen (PSA) biomarker is now widely used to screen patients for prostate cancer. However, few such biomarkers are currently available, and the process of biomarker identification and validation is prolonged and complicated by inefficient methods of discovery and few reliable analytical platforms. Therefore, in this Perspective, we look at the advanced chemistry of aptamer molecules and their significant role as molecular probes in biomarker studies. As a special class of functional nucleic acids evolved from an iterative technology termed Systematic Evolution of Ligands by Exponential Enrichment (SELEX), these single-stranded oligonucleotides can recognize their respective targets with selectivity and affinity comparable to those of protein antibodies. Because of their fast turnaround time and exceptional chemical properties, aptamer probes can serve as novel molecular tools for biomarker investigations, particularly in assisting identification of new disease-related biomarkers. More importantly, aptamers are able to recognize biomarkers from complex biological environments such as blood serum and cell surfaces, which can provide direct evidence for further clinical applications. This Perspective highlights several major advancements of aptamer-based biomarker discovery strategies and their potential contribution to the practice of precision medicine.

  11. Agama lizard: A potential biomarker of environmental heavy metal ...

    African Journals Online (AJOL)

    In this study, the suitability of Agama lizard as a biomarker in assessing environmental pollution levels of arsenium (As), barium (Ba), cadmium (Cd), copper (Cu), manganese (Mn), lead (Pb) and zinc (Zn) was investigated. Samples of top soil and agama lizards were taken from five sites within a university community in ...

  12. The influence of wall stress on AAA growth and biomarkers

    NARCIS (Netherlands)

    Speelman, L.; Hellenthal, F.A.M.V.I.; Pulinx, B.; Bosboom, E.M.H.; Breeuwer, M.; Sambeek, M.R.; Vosse, van de F.N.; Jacobs, M.J.H.M.; Wodzig, W.K.W.H.; Schurink, G.W.H.

    2010-01-01

    Objectives This study investigated the relation between abdominal aortic aneurysm (AAA) wall stress, AAA growth rate and biomarker concentrations. With increasing wall stress, more damage may be caused to the AAA wall, possibly leading to progression of the aneurysm and reflection in up- or

  13. Serological biomarkers in triage of FIT-positive subjects?

    DEFF Research Database (Denmark)

    Nielsen, Hans J; Christensen, Ib Jarle; Andersen, Berit

    2017-01-01

    with neoplastic lesions missed by increased cut-off levels appears to be much higher than expected. Therefore, tests that identify those patients missed by increased FIT cut-off levels must be developed. Preliminary results of determination of one of several biomarker entities currently under investigation show...... that nucleosome blood tests may be one option for identifying some of these patients. Implementation of a triage test consisting of FIT, blood-based biomarkers and plus/minus colonoscopy is suggested to identify subjects with FIT levels between the initial and the increased cut-off level that must be offered...

  14. Early-Phase Studies of Biomarkers

    DEFF Research Database (Denmark)

    Pepe, Margaret S.; Janes, Holly; Li, Christopher I.

    2016-01-01

    of a positive biomarker test in cases (true positive) to cost associated with a positive biomarker test in controls (false positive). Guidance is offered on soliciting the cost/benefit ratio. The calculations are based on the longstanding decision theory concept of providing a net benefit on average...... impact on patient outcomes of using the biomarker to make clinical decisions....

  15. Rostrocaudal Dynamics of CSF Biomarkers

    NARCIS (Netherlands)

    Tarnaris, A.; Toma, A.K.; Chapman, M.D.; Petzold, A.F.S.; Keir, G.; Kitchen, N.D.; Watkins, L.D.

    2011-01-01

    The rostrocaudal gradient (RCG) of markers present in cerebrospinal fluid (CSF) has not been studied adequately due to lack of appropriate control populations and ethical restrictions. The aim of this study is to understand the rostrocaudal gradient of CSF biomarkers. We contacted a study comparing

  16. Imaging Biomarkers for Adult Medulloblastomas

    DEFF Research Database (Denmark)

    Keil, V C; Warmuth-Metz, M; Reh, C

    2017-01-01

    BACKGROUND AND PURPOSE: The occurrence of medulloblastomas in adults is rare; nevertheless, these tumors can be subdivided into genetic and histologic entities each having distinct prognoses. This study aimed to identify MR imaging biomarkers to classify these entities and to uncover differences ...

  17. Biomarkers of satiation and satiety

    NARCIS (Netherlands)

    Graaf, de C.; Blom, W.A.M.; Smeets, P.A.M.; Stafleu, A.; Hendriks, H.F.J.

    2004-01-01

    This review's objective is to give a critical summary of studies that focused on physiologic measures relating to subjectively rated appetite, actual food intake, or both. Biomarkers of satiation and satiety may be used as a tool for assessing the satiating efficiency of foods and for understanding

  18. Bias in Peripheral Depression Biomarkers

    DEFF Research Database (Denmark)

    Carvalho, André F; Köhler, Cristiano A; Brunoni, André R

    2016-01-01

    BACKGROUND: To aid in the differentiation of individuals with major depressive disorder (MDD) from healthy controls, numerous peripheral biomarkers have been proposed. To date, no comprehensive evaluation of the existence of bias favoring the publication of significant results or inflating effect...

  19. Biomarkers of spontaneous preterm birth

    DEFF Research Database (Denmark)

    Polettini, Jossimara; Cobo, Teresa; Kacerovsky, Marian

    2017-01-01

    biomarkers associated with PTB published from January 2005 to March 2014. Retrieved citations (3631) were screened, and relevant studies (33) were selected for full-text reading. Ten studies were included in the review. Forty-two PTB-related proteins were reported, and RANTES and IL-10 (three studies...

  20. Systems biology and biomarker discovery

    Energy Technology Data Exchange (ETDEWEB)

    Rodland, Karin D.

    2010-12-01

    Medical practitioners have always relied on surrogate markers of inaccessible biological processes to make their diagnosis, whether it was the pallor of shock, the flush of inflammation, or the jaundice of liver failure. Obviously, the current implementation of biomarkers for disease is far more sophisticated, relying on highly reproducible, quantitative measurements of molecules that are often mechanistically associated with the disease in question, as in glycated hemoglobin for the diagnosis of diabetes [1] or the presence of cardiac troponins in the blood for confirmation of myocardial infarcts [2]. In cancer, where the initial symptoms are often subtle and the consequences of delayed diagnosis often drastic for disease management, the impetus to discover readily accessible, reliable, and accurate biomarkers for early detection is compelling. Yet despite years of intense activity, the stable of clinically validated, cost-effective biomarkers for early detection of cancer is pathetically small and still dominated by a handful of markers (CA-125, CEA, PSA) first discovered decades ago. It is time, one could argue, for a fresh approach to the discovery and validation of disease biomarkers, one that takes full advantage of the revolution in genomic technologies and in the development of computational tools for the analysis of large complex datasets. This issue of Disease Markers is dedicated to one such new approach, loosely termed the 'Systems Biology of Biomarkers'. What sets the Systems Biology approach apart from other, more traditional approaches, is both the types of data used, and the tools used for data analysis - and both reflect the revolution in high throughput analytical methods and high throughput computing that has characterized the start of the twenty first century.

  1. Sample handling for mass spectrometric proteomic investigations of human sera.

    NARCIS (Netherlands)

    West-Nielsen, M.; Hogdall, E.V.; Marchiori, E.; Hogdall, C.K.; Schou, C.; Heegaard, N.H.H.

    2005-01-01

    Proteomic investigations of sera are potentially of value for diagnosis, prognosis, choice of therapy, and disease activity assessment by virtue of discovering new biomarkers and biomarker patterns. Much debate focuses on the biological relevance and the need for identification of such biomarkers

  2. Nutritional biomarkers for objective dietary assessment.

    Science.gov (United States)

    Kuhnle, Gunter G C

    2012-04-01

    The accurate assessment of dietary exposure is important in investigating associations between diet and disease. Research in nutritional epidemiology, which has resulted in a large amount of information on associations between diet and chronic diseases in the last decade, relies on accurate assessment methods to identify these associations. However, most dietary assessment instruments rely to some extent on self-reporting, which is prone to systematic bias affected by factors such as age, gender, social desirability and approval. Nutritional biomarkers are not affected by these and therefore provide an additional, alternative method to estimate intake. However, there are also some limitations in their application: they are affected by inter-individual variations in metabolism and other physiological factors, and they are often limited to estimating intake of specific compounds and not entire foods. It is therefore important to validate nutritional biomarkers to determine specific strengths and limitations. In this perspective paper, criteria for the validation of nutritional markers and future developments are discussed. Copyright © 2012 Society of Chemical Industry.

  3. Metabolic Imaging Biomarkers of Postradiotherapy Xerostomia

    International Nuclear Information System (INIS)

    Cannon, Blake; Schwartz, David L.; Dong Lei

    2012-01-01

    Purpose: Xerostomia is a major complication of head and neck radiotherapy (RT). Available xerostomia measures remain flawed. [ 18 F]fluorodeoxyglucose-labeled positron emission tomography-computed tomography (FDG-PET-CT) is routinely used for staging and response assessment of head and neck cancer. We investigated quantitative measurement of parotid gland FDG uptake as a potential biomarker for post-RT xerostomia. Methods and Materials: Ninety-eight locally advanced head and neck cancer patients receiving definitive RT underwent baseline and post-RT FDG-PET-CT on a prospective imaging trial. A separate validation cohort of 14 patients underwent identical imaging while prospectively enrolled in a second trial collecting sialometry and patient-reported outcomes. Radiation dose and pre- and post-RT standard uptake values (SUVs) for all voxels contained within parotid gland ROI were deformably registered. Results: Average whole-gland or voxel-by-voxel models incorporating parotid D Met (defined as the pretreatment parotid SUV weighted by dose) accurately predicted posttreatment changes in parotid FDG uptake (e.g., fractional parotid SUV). Fractional loss of parotid FDG uptake closely paralleled early parotid toxicity defined by posttreatment salivary output (p Met may potentially be used to guide function-sparing treatment planning. Prospective validation of FDG-PET-CT as a convenient, quantifiable imaging biomarker of parotid function is warranted and ongoing.

  4. 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...

  5. 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.

  6. Alcohol consumption, mediating biomarkers, and risk of type 2 diabetes among middle-aged women

    NARCIS (Netherlands)

    Beulens, J.W.J.; Rimm, E.B.; Hu, F.B.; Hendriks, H.F.J.; Mukamal, K.J.

    2008-01-01

    OBJECTIVE - The purpose of this study was to investigate whether adiponectin concentrations and biomarkers of inflammation, endothelial dysfunction, and insulin resistance mediate the association between alcohol consumption and diabetes. RESEARCH DESIGN AND METHODS - In a nested case-control study

  7. Identification of biomarkers for genotyping Aspergilli using non-linear methods for clustering and classification

    DEFF Research Database (Denmark)

    Kouskoumvekaki, Irene; Yang, Zhiyong; Jonsdottir, Svava Osk

    2008-01-01

    Background: In the present investigation, we have used an exhaustive metabolite profiling approach to search for biomarkers in recombinant Aspergillus nidulans (mutants that produce the 6- methyl salicylic acid polyketide molecule) for application in metabolic engineering. Results: More than 450...

  8. Identification of an age-dependent biomarker signature in children and adolescents with autism spectrum disorders

    NARCIS (Netherlands)

    Ramsey, J.M.; Guest, P.C.; Broek, J.A.C.; Glennon, J.C.; Rommelse, N.N.J.; Franke, B.; Rahmoune, H.; Buitelaar, J.K.; Bahn, S.

    2013-01-01

    BACKGROUND: Autism spectrum disorders (ASDs) are neurodevelopmental conditions with symptoms manifesting before the age of 3, generally persisting throughout life and affecting social development and communication. Here, we have investigated changes in protein biomarkers in blood during childhood

  9. Identification of an age-dependent biomarker signature in children and adolescents with autism spectrum disorders

    NARCIS (Netherlands)

    J.M. Ramsey (Jordan); P.C. Guest (Paul); J.A.C. Broek (Jantine A.); J.C. Glennon (Jeffrey C); N. Rommelse (Nanda); B. Franke (Barbara); H. Rahmoune (Hassan); J.K. Buitelaar (Jan); S. Bahn (Sabine)

    2013-01-01

    textabstractBackground: Autism spectrum disorders (ASDs) are neurodevelopmental conditions with symptoms manifesting before the age of 3, generally persisting throughout life and affecting social development and communication. Here, we have investigated changes in protein biomarkers in blood during

  10. 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.

  11. 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.

  12. Assessed and Emerging Biomarkers in Stroke and Training-Mediated Stroke Recovery: State of the Art

    Directory of Open Access Journals (Sweden)

    Marialuisa Gandolfi

    2017-01-01

    Full Text Available Since the increasing update of the biomolecular scientific literature, biomarkers in stroke have reached an outstanding and remarkable revision in the very recent years. Besides the diagnostic and prognostic role of some inflammatory markers, many further molecules and biological factors have been added to the list, including tissue derived cytokines, growth factor-like molecules, hormones, and microRNAs. The literatures on brain derived growth factor and other neuroimmune mediators, bone-skeletal muscle biomarkers, cellular and immunity biomarkers, and the role of microRNAs in stroke recovery were reviewed. To date, biomarkers represent a possible challenge in the diagnostic and prognostic evaluation of stroke onset, pathogenesis, and recovery. Many molecules are still under investigation and may become promising and encouraging biomarkers. Experimental and clinical research should increase this list and promote new discoveries in this field, to improve stroke diagnosis and treatment.

  13. 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

  14. Variability of CSF Alzheimer's disease biomarkers: implications for clinical practice.

    Directory of Open Access Journals (Sweden)

    Stephanie J B Vos

    Full Text Available BACKGROUND: Cerebrospinal fluid (CSF biomarkers are increasingly being used for diagnosis of Alzheimer's disease (AD. OBJECTIVE: We investigated the influence of CSF intralaboratory and interlaboratory variability on diagnostic CSF-based AD classification of subjects and identified causes of this variation. METHODS: We measured CSF amyloid-β (Aβ 1-42, total tau (t-tau, and phosphorylated tau (p-tau by INNOTEST enzyme-linked-immunosorbent assays (ELISA in a memory clinic population (n = 126. Samples were measured twice in a single or two laboratories that served as reference labs for CSF analyses in the Netherlands. Predefined cut-offs were used to classify CSF biomarkers as normal or abnormal/AD pattern. RESULTS: CSF intralaboratory variability was higher for Aβ1-42 than for t-tau and p-tau. Reanalysis led to a change in biomarker classification (normal vs. abnormal of 26% of the subjects based on Aβ1-42, 10% based on t-tau, and 29% based on p-tau. The changes in absolute biomarker concentrations were paralleled by a similar change in levels of internal control samples between different assay lots. CSF interlaboratory variability was higher for p-tau than for Aβ1-42 and t-tau, and reanalysis led to a change in biomarker classification of 12% of the subjects based on Aβ1-42, 1% based on t-tau, and 22% based on p-tau. CONCLUSIONS: Intralaboratory and interlaboratory CSF variability frequently led to change in diagnostic CSF-based AD classification for Aβ1-42 and p-tau. Lot-to-lot variation was a major cause of intralaboratory variability. This will have implications for the use of these biomarkers in clinical practice.

  15. Chronic Obstructive Pulmonary Disease Biomarkers

    Directory of Open Access Journals (Sweden)

    Tatsiana Beiko

    2016-04-01

    Full Text Available Despite significant decreases in morbidity and mortality of cardiovascular diseases (CVD and cancers, morbidity and cost associated with chronic obstructive pulmonary disease (COPD continue to be increasing. Failure to improve disease outcomes has been related to the paucity of interventions improving survival. Insidious onset and slow progression halter research successes in developing disease-modifying therapies. In part, the difficulty in finding new therapies is because of the extreme heterogeneity within recognized COPD phenotypes. Novel biomarkers are necessary to help understand the natural history and pathogenesis of the different COPD subtypes. A more accurate phenotyping and the ability to assess the therapeutic response to new interventions and pharmaceutical agents may improve the statistical power of longitudinal clinical studies. In this study, we will review known candidate biomarkers for COPD, proposed pathways of pathogenesis, and future directions in the field.

  16. Glycoscience aids in biomarker discovery

    Directory of Open Access Journals (Sweden)

    Serenus Hua1,2 & Hyun Joo An1,2,*

    2012-06-01

    Full Text Available The glycome consists of all glycans (or carbohydrates within abiological system, and modulates a wide range of important biologicalactivities, from protein folding to cellular communications.The mining of the glycome for disease markers representsa new paradigm for biomarker discovery; however, this effortis severely complicated by the vast complexity and structuraldiversity of glycans. This review summarizes recent developmentsin analytical technology and methodology as applied tothe fields of glycomics and glycoproteomics. Mass spectrometricstrategies for glycan compositional profiling are described, as arepotential refinements which allow structure-specific profiling.Analytical methods that can discern protein glycosylation at aspecific site of modification are also discussed in detail.Biomarker discovery applications are shown at each level ofanalysis, highlighting the key role that glycoscience can play inhelping scientists understand disease biology.

  17. Candidate immune biomarkers for radioimmunotherapy.

    Science.gov (United States)

    Levy, Antonin; Nigro, Giulia; Sansonetti, Philippe J; Deutsch, Eric

    2017-08-01

    Newly available immune checkpoint blockers (ICBs), capable to revert tumor immune tolerance, are revolutionizing the anticancer armamentarium. Recent evidence also established that ionizing radiation (IR) could produce antitumor immune responses, and may as well synergize with ICBs. Multiple radioimmunotherapy combinations are thenceforth currently assessed in early clinical trials. Past examples have highlighted the need for treatment personalization, and there is an unmet need to decipher immunological biomarkers that could allow selecting patients who could benefit from these promising but expensive associations. Recent studies have identified potential predictive and prognostic immune assays at the cellular (tumor microenvironment composition), genomic (mutational/neoantigen load), and peripheral blood levels. Within this review, we collected the available evidence regarding potential personalized immune biomarker-directed radiation therapy strategies that might be used for patient selection in the era of radioimmunotherapy. Copyright © 2017. Published by Elsevier B.V.

  18. 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.

  19. In Vitro Characterization of Inflammatory Biomarkers across Species

    Directory of Open Access Journals (Sweden)

    Elizabeth A. Kenyon

    2012-04-01

    Full Text Available There are currently no validated animal models or suitable biomarkers with which to ascertain the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs in equine, bovine or ovine species during conditions of endotoxemia. This has resulted in approval of only one NSAID, flunixin meglumine, for controlling inflammation due to endotoxemia in bovine and equine animals, while none are approved in ovine animals for this claim. This study aims to investigate biomarkers with which to test efficacy of NSAIDs in these species. To this end, the effects of Escherichia coli lipopolysaccharide (LPS induced inflammation on gene expression were investigated. Whole blood from each species was cultured and stimulated with LPS, after which RNA was extracted at various times. RNA was analyzed via quantitative RT-PCR (qRT-PCR to determine differential expression of biomarkers. Results indicated up-regulation of cluster of differentiation 1 (CD1 gene in bovine and serum amyloid A (SAA gene in ovine cultures. Down-regulation of cluster of differentiation 4 (CD4 gene and Caspase 1 was seen in bovine, and of CD1 in equine cultures. This work demonstrates that LPS stimulation alters expression of these genes in these species. These genes may be useful biomarkers for inflammation which could serve as markers for NSAID efficacy.

  20. 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.

  1. 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.

  2. Apolipoprotein M - a new biomarker in sepsis

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Nielsen, Lars Bo

    2012-01-01

    Care Kumaraswamy and colleagues have investigated whether plasma apolipoprotein M (apoM) is affected during different grades of sepsis, septic shock and systemic inflammatory response syndrome. Interestingly, plasma apoM was significantly decreased in all groups of patients with a relationship...... to severity of disease. This identifies apoM as a potential new biomarker in sepsis. It also underscores the possibility that altered high-density lipoprotein in sepsis patients can affect the course of disease. Thus, since apoM is the carrier of Sphingosine-1-P (S1P), a molecule with great influence...... on vascular barrier function, the study presented raises the interest and relevance for further studies of apoM and S1P in relation to sepsis and inflammation....

  3. 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.

  4. 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.

  5. 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.

  6. Biomarkers of carcinogen exposure and early effects.

    OpenAIRE

    2006-01-01

    The purpose of this review is to summarise the current situation regarding the types and uses of biomarkers of exposure and effect for the main classes of food-derived genotoxic carcinogens, and to consider some aspects of the intercomparison between these biomarkers. The biomarkers of exposure and early effects of carcinogens that have been most extensively developed are those for genotoxic agents and for compounds that generate hydroxyl radicals and other reactive radical species, and it is...

  7. 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...

  8. Exosomal miRNAs as biomarkers for prostate cancer

    Directory of Open Access Journals (Sweden)

    Nina Pettersen Hessvik

    2013-03-01

    Full Text Available miRNAs are small non-coding RNAs that finely regulate gene expression in cells. Alterations in miRNA expression have been associated with development of cancer, and miRNAs are now being investigated as biomarkers for cancer as well as other diseases. Recently, miRNAs have been found outside cells in body fluids. Extracellular miRNAs exist in different forms - associated with Ago2 proteins, loaded into extracellular vesicles (exosomes, microvesicles or apoptotic bodies or into high density lipoprotein particles. These extracellular miRNAs are probably products of distinct cellular processes, and might therefore play different roles. However, their functions in vivo are currently unknown. In spite of this, they are considered as promising, noninvasive diagnostic and prognostic tools. Prostate cancer is the most common cancer in men in the Western world, but the currently used biomarker (prostate specific antigen has low specificity. Therefore, novel biomarkers are highly needed. In this review we will discuss possible biological functions of extracellular miRNAs, as well as the potential use of miRNAs from extracellular vesicles as biomarkers for prostate cancer.

  9. Biomarkers of exposure to new and emerging tobacco delivery products.

    Science.gov (United States)

    Schick, Suzaynn F; Blount, Benjamin C; Jacob, Peyton; Saliba, Najat A; Bernert, John T; El Hellani, Ahmad; Jatlow, Peter; Pappas, R Steven; Wang, Lanqing; Foulds, Jonathan; Ghosh, Arunava; Hecht, Stephen S; Gomez, John C; Martin, Jessica R; Mesaros, Clementina; Srivastava, Sanjay; St Helen, Gideon; Tarran, Robert; Lorkiewicz, Pawel K; Blair, Ian A; Kimmel, Heather L; Doerschuk, Claire M; Benowitz, Neal L; Bhatnagar, Aruni

    2017-09-01

    Accurate and reliable measurements of exposure to tobacco products are essential for identifying and confirming patterns of tobacco product use and for assessing their potential biological effects in both human populations and experimental systems. Due to the introduction of new tobacco-derived products and the development of novel ways to modify and use conventional tobacco products, precise and specific assessments of exposure to tobacco are now more important than ever. Biomarkers that were developed and validated to measure exposure to cigarettes are being evaluated to assess their use for measuring exposure to these new products. Here, we review current methods for measuring exposure to new and emerging tobacco products, such as electronic cigarettes, little cigars, water pipes, and cigarillos. Rigorously validated biomarkers specific to these new products have not yet been identified. Here, we discuss the strengths and limitations of current approaches, including whether they provide reliable exposure estimates for new and emerging products. We provide specific guidance for choosing practical and economical biomarkers for different study designs and experimental conditions. Our goal is to help both new and experienced investigators measure exposure to tobacco products accurately and avoid common experimental errors. With the identification of the capacity gaps in biomarker research on new and emerging tobacco products, we hope to provide researchers, policymakers, and funding agencies with a clear action plan for conducting and promoting research on the patterns of use and health effects of these products.

  10. Identification of Biomarkers for Endometriosis Using Clinical Proteomics

    Directory of Open Access Journals (Sweden)

    Yang Zhao

    2015-01-01

    Full Text Available Background: We investigated possible biomarkers for endometriosis (EM using the ClinProt technique and proteomics methods. Methods: We enrolled 50 patients with EM, 34 with benign ovarian neoplasms and 40 healthy volunteers in this study. Serum proteomic spectra were generated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS combined with weak cationic exchange (WCX magnetic beads. Possible biomarkers were analyzed by a random and repeat pattern model-validation method that we designed, and ClinProtools software, results were refined using online liquid chromatography-tandem MS. Results: We found a cluster of 5 peptides (4210, 5264, 2660, 5635, and 5904 Da, using 3 peptides (4210, 5904, 2660 Da to discriminate EM patients from healthy volunteers, with 96.67% sensitivity and 100% specificity. We selected 4210 and 5904 m/z, which differed most between patients with EM and controls, and identified them as fragments of ATP1B4, and the fibrinogen alpha (FGA isoform 1/2 of the FGA chain precursor, respectively. Conclusions: ClinProt can identify EM biomarkers, which - most notably - distinguish even early-stage or minimal disease. We found 5 stable peaks at 4210, 5264, 2660, 5635, and 5904 Da as potential EM biomarkers, the strongest of which were associated with ATP1B4 (4210 Da and FGA (5904 Da; this indicates that ATP1B4 and FGA are associated with EM pathogenesis.

  11. Cardiovascular biomarkers in clinical studies of type 2 diabetes

    DEFF Research Database (Denmark)

    Baldassarre, M P A; Andersen, A; Consoli, A

    2018-01-01

    biomarkers and 3) novel biomarkers (oxidative stress and endothelial dysfunction biomarkers). Within each category we present the currently best validated biomarkers with special focus on the population of interest (type 2 diabetes). For each individual biomarker, the physiological role, the validation...

  12. Application of mass spectrometry-based proteomics for biomarker discovery in neurological disorders

    Directory of Open Access Journals (Sweden)

    Venugopal Abhilash

    2009-01-01

    Full Text Available Mass spectrometry-based quantitative proteomics has emerged as a powerful approach that has the potential to accelerate biomarker discovery, both for diagnostic as well as therapeutic purposes. Proteomics has traditionally been synonymous with 2D gels but is increasingly shifting to the use of gel-free systems and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS. Quantitative proteomic approaches have already been applied to investigate various neurological disorders, especially in the context of identifying biomarkers from cerebrospinal fluid and serum. This review highlights the scope of different applications of quantitative proteomics in understanding neurological disorders with special emphasis on biomarker discovery.

  13. 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...

  14. The Procalcitonin And Survival Study (PASS) – A Randomised multi-center investigator-initiated trial to investigate whether daily measurements biomarker Procalcitonin and pro-active diagnostic and therapeutic responses to abnormal Procalcitonin levels, can improve survival in intensive care unit patients. Calculated sample size (target population): 1000 patients

    Science.gov (United States)

    Jensen, Jens-Ulrik; Lundgren, Bettina; Hein, Lars; Mohr, Thomas; Petersen, Pernille L; Andersen, Lasse H; Lauritsen, Anne Ø; Hougaard, Sine; Mantoni, Teit; Bømler, Bonnie; Thornberg, Klaus J; Thormar, Katrin; Løken, Jesper; Steensen, Morten; Carl, Peder; Petersen, J Asger; Tousi, Hamid; Søe-Jensen, Peter; Bestle, Morten; Hestad, Søren; Andersen, Mads H; Fjeldborg, Paul; Larsen, Kim M; Rossau, Charlotte; Thomsen, Carsten B; Østergaard, Christian; Kjær, Jesper; Grarup, Jesper; Lundgren, Jens D

    2008-01-01

    Background Sepsis and complications to sepsis are major causes of mortality in critically ill patients. Rapid treatment of sepsis is of crucial importance for survival of patients. The infectious status of the critically ill patient is often difficult to assess because symptoms cannot be expressed and signs may present atypically. The established biological markers of inflammation (leucocytes, C-reactive protein) may often be influenced by other parameters than infection, and may be unacceptably slowly released after progression of an infection. At the same time, lack of a relevant antimicrobial therapy in an early course of infection may be fatal for the patient. Specific and rapid markers of bacterial infection have been sought for use in these patients. Methods Multi-centre randomized controlled interventional trial. Powered for superiority and non-inferiority on all measured end points. Complies with, "Good Clinical Practice" (ICH-GCP Guideline (CPMP/ICH/135/95, Directive 2001/20/EC)). Inclusion: 1) Age ≥ 18 years of age, 2) Admitted to the participating intensive care units, 3) Signed written informed consent. Exclusion: 1) Known hyper-bilirubinaemia. or hypertriglyceridaemia, 2) Likely that safety is compromised by blood sampling, 3) Pregnant or breast feeding. Computerized Randomisation: Two arms (1:1), n = 500 per arm: Arm 1: standard of care. Arm 2: standard of care and Procalcitonin guided diagnostics and treatment of infection. Primary Trial Objective: To address whether daily Procalcitonin measurements and immediate diagnostic and therapeutic response on day-to-day changes in procalcitonin can reduce the mortality of critically ill patients. Discussion For the first time ever, a mortality-endpoint, large scale randomized controlled trial with a biomarker-guided strategy compared to the best standard of care, is conducted in an Intensive care setting. Results will, with a high statistical power answer the question: Can the survival of critically ill

  15. The Procalcitonin And Survival Study (PASS – A Randomised multi-center investigator-initiated trial to investigate whether daily measurements biomarker Procalcitonin and pro-active diagnostic and therapeutic responses to abnormal Procalcitonin levels, can improve survival in intensive care unit patients. Calculated sample size (target population: 1000 patients

    Directory of Open Access Journals (Sweden)

    Fjeldborg Paul

    2008-07-01

    Full Text Available Abstract Background Sepsis and complications to sepsis are major causes of mortality in critically ill patients. Rapid treatment of sepsis is of crucial importance for survival of patients. The infectious status of the critically ill patient is often difficult to assess because symptoms cannot be expressed and signs may present atypically. The established biological markers of inflammation (leucocytes, C-reactive protein may often be influenced by other parameters than infection, and may be unacceptably slowly released after progression of an infection. At the same time, lack of a relevant antimicrobial therapy in an early course of infection may be fatal for the patient. Specific and rapid markers of bacterial infection have been sought for use in these patients. Methods Multi-centre randomized controlled interventional trial. Powered for superiority and non-inferiority on all measured end points. Complies with, "Good Clinical Practice" (ICH-GCP Guideline (CPMP/ICH/135/95, Directive 2001/20/EC. Inclusion: 1 Age ≥ 18 years of age, 2 Admitted to the participating intensive care units, 3 Signed written informed consent. Exclusion: 1 Known hyper-bilirubinaemia. or hypertriglyceridaemia, 2 Likely that safety is compromised by blood sampling, 3 Pregnant or breast feeding. Computerized Randomisation: Two arms (1:1, n = 500 per arm: Arm 1: standard of care. Arm 2: standard of care and Procalcitonin guided diagnostics and treatment of infection. Primary Trial Objective: To address whether daily Procalcitonin measurements and immediate diagnostic and therapeutic response on day-to-day changes in procalcitonin can reduce the mortality of critically ill patients. Discussion For the first time ever, a mortality-endpoint, large scale randomized controlled trial with a biomarker-guided strategy compared to the best standard of care, is conducted in an Intensive care setting. Results will, with a high statistical power answer the question: Can the survival

  16. Development of a Personalized Model for Pressure Ulcer Prevention Acutely Following Spinal Cord Injury: Biomarkers of Muscle Composition and Resilience

    Science.gov (United States)

    2015-10-01

    15. SUBJECT TERMS Spinal cord injury, pressure ulcer prevention, biomarkers, personalized healthcare 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...pressure ulcer prevention, biomarkers, personalized healthcare 3. Accomplishments Major Project Goals Task 1: Subject Recruitment and Data...months (Co-Investigator) Clinically translatable nanotechnology : hemostasis and neuroprotection New studies 09/30/14 -09/30/15 Started 01/01/15

  17. Serum Antibody Biomarkers for ASD

    Science.gov (United States)

    2015-10-01

    typically developing control. US, unaffected sibling control. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a...typically developing (TD) children (e.g., Warren et al., 1990; Singh, 2009). The goal of this study is to identify a serum antibody biomarker for ASD using...50% less IgG1 antibody in ASD boys vs . TD boys (p=0.0096). The level of ASD1 binding to the AM group was the same as to the ASD boys. These data

  18. CURRENT APPROACHES FOR RESEARCH OF MULTIPLE SCLEROSIS BIOMARKERS

    Directory of Open Access Journals (Sweden)

    Kolyada T.I

    2016-12-01

    techniques (including full genome resequencing, targeted resequencing of the genome. The results obtained with these techniques became the basis for the further development of screening technologies. Disadvantages of the "classical" methods are associated not only with their resolution or other technical limitations but also to the fact that the range of pathological processes in MS may vary significantly from patient to patient and single biomarkers suitable for one group of patients may be inappropriate for another group of patients. Due to the complexity of MS the reflection of pathological changes may be determined not by single biomarkers but by isolated biomarkers panel from different compartments. The solution of this problem seems to be possible due to the development of microarray methods including biochips technology. Biochips are used for screening of MS patients and allow determining the rare MS-associated gene variants that have a significant impact on the development of the disease. In conjunction with the "classical" methods, microarrays allowed to apply systems biology approaches (i.e. genomics, transcriptomics, proteomics, metabolomics, epigenomics in the study of MS biomarkers. Addition of bioinformatics methods to "classical" and microarray laboratory methods allows not only to find new biomarkers but to identify complex patterns of biomarkers while single biomarkers informative value is not sufficient. To date, the use of genome-wide association study (GWAS revealed more than a hundred genetic variants associated with the development of MS, while the total number of investigated genetic variants including the candidate ones exceeded two hundred. GWAS is used to identify correlations of genetic variants with the disease, including the identification of variants associated with a risk of developing MS, but cannot answer the question of the causal links between specific genes polymorphism and the pathogenesis of MS. Current studies of biomarkers of disease

  19. Metabolic Imaging Biomarkers of Postradiotherapy Xerostomia

    Energy Technology Data Exchange (ETDEWEB)

    Cannon, Blake [Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Schwartz, David L., E-mail: dschwartz3@nshs.edu [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Department of Radiation Medicine, Hofstra North Shore-LIJ School of Medicine, New Hyde Park, New York (United States); Feinstein Institute for Medical Research, Manhasset, New York (United States); Dong Lei [Department of Radiation Physics, University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States)

    2012-08-01

    Purpose: Xerostomia is a major complication of head and neck radiotherapy (RT). Available xerostomia measures remain flawed. [{sup 18}F]fluorodeoxyglucose-labeled positron emission tomography-computed tomography (FDG-PET-CT) is routinely used for staging and response assessment of head and neck cancer. We investigated quantitative measurement of parotid gland FDG uptake as a potential biomarker for post-RT xerostomia. Methods and Materials: Ninety-eight locally advanced head and neck cancer patients receiving definitive RT underwent baseline and post-RT FDG-PET-CT on a prospective imaging trial. A separate validation cohort of 14 patients underwent identical imaging while prospectively enrolled in a second trial collecting sialometry and patient-reported outcomes. Radiation dose and pre- and post-RT standard uptake values (SUVs) for all voxels contained within parotid gland ROI were deformably registered. Results: Average whole-gland or voxel-by-voxel models incorporating parotid D{sub Met} (defined as the pretreatment parotid SUV weighted by dose) accurately predicted posttreatment changes in parotid FDG uptake (e.g., fractional parotid SUV). Fractional loss of parotid FDG uptake closely paralleled early parotid toxicity defined by posttreatment salivary output (p < 0.01) and Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer xerostomia scores (p < 0.01). Conclusions: In this pilot series, loss of parotid FDG uptake was strongly associated with acute clinical post-RT parotid toxicity. D{sub Met} may potentially be used to guide function-sparing treatment planning. Prospective validation of FDG-PET-CT as a convenient, quantifiable imaging biomarker of parotid function is warranted and ongoing.

  20. Evaluation of Multimodal Imaging Biomarkers of Prostate Cancer

    Science.gov (United States)

    2016-11-01

    relationship prostate cancer growth, androgen receptor (AR) levels, hypoxia, and translocator protein (TSPO) levels. As described in the statement of work... bladder uptake) that enable robust detection of small prostate cancers . In contrast, high background and variable uptake of FDHT and FMISO confounded the...Award Number: W81XWH-12-1-0245 TITLE: Evaluation of Multimodal Imaging Biomarkers of Prostate Cancer PRINCIPAL INVESTIGATOR: Christopher Chad

  1. Biomarkers for Autism and for Gastrointestinal and Sleep Problems in Autism

    Science.gov (United States)

    2015-12-01

    Award Number: W81XWH-10-1-0889 TITLE: Biomarkers for Autism and for Gastrointestinal and Sleep Problems in Autism PRINCIPAL INVESTIGATOR...29Sep2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER AR093240 Biomarkers for Autism and for Gastrointestinal and Sleep Problems in Autism 5b. GRANT NUMBER...and daytime excretions of melatonin sulfate were not significantly different between typically developing (TD) toddlers and toddlers with autism

  2. Measuring biomarkers in wastewater as a new source of epidemiological information: Current state and future perspectives

    DEFF Research Database (Denmark)

    Gracia-Lor, Emma; Castiglioni, Sara; Bade, Richard

    2017-01-01

    The information obtained from the chemical analysis of specific human excretion products (biomarkers) in urban wastewater can be used to estimate the exposure or consumption of the population under investigation to a defined substance. A proper biomarker can provide relevant information about...... and pharmacokinetic data (i.e. metabolism and urinary excretion profile) has been reviewed. Finally, several needs and recommendations for future research are proposed....

  3. Molecular Characterization of H.pylori Strains and Biomarkers in Gastric Cancer

    Science.gov (United States)

    2017-07-01

    AWARD NUMBER: W81XWH-16-1-0274 TITLE: Molecular Characterization of H.pylori Strains and Biomarkers in Gastric Cancer PRINCIPAL INVESTIGATOR...SUBTITLE Molecular Characterization of H.pylori Strains and Biomarkers in Gastric Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0274 5c...organoid technology via collaboration with Dr. Mary Estes (Baylor College of Medicine ) and her lab, via one-on-one visits, has guided Dr. Alex Peniche with

  4. Bone remodeling and regulating biomarkers in women at the time of breast cancer diagnosis.

    Science.gov (United States)

    Yao, Song; Zhang, Yali; Tang, Li; Roh, Janise M; Laurent, Cecile A; Hong, Chi-Chen; Hahn, Theresa; Lo, Joan C; Ambrosone, Christine B; Kushi, Lawrence H; Kwan, Marilyn L

    2017-02-01

    The majority of breast cancer patients receive endocrine therapy, including aromatase inhibitors known to cause increased bone resorption. Bone-related biomarkers at the time of breast cancer diagnosis may predict future risk of osteoporosis and fracture after endocrine therapy. In a large population of 2,401 female breast cancer patients who later underwent endocrine therapy, we measured two bone remodeling biomarkers, TRAP5b and BAP, and two bone regulating biomarkers, RANKL and OPG, in serum samples collected at the time of breast cancer diagnosis. We analyzed these biomarkers and their ratios with patients' demographic, lifestyle, clinical tumor characteristics, as well as bone health history. The presence of bone metastases, prior bisphosphonate (BP) treatment, and blood collection after chemotherapy had a significant impact on biomarker levels. After excluding these cases and controlling for blood collection time, several factors, including age, race/ethnicity, body mass index, physical activity, alcohol consumption, smoking, and hormonal replacement therapy, were significantly associated with bone biomarkers, while vitamin D or calcium supplements and tumor characteristics were not. When prior BP users were included in, recent history of osteoporosis and fracture was also associated. Our findings support further investigation of these biomarkers with bone health outcomes after endocrine therapy initiation in women with breast cancer.

  5. The Growing Need for Validated Biomarkers and Endpoints for Dry Eye Clinical Research.

    Science.gov (United States)

    Roy, Neeta S; Wei, Yi; Kuklinski, Eric; Asbell, Penny A

    2017-05-01

    medical challenge with a prevalence rate ranging from 8% to 50%. Many clinicians and researchers across the globe are searching for better answers to understand the mechanisms related to the development and chronicity of DED. Though there have been many clinical trials for DED, few new treatments have emerged over the last decade. Biomarkers may provide the needed breakthrough to propel our understanding of DED to the next level and the potential to realize our goal of truly personalized medicine based on scientific evidence. Clinical trials and research on DED have suffered from the lack of validated biomarkers and less than objective and reproducible endpoints. Current work on biomarkers has provided the groundwork to move forward. This review highlights primarily ocular biomarkers that have been investigated for use in DED, discusses the methodologic outcomes in providing objective metrics for clinical research, and suggests recommendations for further work.

  6. 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

  7. A Systematic Review and Meta-Analysis of Circulating Biomarkers Associated with Failure of Arteriovenous Fistulae for Haemodialysis.

    Directory of Open Access Journals (Sweden)

    Susan K Morton

    Full Text Available Arteriovenous fistula (AVF failure is a significant cause of morbidity and expense in patients on maintenance haemodialysis (HD. Circulating biomarkers could be valuable in detecting patients at risk of AVF failure and may identify targets to improve AVF outcome. Currently there is little consensus on the relationship between circulating biomarkers and AVF failure. The aim of this systematic review was to identify circulating biomarkers associated with AVF failure.Studies evaluating the association between circulating biomarkers and the presence or risk of AVF failure were systematically identified from the MEDLINE, EMBASE and Cochrane Library databases. No restrictions on the type of study were imposed. Concentrations of circulating biomarkers of routine HD patients with and without AVF failure were recorded and meta-analyses were performed on biomarkers that were assessed in three or more studies with a composite population of at least 100 participants. Biomarker concentrations were synthesized into inverse-variance random-effects models to calculate standardized mean differences (SMD and 95% confidence intervals (CI.Thirteen studies comprising a combined population of 1512 participants were included after screening 2835 unique abstracts. These studies collectively investigated 48 biomarkers, predominantly circulating molecules which were assessed as part of routine clinical care. Meta-analysis was performed on twelve eligible biomarkers. No significant association between any of the assessed biomarkers and AVF failure was observed.This paper is the first systematic review of biomarkers associated with AVF failure. Our results suggest that blood markers currently assessed do not identify an at-risk AVF. Further, rigorously designed studies assessing biological plausible biomarkers are needed to clarify whether assessment of circulating markers can be of any clinical value. PROSPERO registration number CRD42016033845.

  8. A new approach towards biomarker selection in estimation of human exposure to chiral chemicals: a case study of mephedrone.

    Science.gov (United States)

    Castrignanò, Erika; Mardal, Marie; Rydevik, Axel; Miserez, Bram; Ramsey, John; Shine, Trevor; Pantoș, G Dan; Meyer, Markus R; Kasprzyk-Hordern, Barbara

    2017-11-02

    Wastewater-based epidemiology is an innovative approach to estimate public health status using biomarker analysis in wastewater. A new compound detected in wastewater can be a potential biomarker of an emerging trend in public health. However, it is currently difficult to select new biomarkers mainly due to limited human metabolism data. This manuscript presents a new framework, which enables the identification and selection of new biomarkers of human exposure to drugs with scarce or unknown human metabolism data. Mephedrone was targeted to elucidate the assessment of biomarkers for emerging drugs of abuse using a four-step analytical procedure. This framework consists of: (i) identification of possible metabolic biomarkers present in wastewater using an in-vivo study; (ii) verification of chiral signature of the target compound; (iii) confirmation of human metabolic residues in in-vivo/vitro studies and (iv) verification of stability of biomarkers in wastewater. Mephedrone was selected as a suitable biomarker due to its high stability profile in wastewater. Its enantiomeric profiling was studied for the first time in biological and environmental matrices, showing stereoselective metabolism of mephedrone in humans. Further biomarker candidates were also proposed for future investigation: 4'-carboxy-mephedrone, 4'-carboxy-normephedrone, 1-dihydro-mephedrone, 1-dihydro-normephedrone and 4'-hydroxy-normephedrone.

  9. Proteomic Biomarkers for Spontaneous Preterm Birth

    DEFF Research Database (Denmark)

    Kacerovsky, Marian; Lenco, Juraj; Musilova, Ivana

    2014-01-01

    This review aimed to identify, synthesize, and analyze the findings of studies on proteomic biomarkers for spontaneous preterm birth (PTB). Three electronic databases (Medline, Embase, and Scopus) were searched for studies in any language reporting the use of proteomic biomarkers for PTB published...

  10. Biomarkers of Renal Function : Towards Clinical Actionability

    NARCIS (Netherlands)

    Binnenmars, S Heleen; Hijmans, R S; Navis, G; de Borst, M H

    This review provides an overview of the clinical value of themost relevant renal biomarkers, focusing on two main clinical conditions: acute kidney injury and chronic kidney disease. We categorize biomarkers according to their actionability, in terms of a documented response to treatment in relation

  11. MicroRNA biomarkers in glioblastoma

    DEFF Research Database (Denmark)

    Hermansen, Simon Kjær; Kristensen, Bjarne Winther

    2013-01-01

    tissues. Understanding these alterations is key to developing new biomarkers and intelligent treatment strategies. This review presents an overview of current knowledge about miRNA alterations in glioblastoma while focusing on the clinical future of miRNAs as biomarkers and discussing the strengths...

  12. Stable isotopes and biomarkers in microbial ecology

    NARCIS (Netherlands)

    Boschker, H.T.S.; Middelburg, J.J.

    2002-01-01

    The use of biomarkers in combination with stable isotope analysis is a new approach in microbial ecology and a number of papers on a variety of subjects have appeared. We will first discuss the techniques for analysing stable isotopes in biomarkers, primarily gas chromatography-combustion-isotope

  13. 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.

  14. Bias in emerging biomarkers for bipolar disorder

    DEFF Research Database (Denmark)

    Carvalho, A F; Köhler, C A; Fernandes, B S

    2016-01-01

    BACKGROUND: To date no comprehensive evaluation has appraised the likelihood of bias or the strength of the evidence of peripheral biomarkers for bipolar disorder (BD). Here we performed an umbrella review of meta-analyses of peripheral non-genetic biomarkers for BD. METHOD: The Pubmed/Medline, E...

  15. Imaging biomarker roadmap for cancer studies

    NARCIS (Netherlands)

    O'Connor, James P. B.; Aboagye, Eric O.; Adams, Judith E.; Aerts, Hugo J. W. L.; Barrington, Sally F.; Beer, Ambros J.; Boellaard, Ronald; Bohndiek, Sarah E.; Brady, Michael; Brown, Gina; Buckley, David L.; Chenevert, Thomas L.; Clarke, Laurence P.; Collette, Sandra; Cook, Gary J.; Desouza, Nandita M.; Dickson, John C.; Dive, Caroline; Evelhoch, Jeffrey L.; Faivre-Finn, Corinne; Gallagher, Ferdia A.; Gilbert, Fiona J.; Gillies, Robert J.; Goh, Vicky; Griffiths, J. R.; Groves, Ashley M.; Halligan, Steve; Harris, Adrian L.; Hawkes, David J.; Hoekstra, Otto S.; Huang, Erich P.; Hutton, Brian F.; Jackson, Edward F.; Jayson, Gordon C.; Jones, Andrew; Koh, Dow-Mu; Lacombe, Denis; Lambin, Philippe; Lassau, Nathalie; Leach, Martin O.; Lee, Ting-Yim; Leen, Edward L.; Lewis, Jason S.; Liu, Yan; Lythgoe, Mark F.; Manoharan, Prakash; Maxwell, Ross J.; Miles, Kenneth A.; Morgan, Bruno; Morris, Steve; Ng, Tony; Padhani, Anwar R.; Parker, Geoff J. M.; Partridge, Mike; Pathak, Arvind P.; Peet, Andrew C.; Punwani, Shonit; Reynolds, Andrew R.; Robinson, Simon P.; Shankar, Lalitha K.; Sharma, Ricky A.; Soloviev, Dmitry; Stroobants, Sigrid G.; Sullivan, Daniel C.; Taylor, Stuart A.; Tofts, Paul S.; Tozer, Gillian M.; van Herk, Marcel B.; Walker-Samuel, Simon; Wason, James; Williams, Kaye J.; Workman, Paul; Yankeelov, Thomas E.; Brindle, Kevin M.; McShane, Lisa M.; Jackson, Alan; Waterton, John C.

    Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and

  16. Fluid biomarkers in multiple system atrophy

    DEFF Research Database (Denmark)

    Laurens, Brice; Constantinescu, Radu; Freeman, Roy

    2015-01-01

    Despite growing research efforts, no reliable biomarker currently exists for the diagnosis and prognosis of multiple system atrophy (MSA). Such biomarkers are urgently needed to improve diagnostic accuracy, prognostic guidance and also to serve as efficacy measures or surrogates of target...... engagement for future clinical trials. We here review candidate fluid biomarkers for MSA and provide considerations for further developments and harmonization of standard operating procedures. A PubMed search was performed until April 24, 2015 to review the literature with regard to candidate blood...... and cerebrospinal fluid (CSF) biomarkers for MSA. Abstracts of 1760 studies were retrieved and screened for eligibility. The final list included 60 studies assessing fluid biomarkers in patients with MSA. Most studies have focused on alpha-synuclein, markers of axonal degeneration or catecholamines. Their results...

  17. RECENT ADVANCES IN BIOMARKERS IN SEVERE BURNS.

    Science.gov (United States)

    Ruiz-Castilla, Mireia; Roca, Oriol; Masclans, Joan R; Barret, Joan P

    2016-02-01

    The pathophysiology of burn injuries is tremendously complex. A thorough understanding is essential for correct treatment of the burned area and also to limit the appearance of organ dysfunction, which, in fact, is a key determinant of morbidity and mortality. In this context, research into biomarkers may play a major role. Biomarkers have traditionally been considered an important area of medical research: the measurement of certain biomarkers has led to a better understanding of pathophysiology, while others have been used either to assess the effectiveness of specific treatments or for prognostic purposes. Research into biomarkers may help to improve the prognosis of patients with severe burn injury. The aim of the present clinical review is to discuss new evidence of the value of biomarkers in this setting.

  18. 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.

  19. The Indian Consensus Document on cardiac biomarker

    Directory of Open Access Journals (Sweden)

    I. Satyamurthy

    2014-01-01

    Full Text Available Despite recent advances, the diagnosis and management of heart failure evades the clinicians. The etiology of congestive heart failure (CHF in the Indian scenario comprises of coronary artery disease, diabetes mellitus and hypertension. With better insights into the pathophysiology of CHF, biomarkers have evolved rapidly and received diagnostic and prognostic value. In CHF biomarkers prove as measures of the extent of pathophysiological derangement; examples include biomarkers of myocyte necrosis, myocardial remodeling, neurohormonal activation, etc. In CHF biomarkers act as indicators for the presence, degree of severity and prognosis of the disease, they may be employed in combination with the present conventional clinical assessments. These make the biomarkers feasible options against the present expensive measurements and may provide clinical benefits.

  20. Biomarkers: in medicine, drug discovery, and environmental health

    National Research Council Canada - National Science Library

    Vaidya, Vishal S; Bonventre, Joseph V

    2010-01-01

    ... Identification Using Mass Spectrometry Sample Preparation Protein Quantitation Examples of Biomarker Discovery and Evaluation Challenges in Proteomic Biomarker Discovery The Road Forward: Targeted ...

  1. Biomarkers and insulin sensitivity in women with Polycystic Ovary Syndrome: Characteristics and predictive capacity.

    Science.gov (United States)

    Cassar, Samantha; Teede, Helena J; Harrison, Cheryce L; Joham, Anju E; Moran, Lisa J; Stepto, Nigel K

    2015-07-01

    Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with metabolic complications. Metabolic biomarkers with roles in obesity, glycaemic control and lipid metabolism are potentially relevant in PCOS. The aim was to investigate metabolic biomarkers in lean and overweight women with and without PCOS and to determine whether any biomarker was able to predict insulin resistance in PCOS. Cross-sectional study. Eighty-four women (22 overweight and 22 lean women with PCOS, 18 overweight and 22 lean women without PCOS) were recruited from the community and categorized based on PCOS and BMI status. Primary outcomes were metabolic biomarkers [ghrelin, resistin, visfatin, glucagon-like peptide-1 (GLP-1), leptin, plasminogen activator inhibitor -1 (PAI-1), glucose-dependent insulinotropic polypeptide (GIP) and C-Peptide] measured using the Bio-Plex Pro Diabetes assay and insulin sensitivity as assessed by glucose infusion rate on euglycaemic-hyperinsulinaemic clamp. The biomarkers C-peptide, leptin, ghrelin and visfatin were different between overweight and lean women, irrespective of PCOS status. The concentration of circulating biomarkers did not differ between women with PCOS diagnosed by the Rotterdam criteria or National Institute of Health criteria. PAI-1 was the only biomarker that significantly predicted insulin resistance in both control women (P = 0.04) and women with PCOS (P = 0.01). Biomarkers associated with metabolic diseases appear more strongly associated with obesity rather than PCOS status. PAI-1 may also be a novel independent biomarker and predictor of insulin resistance in women with and without PCOS. © 2014 John Wiley & Sons Ltd.

  2. PET Metabolic Biomarkers for Cancer

    Directory of Open Access Journals (Sweden)

    Etienne Croteau

    2016-01-01

    Full Text Available The body's main fuel sources are fats, carbohydrates (glucose, proteins, and ketone bodies. It is well known that an important hallmark of cancer cells is the overconsumption of glucose. Positron emission tomography (PET imaging using the glucose analog 18 F-fluorodeoxyglucose ( 18 F-FDG has been a powerful cancer diagnostic tool for many decades. Apart from surgery, chemotherapy and radiotherapy represent the two main domains for cancer therapy, targeting tumor proliferation, cell division, and DNA replication–-all processes that require a large amount of energy. Currently, in vivo clinical imaging of metabolism is performed almost exclusively using PET radiotracers that assess oxygen consumption and mechanisms of energy substrate consumption. This paper reviews the utility of PET imaging biomarkers for the detection of cancer proliferation, vascularization, metabolism, treatment response, and follow-up after radiation therapy, chemotherapy, and chemotherapy-related side effects.

  3. Measuring biomarkers in wastewater as a new source of epidemiological information: Current state and future perspectives

    DEFF Research Database (Denmark)

    Gracia-Lor, Emma; Castiglioni, Sara; Bade, Richard

    2017-01-01

    The information obtained from the chemical analysis of specific human excretion products (biomarkers) in urban wastewater can be used to estimate the exposure or consumption of the population under investigation to a defined substance. A proper biomarker can provide relevant information about...... lifestyle habits, health and wellbeing, but its selection is not an easy task as it should fulfil several specific requirements in order to be successfully employed. This paper aims to summarize the current knowledge related to the most relevant biomarkers used so far. In addition, some potential wastewater...... in the environment and food, (iii) those that have the potential to provide information about public health and illness and (iv) those used to estimate the population size. To facilitate the evaluation of the eligibility of a compound as a biomarker, information, when available, on stability in urine and wastewater...

  4. Serum Glutamine Levels as a Potential Diagnostic Biomarker in Sepsis following Surgery for Peritonitis.

    Science.gov (United States)

    Yang, Chun-Ju; Huang, Ting-Shuo; Lee, Tung-Liang; Yang, Kang-Chung; Yuan, Shin-Sheng; Lu, Ruey-Hwa; Hsieh, Chung-Ho; Shyu, Yu-Chiau

    2017-12-31

    Few diagnostic biomarkers for sepsis after emergency peritonitis surgery are available to clinicians, and, thus, it is important to develop new biomarkers for patients undergoing this procedure. We investigated whether serum glutamine and selenium levels could be diagnostic biomarkers of sepsis in individuals recovering from emergency peritonitis surgery. From February 2012 to March 2013, patients who had peritonitis diagnosed at the emergency department and underwent emergency surgery were screened for eligibility. Serum glutamine and selenium levels were obtained at pre-operative, post-operative and recovery time points. The average level of pre-operation serum glutamine was significantly different from that on the recovery day (0.317 ± 0.168 vs. 0.532 ± 0.155 mM, P peritonitis. We recommend including glutamine as a biomarker for sepsis severity assessment in addition to the commonly used clinical indicators.

  5. The Immune System, Cytokines, and Biomarkers in Autism Spectrum Disorder

    Institute of Scientific and Technical Information of China (English)

    Anne Masi; Nicholas Glozier; Russell Dale; Adam J.Guastella

    2017-01-01

    Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental condition characterized by variable impairments in communication and social interaction as well as restricted interests and repetitive behaviors.Heterogeneity of presentation is a hallmark.Investigations of immune system problems in ASD,including aberrations in cytokine profiles and signaling,have been increasing in recent times and are the subject of ongoing interest.With the aim of establishing whether cytokines have utility as potential biomarkers that may define a subgroup of ASD,or function as an objective measure of response to treatment,this review summarizes the role of the immune system,discusses the relationship between the immune system,the brain,and behavior,and presents previouslyidentified immune system abnormalities in ASD,specifically addressing the role of cytokines in these aberrations.The roles and identification of biomarkers are also addressed,particularly with respect to cytokine profiles in ASD.

  6. NanoSIMS analysis of Archean fossils and biomarkers

    International Nuclear Information System (INIS)

    Kilburn, M.R.; Wacey, D.

    2008-01-01

    The study of fossils and biomarkers from Archean rocks is of vital importance to reveal how life arose on Earth and what we might expect to find on other planets such as Mars. The Cameca NanoSIMS 50 has the unique ability to measure stable isotopes and map biologically relevant elements at the micron-scale, in situ. This makes it the perfect tool for testing the biogenicity of a range of putative biomarkers from early Archean rocks (∼3.50 billion-year-old). NanoSIMS has been used to investigate ambient inclusion trails (AITs) in a 3.43 Ga beach sand deposit from the Pilbara craton, Western Australia. Chemical maps of the light elements necessary for life (C, N and O) and several transition metals commonly associated with biological processing (Ni, Zn and Fe), coupled with 13 C/ 12 C isotope ratios from carbonaceous linings, strongly suggest a biological component in the formation of AITs

  7. 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...

  8. Hemostatic biomarkers in dogs with chronic congestive heart failure

    DEFF Research Database (Denmark)

    Tarnow, Inge; Falk, Torkel; Tidholm, Anna

    2007-01-01

    Background: Chronic congestive heart failure (CHF) in humans is associated with abnormal hemostasis, and abnormalities in hemostatic biomarkers carry a poor prognosis. Alterations in hemostatic pathways can be involved in the pathogenesis of CHF in dogs, and microthrombosis in the myocardium could...... contribute to increased mortality. Hypothesis: That plasma concentration or activity of hemostatic biomarkers is altered in dogs with CHF and that these factors predict mortality. Animals: Thirty-four dogs with CHF caused by either dilated cardiomyopathy (DCM, n = 14) or degenerative valvular disease (CDVD......, n = 20) compared with 23 healthy age-matched control dogs were included in this study. Dogs with CHF were recruited from 2 referral cardiology clinics, and control dogs were owned by friends or colleagues of the investigators. Methods: Clinical examination and echocardiography were performed in all...

  9. The Immune System, Cytokines, and Biomarkers in Autism Spectrum Disorder.

    Science.gov (United States)

    Masi, Anne; Glozier, Nicholas; Dale, Russell; Guastella, Adam J

    2017-04-01

    Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental condition characterized by variable impairments in communication and social interaction as well as restricted interests and repetitive behaviors. Heterogeneity of presentation is a hallmark. Investigations of immune system problems in ASD, including aberrations in cytokine profiles and signaling, have been increasing in recent times and are the subject of ongoing interest. With the aim of establishing whether cytokines have utility as potential biomarkers that may define a subgroup of ASD, or function as an objective measure of response to treatment, this review summarizes the role of the immune system, discusses the relationship between the immune system, the brain, and behavior, and presents previously-identified immune system abnormalities in ASD, specifically addressing the role of cytokines in these aberrations. The roles and identification of biomarkers are also addressed, particularly with respect to cytokine profiles in ASD.

  10. 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.)

  11. 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.

  12. CBD: a biomarker database for colorectal cancer.

    Science.gov (United States)

    Zhang, Xueli; Sun, Xiao-Feng; Cao, Yang; Ye, Benchen; Peng, Qiliang; Liu, Xingyun; Shen, Bairong; Zhang, Hong

    2018-01-01

    Colorectal cancer (CRC) biomarker database (CBD) was established based on 870 identified CRC biomarkers and their relevant information from 1115 original articles in PubMed published from 1986 to 2017. In this version of the CBD, CRC biomarker data were collected, sorted, displayed and analysed. The CBD with the credible contents as a powerful and time-saving tool provide more comprehensive and accurate information for further CRC biomarker research. The CBD was constructed under MySQL server. HTML, PHP and JavaScript languages have been used to implement the web interface. The Apache was selected as HTTP server. All of these web operations were implemented under the Windows system. The CBD could provide to users the multiple individual biomarker information and categorized into the biological category, source and application of biomarkers; the experiment methods, results, authors and publication resources; the research region, the average age of cohort, gender, race, the number of tumours, tumour location and stage. We only collect data from the articles with clear and credible results to prove the biomarkers are useful in the diagnosis, treatment or prognosis of CRC. The CBD can also provide a professional platform to researchers who are interested in CRC research to communicate, exchange their research ideas and further design high-quality research in CRC. They can submit their new findings to our database via the submission page and communicate with us in the CBD.Database URL: http://sysbio.suda.edu.cn/CBD/.

  13. 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

  14. Biomarkers in DILI: one more step forward

    Directory of Open Access Journals (Sweden)

    Mercedes Robles-Díaz

    2016-08-01

    Full Text Available Despite being relatively rare, drug-induced liver injury (DILI is a serious condition, both for the individual patient due to the risk of acute liver failure, and for the drug development industry and regulatory agencies due to associations with drug development attritions, black box warnings and postmarketing withdrawals. A major limitation in DILI diagnosis and prediction is the current lack of specific biomarkers. Despite refined usage of traditional liver biomarkers in DILI, reliable disease outcome predictions are still difficult to make. These limitations have driven the growing interest in developing new more sensitive and specific DILI biomarkers, which can improve early DILI prediction, diagnosis and course of action. Several promising DILI biomarker candidates have been discovered to date, including mechanistic-based biomarker candidates such as glutamate dehydrogenase, high-mobility group box 1 protein and keratin-18, which can also provide information on the injury mechanism of different causative agents. Furthermore, microRNAs have received much attention lately as potential non-invasive DILI biomarker candidates, in particular miR-122. Advances in omics technologies offer a new approach for biomarker exploration studies. The ability to screen a large number of molecules (for example metabolites, proteins or DNA simultaneously enables the identification of ‘toxicity signatures’, which may be used to enhance preclinical safety assessments and disease diagnostics. Omics-based studies can also provide information on the underlying mechanisms of distinct forms of DILI that may further facilitate the identification of early diagnostic biomarkers and safer implementation of personalized medicine. In this review we summarize recent advances in the area of DILI biomarker studies.

  15. Biomarkers for equine joint injury and osteoarthritis.

    Science.gov (United States)

    McIlwraith, C Wayne; Kawcak, Christopher E; Frisbie, David D; Little, Christopher B; Clegg, Peter D; Peffers, Mandy J; Karsdal, Morten A; Ekman, Stina; Laverty, Sheila; Slayden, Richard A; Sandell, Linda J; Lohmander, L S; Kraus, Virginia B

    2018-03-01

    We report the results of a symposium aimed at identifying validated biomarkers that can be used to complement clinical observations for diagnosis and prognosis of joint injury leading to equine osteoarthritis (OA). Biomarkers might also predict pre-fracture change that could lead to catastrophic bone failure in equine athletes. The workshop was attended by leading scientists in the fields of equine and human musculoskeletal biomarkers to enable cross-disciplinary exchange and improve knowledge in both. Detailed proceedings with strategic planning was written, added to, edited and referenced to develop this manuscript. The most recent information from work in equine and human osteoarthritic biomarkers was accumulated, including the use of personalized healthcare to stratify OA phenotypes, transcriptome analysis of anterior cruciate ligament (ACL) and meniscal injuries in the human knee. The spectrum of "wet" biomarker assays that are antibody based that have achieved usefulness in both humans and horses, imaging biomarkers and the role they can play in equine and human OA was discussed. Prediction of musculoskeletal injury in the horse remains a challenge, and the potential usefulness of spectroscopy, metabolomics, proteomics, and development of biobanks to classify biomarkers in different stages of equine and human OA were reviewed. The participants concluded that new information and studies in equine musculoskeletal biomarkers have potential translational value for humans and vice versa. OA is equally important in humans and horses, and the welfare issues associated with catastrophic musculoskeletal injury in horses add further emphasis to the need for good validated biomarkers in the horse. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:823-831, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  16. Cardiac Biomarkers and Cycling Race

    Directory of Open Access Journals (Sweden)

    Caroline Le Goff, Jean-François Kaux, Sébastien Goffaux, Etienne Cavalier

    2015-06-01

    Full Text Available In cycling as in other types of strenuous exercise, there exists a risk of sudden death. It is important both to understand its causes and to see if the behavior of certain biomarkers might highlight athletes at risk. Many reports describe changes in biomarkers after strenuous exercise (Nie et al., 2011, but interpreting these changes, and notably distinguishing normal physiological responses from pathological changes, is not easy. Here we have focused on the kinetics of different cardiac biomarkers: creatin kinase (CK, creating kinase midbrain (CK-MB, myoglobin (MYO, highly sensitive troponin T (hs-TnT and N-terminal brain natriuretic peptide (NT-proBNP. The population studied was a group of young trained cyclists participating in a 177-km cycling race. The group of individuals was selected for maximal homogeneity. Their annual training volume was between 10,000 and 16,000 kilometers. The rhythm of races is comparable and averages 35 km/h, depending on the race’s difficulty. The cardiac frequency was recorded via a heart rate monitor. Three blood tests were taken. The first blood test, T0, was taken approximately 2 hours before the start of the race and was intended to gather values which would act as references for the following tests. The second blood test, T1, was realized within 5 minutes of their arrival. The third and final blood test, T3, was taken 3 hours following their arrival. The CK, CK-MB, MYO, hs-TnT and NT-proBNP were measured on the Roche Diagnostic modular E (Manhein, Germany. For the statistical analysis, an ANOVA and post hoc test of Scheffé were calculated with the Statistica Software version 9.1. We noticed an important significant variation in the cardiac frequency between T0 and T1 (p < 0.0001, T0 and T3 (p < 0.0001, and T1 and T3 (p < 0.01. Table 1 shows the results obtained for the different biomarkers. CK and CK-MB showed significant variation between T0-T1 and T0-T3 (p < 0.0001. Myoglobin increased significantly

  17. Mining biomarker information in biomedical literature

    Directory of Open Access Journals (Sweden)

    Younesi Erfan

    2012-12-01

    Full Text Available Abstract Background For selection and evaluation of potential biomarkers, inclusion of already published information is of utmost importance. In spite of significant advancements in text- and data-mining techniques, the vast knowledge space of biomarkers in biomedical text has remained unexplored. Existing named entity recognition approaches are not sufficiently selective for the retrieval of biomarker information from the literature. The purpose of this study was to identify textual features that enhance the effectiveness of biomarker information retrieval for different indication areas and diverse end user perspectives. Methods A biomarker terminology was created and further organized into six concept classes. Performance of this terminology was optimized towards balanced selectivity and specificity. The information retrieval performance using the biomarker terminology was evaluated based on various combinations of the terminology's six classes. Further validation of these results was performed on two independent corpora representing two different neurodegenerative diseases. Results The current state of the biomarker terminology contains 119 entity classes supported by 1890 different synonyms. The result of information retrieval shows improved retrieval rate of informative abstracts, which is achieved by including clinical management terms and evidence of gene/protein alterations (e.g. gene/protein expression status or certain polymorphisms in combination with disease and gene name recognition. When additional filtering through other classes (e.g. diagnostic or prognostic methods is applied, the typical high number of unspecific search results is significantly reduced. The evaluation results suggest that this approach enables the automated identification of biomarker information in the literature. A demo version of the search engine SCAIView, including the biomarker retrieval, is made available to the public through http

  18. Inflammatory biomarkers in asthma-COPD overlap syndrome

    Directory of Open Access Journals (Sweden)

    Kobayashi S

    2016-09-01

    Full Text Available Seiichi Kobayashi, Masakazu Hanagama, Shinsuke Yamanda, Masatsugu Ishida, Masaru YanaiDepartment of Respiratory Medicine, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, JapanBackground: The clinical phenotypes and underlying mechanisms of asthma-COPD overlap syndrome (ACOS remain elusive. This study aimed to investigate a comparison of COPD patients with and without ACOS, focusing on inflammatory biomarkers, in an outpatient COPD cohort.Methods: We conducted a cross-sectional study analyzing prospectively collected data from the Ishinomaki COPD Network registry. All participants were diagnosed with COPD, confirmed by using spirometry, and were aged 40–90 years and former smokers. Patients with features of asthma including both variable respiratory symptoms and variable expiratory airflow limitation were identified and defined as having ACOS. Then, the inflammatory biomarkers such as fractional exhaled nitric oxide level, blood eosinophil count and percentage, total immunoglobulin E (IgE level, and presence of antigen-specific IgE were evaluated.Results: A total of 257 patients with COPD were identified, including 37 (14.4% with ACOS. Patients with ACOS tended to be younger, have a shorter smoking history, and use more respiratory medications, especially inhaled corticosteroids and theophylline. Mean fractional exhaled nitric oxide level was significantly higher in those with ACOS than in those without ACOS (38.5 parts per billion [ppb] vs 20.3 ppb, P<0.001. Blood eosinophil count and percentage were significantly increased in those with ACOS (295/mm3 vs 212/mm3, P=0.032; 4.7% vs 3.2%, P=0.003, respectively. Total IgE level was also significantly higher, and presence of antigen-specific IgE was observed more frequently in patients with ACOS. Receiver operating characteristic curve analysis indicated that the sensitivity and specificity of these biomarkers were relatively low, but combinations of these biomarkers showed high specificity for

  19. Dietary and health biomarkers-time for an update

    NARCIS (Netherlands)

    Dragsted, L.O.; Gao Qizian,; Praticò, G.; Manach, Claudine; Wishart, D.S.; Scalbert, A.; Feskens, E.J.M.

    2017-01-01

    In the dietary and health research area, biomarkers are extensively used for multiple purposes. These include biomarkers of dietary intake and nutrient status, biomarkers used to measure the biological effects of specific dietary components, and biomarkers to assess the effects of diet on health.

  20. 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

  1. 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

  2. Biomarker monitoring in sports doping control.

    Science.gov (United States)

    Pottgiesser, Torben; Schumacher, Yorck Olaf

    2012-06-01

    Biomarker monitoring can be considered a new era in the effort against doping. Opposed to the old concept in doping control of direct detection of a prohibited substance in a biological sample such as urine or blood, the new paradigm allows a personalized longitudinal monitoring of biomarkers that indicate non-physiological responses independently of the used doping technique or substance, and may cause sanctioning of illicit practices. This review presents the development of biomarker monitoring in sports doping control and focuses on the implementation of the Athlete Biological Passport as the current concept of the World Anti Doping Agency for the detection of blood doping (hematological module). The scope of the article extends to the description of novel biomarkers and future concepts of application.

  3. 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...

  4. Radiation Biomarker Research Using Mass Spectrometry

    National Research Council Canada - National Science Library

    Bach, Stephan B; Hubert, Walter

    2007-01-01

    .... This review is intended to give an overview of mass spectrometry and its application to biological systems and biomarker discovery and how that might relate to relevant radiation dosimetry studies...

  5. 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

  6. International Team Identifies Biomarker for Scleroderma

    Science.gov (United States)

    ... Spotlight on Research International Team Identifies Biomarker for Scleroderma By Kirstie Saltsman, Ph.D. | May 5, 2014 ... molecule correlates with a more severe form of scleroderma, a chronic autoimmune disorder that involves the abnormal ...

  7. Biomarkers in psoriasis and psoriatic arthritis.

    Science.gov (United States)

    Villanova, Federica; Di Meglio, Paola; Nestle, Frank O

    2013-04-01

    Psoriasis is a common immune-mediated disease of the skin, which associates in 20-30% of patients with psoriatic arthritis (PsA). The immunopathogenesis of both conditions is not fully understood as it is the result of a complex interaction between genetic, environmental and immunological factors. At present there is no cure for psoriasis and there are no specific markers that can accurately predict disease progression and therapeutic response. Therefore, biomarkers for disease prognosis and response to treatment are urgently needed to help clinicians with objective indications to improve patient management and outcomes. Although many efforts have been made to identify psoriasis/PsA biomarkers none of them has yet been translated into routine clinical practice. In this review we summarise the different classes of possible biomarkers explored in psoriasis and PsA so far and discuss novel strategies for biomarker discovery.

  8. Novel Biomarker for Prognosis, Treatment Response

    Science.gov (United States)

    An NCI Cancer Currents blog about a study of a new type of cancer biomarker that measures the extent of chromosomal instability as a way to potentially predict patient prognosis and help guide cancer treatment choices.

  9. 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.

  10. 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.

  11. Impact of coexposure on toluene biomarkers in rats.

    Science.gov (United States)

    Cosnier, Frédéric; Nunge, Hervé; Brochard, Céline; Burgart, Manuella; Rémy, Aurélie; Décret, Marie-Josèphe; Cossec, Benoît; Campo, Pierre

    2014-03-01

    1. Toluene (TOL) is widely used in industry. Occupational exposure to TOL is commonly assessed using TOL in blood, hippuric acid and ortho-cresol. Levels of these biomarkers may depend on factors potentially interfering with TOL biotransformation, such as the presence of other solvents in the workplace. Mercapturic acids (MAs) could be an alternative to the "traditional" TOL biomarkers. 2. This study aims (1) to investigate in rat the effects of an exposure to vapours mixtures on the TOL metabolism, and (2) to assess how well MAs performed in these contexts compared to the traditional TOL biomarkers. 3. Rats were exposed by inhalation to binary mixtures of TOL with n-butanol (BuOH), ethyl acetate (EtAc), methyl ethyl ketone (MEK) or xylenes (XYLs); biological exposure indicators were then measured. 4. Depending on the compounds in the mixture and their concentrations, TOL metabolism was accelerated (with BuOH), unchanged (with EtAc) or inhibited (with XYLs and MEK). Inhibition leads to an increase in blood TOL concentrations, even at authorized atmospheric concentrations, which may potentiate the effect of TOL. 5. MAs excretions are little affected by coexposure scenarios, their levels correlating well with atmospheric TOL levels. They could thus be suitable bioindicators of atmospheric TOL exposure.

  12. Research on Potential Biomarkers in Hereditary Haemorrhagic Telangiectasia

    Directory of Open Access Journals (Sweden)

    Luisa Maria Botella

    2015-03-01

    Full Text Available Hereditary Hemorrhagic Telangiectasia (HHT is a genetically heterogeneous disorder, involving mutations in two predominant genes known as Endoglin (ENG; HHT1 and Activin receptor like kinase 1 (ACVRL1/ALK1; HHT2, as well as in some less frequent genes, such as MADH4/SMAD4 (JP-HHT or BMP9/GDF2 (HHT5. The diagnosis of HHT patients currently remains at the clinical level, according to the Curaçao criteria, whereas the molecular diagnosis is used to confirm or rule out suspected HHT cases, especially when a well characterized index case is present in the family or in an isolated population. Unfortunately, many suspected patients do not present a clear HHT diagnosis or do not show pathogenic mutations in HHT genes, prompting the need to investigate additional biomarkers of the disease. Here, several HHT biomarkers and novel methodological approaches developed during the last years will be reviewed. On one hand, products detected in plasma or serum samples: soluble proteins (VEGF, TGF-β1, soluble endoglin, angiopoietin-2 and microRNA variants (miR-27a, miR-205, miR-210. On the other hand, differential HHT gene expression fingerprinting, Next Generation Sequencing (NGS of a panel of genes involved in HHT, and infrared spectroscopy combined with Artificial Neural Network (ANN patterns will also be reviewed. All these biomarkers might help to improve and refine HHT diagnosis by distinguishing from the non-HHT population.

  13. Biomarkers in neonatology: the new "omics" of bronchopulmonary dysplasia.

    Science.gov (United States)

    Piersigilli, Fiammetta; Bhandari, Vineet

    2016-01-01

    Bronchopulmonary dysplasia (BPD) is a complex disorder resulting from gene-environmental interactions. An improved understanding of the pathogenesis of this most common chronic lung disease in infants has been made by utilizing animal models and correlating with human data. Currently, while some (vitamin A, caffeine) pharmacotherapeutic options are being utilized to ameliorate this condition, there is still no specific or effective treatment for BPD. It would be helpful for prognostication and targeted potential novel therapeutic strategies to identify those babies accurately who are at risk for developing this disease. A reliable biomarker would have the capacity to be detected in the initial phase of the disease, to allow early interventions to avoid or minimize the detrimental effects of the disease. This review will focus on human studies performed with the "omic" techniques, specifically genomics, epigenomics, microbiomics, transciptomics, proteomics and metabolomics, and summarize the information available in the literature, as it pertains to biomarker identification for BPD. Using "omics" technologies, investigators have reported markers that have the potential to be used as biomarkers of BPD: SPOCK2, VEGF -624C > G, VEGF -460T > C, mast cells specific markers, miR-219 pathway, miR-152, -30a-3p, -133b, -206, -7, lactate, taurine, trimethylamine-N-oxide, gluconate, myoinositol and alterations in surfactant lipid profile.

  14. Immunohistochemistry of colorectal cancer biomarker phosphorylation requires controlled tissue fixation.

    Directory of Open Access Journals (Sweden)

    Abbey P Theiss

    Full Text Available Phosphorylated signaling molecules are biomarkers of cancer pathophysiology and resistance to therapy, but because phosphoprotein analytes are often labile, poorly controlled clinical laboratory practices could prevent translation of research findings in this area from the bench to the bedside. We therefore compared multiple biomarker and phosphoprotein immunohistochemistry (IHC results in 23 clinical colorectal carcinoma samples after either a novel, rapid tissue fixation protocol or a standard tissue fixation protocol employed by clinical laboratories, and we also investigated the effect of a defined post-operative "cold" ischemia period on these IHC results. We found that a one-hour cold ischemia interval, allowed by ASCO/CAP guidelines for certain cancer biomarker assays, is highly deleterious to certain phosphoprotein analytes, specifically the phosphorylated epidermal growth factor receptor (pEGFR, but shorter ischemic intervals (less than 17 minutes facilitate preservation of phosphoproteins. Second, we found that a rapid 4-hour, two temperature, formalin fixation yielded superior staining in several cases with select markers (pEGFR, pBAD, pAKT compared to a standard overnight room temperature fixation protocol, despite taking less time. These findings indicate that the future research and clinical utilities of phosphoprotein IHC for assessing colorectal carcinoma pathophysiology absolutely depend upon attention to preanalytical factors and rigorously controlled tissue fixation protocols.

  15. Computational design of in vivo biomarkers

    International Nuclear Information System (INIS)

    Somogyi, Bálint; Gali, Adam

    2014-01-01

    Fluorescent semiconductor nanocrystals (or quantum dots) are very promising agents for bioimaging applications because their optical properties are superior compared to those of conventional organic dyes. However, not all the properties of these quantum dots suit the stringent criteria of in vivo applications, i.e. their employment in living organisms that might be of importance in therapy and medicine. In our review, we first summarize the properties of an ‘ideal’ biomarker needed for in vivo applications. Despite recent efforts, no such hand-made fluorescent quantum dot exists that may be considered as ‘ideal’ in this respect. We propose that ab initio atomistic simulations with predictive power can be used to design ‘ideal’ in vivo fluorescent semiconductor nanoparticles. We briefly review such ab initio methods that can be applied to calculate the electronic and optical properties of very small nanocrystals, with extra emphasis on density functional theory (DFT) and time-dependent DFT which are the most suitable approaches for the description of these systems. Finally, we present our recent results on this topic where we investigated the applicability of nanodiamonds and silicon carbide nanocrystals for in vivo bioimaging. (topical review)

  16. Biomarkers in diverticular diseases of the colon.

    Science.gov (United States)

    Tursi, Antonio

    2012-01-01

    Recent data found that diverticular disease (DD) of the colon shows similarities with inflammatory bowel diseases (IBD). In particular, the detection of microscopic inflammation and the clinical response to mesalazine seem to confirm the hypothesis that inflammation may be a key point for the appearance of symptoms and development of complications. In light of this hypothesis, several studies have recently focused their attention on the role of biomarkers in predicting and monitoring the course of the disease. C-reactive protein (CRP), white blood cell count, erythrocyte sedimentation rate, and fecal calprotectin (FC) have therefore been investigated. As in IBD, CRP seems to be the most effective marker of histological and clinical severity of the disease. In particular, CRP below 50 mg/l suggests an acute uncomplicated diverticulitis (AUD), whereas CRP higher than 200 mg/l is a strong indicator of DD complicated by perforation. As in IBD, FC seems to be a noninvasive sensitive marker of DD severity. In particular, FC may show slight increased valued already in symptomatic uncomplicated DD (SUDD) (FC value ≥15 μg/ml seems to be predictive of SUDD). As expected, FC shows higher values in AUD (FC value ≥60 μg/ml seems to be predictive of AUD). Finally, FC seems to be useful also in monitoring the therapeutic response in DD. In fact, FC values decreased significantly in patients responding to therapy, whereas they persisted to increase in patients who failed to obtain remission. Copyright © 2012 S. Karger AG, Basel.

  17. Salivary pH: A diagnostic biomarker

    OpenAIRE

    Baliga, Sharmila; Muglikar, Sangeeta; Kale, Rahul

    2013-01-01

    Objectives: Saliva contains a variety of host defense factors. It influences calculus formation and periodontal disease. Different studies have been done to find exact correlation of salivary biomarkers with periodontal disease. With a multitude of biomarkers and complexities in their determination, the salivary pH may be tried to be used as a quick chairside test. The aim of this study was to analyze the pH of saliva and determine its relevance to the severity of periodontal disease. Study D...

  18. 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.

  19. Biomarkers of disease activity in vitiligo: A systematic review.

    Science.gov (United States)

    Speeckaert, R; Speeckaert, M; De Schepper, S; van Geel, N

    2017-09-01

    The pathophysiology of vitiligo is complex although recent research has discovered several markers which are linked to vitiligo and associated with disease activity. Besides providing insights into the driving mechanisms of vitiligo, these findings could reveal potential biomarkers. Activity markers can be used to monitor disease activity in clinical trials and may also be useful in daily practice. The aim of this systematic review was to document which factors have been associated with vitiligo activity in skin and blood. A second goal was to determine how well these factors are validated in terms of sensitivity and specificity as biomarkers to determine vitiligo activity. Both in skin (n=43) as in blood (n=66) an adequate number of studies fulfilled the predefined inclusion criteria. These studies used diverse methods and investigated a broad range of plausible biomarkers. Unfortunately, sensitivity and specificity analyses were scarce. In skin, simple histopathology with or without supplemental CD4 and CD8 stainings can still be considered as the gold standard, although more recently chemokine (C-X-C motif) ligand (CXCL) 9 and NLRP1 have demonstrated a good and possibly even better association with progressive disease. Regarding circulating biomarkers, cytokines (IL-1β, IL-17, IFN-γ, TGF-β), autoantibodies, oxidative stress markers, immune cells (Tregs), soluble CDs (sCD25, sCD27) and chemokines (CXCL9, CXCL10) are still competing. However, the two latter may be preferable as both chemokines and soluble CDs are easy to measure and the available studies display promising results. A large multicenter study could make more definitive statements regarding their sensitivity and specificity. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Quality assurance in biomarker measurement.

    Science.gov (United States)

    Aitio, A; Apostoli, P

    1995-05-01

    Quality assurance (QA) concerns the validity of all the analytical processes (from collection of the samples to interpretation of the results). It is not an abstract concept but must be adapted to the different situations such as the different exposure levels, the different analytical methods, and the context of use (risk assessment procedures, research, routine determinations). The main requirements in QA programmes regard the control of all the known sources of preanalytical and analytical variations, while the instruments with which adequate QA can be implemented are the certified materials and the quality control programmes (quality manual, internal and external quality controls). Another important concept in QA is that measurements must be placed a different metrological levels: at the highest there are the methods (definitive, reference) to be used for assessing accuracy of routine methods. QA programmes should enable a grading of biomarkers (from experimental only to full evaluated) and of the laboratories in order to identify the significance of the test and to assess the level at which a laboratory could operate.

  1. Shotgun Proteomics and Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    W. Hayes McDonald

    2002-01-01

    Full Text Available Coupling large-scale sequencing projects with the amino acid sequence information that can be gleaned from tandem mass spectrometry (MS/MS has made it much easier to analyze complex mixtures of proteins. The limits of this “shotgun” approach, in which the protein mixture is proteolytically digested before separation, can be further expanded by separating the resulting mixture of peptides prior to MS/MS analysis. Both single dimensional high pressure liquid chromatography (LC and multidimensional LC (LC/LC can be directly interfaced with the mass spectrometer to allow for automated collection of tremendous quantities of data. While there is no single technique that addresses all proteomic challenges, the shotgun approaches, especially LC/LC-MS/MS-based techniques such as MudPIT (multidimensional protein identification technology, show advantages over gel-based techniques in speed, sensitivity, scope of analysis, and dynamic range. Advances in the ability to quantitate differences between samples and to detect for an array of post-translational modifications allow for the discovery of classes of protein biomarkers that were previously unassailable.

  2. Application of biomarkers to assess the condition of European Marine Sites

    Energy Technology Data Exchange (ETDEWEB)

    Hagger, Josephine A., E-mail: j.hagger@exeter.ac.u [School of Biosciences, University of Exeter, Prince of Wales Road, Exeter, Devon EX4 4PS (United Kingdom); Galloway, Tamara S. [School of Biosciences, University of Exeter, Prince of Wales Road, Exeter, Devon EX4 4PS (United Kingdom); Langston, William J. [Marine Biological Association, Citadel Hill, Plymouth PL1 2PB, Devon (United Kingdom); Jones, Malcolm B. [School of Biological Sciences, University of Plymouth, Drake Circus, Plymouth PL4 8AA, Devon (United Kingdom)

    2009-07-15

    A series of European Marine Sites has been designated as Special Areas of Conservation (SAC) in England. The aim of this study was to develop a practical methodology to assess the condition of SACs by applying a suite of biomarkers. Biomarkers were applied to the blue mussel Mytilus edulis and the shore crab Carcinus maenas from the Fal and Helford SAC (Cornwall). Individual biomarkers provided useful diagnostic information on the activity of certain classes of contaminants and an integrated Biomarker Response Index (BRI) was used to achieve a more holistic understanding of the condition of the SAC. The BRI indicated that the general health of both organisms was impacted in the upper part of the SAC (Fal Estuary) which correlated well with known chemical hotspots and sources of contamination. The BRI allows a pragmatic way to prioritise SAC sites that may require further investigative studies. - A suite of biomarkers was successfully used to create a Biomarker Response Index to assess the health of aquatic organisms from European Marine Sites.

  3. Biomarker Identification and Pathway Analysis by Serum Metabolomics of Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yingrong Chen

    2015-01-01

    Full Text Available Lung cancer is one of the most common causes of cancer death, for which no validated tumor biomarker is sufficiently accurate to be useful for diagnosis. Additionally, the metabolic alterations associated with the disease are unclear. In this study, we investigated the construction, interaction, and pathways of potential lung cancer biomarkers using metabolomics pathway analysis based on the Kyoto Encyclopedia of Genes and Genomes database and the Human Metabolome Database to identify the top altered pathways for analysis and visualization. We constructed a diagnostic model using potential serum biomarkers from patients with lung cancer. We assessed their specificity and sensitivity according to the area under the curve of the receiver operator characteristic (ROC curves, which could be used to distinguish patients with lung cancer from normal subjects. The pathway analysis indicated that sphingolipid metabolism was the top altered pathway in lung cancer. ROC curve analysis indicated that glycerophospho-N-arachidonoyl ethanolamine (GpAEA and sphingosine were potential sensitive and specific biomarkers for lung cancer diagnosis and prognosis. Compared with the traditional lung cancer diagnostic biomarkers carcinoembryonic antigen and cytokeratin 19 fragment, GpAEA and sphingosine were as good or more appropriate for detecting lung cancer. We report our identification of potential metabolic diagnostic and prognostic biomarkers of lung cancer and clarify the metabolic alterations in lung cancer.

  4. Biomarkers identified by urinary metabonomics for noninvasive diagnosis of nutritional rickets.

    Science.gov (United States)

    Wang, Maoqing; Yang, Xue; Ren, Lihong; Li, Songtao; He, Xuan; Wu, Xiaoyan; Liu, Tingting; Lin, Liqun; Li, Ying; Sun, Changhao

    2014-09-05

    Nutritional rickets is a worldwide public health problem; however, the current diagnostic methods retain shortcomings for accurate diagnosis of nutritional rickets. To identify urinary biomarkers associated with nutritional rickets and establish a noninvasive diagnosis method, urinary metabonomics analysis by ultra-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis were employed to investigate the metabolic alterations associated with nutritional rickets in 200 children with or without nutritional rickets. The pathophysiological changes and pathogenesis of nutritional rickets were illustrated by the identified biomarkers. By urinary metabolic profiling, 31 biomarkers of nutritional rickets were identified and five candidate biomarkers for clinical diagnosis were screened and identified by quantitative analysis and receiver operating curve analysis. Urinary levels of five candidate biomarkers were measured using mass spectrometry or commercial kits. In the validation step, the combination of phosphate and sebacic acid was able to give a noninvasive and accurate diagnostic with high sensitivity (94.0%) and specificity (71.2%). Furthermore, on the basis of the pathway analysis of biomarkers, our urinary metabonomics analysis gives new insight into the pathogenesis and pathophysiology of nutritional rickets.

  5. Influence of surgical decompression on the expression of inflammatory and tissue repair biomarkers in periapical cysts.

    Science.gov (United States)

    Rodrigues, Janderson Teixeira; Dos Santos Antunes, Henrique; Armada, Luciana; Pires, Fábio Ramôa

    2017-12-01

    The biologic effects of surgical decompression on the epithelium and connective tissues of periapical cysts are not fully understood. The aim of this study was to evaluate the expression of tissue repair and inflammatory biomarkers in periapical cysts before and after surgical decompression. Nine specimens of periapical cysts treated with decompression before undergoing complete enucleation were immunohistochemically analyzed to investigate the expression of interleukin-1β, tumor necrosis factor-α, transforming growth factor-β1, matrix metalloproteinase-9, Ki-67, and epidermal growth factor receptor. Expression of the biomarkers was classified as positive, focal, or negative. Ki-67 immunoexpression was calculated as a cell proliferation index. The expression of the biomarkers was compared in the specimens from decompression and from the final surgical procedure. Computed tomography demonstrated that volume was reduced in all cysts after decompression. There were no differences in the immunoexpression of the proinflammatory and tissue repair biomarkers when comparing the specimens obtained before and after the decompression. Surgical decompression was efficient in reducing the volume of periapical cysts before complete enucleation. When comparing the specimens obtained from surgical decompression and from complete surgical removal, the immunohistochemical analysis did not show a decrease in proinflammatory biomarkers; neither did it show an increase in tissue repair biomarkers. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Application of biomarkers to assess the condition of European Marine Sites

    International Nuclear Information System (INIS)

    Hagger, Josephine A.; Galloway, Tamara S.; Langston, William J.; Jones, Malcolm B.

    2009-01-01

    A series of European Marine Sites has been designated as Special Areas of Conservation (SAC) in England. The aim of this study was to develop a practical methodology to assess the condition of SACs by applying a suite of biomarkers. Biomarkers were applied to the blue mussel Mytilus edulis and the shore crab Carcinus maenas from the Fal and Helford SAC (Cornwall). Individual biomarkers provided useful diagnostic information on the activity of certain classes of contaminants and an integrated Biomarker Response Index (BRI) was used to achieve a more holistic understanding of the condition of the SAC. The BRI indicated that the general health of both organisms was impacted in the upper part of the SAC (Fal Estuary) which correlated well with known chemical hotspots and sources of contamination. The BRI allows a pragmatic way to prioritise SAC sites that may require further investigative studies. - A suite of biomarkers was successfully used to create a Biomarker Response Index to assess the health of aquatic organisms from European Marine Sites.

  7. The presence and progression of emphysema in COPD as determined by CT scanning and biomarker expression

    DEFF Research Database (Denmark)

    Coxson, Harvey O; Dirksen, Asger; Edwards, Lisa D

    2013-01-01

    Emphysema is a key contributor to airflow limitation in chronic obstructive pulmonary disease (COPD) and can be quantified using CT scanning. We investigated the change in CT lung density in a longitudinal, international cohort of patients with COPD. We also explored the potential relation between...... emphysema and patient characteristics, and investigated if certain circulating biomarkers were associated with decline in CT lung density....

  8. Plasma alkylresorcinols, biomarkers of whole-grain wheat and rye intake, and incidence of colorectal cancer

    NARCIS (Netherlands)

    Kyrø, Cecilie; Olsen, Anja; Landberg, Rikard; Skeie, Guri; Loft, Steffen; Åman, Per; Leenders, Max; Dik, Vincent K.; Siersema, Peter D.; Pischon, Tobias; Christensen, Jane; Overvad, Kim; Boutron-Ruault, Marie Christine; Fagherazzi, Guy; Cottet, Vanessa; Kühn, Tilman; Chang-Claude, Jenny; Boeing, Heiner; Trichopoulou, Antonia; Bamia, Christina; Trichopoulos, Dimitrios; Palli, Domenico; Krogh, Vittorio; Tumino, Rosario; Vineis, Paolo; Panico, Salvatore; Peeters, Petra H.; Weiderpass, Elisabete; Bakken, Toril; Åsli, Lene Angell; Argüelles, Marcial; Jakszyn, Paula; Sánchez, María José; Amiano, Pilar; Huerta, José María; Barricarte, Aurelio; Ljuslinder, Ingrid; Palmqvist, Richard; Khaw, Kay Tee; Wareham, Nick; Key, Timothy J.; Travis, Ruth C.; Ferrari, Pietro; Freisling, Heinz; Jenab, Mazda; Gunter, Marc J.; Murphy, Neil; Riboli, Eilo; Tjønneland, Anne; Bueno-De-Mesquita, H. B.

    2014-01-01

    BackgroundFew studies have investigated the association between whole-grain intake and colorectal cancer. Because whole-grain intake estimation might be prone to measurement errors, more objective measures (eg, biomarkers) could assist in investigating such associations.MethodsThe association

  9. Association between biomarkers and clinical characteristics in chronic subdural hematoma patients assessed with lasso regression.

    Directory of Open Access Journals (Sweden)

    Are Hugo Pripp

    Full Text Available Chronic subdural hematoma (CSDH is characterized by an "old" encapsulated collection of blood and blood breakdown products between the brain and its outermost covering (the dura. Recognized risk factors for development of CSDH are head injury, old age and using anticoagulation medication, but its underlying pathophysiological processes are still unclear. It is assumed that a complex local process of interrelated mechanisms including inflammation, neomembrane formation, angiogenesis and fibrinolysis could be related to its development and propagation. However, the association between the biomarkers of inflammation and angiogenesis, and the clinical and radiological characteristics of CSDH patients, need further investigation. The high number of biomarkers compared to the number of observations, the correlation between biomarkers, missing data and skewed distributions may limit the usefulness of classical statistical methods. We therefore explored lasso regression to assess the association between 30 biomarkers of inflammation and angiogenesis at the site of lesions, and selected clinical and radiological characteristics in a cohort of 93 patients. Lasso regression performs both variable selection and regularization to improve the predictive accuracy and interpretability of the statistical model. The results from the lasso regression showed analysis exhibited lack of robust statistical association between the biomarkers in hematoma fluid with age, gender, brain infarct, neurological deficiencies and volume of hematoma. However, there were associations between several of the biomarkers with postoperative recurrence requiring reoperation. The statistical analysis with lasso regression supported previous findings that the immunological characteristics of CSDH are local. The relationship between biomarkers, the radiological appearance of lesions and recurrence requiring reoperation have been inclusive using classical statistical methods on these data

  10. Resolving breast cancer heterogeneity by searching reliable protein cancer biomarkers in the breast fluid secretome

    International Nuclear Information System (INIS)

    Mannello, Ferdinando; Ligi, Daniela

    2013-01-01

    One of the major goals in cancer research is to find and evaluate the early presence of biomarkers in human fluids and tissues. To resolve the complex cell heterogeneity of a tumor mass, it will be useful to characterize the intricate biomolecular composition of tumor microenvironment (the so called cancer secretome), validating secreted proteins as early biomarkers of cancer initiation and progression. This approach is not broadly applicable because of the paucity of well validated and FDA-approved biomarkers and because most of the candidate biomarkers are mainly organ-specific rather than tumor-specific. For these reasons, there is an urgent need to identify and validate a panel of biomarker combinations for early detection of human tumors. This is especially important for breast cancer, the cancer spread most worldwide among women. It is well known that patients with early diagnosed breast cancer live longer, require less extensive treatment and fare better than patients with more aggressive and/or advanced disease. In the frame of searching breast cancer biomarkers (especially using nipple aspirate fluid mirroring breast microenvironment), studies have highlighted an optimal combination of well-known biomarkers: uPA + PAI-1 + TF. When individually investigated they did not show perfect accuracy in predicting the presence of breast cancer, whereas the triple combination has been demonstrated to be highly predictive of pre-cancer and/or cancerous conditions, approaching 97-100% accuracy. Despite the heterogeneous composition of breast cancer and the difficulties to find specific breast cancer biomolecules, the noninvasive analysis of the nipple aspirate fluid secretome may significantly improve the discovery of promising biomarkers, helping also the differentiation among benign and invasive breast diseases, opening new frontiers in early oncoproteomics

  11. 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

  12. 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.

  13. COPD association and repeatability of blood biomarkers in the ECLIPSE cohort

    Directory of Open Access Journals (Sweden)

    Dickens Jennifer A

    2011-11-01

    utility in subsets of patients. Fibrinogen in particular has emerged as a potentially useful biomarker from this cohort and requires further investigation. Trial Registration SCO104960, clinicaltrials.gov identifier NCT00292552

  14. Biomarkers as Common Data Elements for Symptom and Self-Management Science.

    Science.gov (United States)

    Page, Gayle G; Corwin, Elizabeth J; Dorsey, Susan G; Redeker, Nancy S; McCloskey, Donna Jo; Austin, Joan K; Guthrie, Barbara J; Moore, Shirley M; Barton, Debra; Kim, Miyong T; Docherty, Sharron L; Waldrop-Valverde, Drenna; Bailey, Donald E; Schiffman, Rachel F; Starkweather, Angela; Ward, Teresa M; Bakken, Suzanne; Hickey, Kathleen T; Renn, Cynthia L; Grady, Patricia

    2018-05-01

    Biomarkers as common data elements (CDEs) are important for the characterization of biobehavioral symptoms given that once a biologic moderator or mediator is identified, biologically based strategies can be investigated for treatment efforts. Just as a symptom inventory reflects a symptom experience, a biomarker is an indicator of the symptom, though not the symptom per se. The purposes of this position paper are to (a) identify a "minimum set" of biomarkers for consideration as CDEs in symptom and self-management science, specifically biochemical biomarkers; (b) evaluate the benefits and limitations of such a limited array of biomarkers with implications for symptom science; (c) propose a strategy for the collection of the endorsed minimum set of biologic samples to be employed as CDEs for symptom science; and (d) conceptualize this minimum set of biomarkers consistent with National Institute of Nursing Research (NINR) symptoms of fatigue, depression, cognition, pain, and sleep disturbance. From May 2016 through January 2017, a working group consisting of a subset of the Directors of the NINR Centers of Excellence funded by P20 or P30 mechanisms and NINR staff met bimonthly via telephone to develop this position paper suggesting the addition of biomarkers as CDEs. The full group of Directors reviewed drafts, provided critiques and suggestions, recommended the minimum set of biomarkers, and approved the completed document. Best practices for selecting, identifying, and using biological CDEs as well as challenges to the use of biological CDEs for symptom and self-management science are described. Current platforms for sample outcome sharing are presented. Finally, biological CDEs for symptom and self-management science are proposed along with implications for future research and use of CDEs in these areas. The recommended minimum set of biomarker CDEs include pro- and anti-inflammatory cytokines, a hypothalamic-pituitary-adrenal axis marker, cortisol, the

  15. Multimodal lung cancer screening using the ITALUNG biomarker panel and low dose computed tomography. Results of the ITALUNG biomarker study.

    Science.gov (United States)

    Carozzi, Francesca Maria; Bisanzi, Simonetta; Carrozzi, Laura; Falaschi, Fabio; Lopes Pegna, Andrea; Mascalchi, Mario; Picozzi, Giulia; Peluso, Marco; Sani, Cristina; Greco, Luana; Ocello, Cristina; Paci, Eugenio

    2017-07-01

    Asymptomatic high-risk subjects, randomized in the intervention arm of the ITALUNG trial (1,406 screened for lung cancer), were enrolled for the ITALUNG biomarker study (n = 1,356), in which samples of blood and sputum were analyzed for plasma DNA quantification (cut off 5 ng/ml), loss of heterozygosity and microsatellite instability. The ITALUNG biomarker panel (IBP) was considered positive if at least one of the two biomarkers included in the panel was positive. Subjects with and without lung cancer diagnosis at the end of the screening cycle with LDCT (n = 517) were evaluated. Out of 18 baseline screen detected lung cancer cases, 17 were IBP positive (94%). Repeat screen-detected lung cancer cases were 18 and 12 of them positive at baseline IBP test (66%). Interval cancer cases (2-years) and biomarker tests after a suspect Non Calcific Nodule follow-up were investigated. The single test versus multimodal screening measures of accuracy were compared in a simulation within the screened ITALUNG intervention arm, considering screen-detected and interval cancer cases. Sensitivity was 90% at baseline screening. Specificity was 71 and 61% for LDCT and IBP as baseline single test, and improved at 89% with multimodal, combined screening. The positive predictive value was 4.3% for LDCT at baseline and 10.6% for multimodal screening. Multimodal screening could improve the screening efficiency at baseline and strategies for future implementation are discussed. If IBP was used as primary screening test, the LDCT burden might decrease of about 60%. © 2017 UICC.

  16. Candidate proteomic biomarkers for non-alcoholic fatty liver disease (steatosis and non-alcoholic steatohepatitis) discovered with mass-spectrometry: a systematic review.

    Science.gov (United States)

    Lădaru, Anca; Bălănescu, Paul; Stan, Mihaela; Codreanu, Ioana; Anca, Ioana Alina

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation in the liver which is accompanied by a series of metabolic deregulations. There are sustained research efforts focusing upon biomarker discovery for NAFLD diagnosis and its prognosis in order investigate and follow-up patients as minimally invasive as possible. The objective of this study is to critically review proteomic studies that used mass spectrometry techniques and summarize relevant proteomic NAFLD candidate biomarkers. Medline and Embase databases were searched from inception to December 2014. A final number of 22 records were included that identified 251 candidate proteomic biomarkers. Thirty-three biomarkers were confirmed - 14 were found in liver samples, 21 in serum samples, and two from both serum and liver samples. Some of the biomarkers identified have already been extensively studied regarding their diagnostic and prognostic capacity. However, there are also more potential biomarkers that still need to be addressed in future studies.

  17. Biomarkers, Natural Course and Prognosis.

    Science.gov (United States)

    Arenillas, Juan F; López-Cancio, Elena; Wong, Ka Sing

    2016-01-01

    Increasing our knowledge about intracranial atherosclerosis (ICAS) natural history and prognostic factors is essential to improve its preventive therapy and thus reduce the dramatic clinical consequences caused by this entity. ICAS is characterized by a chronic and progressive course until it becomes symptomatic, mostly through complication of an unstable intracranial atherosclerotic plaque. Population-based studies in healthy subjects have shown that the prevalence of asymptomatic ICAS is higher in Asian than in Caucasian populations. In both settings, asymptomatic ICAS is associated with classical vascular risk factors and with the metabolic syndrome, and it is burdened with an increasing risk of having incident stroke and cognitive impairment. When it reaches its symptomatic stage, ICAS is a dynamic and aggressive condition, and affected patients are at high risk of having recurrent stroke and other major vascular events. The Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis (SAMMPRIS) trial has recently shown a robust impact of intensive medical therapy reducing the risk of clinical recurrence of symptomatic ICAS. However, even under best medical therapy and degree of risk factor control, symptomatic ICAS-related recurrence risk continues to be the highest among all stroke etiologic subtypes. The second part of the chapter reviews the current understanding of prognostic factors that may help discriminate the high-risk ICAS patients, divided into local factors (vulnerable ICAS plaque) and systemic factors (vulnerable ICAS patient). Regarding research on local factors, high-resolution magnetic resonance imaging (HRMRI) is an emerging technique that allows in vivo evaluation of intracranial arterial wall, which is displacing our research focus from intracranial stenosis degree towards intracranial atherosclerotic plaque composition and activity. Characterization of the vulnerable ICAS patient may be improved with biomarker research. The

  18. Protein biomarker enrichment by biomarker antibody complex elution for immunoassay biosensing

    NARCIS (Netherlands)

    Sabatté, G.S.; Feitsma, H.; Evers, T.H.; Prins, M.W.J.

    2011-01-01

    It is very challenging to perform sample enrichment for protein biomarkers because proteins can easily change conformation and denature. In this paper we demonstrate protein enrichment suited for high-sensitivity integrated immuno-biosensing. The method enhances the concentration of the biomarkers

  19. Validation of biomarkers of food intake − critical assessment of candidate biomarkers

    DEFF Research Database (Denmark)

    Dragsted, Lars Ove; Gao, Qian; Scalbert, Augustin

    2018-01-01

    Biomarkers of food intake (BFIs) are a promising tool for limiting misclassification in nutrition research where more subjective dietary assessment instruments are used. They may also be used to assess compliance to dietary guidelines or to a dietary intervention. Biomarkers therefore hold promis...

  20. Introduction of the land snail Eobania vermiculata as a bioindicator organism of terrestrial pollution using a battery of biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Itziou, A., E-mail: itziou@bio.auth.gr; Dimitriadis, V.K., E-mail: vdimitr@bio.auth.gr

    2011-02-15

    The present study aimed to enrich the group of sentinel organisms of terrestrial pollution biomonitoring, by investigating the efficacy of the land snail Eobania vermiculata. For this reason, a package of biomarkers was performed on land snails E. vermiculata collected from polluted areas in the field or treated with heavy metals in the laboratory. The biomarkers used were neutral red lysosomal retention assay of the haemocytes, acetylcholinesterase activity in the digestive gland and the haemolymph, and metallothionein content of the digestive gland. Moreover, the morphometric changes in the lysosomal system and the morphometric alterations of the neutral lipids were also investigated. In addition, the content of cadmium, lead and copper was evaluated in the digestive gland of the snails. The results revealed appreciable alterations in the biomarker values both in field- and laboratory-conditions, accompanied by significant correlations among the biomarkers. Therefore, this exploratory study suggests the utility of E. vermiculata as a sentinel organism for biomonitoring the biologic impact of terrestrial pollution, and supports the package's efficacy of the selected biomarkers. - Research Highlights: {yields} Significant changes were noted in the values of the applied biomarkers. {yields} A package of biomarkers is supported to be an efficient tool for biomoniroting studies. {yields} The land snail Eobania vermiculata is proposed to be a good bioindicator organism in terrestrial pollution studies.

  1. 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

  2. Dietary and health biomarkers - time for an update

    DEFF Research Database (Denmark)

    Dragsted, Lars Ove; Gao, Qian; Pratico, Giulia

    2017-01-01

    for these biomarker classes, and no recent systematic review of all proposed biomarkers for food intake. While advanced databases exist for the human and food metabolomes, additional tools are needed to curate and evaluate current data on dietary and health biomarkers. The Food Biomarkers Alliance (FoodBAll) under......In the dietary and health research area, biomarkers are extensively used for multiple purposes. These include biomarkers of dietary intake and nutrient status, biomarkers used to measure the biological effects of specific dietary components, and biomarkers to assess the effects of diet on health...... much mechanistic insight into the effects of food components and diets. Although hundreds of papers in nutrition are published annually, there is no current ontology for the area, no generally accepted classification terminology for biomarkers in nutrition and health, no systematic validation scheme...

  3. Ghrelin and melatonin as biomarkers in patients with giardiasis

    Directory of Open Access Journals (Sweden)

    Saleem Khteer Al-Hadraawy

    2016-05-01

    Full Text Available Giardia is the most frequently reported intestinal parasite worldwide. The aim of this study was to investigate the ghrelin, melatonin, glucose and cholesterol concentration in male patients infected with Giardia lamblia. We enrolled 66 patients with Giardiasis and the control groups consisted of healthy subjects (n = 30. The results demonstrated that there was a significant decrease (P < 0.05 in ghrelin levels, while the melatonin, glucose and cholesterol levels were significantly increased (P < 0.05 in giardiasis patients as compared to the healthy group. The obtained results suggest that ghrelin and melatonin could serve as biomarkers in patients infected with G. lamblia.

  4. Biomarker in Cisplatin-Based Chemotherapy for Urinary Bladder Cancer.

    Science.gov (United States)

    Ecke, Thorsten H

    2015-01-01

    The treatment of metastasized bladder cancer has been evolving during recent years. Cisplatin based chemotherapy combinations are still gold standard in the treatment of advanced and metastasized bladder cancer. But new therapies are approaching. Based to this fact biological markers will become more important for decisions in bladder cancer treatment. A systematic MEDLINE search of the key words "cisplatin", "bladder cancer", "DNA marker", "protein marker", "methylation biomarker", "predictive marker", "prognostic marker" has been made. This review aims to highlight the most relevant clinical and experimental studies investigating markers for metastasized transitional carcinoma of the urothelium treated by cisplatin based regimens.

  5. Searching for new biomarkers in ovarian cancer patients

    DEFF Research Database (Denmark)

    Hentze, Julie L.; Høgdall, Claus; Kjær, Susanne K.

    2017-01-01

    , will be examined. Relevant microRNAs and DNA methylation patterns will be investigated using array technology. Patient exomes will be fully sequenced, and identified genetic variations will be validated with Next Generation Sequencing. In all cases, data will be correlated with clinical information on the patient...... of cancer and the discovery of new drugs. Moreover, biomarkers are a prerequisite for the development of precision medicine. This study will attack the ovarian cancer problem from several angles, thereby increasing the chance of successfully contributing to saving lives....

  6. 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

    biological fluids with varying immunoreactivity which can present bioanalytical challenges when first discovered. The potential success of these efforts is greatly enhanced by recent advances in two closely linked technologies, toxicoproteomics and targeted, quantitative mass spectrometry. This review focuses on the examination of the current status of these technologies as they relate to the discovery and development of novel preclinical biomarkers of hepatotoxicity. A critical assessment of the current literature reveals two distinct lines of safety biomarker investigation, (1) peripheral fluid biomarkers of organ toxicity and (2) tissue or cell-based toxicity signatures. Improved peripheral fluid biomarkers should allow the sensitive detection of potential organ toxicity prior to the onset of overt organ pathology. Advancements in tissue or cell-based toxicity biomarkers will provide sensitive in vitro or ex vivo screening systems based on toxicity pathway markers. An examination of the current practices in clinical pathology and the critical evaluation of some recently proposed biomarker candidates in comparison to the desired characteristics of an ideal toxicity biomarker lead this author to conclude that a combination of selected biomarkers will be more informative if not predictive of potential animal organ toxicity than any single biomarker, new or old. For the practical assessment of combinations of conventional and/or novel toxicity biomarkers in rodent and large animal preclinical species, mass spectrometry has emerged as the premier analytical tool compared to specific immunoassays or functional assays. Selected and multiple reaction monitoring mass spectrometry applications make it possible for this same basic technology to be used in the progressive stages of biomarker discovery, development, and more importantly, routine study applications without the use of specific antibody reagents. This technology combined with other 'omics' technologies can provide added

  7. Taking a new biomarker into routine use – A perspective from the routine clinical biochemistry laboratory

    Science.gov (United States)

    Sturgeon, Catharine; Hill, Robert; Hortin, Glen L; Thompson, Douglas

    2010-01-01

    There is increasing pressure to provide cost-effective healthcare based on “best practice.” Consequently, new biomarkers are only likely to be introduced into routine clinical biochemistry departments if they are supported by a strong evidence base and if the results will improve patient management and outcome. This requires convincing evidence of the benefits of introducing the new test, ideally reflected in fewer hospital admissions, fewer additional investigations and/or fewer clinic visits. Carefully designed audit and cost-benefit studies in relevant patient groups must demonstrate that introducing the biomarker delivers an improved and more effective clinical pathway. From the laboratory perspective, pre-analytical requirements must be thoroughly investigated at an early stage. Good stability of the biomarker in relevant physiological matrices is essential to avoid the need for special processing. Absence of specific timing requirements for sampling and knowledge of the effect of medications that might be used to treat the patients in whom the biomarker will be measured is also highly desirable. Analytically, automation is essential in modern high-throughput clinical laboratories. Assays must therefore be robust, fulfilling standard requirements for linearity on dilution, precision and reproducibility, both within- and between-run. Provision of measurements by a limited number of specialized reference laboratories may be most appropriate, especially when a new biomarker is first introduced into routine practice. PMID:21137030

  8. Smoking affects diagnostic salivary periodontal disease biomarker levels in adolescents.

    Science.gov (United States)

    Heikkinen, Anna Maria; Sorsa, Timo; Pitkäniemi, Janne; Tervahartiala, Taina; Kari, Kirsti; Broms, Ulla; Koskenvuo, Markku; Meurman, Jukka H

    2010-09-01

    The effects of smoking on periodontal biomarkers in adolescents are unknown. This study investigates matrix metalloproteinase (MMP)-8 and polymorphonuclear leukocyte elastase levels in saliva together with periodontal health indices accounting for body mass index and smoking in a birth cohort from Finland. The oral health of boys (n = 258) and girls (n = 243) aged 15 to 16 years was examined clinically. Health habits were assessed by questionnaire. Saliva samples were collected and analyzed by immunofluorometric and peptide assays for MMP-8 levels and polymorphonuclear leukocyte elastase activities, and investigated statistically with the background factors. Median MMP-8 values of male smokers were 112.03 microg/l compared to 176.89 microg/l of non-smokers (P = 0.05). For female smokers corresponding values were 170.88 microg/l versus 177.92 microg/l in non-smokers (not statistically significant). Elastase values in male smokers were 5.88 x 10(-3) Delta OD(405)/h versus 11.0 x 10(-3) Delta OD(405)/h in non-smokers (P = 0.02), and in female smokers 9.16 x 10(-3) Delta OD(405)/h versus 10.88 x 10(-3) Delta OD(405)/h in non-smokers (P = 0.72). The effect was strengthened by high pack-years of smoking (MMP-8, P = 0.04; elastase, P = 0.01). Both biomarkers increased with gingival bleeding. However, statistically significant associations were observed with bleeding on probing and MMP-8 (P = 0.04); MMP-8 was suggestively associated with probing depth (P = 0.09) in non-smoking boys. In smokers with calculus, MMP-8 increased after adjusting with body mass index (P = 0.03). No corresponding differences were seen in girls. Smoking significantly decreased both biomarkers studied. Compared to girls, boys seem to have enhanced susceptibility for periodontitis as reflected in salivary MMP-8 values.

  9. 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)

  10. Using Aptamers for Cancer Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    Yun Min Chang

    2013-01-01

    Full Text Available Aptamers are single-stranded synthetic DNA- or RNA-based oligonucleotides that fold into various shapes to bind to a specific target, which includes proteins, metals, and molecules. Aptamers have high affinity and high specificity that are comparable to that of antibodies. They are obtained using iterative method, called (Systematic Evolution of Ligands by Exponential Enrichment SELEX and cell-based SELEX (cell-SELEX. Aptamers can be paired with recent advances in nanotechnology, microarray, microfluidics, and other technologies for applications in clinical medicine. One particular area that aptamers can shed a light on is biomarker discovery. Biomarkers are important in diagnosis and treatment of cancer. In this paper, we will describe ways in which aptamers can be used to discover biomarkers for cancer diagnosis and therapeutics.

  11. Biomarkers in pancreatic adenocarcinoma: current perspectives.

    Science.gov (United States)

    Swords, Douglas S; Firpo, Matthew A; Scaife, Courtney L; Mulvihill, Sean J

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of 7.7%. Most patients are diagnosed at an advanced stage not amenable to potentially curative resection. A substantial portion of this review is dedicated to reviewing the current literature on carbohydrate antigen (CA 19-9), which is currently the only guideline-recommended biomarker for PDAC. It provides valuable prognostic information, can predict resectability, and is useful in decision making about neoadjuvant therapy. We also discuss carcinoembryonic antigen (CEA), CA 125, serum biomarker panels, circulating tumor cells, and cell-free nucleic acids. Although many biomarkers have now been studied in relation to PDAC, significant work still needs to be done to validate their usefulness in the early detection of PDAC and management of patients with PDAC.

  12. Oral Metagenomic Biomarkers in Rheumatoid Arthritis

    Science.gov (United States)

    2017-09-01

    individuals with rheumatoid arthritis (RA). The goal is to test the  hypothesis that oral microbiome and metagenomic analyses will allow  us  to identify new...biomarkers  that are  useful  for the diagnosis of early RA and/or biomarkers that help to predict the efficacy of  specific therapeutic interventions... RNA  microbiome analysis as well as whole genome shotgun sequencing.  Upon completion of these aims, any identified bacterial biomarkers may be

  13. 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.

  14. Other biomarkers for detecting prostate cancer.

    Science.gov (United States)

    Nogueira, Lucas; Corradi, Renato; Eastham, James A

    2010-01-01

    Prostate-specific antigen (PSA) has been used for detecting prostate cancer since 1994. Although it is the best cancer biomarker available, PSA is not perfect. It lacks both the sensitivity and specificity to accurately detect the presence of prostate cancer. None of the PSA thresholds currently in use consistently identify patients with prostate cancer and exclude patients without cancer. Novel approaches to improve our ability to detect prostate cancer and predict the course of the disease are needed. Additional methods for detecting prostate cancer have been evaluated. Despite the discovery of many new biomarkers, only a few have shown some clinical value. These markers include human kallikrein 2, urokinase-type plasminogen activator receptor, prostate-specific membrane antigen, early prostate cancer antigen, PCA3, alpha-methylacyl-CoA racemase and glutathione S-transferase pi hypermethylation. We review the reports on biomarkers for prostate cancer detection, and their possible role in the clinical practice.

  15. Molecular biomarkers in idiopathic pulmonary fibrosis

    Science.gov (United States)

    Ley, Brett; Brown, Kevin K.

    2014-01-01

    Molecular biomarkers are highly desired in idiopathic pulmonary fibrosis (IPF), where they hold the potential to elucidate underlying disease mechanisms, accelerated drug development, and advance clinical management. Currently, there are no molecular biomarkers in widespread clinical use for IPF, and the search for potential markers remains in its infancy. Proposed core mechanisms in the pathogenesis of IPF for which candidate markers have been offered include alveolar epithelial cell dysfunction, immune dysregulation, and fibrogenesis. Useful markers reflect important pathological pathways, are practically and accurately measured, have undergone extensive validation, and are an improvement upon the current approach for their intended use. The successful development of useful molecular biomarkers is a central challenge for the future of translational research in IPF and will require collaborative efforts among those parties invested in advancing the care of patients with IPF. PMID:25260757

  16. 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

  17. 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.

  18. Searching for new biomarkers in ovarian cancer patients: Rationale and design of a retrospective study under the Mermaid III project

    Directory of Open Access Journals (Sweden)

    Julie L. Hentze

    2017-12-01

    A thorough investigation of biomarkers in ovarian cancer, including large numbers of different markers, has never been done before. Besides from improving diagnosis and treatment, other outcomes could be markers for screening, knowledge of the molecular aspects of cancer and the discovery of new drugs. Moreover, biomarkers are a prerequisite for the development of precision medicine. This study will attack the ovarian cancer problem from several angles, thereby increasing the chance of successfully contributing to saving lives.

  19. Relationships between metal compartmentalization and biomarkers in earthworms exposed to field-contaminated soils.

    Science.gov (United States)

    Beaumelle, Léa; Hedde, Mickaël; Vandenbulcke, Franck; Lamy, Isabelle

    2017-05-01

    Partitioning tissue metal concentration into subcellular compartments reflecting toxicologically available pools may provide good descriptors of the toxicological effects of metals on organisms. Here we investigated the relationships between internal compartmentalization of Cd, Pb and Zn and biomarker responses in a model soil organism: the earthworm. The aim of this study was to identify metal fractions reflecting the toxic pressure in an endogeic, naturally occurring earthworm species (Aporrectodea caliginosa) exposed to realistic field-contaminated soils. After a 21 days exposure experiment to 31 field-contaminated soils, Cd, Pb and Zn concentrations in earthworms and in three subcellular fractions (cytosol, debris and granules) were quantified. Different biomarkers were measured: the expression of a metallothionein gene (mt), the activity of catalase (CAT) and of glutathione-s-transferase (GST), and the protein, lipid and glycogen reserves. Biomarkers were further combined into an integrated biomarker index (IBR). The subcellular fractionation provided better predictors of biomarkers than the total internal contents hence supporting its use when assessing toxicological bioavailability of metals to earthworms. The most soluble internal pools of metals were not always the best predictors of biomarker responses. metallothionein expression responded to increasing concentrations of Cd in the insoluble fraction (debris + granules). Protein and glycogen contents were also mainly related to Cd and Pb in the insoluble fraction. On the other hand, GST activity was better explained by Pb in the cytosolic fraction. CAT activity and lipid contents variations were not related to metal subcellular distribution. The IBR was best explained by both soluble and insoluble fractions of Pb and Cd. This study further extends the scope of mt expression as a robust and specific biomarker in an ecologically representative earthworm species exposed to field-contaminated soils. The

  20. Biomarkers and Targeted Therapy in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Fataneh Karandish

    2016-01-01

    Full Text Available Pancreatic ductal adenocarcinoma (PDAC constitutes 90% of pancreatic cancers. PDAC is a complex and devastating disease with only 1%–3% survival rate in five years after the second stage. Treatment of PDAC is complicated due to the tumor microenvironment, changing cell behaviors to the mesenchymal type, altered drug delivery, and drug resistance. Considering that pancreatic cancer shows early invasion and metastasis, critical research is needed to explore different aspects of the disease, such as elaboration of biomarkers, specific signaling pathways, and gene aberration. In this review, we highlight the biomarkers, the fundamental signaling pathways, and their importance in targeted drug delivery for pancreatic cancers.

  1. Biomarkers and Targeted Therapy in Pancreatic Cancer.

    Science.gov (United States)

    Karandish, Fataneh; Mallik, Sanku

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) constitutes 90% of pancreatic cancers. PDAC is a complex and devastating disease with only 1%-3% survival rate in five years after the second stage. Treatment of PDAC is complicated due to the tumor microenvironment, changing cell behaviors to the mesenchymal type, altered drug delivery, and drug resistance. Considering that pancreatic cancer shows early invasion and metastasis, critical research is needed to explore different aspects of the disease, such as elaboration of biomarkers, specific signaling pathways, and gene aberration. In this review, we highlight the biomarkers, the fundamental signaling pathways, and their importance in targeted drug delivery for pancreatic cancers.

  2. Biomarkers of multiorgan injury in neonatal encephalopathy.

    Science.gov (United States)

    Aslam, Saima; Molloy, Eleanor J

    2015-01-01

    Neonatal encephalopathy (NE) is a major contributor to neurodevelopmental deficits including cerebral palsy in term and near-term infants. The long-term neurodevelopmental outcome is difficult to predict with certainty in first few days of life. Multiorgan involvement is common but not part of the diagnostic criteria for NE. The most frequently involved organs are the heart, liver, kidneys and hematological system. Cerebral and organ involvement is associated with the release of organ specific biomarkers in cerebrospinal fluid, urine and blood. These biomarkers may have a role in the assessment of the severity of asphyxia and long-term outcome in neonates with NE.

  3. Biomarkers of necrotising soft tissue infections

    DEFF Research Database (Denmark)

    Hansen, Marco Bo; Simonsen, Ulf; Garred, Peter

    2015-01-01

    INTRODUCTION: The mortality and amputation rates are still high in patients with necrotising soft tissue infections (NSTIs). It would be ideal to have a set of biomarkers that enables the clinician to identify high-risk patients with NSTI on admission. The objectives of this study are to evaluate...... and mortality in patients with NSTI and that HBOT reduces the inflammatory response. METHODS AND ANALYSIS: This is a prospective, observational study being conducted in a tertiary referral centre. Biomarkers will be measured in 114 patients who have been operatively diagnosed with NSTI. On admission, baseline...

  4. De Novo Identification of Biomarker Proteins Using Tandem Mass Spectrometry

    Science.gov (United States)

    Many studies have shown that biological fluids contain an important number of biomarkers associated with various pathologies. For instance, there has been extensive research to identify effective biomarkers as prognostic indicators of breast cancer. An effective approach for biom...

  5. 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

  6. Biomarker Detection using PS2-Thioaptamers, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — AM Biotechnologies (AM) will develop a system to detect and quantify bone demineralization biomarkers as outlined in SBIR Topic "Technologies to Detect Biomarkers"....

  7. Molecular Biomarkers: Their significance and application in marine pollution monitoring

    Digital Repository Service at National Institute of Oceanography (India)

    Sarkar, A.; Ray, D.; Shrivastava, A.N.; Sarkar, S.

    worldwide. Among the various types of biomarkers, the following have received special attention: cytochrome P4501A induction, DNA integrity, acetylcholinesterase activity and metallothionein induction. These biomarkers are being used to evaluate exposure...

  8. 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

  9. Comparison of peripheral and central schizophrenia biomarker profiles.

    Directory of Open Access Journals (Sweden)

    Laura W Harris

    Full Text Available We have recently shown that a molecular biomarker signature comprised of inflammatory, hormonal and growth factors occurs in the blood serum from first onset schizophrenia patients. Here, we use the same platform to investigate post mortem brain tissue (Brodmann area 10 from schizophrenia patients who were mainly chronically ill and drug treated. Twenty-one analytes are differentially expressed in post-mortem brain tissue. Comparison with our previous mRNA profiling studies of the same patient samples in another frontal cortical area showed that 9 of these molecules were also altered at the transcriptional level. Furthermore, 9 of the molecules were also altered in serum from living first onset schizophrenia patients compared to controls. We propose a model in which the brain and periphery are coordinated through hormones and other regulatory molecules released into the blood via the diffuse neuroendocrine system. These findings provide further evidence for the systemic nature of schizophrenia and give added validity to the concept that schizophrenia can be investigated through studies of blood-based biomarkers.

  10. 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

  11. 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

  12. Total Protein of Whole Saliva as a Biomarker of Anaerobic Threshold

    Science.gov (United States)

    Bortolini, Miguel Junior Sordi; De Agostini, Guilherme Gularte; Reis, Ismair Teodoro; Lamounier, Romeu Paulo Martins Silva; Blumberg, Jeffrey B.; Espindola, Foued Salmen

    2009-01-01

    Saliva provides a convenient and noninvasive matrix for assessing specific physiological parameters, including some biomarkers of exercise. We investigated whether the total protein concentration of whole saliva (TPWS) would reflect the anaerobic threshold during an incremental exercise test. After a warm-up period, 13 nonsmoking men performed a…

  13. Differential effects of environmental chemicals and food contaminants on adipogenesis, biomarker release and PPARγ activation

    DEFF Research Database (Denmark)

    Taxvig, Camilla; Sørensen, Karin Dreisig; Boberg, Julie

    2012-01-01

    Eleven environmental relevant chemicals were investigated for their ability to affect adipogenesis in vitro, biomarker release from adipocytes and PPARα and γ activation. We found that butylparaben stimulated adipogenesis in 3T3-L1 adipocytes and increased release of leptin, adiponectin and resis...

  14. 1-Hydroxypyrene as a biomarker of PAH exposure in the marine polychaete Nereis diversicolor

    DEFF Research Database (Denmark)

    Tairova, Zhanna; Giessing, Anders; Hansen, Rikke

    2009-01-01

    The possibility of using the pyrene metabolite I-hydroxypyrene as a biomarker of polycyclic aromatic hydrocarbons (PAHs) exposure was investigated by exposure of the marine polychaete Nereis diversicolor to several PAHs in the laboratory. Animals were exposed to pyrene alone and to five different...

  15. Cerebrospinal fluid biomarkers of neurodegeneration are decreased or normal in narcolepsy

    DEFF Research Database (Denmark)

    Jennum, Poul Jørgen; Pedersen, Lars Østergaard; Bahl, Justyna Maria Czarna

    2017-01-01

    OBJECTIVES: To investigate whether cerebrospinal fluid (CSF) biomarkers of neurodegeneration are altered in narcolepsy in order to evaluate whether the hypocretin deficiency and abnormal sleep-wake pattern in narcolepsy leads to neurodegeneration. METHODS: Twenty-one patients with central...... that hypocretin deficiency and an abnormal sleep-wake pattern alter the turnover of these proteins in CNS....

  16. Structural and isotopic analysis of kerogens in sediments rich in free sulfurised Botryococcus braunii biomarkers

    NARCIS (Netherlands)

    Sinninghe Damsté, J.S.; Grice, K.; Schouten, S.; Blokker, P.; Derenne, S.; Largeau, C.; Nissenbaum, A.

    2003-01-01

    Type I kerogens of two relatively immature, unusual hypersaline sediments [with extracts rich in sulfurised Botryococcus braunii (B. braunii) biomarkers] of Miocene/Pliocene age from the Sdom Formation (Dead Sea, Israel), have been investigated using a variety of organic geochemical techniques. Py

  17. Relationships between Rapid Eye Movement Sleep Behavior Disorder and Neurodegenerative Diseases: Clinical Assessments, Biomarkers, and Treatment

    Directory of Open Access Journals (Sweden)

    Min Li

    2018-01-01

    Conclusions: More longitudinal studies should be conducted to evaluate the predictive value of biomarkers of RBD. Moreover, because the glucose and dopamine metabolisms are not specific for assessing cognitive cognition, the molecular metabolism directly related to cognition should be investigated. There is a need for more treatment trials to determine the effectiveness of interventions of RBD on preventing the conversion to neurodegenerative diseases.

  18. Synovial tissue heterogeneity in rheumatoid arthritis in relation to disease activity and biomarkers in peripheral blood

    NARCIS (Netherlands)

    van Baarsen, Lisa G. M.; Wijbrandts, Carla A.; Timmer, Trieneke C. G.; van der Pouw Kraan, Tineke C. T. M.; Tak, Paul P.; Verweij, Cornelis L.

    2010-01-01

    OBJECTIVE: To investigate the clinical relevance of synovial tissue subtypes in rheumatoid arthritis (RA) and to search for peripheral blood (PB) markers that may serve as biomarkers for tissue subtypes. METHODS: Gene expression analysis using complementary DNA microarrays was applied on paired

  19. Further Development of an Exhaled microRNA Biomarker of Lung Cancer Risk

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-16-1-0328 TITLE: Further Development of an Exhaled microRNA Biomarker of Lung Cancer Risk PRINCIPAL INVESTIGATOR: Dr...4. TITLE AND SUBTITLE Further Development of an Exhaled microRNA Biomarker of Lung Cancer Risk 5b. GRANT NUMBER W81XWH 16-1-0328 5c. PROGRAM...devise a non-invasive airway based exhaled microRNA metric for lung cancer risk, initial work to be tested in a case control study. We expanded the

  20. Urinary apolipoprotein M as a biomarker of acute kidney injury in children undergoing heart surgery

    DEFF Research Database (Denmark)

    Svarrer, Eva Martha Madsen; Andersen, Henrik Ørbæk; Helvind, Morten

    2016-01-01

    AIM: To investigate whether apoM is excreted in urine of children undergoing heart surgery and the potential of apoM as early biomarker of acute kidney injury (AKI). MATERIALS & METHODS: Urine was collected in children undergoing heart surgery. ApoM was measured with ELISA. U-apoM was characterized.......018). Sensitivity was 0.71 and specificity was 0.68 at a cutoff level at 1.45 nmol/l. CONCLUSION: ApoM is excreted in the urine of children after cardiac surgery. Its potential as biomarker of AKI deserves exploration....

  1. The role of biomarkers in evaluating human health concerns from fungal contaminants in food.

    Science.gov (United States)

    Turner, Paul C; Flannery, Brenna; Isitt, Catherine; Ali, Mariyam; Pestka, James

    2012-06-01

    Mycotoxins are toxic secondary metabolites that globally contaminate an estimated 25 % of cereal crops and thus exposure is frequent in many populations. Aflatoxins, fumonisins and deoxynivalenol are amongst those mycotoxins of particular concern from a human health perspective. A number of risks to health are suggested including cancer, growth faltering, immune suppression and neural tube defects; though only the demonstrated role for aflatoxin in the aetiology of liver cancer is widely recognised. The heterogeneous distribution of mycotoxins in food restricts the usefulness of food sampling and intake estimates; instead biomarkers provide better tools for informing epidemiological investigations. Validated exposure biomarkers for aflatoxin (urinary aflatoxin M(1), aflatoxin-N7-guaunine, serum aflatoxin-albumin) were established almost 20 years ago and were critical in confirming aflatoxins as potent liver carcinogens. Validation has included demonstration of assay robustness, intake v. biomarker level, and stability of stored samples. More recently, aflatoxin exposure biomarkers are revealing concerns of growth faltering and immune suppression; importantly, they are being used to assess the effectiveness of intervention strategies. For fumonisins and deoxynivalenol these steps of development and validation have significantly advanced in recent years. Such biomarkers should better inform epidemiological studies and thus improve our understanding of their potential risk to human health.

  2. Mycotoxin exposure in rural residents in northern Nigeria: a pilot study using multi-urinary biomarkers.

    Science.gov (United States)

    Ezekiel, Chibundu N; Warth, Benedikt; Ogara, Isaac M; Abia, Wilfred A; Ezekiel, Victoria C; Atehnkeng, Joseph; Sulyok, Michael; Turner, Paul C; Tayo, Grace O; Krska, Rudolf; Bandyopadhyay, Ranajit

    2014-05-01

    A pilot, cross-sectional, correlational study was conducted in eight rural communities in northern Nigeria to investigate mycotoxin exposures in 120 volunteers (19 children, 20 adolescents and 81 adults) using a modern LC-MS/MS based multi-biomarker approach. First morning urine samples were analyzed and urinary biomarker levels correlated with mycotoxin levels in foods consumed the day before urine collection. A total of eight analytes were detected in 61/120 (50.8%) of studied urine samples, with ochratoxin A, aflatoxin M1 and fumonisin B1 being the most frequently occurring biomarkers of exposure. These mycotoxin biomarkers were present in samples from all age categories, suggestive of chronic (lifetime) exposures. Rough estimates of mycotoxin intake suggested some exposures were higher than the tolerable daily intake. Overall, rural consumer populations from Nasarawa were more exposed to several mixtures of mycotoxins in their diets relative to those from Kaduna as shown by food and urine biomarker data. This study has shown that mycotoxin co-exposure may be a major public health challenge in rural Nigeria; this calls for urgent intervention. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Differential neurotoxic effects of silver nanoparticles: A review with special emphasis on potential biomarkers

    Directory of Open Access Journals (Sweden)

    M. Safari

    2016-04-01

    Full Text Available Silver Nanoparticles (AgNPs have gained considerable interests during the last decade due to their excellent antimicrobial activities. Despite their extensive use, the potential toxicity of these nanoparticles and possible mechanisms by which they may induce adverse reactions have not received sufficient attention and no specific biomarker exist to describe and quantify their toxic effects. Nanoparticles, depending on their physicochemical characteristics and compositions, can interact with vital organs such as the brain and induce toxic effects. A specific concern is that any contact with AgNPs independent of the route of administration is thought to result in significant systemic uptake, internal exposure of sensitive organs, especially in the central nervous system (CNS and different toxic responses. There are considerable evidences that AgNPs can disrupt the Blood-Brain Barrier (BBB and induce subsequent brain edema formation. Therefore, it is essential to understand the differential effects of AgNPs on brain cell with especial emphasis on the possible mechanisms of action. Recently, biomarkers are increasingly used as surrogate indicators of toxic responses in biological monitoring due to the inaccessibility of target organs. Moreover, as the most nanoscale contaminants occur at low concentrations, physiological biomarkers may be better indicators of potential impact of nanomaterials than traditional toxicity testing. This review aims to investigate the effects of AgNPs on CNS targets of toxicity and clarify the role of existing biomarkers especially the role of dopamine levels as a potential biomarker of Ag-NPs neurotoxicity.

  4. Consensus Guidelines for CSF and Blood Biobanking for CNS Biomarker Studies

    Directory of Open Access Journals (Sweden)

    Charlotte E. Teunissen

    2011-01-01

    Full Text Available There is a long history of research into body fluid biomarkers in neurodegenerative and neuroinflammatory diseases. However, only a few biomarkers in cerebrospinal fluid (CSF are being used in clinical practice. Anti-aquaporin-4 antibodies in serum are currently useful for the diagnosis of neuromyelitis optica (NMO, but we could expect novel CSF biomarkers that help define prognosis and response to treatment for this disease. One of the most critical factors in biomarker research is the inadequate powering of studies performed by single centers. Collaboration between investigators is needed to establish large biobanks of well-defined samples. A key issue in collaboration is to establish standardized protocols for biobanking to ensure that the statistical power gained by increasing the numbers of CSF samples is not compromised by pre-analytical factors. Here, consensus guidelines for CSF collection and biobanking are presented, based on the guidelines that have been published by the BioMS-eu network for CSF biomarker research. We focussed on CSF collection procedures, pre-analytical factors and high quality clinical and paraclinical information. Importantly, the biobanking protocols are applicable for CSF biobanks for research targeting any neurological disease.

  5. Metabolomics, Nutrition, and Potential Biomarkers of Food Quality, Intake, and Health Status.

    Science.gov (United States)

    Sébédio, Jean-Louis

    Diet, dietary patterns, and other environmental factors such as exposure to toxins are playing an important role in the prevention/development of many diseases, like obesity, type 2 diabetes, and consequently on the health status of individuals. A major challenge nowadays is to identify novel biomarkers to detect as early as possible metabolic dysfunction and to predict evolution of health status in order to refine nutritional advices to specific population groups. Omics technologies such as genomics, transcriptomics, proteomics, and metabolomics coupled with statistical and bioinformatics tools have already shown great potential in this research field even if so far only few biomarkers have been validated. For the past two decades, important analytical techniques have been developed to detect as many metabolites as possible in human biofluids such as urine, blood, and saliva. In the field of food science and nutrition, many studies have been carried out for food authenticity, quality, and safety, as well as for food processing. Furthermore, metabolomic investigations have been carried out to discover new early biomarkers of metabolic dysfunction and predictive biomarkers of developing pathologies (obesity, metabolic syndrome, type-2 diabetes, etc.). Great emphasis is also placed in the development of methodologies to identify and validate biomarkers of nutrients exposure. © 2017 Elsevier Inc. All rights reserved.

  6. Receiver Operating Characteristic (ROC to Determine Cut-Off Points of Biomarkers in Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Heidi L. Weiss

    2004-01-01

    Full Text Available The role of biomarkers in disease prognosis continues to be an important investigation in many cancer studies. In order for these biomarkers to have practical application in clinical decision making regarding patient treatment and follow-up, it is common to dichotomize patients into those with low vs. high expression levels. In this study, receiver operating characteristic (ROC curves, area under the curve (AUC of the ROC, sensitivity, specificity, as well as likelihood ratios were calculated to determine levels of growth factor biomarkers that best differentiate lung cancer cases versus control subjects. Selected cut-off points for p185erbB-2 and EGFR membrane appear to have good discriminating power to differentiate control tissues versus uninvolved tissues from patients with lung cancer (AUC = 89% and 90%, respectively; while AUC increased to at least 90% for selected cut-off points for p185erbB-2 membrane, EGFR membrane, and FASE when comparing between control versus carcinoma tissues from lung cancer cases. Using data from control subjects compared to patients with lung cancer, we presented a simple and intuitive approach to determine dichotomized levels of biomarkers and validated the value of these biomarkers as surrogate endpoints for cancer outcome.

  7. 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.

  8. Beneficial effect of bilingualism on Alzheimer's disease CSF biomarkers and cognition.

    Science.gov (United States)

    Estanga, Ainara; Ecay-Torres, Mirian; Ibañez, Almudena; Izagirre, Andrea; Villanua, Jorge; Garcia-Sebastian, Maite; Iglesias Gaspar, M Teresa; Otaegui-Arrazola, Ane; Iriondo, Ane; Clerigue, Monserrat; Martinez-Lage, Pablo

    2017-02-01

    Bilingualism as a component of cognitive reserve has been claimed to delay the onset of Alzheimer's disease (AD). However, its effect on cerebrospinal fluid (CSF) AD-biomarkers has not been investigated. We assessed cognitive performance and CSF AD-biomarkers, and potential moderation effect of bilingualism on the association between age, CSF AD-biomarkers, and cognition. Cognitively healthy middle-aged participants classified as monolinguals (n = 100, n CSF  = 59), early (n = 81, n CSF  = 55) and late bilinguals (n = 97, n CSF  = 52) were evaluated. Models adjusted for confounders showed that bilinguals performed better than monolinguals on digits backwards (early-bilinguals p = 0.003), Judgment of Line Orientation (JLO) (early-bilinguals p = 0.018; late-bilinguals p = 0.004), and Trail Making Test-B (late-bilinguals p = 0.047). Early bilingualism was associated with lower CSF total-tau (p = 0.019) and lower prevalence of preclinical AD (NIA-AA classification) (p = 0.02). Bilingualism showed a moderation effect on the relationship between age and CSF AD-biomarkers and the relationship between age and executive function. We conclude that bilingualism contributes to cognitive reserve enhancing executive and visual-spatial functions. For the first time, this study reveals that early bilingualism is associated with more favorable CSF AD-biomarker profile. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. 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.

  10. Candidate Biomarkers in Children with Autism Spectrum Disorder: A Review of MRI Studies

    Institute of Scientific and Technical Information of China (English)

    Dongyun Li; Hans-Otto Karnath; Xiu Xu

    2017-01-01

    Searching for effective biomarkers is one of the most challenging tasks in the research field of Autism Spectrum Disorder (ASD).Magnetic resonance imaging (MRI) provides a non-invasive and powerful tool for investigating changes in the structure,function,maturation,connectivity,and metabolism of the brain of children with ASD.Here,we review the more recent MRI studies in young children with ASD,aiming to provide candidate biomarkers for the diagnosis of childhood ASD.The review covers structural imaging methods,diffusion tensor imaging,resting-state functional MRI,and magnetic reso nance spectroscopy.Future advances in neuroimaging techniques,as well as cross-disciplinary studies and largescale collaborations will be needed for an integrated approach linking neuroimaging,genetics,and phenotypic data to allow the discovery of new,effective biomarkers.

  11. 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.

  12. Challenging homeostasis to define biomarkers for nutrition related health

    NARCIS (Netherlands)

    Ommen, van B.; Keijer, J.; Heil, S.G.; Kaput, J.

    2009-01-01

    A primary goal of nutrition research is to optimize health and prevent or delay disease. Biomarkers to quantify health optimization are needed since many if not most biomarkers are developed for diseases. Quantifying normal homeostasis and developing validated biomarkers are formidable tasks because

  13. Biomarkers: Delivering on the expectation of molecularly driven, quantitative health.

    Science.gov (United States)

    Wilson, Jennifer L; Altman, Russ B

    2018-02-01

    Biomarkers are the pillars of precision medicine and are delivering on expectations of molecular, quantitative health. These features have made clinical decisions more precise and personalized, but require a high bar for validation. Biomarkers have improved health outcomes in a few areas such as cancer, pharmacogenetics, and safety. Burgeoning big data research infrastructure, the internet of things, and increased patient participation will accelerate discovery in the many areas that have not yet realized the full potential of biomarkers for precision health. Here we review themes of biomarker discovery, current implementations of biomarkers for precision health, and future opportunities and challenges for biomarker discovery. Impact statement Precision medicine evolved because of the understanding that human disease is molecularly driven and is highly variable across patients. This understanding has made biomarkers, a diverse class of biological measurements, more relevant for disease diagnosis, monitoring, and selection of treatment strategy. Biomarkers' impact on precision medicine can be seen in cancer, pharmacogenomics, and safety. The successes in these cases suggest many more applications for biomarkers and a greater impact for precision medicine across the spectrum of human disease. The authors assess the status of biomarker-guided medical practice by analyzing themes for biomarker discovery, reviewing the impact of these markers in the clinic, and highlight future and ongoing challenges for biomarker discovery. This work is timely and relevant, as the molecular, quantitative approach of precision medicine is spreading to many disease indications.

  14. Biomarkører for anorexia nervosa

    DEFF Research Database (Denmark)

    Sjögren, Magnus

    2017-01-01

    Biomarkers for anorexia nervosa (AN) which reflect the pathophysiology and relate to the aetiology of the disease, are warranted and could bring us one step closer to targeted treatment of AN. Some leads may be found in the biochemistry which often is found disturbed in AN, although normalization...

  15. Plasma inflammatory biomarkers response to aerobic versus ...

    African Journals Online (AJOL)

    Plasma inflammatory biomarkers response to aerobic versus resisted exercise training for chronic obstructive pulmonary disease patients. ... Recent studies proved that morbidity and mortality of COPD is related to systemic inflammation as it contributes to the pathogenesis of atherosclerosis and cardiovascular disease.

  16. Stratum corneum biomarkers for inflammatory skin diseases

    NARCIS (Netherlands)

    Koppes, S.A.

    2017-01-01

    This thesis focusses on development of biomarkers, obtained by a non-invasive sampling method, for skin inflammatory diseases relevant for occupational settings; irritant contact dermatitis (ICD), allergic contact dermatitis (ACD) and atopic dermatitis (AD). In various studies, in which different

  17. 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...

  18. Biomarkers of problem drinking in homeless patients

    DEFF Research Database (Denmark)

    Hesse, Morten; Thiesen, Henrik

    2010-01-01

    Objective. In the search for optimal biomarkers of excessive drinking, a central limitation has been the lack of sensitivity of measures. Many patients have apparently normal values of liver markers despite a considerable alcohol intake. This study aimed to test a novel combined indicator...

  19. Biomarkers in pancreatic adenocarcinoma: current perspectives

    Directory of Open Access Journals (Sweden)

    Swords DS

    2016-12-01

    Full Text Available Douglas S Swords, Matthew A Firpo, Courtney L Scaife, Sean J Mulvihill Department of Surgery, University of Utah Health Sciences, Salt Lake City, UT, USA Abstract: Pancreatic ductal adenocarcinoma (PDAC has a poor prognosis, with a 5-year survival rate of 7.7%. Most patients are diagnosed at an advanced stage not amenable to potentially curative resection. A substantial portion of this review is dedicated to reviewing the current literature on carbohydrate antigen (CA 19-9, which is currently the only guideline-recommended biomarker for PDAC. It provides valuable prognostic information, can predict resectability, and is useful in decision making about neoadjuvant therapy. We also discuss carcinoembryonic antigen (CEA, CA 125, serum biomarker panels, circulating tumor cells, and cell-free nucleic acids. Although many biomarkers have now been studied in relation to PDAC, significant work still needs to be done to validate their usefulness in the early detection of PDAC and management of patients with PDAC. Keywords: pancreatic cancer, biomarkers, screening, CA 19-9, CEA

  20. Quantitative multiplex detection of pathogen biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Mukundan, Harshini; Xie, Hongzhi; Swanson, Basil I.; Martinez, Jennifer; Grace, Wynne K.

    2016-02-09

    The present invention addresses the simultaneous detection and quantitative measurement of multiple biomolecules, e.g., pathogen biomarkers through either a sandwich assay approach or a lipid insertion approach. The invention can further employ a multichannel, structure with multi-sensor elements per channel.

  1. Quantitative multiplex detection of pathogen biomarkers

    Science.gov (United States)

    Mukundan, Harshini; Xie, Hongzhi; Swanson, Basil I; Martinez, Jennifer; Grace, Wynne K

    2014-10-14

    The present invention addresses the simultaneous detection and quantitative measurement of multiple biomolecules, e.g., pathogen biomarkers through either a sandwich assay approach or a lipid insertion approach. The invention can further employ a multichannel, structure with multi-sensor elements per channel.

  2. BLOOD BIOMARKERS FOR EVALUATION OF PERINATAL ENCEPHALOPATHY

    Directory of Open Access Journals (Sweden)

    Ernest Marshall Graham

    2016-07-01

    Full Text Available Recent research in identification of brain injury after trauma shows many possible blood biomarkers that may help identify the fetus and neonate with encephalopathy. Traumatic brain injury shares many common features with perinatal hypoxic-ischemic encephalopathy. Trauma has a hypoxic component, and one of the 1st physiologic consequences of moderate-severe traumatic brain injury is apnea. Trauma and hypoxia-ischemia initiate an excitotoxic cascade and free radical injury followed by the inflammatory cascade, producing injury in neurons, glial cells and white matter. Increased excitatory amino acids, lipid peroxidation products and alteration in microRNAs and inflammatory markers are common to both traumatic brain injury and perinatal encephalopathy. The blood-brain barrier is disrupted in both leading to egress of substances normally only found in the central nervous system. Brain exosomes may represent ideal biomarker containers, as RNA and protein transported within the vesicles are protected from enzymatic degradation. Evaluation of fetal or neonatal brain derived exosomes that cross the blood-brain barrier and circulate peripherally has been referred to as the liquid brain biopsy. A multiplex of serum biomarkers could improve upon the current imprecise methods of identifying fetal and neonatal brain injury such as fetal heart rate abnormalities, meconium, cord gases at delivery, and Apgar scores. Quantitative biomarker measurements of perinatal brain injury and recovery could lead to operative delivery only in the presence of significant fetal risk, triage to appropriate therapy after birth and measure the effectiveness of treatment.

  3. Biomarker Guided Therapy in Chronic Heart Failure

    Science.gov (United States)

    Bektas, Sema

    2015-01-01

    This review article addresses the question of whether biomarker-guided therapy is ready for clinical implementation in chronic heart failure. The most well-known biomarkers in heart failure are natriuretic peptides, namely B-type natriuretic peptide (BNP) and N-terminal pro-BNP. They are well-established in the diagnostic process of acute heart failure and prediction of disease prognosis. They may also be helpful in screening patients at risk of developing heart failure. Although studied by 11 small- to medium-scale trials resulting in several positive meta-analyses, it is less well-established whether natriuretic peptides are also helpful for guiding chronic heart failure therapy. This uncertainty is expressed by differences in European and American guideline recommendations. In addition to reviewing the evidence surrounding the use of natriuretic peptides to guide chronic heart failure therapy, this article gives an overview of the shortcomings of the trials, how the results may be interpreted and the future directions necessary to fill the current gaps in knowledge. Therapy guidance in chronic heart failure using other biomarkers has not been prospectively tested to date. Emerging biomarkers, such as galectin-3 and soluble ST2, might be useful in this regard, as suggested by several post-hoc analyses. PMID:28785440

  4. 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.

  5. 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.)

  6. Phospholipids as Biomarkers for Excessive Alcohol Use

    Science.gov (United States)

    2013-10-01

    NUMBER Phospholipids as Biomarkers for Excessive Alcohol Use 5b. GRANT NUMBER W81XWH-12-1-0497 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...suspected of alcohol abuse. Toxicol Lett, 151(1), 235-241. Graham, D. P., Cardon , A. L., & Uhl, G. R. (2008). An update on substance use and treatment

  7. 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.

  8. Plasma biomarker of dietary phytosterol intake.

    Directory of Open Access Journals (Sweden)

    Xiaobo Lin

    Full Text Available Dietary phytosterols, plant sterols structurally similar to cholesterol, reduce intestinal cholesterol absorption and have many other potentially beneficial biological effects in humans. Due to limited information on phytosterol levels in foods, however, it is difficult to quantify habitual dietary phytosterol intake (DPI. Therefore, we sought to identify a plasma biomarker of DPI.Data were analyzed from two feeding studies with a total of 38 subjects during 94 dietary periods. DPI was carefully controlled at low, intermediate, and high levels. Plasma levels of phytosterols and cholesterol metabolites were assessed at the end of each diet period. Based on simple ordinary least squares regression analysis, the best biomarker for DPI was the ratio of plasma campesterol to the endogenous cholesterol metabolite 5-α-cholestanol (R2 = 0.785, P 0.600; P < 0.01.The ratio of plasma campesterol to the coordinately regulated endogenous cholesterol metabolite 5-α-cholestanol is a biomarker of dietary phytosterol intake. Conversely, plasma phytosterol levels alone are not ideal biomarkers of DPI because they are confounded by large inter-individual variation in absorption and turnover of non-cholesterol sterols. Further work is needed to assess the relation between non-cholesterol sterol metabolism and associated cholesterol transport in the genesis of coronary heart disease.

  9. Cellular biomarker responses of bagrid catfish, Chrysichthys ...

    African Journals Online (AJOL)

    An assessment of the pollution status of Agboyi creek, a water body associated with various anthropogenic activities was carried out in order to determine responses induced in Catfishes, Chrysichthys nigrodigitatus inhabiting it. Cellular biomarkers of stress including the antioxidative stress enzyme, catalase (CAT), lipid ...

  10. 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

  11. 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

  12. Biomarkers and Prognosis in Malignant Lymphomas

    NARCIS (Netherlands)

    Hagenbeek, Anton; Gascoyne, Randy D.; Dreyling, Martin; Kluin, Philip; Engert, Andreas; Salles, Gilles

    2009-01-01

    Approximately 100 hematologists and pathologists from Europe, the United States, and Canada participated in the workshop Biomarkers and Prognosis in Malignant Lymphomas, held in Mandelieu, France,April 11-13, 2008, under the leadership of Anton Hagenbeek, Randy Gascoyne, and Gilles Salles.

  13. Biomarkers of Induced Active and Passive Smoking Damage

    Directory of Open Access Journals (Sweden)

    2009-02-01

    Full Text Available In addition to thewell-known link between smoking and lung cancer, large epidemiological studies have shown a relationship between smoking and cancers of the nose, oral cavity, oropharynx, larynx, esophagus, pancreas, bladder, kidney, stomach, liver, colon and cervix, as well as myeloid leukemia. Epidemiological evidence has reported a direct link between exposure of non-smokers to environmental tobacco smoke and disease, most notably, lung cancer. Much evidence demonstrates that carcinogenic-DNA adducts are useful markers of tobacco smoke exposure, providing an integrated measurement of carcinogen intake, metabolic activation, and delivery to the DNA in target tissues. Monitoring accessible surrogate tissues, such as white blood cells or bronchoalveolar lavage (BAL cells, also provides a means of investigating passive and active tobacco exposure in healthy individuals and cancer patients. Levels of DNA adducts measured in many tissues of smokers are significantly higher than in non-smokers. While some studies have demonstrated an association between carcinogenic DNA adducts and cancer in current smokers, no association has been observed in ex or never smokers. The role of genetic susceptibility in the development of smoking related-cancer is essential. In order to establish whether smoking-related DNA adducts are biomarkers of tobacco smoke exposure and/or its carcinogenic activity we summarized all data that associated tobacco smoke exposure and smoking-related DNA adducts both in controls and/or in cancer cases and studies where the effect of genetic polymorphisms involved in the activation and deactivation of carcinogens were also evaluated. In the future we hope we will be able to screen for lung cancer susceptibility by using specific biomarkers and that subjects of compared groups can be stratified for multiple potential modulators of biomarkers, taking into account various confounding factors.

  14. Identification and dynamic modeling of biomarkers for bacterial uptake and effect of sulfonamide antimicrobials

    International Nuclear Information System (INIS)

    Richter, Merle K.; Focks, Andreas; Siegfried, Barbara; Rentsch, Daniel; Krauss, Martin; Schwarzenbach, René P.; Hollender, Juliane

    2013-01-01

    The effects of sulfathiazole (STA) on Escherichia coli with glucose as a growth substrate was investigated to elucidate the effect-based reaction of sulfonamides in bacteria and to identify biomarkers for bacterial uptake and effect. The predominant metabolite was identified as pterine-sulfathiazole by LC-high resolution mass spectrometry. The formation of pterine-sulfathiazole per cell was constant and independent of the extracellular STA concentrations, as they exceeded the modeled half-saturation concentration K M S of 0.011 μmol L −1 . The concentration of the dihydrofolic acid precursor para-aminobenzoic acid (pABA) increased with growth and with concentrations of the competitor STA. This increase was counteracted for higher STA concentrations by growth inhibition as verified by model simulation of pABA dynamics. The EC value for the inhibition of pABA increase was 6.9 ± 0.7 μmol L −1 STA, which is similar to that calculated from optical density dynamics indicating that pABA is a direct biomarker for the SA effect. - Highlights: ► Elucidation of the effect-based reaction of sulfonamides in bacteria. ► Identification of a biomarker for uptake and effect-based reaction of sulfonamides. ► Investigation of a biomarker for the bacterial growth inhibition by sulfonamides. ► Quantitative mechanistic modeling of biomarker dynamics using enzyme kinetics. ► Mechanistic quantitative linking of sulfonamide concentrations and effects. - Identification of specific biomarkers for the uptake and effect-based reaction of sulfonamides in bacteria and resulting growth inhibition.

  15. 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.

  16. 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

  17. The Gingival Crevicular Fluid as a Source of Biomarkers to Enhance Efficiency of Orthodontic and Functional Treatment of Growing Patients

    Directory of Open Access Journals (Sweden)

    Mariana Caires Sobral de Aguiar

    2017-01-01

    Full Text Available Gingival crevicular fluid (GCF is a biological exudate and quantification of its constituents is a current method to identify specific biomarkers with reasonable sensitivity for several biological events. Studies are being performed to evaluate whether the GCF biomarkers in growing subjects reflect both the stages of individual skeletal maturation and the local tissue remodeling triggered by orthodontic force. Present evidence is still little regarding whether and which GCF biomarkers are correlated with the growth phase (mainly pubertal growth spurt, while huge investigations have been reported on several GCF biomarkers (for inflammation, tissue damage, bone deposition and resorption, and other biological processes in relation to the orthodontic tooth movement. In spite of these investigations, the clinical applicability of the method is still limited with further data needed to reach a full diagnostic utility of specific GCF biomarkers in orthodontics. Future studies are warranted to elucidate the role of main GCF biomarkers and how they can be used to enhance functional treatment, optimize orthodontic force intensity, or prevent major tissue damage consequent to orthodontic treatment.

  18. Spontaneous brain activity as a biomarker for schizophrenia

    DEFF Research Database (Denmark)

    Anhøj, Simon Jesper; Glenthøj, Birte Yding; Rostrup, Egill

    2014-01-01

    Background and aim: One of the most direct ways to get insight into the functional organization of the human brain is to measure the BOLD-signal with fMRI during rest. This signal is not a random signal but is highly organized in several functional networks (RSN's) believed to be a fundamental...... function of the brain. Very few studies have investigated RSN's in Antipsychotic Naïve First Episode patients (ANFE). In this study we wanted to investigate the potential of using the RSN’s as a biomarker for schizophrenia and for effect of treatment in ANFE patients. Especially, we wanted to test...... subjects were scanned and re-scanned with 10 min resting state fMRI. The analysis contains 50 patients and 50 controls at baseline and 35 patients and 35 controls at follow up. The methods used to measure the functional connectivity are Amplitude of Low Frequency Fluctuations (ALFF), a seed-based approach...

  19. Phase II cancer clinical trials for biomarker-guided treatments.

    Science.gov (United States)

    Jung, Sin-Ho

    2018-01-01

    The design and analysis of cancer clinical trials with biomarker depend on various factors, such as the phase of trials, the type of biomarker, whether the used biomarker is validated or not, and the study objectives. In this article, we demonstrate the design and analysis of two Phase II cancer clinical trials, one with a predictive biomarker and the other with an imaging prognostic biomarker. Statistical testing methods and their sample size calculation methods are presented for each trial. We assume that the primary endpoint of these trials is a time to event variable, but this concept can be used for any type of endpoint.

  20. Overview of Biomarkers and Surrogate Endpoints in Drug Development

    Directory of Open Access Journals (Sweden)

    John A. Wagner

    2002-01-01

    Full Text Available There are numerous factors that recommend the use of biomarkers in drug development including the ability to provide a rational basis for selection of lead compounds, as an aid in determining or refining mechanism of action or pathophysiology, and the ability to work towards qualification and use of a biomarker as a surrogate endpoint. Examples of biomarkers come from many different means of clinical and laboratory measurement. Total cholesterol is an example of a clinically useful biomarker that was successfully qualified for use as a surrogate endpoint. Biomarkers require validation in most circumstances. Validation of biomarker assays is a necessary component to delivery of high-quality research data necessary for effective use of biomarkers. Qualification is necessary for use of a biomarker as a surrogate endpoint. Putative biomarkers are typically identified because of a relationship to known or hypothetical steps in a pathophysiologic cascade. Biomarker discovery can also be effected by expression profiling experiment using a variety of array technologies and related methods. For example, expression profiling experiments enabled the discovery of adipocyte related complement protein of 30 kD (Acrp30 or adiponectin as a biomarker for in vivo activation of peroxisome proliferator-activated receptors (PPAR γ activity.

  1. More Accurate Oral Cancer Screening with Fewer Salivary Biomarkers

    Directory of Open Access Journals (Sweden)

    James Michael Menke

    2017-10-01

    Full Text Available Signal detection and Bayesian inferential tools were applied to salivary biomarkers to improve screening accuracy and efficiency in detecting oral squamous cell carcinoma (OSCC. Potential cancer biomarkers are identified by significant differences in assay concentrations, receiver operating characteristic areas under the curve (AUCs, sensitivity, and specificity. However, the end goal is to report to individual patients their risk of having disease given positive or negative test results. Likelihood ratios (LRs and Bayes factors (BFs estimate evidential support and compile biomarker information to optimize screening accuracy. In total, 26 of 77 biomarkers were mentioned as having been tested at least twice in 137 studies and published in 16 summary papers through 2014. Studies represented 10 212 OSCC and 25 645 healthy patients. The measure of biomarker and panel information value was number of biomarkers needed to approximate 100% positive predictive value (PPV. As few as 5 biomarkers could achieve nearly 100% PPV for a disease prevalence of 0.2% when biomarkers were ordered from highest to lowest LR. When sequentially interpreting biomarker tests, high specificity was more important than test sensitivity in achieving rapid convergence toward a high PPV. Biomarkers ranked from highest to lowest LR were more informative and easier to interpret than AUC or Youden index. The proposed method should be applied to more recently published biomarker data to test its screening value.

  2. Serum Biomarker Identification by Mass Spectrometry in Acute Aortic Dissection

    Directory of Open Access Journals (Sweden)

    Yong Ren

    2017-12-01

    Full Text Available Background/Aims: Aortic dissection (AD is also known as intramural hematoma. This study aimed to screen peripheral blood biomarkers of small molecule metabolites for AD using high-performance liquid chromatography-mass spectrometry (HPLC-MS. Methods: Sera from 25 healthy subjects, 25 patients with well-established AD, and 25 patients with well-established hypertension were investigated by HPLC-MS to detect metabolites, screen differentially expressed metabolites, and analyze metabolic pathways. Results: Twenty-six and four metabolites were significantly up- and down-regulated in the hypertensive patients compared with the healthy subjects; 165 metabolites were significantly up-regulated and 109 significantly down-regulated in the AD patients compared with the hypertensive patients. Of these metabolites, 35 were up-regulated and 105 down-regulated only in AD patients. The metabolites that were differentially expressed in AD are mainly involved in tryptophan, histidine, glycerophospholipid, ether lipid, and choline metabolic pathways. As AD alters the peripheral blood metabolome, analysis of peripheral blood metabolites can be used in auxiliary diagnosis of AD. Conclusion: Eight metabolites are potential biomarkers for AD, 3 of which were differentially expressed and can be used for auxiliary diagnosis of AD and evaluation of treatment effectiveness.

  3. Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis.

    Science.gov (United States)

    Wen, Chengping; Zheng, Zhijun; Shao, Tiejuan; Liu, Lin; Xie, Zhijun; Le Chatelier, Emmanuelle; He, Zhixing; Zhong, Wendi; Fan, Yongsheng; Zhang, Linshuang; Li, Haichang; Wu, Chunyan; Hu, Changfeng; Xu, Qian; Zhou, Jia; Cai, Shunfeng; Wang, Dawei; Huang, Yun; Breban, Maxime; Qin, Nan; Ehrlich, Stanislav Dusko

    2017-07-27

    The assessment and characterization of the gut microbiome has become a focus of research in the area of human autoimmune diseases. Ankylosing spondylitis is an inflammatory autoimmune disease and evidence showed that ankylosing spondylitis may be a microbiome-driven disease. To investigate the relationship between the gut microbiome and ankylosing spondylitis, a quantitative metagenomics study based on deep shotgun sequencing was performed, using gut microbial DNA from 211 Chinese individuals. A total of 23,709 genes and 12 metagenomic species were shown to be differentially abundant between ankylosing spondylitis patients and healthy controls. Patients were characterized by a form of gut microbial dysbiosis that is more prominent than previously reported cases with inflammatory bowel disease. Specifically, the ankylosing spondylitis patients demonstrated increases in the abundance of Prevotella melaninogenica, Prevotella copri, and Prevotella sp. C561 and decreases in Bacteroides spp. It is noteworthy that the Bifidobacterium genus, which is commonly used in probiotics, accumulated in the ankylosing spondylitis patients. Diagnostic algorithms were established using a subset of these gut microbial biomarkers. Alterations of the gut microbiome are associated with development of ankylosing spondylitis. Our data suggest biomarkers identified in this study might participate in the pathogenesis or development process of ankylosing spondylitis, providing new leads for the development of new diagnostic tools and potential treatments.

  4. Serum Biomarker Identification by Mass Spectrometry in Acute Aortic Dissection.

    Science.gov (United States)

    Ren, Yong; Tang, Qizhu; Liu, Wenwei; Tang, Yongqian; Zhu, Rui; Li, Bin

    2017-01-01

    Aortic dissection (AD) is also known as intramural hematoma. This study aimed to screen peripheral blood biomarkers of small molecule metabolites for AD using high-performance liquid chromatography-mass spectrometry (HPLC-MS). Sera from 25 healthy subjects, 25 patients with well-established AD, and 25 patients with well-established hypertension were investigated by HPLC-MS to detect metabolites, screen differentially expressed metabolites, and analyze metabolic pathways. Twenty-six and four metabolites were significantly up- and down-regulated in the hypertensive patients compared with the healthy subjects; 165 metabolites were significantly up-regulated and 109 significantly down-regulated in the AD patients compared with the hypertensive patients. Of these metabolites, 35 were up-regulated and 105 down-regulated only in AD patients. The metabolites that were differentially expressed in AD are mainly involved in tryptophan, histidine, glycerophospholipid, ether lipid, and choline metabolic pathways. As AD alters the peripheral blood metabolome, analysis of peripheral blood metabolites can be used in auxiliary diagnosis of AD. Eight metabolites are potential biomarkers for AD, 3 of which were differentially expressed and can be used for auxiliary diagnosis of AD and evaluation of treatment effectiveness. © 2017 The Author(s). Published by S. Karger AG, Basel.

  5. Biomarkers for Anti-Angiogenic Therapy in Cancer

    Directory of Open Access Journals (Sweden)

    Markus Wehland

    2013-04-01

    Full Text Available Angiogenesis, the development of new vessels from existing vasculature, plays a central role in tumor growth, survival, and progression. On the molecular level it is controlled by a number of pro- and anti-angiogenic cytokines, among which the vascular endothelial growth factors (VEGFs, together with their related VEGF-receptors, have an exceptional position. Therefore, the blockade of VEGF signaling in order to inhibit angiogenesis was deemed an attractive approach for cancer therapy and drugs interfering with the VEGF-ligands, the VEGF receptors, and the intracellular VEGF-mediated signal transduction were developed. Although promising in pre-clinical trials, VEGF-inhibition proved to be problematic in the clinical context. One major drawback was the generally high variability in patient response to anti-angiogenic drugs and the rapid development of therapy resistance, so that, in total, only moderate effects on progression-free and overall survival were observed. Biomarkers predicting the response to VEGF-inhibition might attenuate this problem and help to further individualize drug and dosage determination. Although up to now no definitive biomarker has been identified for this purpose, several candidates are currently under investigation. This review aims to give an overview of the recent developments in this field, focusing on the most prevalent tumor species.

  6. Biomarkers in Scleroderma: Progressing from Association to Clinical Utility.

    Science.gov (United States)

    Ligon, Colin; Hummers, Laura K

    2016-03-01

    Scleroderma is a heterogenous disease characterized by autoimmunity, a characteristic vasculopathy, and often widely varying extents of deep organ fibrosis. Recent advances in the understanding of scleroderma's evolution have improved the ability to identify subgroups of patients with similar prognosis in order to improve risk stratification, enrich clinical trials for patients likely to benefit from specific therapies, and identify promising therapeutic targets for intervention. High-throughput technologies have recently identified fibrotic and inflammatory effectors in scleroderma that exhibit strong prognostic ability and may be tied to disease evolution. Increasingly, the use of collections of assayed circulating proteins and patterns of gene expression in tissue has replaced single-marker investigations in understanding the evolution of scleroderma and in objectively characterizing disease extent. Lastly, identification of shared patterns of disease evolution has allowed classification of patients into latent disease subtypes, which may allow rapid clinical prognostication and targeted management in both clinical and research settings. The concept of biomarkers in scleroderma is expanding to include nontraditional measures of aggregate protein signatures and disease evolution. This review examines the recent advances in biomarkers with a focus on those approaches poised to guide prospective management or themselves serve as quantitative surrogate disease outcomes.

  7. Neuropsychological testing and biomarkers in the management of brain metastases

    International Nuclear Information System (INIS)

    Baschnagel, Andrew; Wolters, Pamela L; Camphausen, Kevin

    2008-01-01

    Prognosis for patients with brain metastasis remains poor. Whole brain radiation therapy is the conventional treatment option; it can improve neurological symptoms, prevent and improve tumor associated neurocognitive decline, and prevents death from neurologic causes. In addition to whole brain radiation therapy, stereotactic radiosurgery, neurosurgery and chemotherapy also are used in the management of brain metastases. Radiosensitizers are now currently being investigated as potential treatment options. All of these treatment modalities carry a risk of central nervous system (CNS) toxicity that can lead to neurocognitive impairment in long term survivors. Neuropsychological testing and biomarkers are potential ways of measuring and better understanding CNS toxicity. These tools may help optimize current therapies and develop new treatments for these patients. This article will review the current management of brain metastases, summarize the data on the CNS effects associated with brain metastases and whole brain radiation therapy in these patients, discuss the use of neuropsychological tests as outcome measures in clinical trials evaluating treatments for brain metastases, and give an overview of the potential of biomarker development in brain metastases research

  8. Update on Inflammatory Biomarkers and Treatments in Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Aldo Bonaventura

    2016-11-01

    Full Text Available After an acute ischemic stroke (AIS, inflammatory processes are able to concomitantly induce both beneficial and detrimental effects. In this narrative review, we updated evidence on the inflammatory pathways and mediators that are investigated as promising therapeutic targets. We searched for papers on PubMed and MEDLINE up to August 2016. The terms searched alone or in combination were: ischemic stroke, inflammation, oxidative stress, ischemia reperfusion, innate immunity, adaptive immunity, autoimmunity. Inflammation in AIS is characterized by a storm of cytokines, chemokines, and Damage-Associated Molecular Patterns (DAMPs released by several cells contributing to exacerbate the tissue injury both in the acute and reparative phases. Interestingly, many biomarkers have been studied, but none of these reflected the complexity of systemic immune response. Reperfusion therapies showed a good efficacy in the recovery after an AIS. New therapies appear promising both in pre-clinical and clinical studies, but still need more detailed studies to be translated in the ordinary clinical practice. In spite of clinical progresses, no beneficial long-term interventions targeting inflammation are currently available. Our knowledge about cells, biomarkers, and inflammatory markers is growing and is hoped to better evaluate the impact of new treatments, such as monoclonal antibodies and cell-based therapies.

  9. Plasma biomarkers of depressive symptoms in older adults.

    Science.gov (United States)

    Arnold, S E; Xie, S X; Leung, Y-Y; Wang, L-S; Kling, M A; Han, X; Kim, E J; Wolk, D A; Bennett, D A; Chen-Plotkin, A; Grossman, M; Hu, W; Lee, V M-Y; Mackin, R Scott; Trojanowski, J Q; Wilson, R S; Shaw, L M

    2012-01-03

    The pathophysiology of negative affect states in older adults is complex, and a host of central nervous system and peripheral systemic mechanisms may play primary or contributing roles. We conducted an unbiased analysis of 146 plasma analytes in a multiplex biochemical biomarker study in relation to number of depressive symptoms endorsed by 566 participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) at their baseline and 1-year assessments. Analytes that were most highly associated with depressive symptoms included hepatocyte growth factor, insulin polypeptides, pregnancy-associated plasma protein-A and vascular endothelial growth factor. Separate regression models assessed contributions of past history of psychiatric illness, antidepressant or other psychotropic medicine, apolipoprotein E genotype, body mass index, serum glucose and cerebrospinal fluid (CSF) τ and amyloid levels, and none of these values significantly attenuated the main effects of the candidate analyte levels for depressive symptoms score. Ensemble machine learning with Random Forests found good accuracy (~80%) in classifying groups with and without depressive symptoms. These data begin to identify biochemical biomarkers of depressive symptoms in older adults that may be useful in investigations of pathophysiological mechanisms of depression in aging and neurodegenerative dementias and as targets of novel treatment approaches.

  10. The path from biomarker discovery to regulatory qualification

    CERN Document Server

    Goodsaid, Federico

    2013-01-01

    The Path from Biomarker Discovery to Regulatory Qualification is a unique guide that focuses on biomarker qualification, its history and current regulatory settings in both the US and abroad. This multi-contributed book provides a detailed look at the next step to developing biomarkers for clinical use and covers overall concepts, challenges, strategies and solutions based on the experiences of regulatory authorities and scientists. Members of the regulatory, pharmaceutical and biomarker development communities will benefit the most from using this book-it is a complete and practical guide to biomarker qualification, providing valuable insight to an ever-evolving and important area of regulatory science. For complimentary access to chapter 13, 'Classic' Biomarkers of Liver Injury, by John R. Senior, Associate Director for Science, Food and Drug Administration, Silver Spring, Maryland, USA, please visit the following site:  http://tinyurl.com/ClassicBiomarkers Contains a collection of experiences of different...

  11. Biomarkers of intermediate endpoints in environmental and occupational health

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E; Hansen, Ase M

    2007-01-01

    The use of biomarkers in environmental and occupational health is increasing due to increasing demands on information about health risks from unfavourable exposures. Biomarkers provide information about individual loads. Biomarkers of intermediate endpoints benefit in comparison with biomarkers...... of exposure from the fact that they are closer to the adverse outcome in the pathway from exposure to health effects and may provide powerful information for intervention. Some biomarkers are specific, e.g., DNA and protein adducts, while others are unspecific like the cytogenetic biomarkers of chromosomal...... health effect from the result of the measurement has been performed for the cytogenetic biomarkers showing a predictive value of high levels of CA and increased risk of cancer. The use of CA in future studies is, however, limited by the laborious and sensitive procedure of the test and lack of trained...

  12. Using gene co-expression network analysis to predict biomarkers for chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Borlawsky Tara B

    2010-10-01

    Full Text Available Abstract Background Chronic lymphocytic leukemia (CLL is the most common adult leukemia. It is a highly heterogeneous disease, and can be divided roughly into indolent and progressive stages based on classic clinical markers. Immunoglobin heavy chain variable region (IgVH mutational status was found to be associated with patient survival outcome, and biomarkers linked to the IgVH status has been a focus in the CLL prognosis research field. However, biomarkers highly correlated with IgVH mutational status which can accurately predict the survival outcome are yet to be discovered. Results In this paper, we investigate the use of gene co-expression network analysis to identify potential biomarkers for CLL. Specifically we focused on the co-expression network involving ZAP70, a well characterized biomarker for CLL. We selected 23 microarray datasets corresponding to multiple types of cancer from the Gene Expression Omnibus (GEO and used the frequent network mining algorithm CODENSE to identify highly connected gene co-expression networks spanning the entire genome, then evaluated the genes in the co-expression network in which ZAP70 is involved. We then applied a set of feature selection methods to further select genes which are capable of predicting IgVH mutation status from the ZAP70 co-expression network. Conclusions We have identified a set of genes that are potential CLL prognostic biomarkers IL2RB, CD8A, CD247, LAG3 and KLRK1, which can predict CLL patient IgVH mutational status with high accuracies. Their prognostic capabilities were cross-validated by applying these biomarker candidates to classify patients into different outcome groups using a CLL microarray datasets with clinical information.

  13. Biomarkers and their stable isotopes in Cenozoic sediments above the Chicxulub impact crater

    Science.gov (United States)

    Grice, K.; Schaefer, B.; Coolen, M.; Greenwood, P. F.; Scarlett, A. G.; Freeman, K.; Lyons, S. L.

    2017-12-01

    The most widely accepted hypothesis for the cause of the End-Cretaceous mass extinction (K/Pg event) 66 Ma ago is the impact of an extra-terrestrial body, which produced the 200 km wide Chicxulub impact structure. This event led to an extinction of 75% of all species on Earth. The massive extinction in the terrestrial realm is partly attributed to the intense heat pulse, the widespread wild fires caused by the impact and the ensuing darkness, as dust and sulfate aerosols blocked out the sun leading to photosynthesis shut off and productivity collapse in both the terrestrial and marine realms. The marine realm may additionally have experienced ocean acidification resulting in mass extinction of plankton (foraminifera and coccolithophorids) and marine reptiles. Samples from the Cenozoic marine sediments including the Paleocene-Eocene Thermal Maximum (PETM) have been extracted for hydrocarbons and analysed to investigate the molecular and isotopic organic record of biotic and environmental change after the K/Pg boundary event. Specific biomarker-precursor relationship has been established by the direct correlation of sedimentary biomarkers with the biochemicals (e.g. lipids) of extant biological systems. The structural characterisation of biomarkers as well as their stable isotopic compositions (C, H and N) are used to evaluate the source(s) of organic matter (OM) and to reconstruct paleoenvironmental depositional conditions. Throughout the Cenozoic sediments (including the PETM) the biomarker distribution suggests a variation in the source of organic matter from terrestrial to marine. Furthermore, the presence of sulfurised biomarkers indicates euxinic environmental conditions at the time of deposition. Biomarker distributions indicative of green sulfur bacteria reveal persistent photic zone euxinic conditions at several intervals in the Cenozoic. Further compound specific isotope analyses will provide insights into the long-term biogeochemical cycling of C, H and S

  14. Molecular alterations and biomarkers in colorectal cancer

    Science.gov (United States)

    Grady, William M.; Pritchard, Colin C.

    2013-01-01

    The promise of precision medicine is now a clinical reality. Advances in our understanding of the molecular genetics of colorectal cancer genetics is leading to the development of a variety of biomarkers that are being used as early detection markers, prognostic markers, and markers for predicting treatment responses. This is no more evident than in the recent advances in testing colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor (EGFR). In this review, we update a prior review published in 2010 and describe our current understanding of the molecular pathogenesis of colorectal cancer and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers), and the prediction of treatment responses (predictive markers). PMID:24178577

  15. Flavonoids as fruit and vegetable intake biomarkers

    DEFF Research Database (Denmark)

    Krogholm, Kirstine Suszkiewicz

    of fruit and vegetable intakes. In Paper I, the urinary recovery of the 7 flavonoids in morning spot urine (i.e. all urine voids from midnight including the first morning void) was also found to respond to moderate increases in the intake of fruits and vegetables. However, the association was somewhat...... weaker than in 24h urine samples, indicating that the 24h urinary recovery of the 7 flavonoids is a stronger biomarker of the intake of fruit and vegetables than the urinary recovery of the 7 flavonoids in morning spot urine. In Paper II, the biokinetic profiles of some of the most important dietary......-individual variation in the absorption and urinary recovery of the flavonoids, and this makes it very difficult to separate individuals according to intake by use of the flavonoid biomarker in urine. The intra-individual variation was on the contrary low, and Paper II therefore supports the assumption, that 24h...

  16. Mass Spectrometry-Based Biomarker Discovery.

    Science.gov (United States)

    Zhou, Weidong; Petricoin, Emanuel F; Longo, Caterina

    2017-01-01

    The discovery of candidate biomarkers within the entire proteome is one of the most important and challenging goals in proteomic research. Mass spectrometry-based proteomics is a modern and promising technology for semiquantitative and qualitative assessment of proteins, enabling protein sequencing and identification with exquisite accuracy and sensitivity. For mass spectrometry analysis, protein extractions from tissues or body fluids and subsequent protein fractionation represent an important and unavoidable step in the workflow for biomarker discovery. Following extraction of proteins, the protein mixture must be digested, reduced, alkylated, and cleaned up prior to mass spectrometry. The aim of our chapter is to provide comprehensible and practical lab procedures for sample digestion, protein fractionation, and subsequent mass spectrometry analysis.

  17. Methylated genes as new cancer biomarkers.

    LENUS (Irish Health Repository)

    Duffy, M J

    2012-02-01

    Aberrant hypermethylation of promoter regions in specific genes is a key event in the formation and progression of cancer. In at least some situations, these aberrant alterations occur early in the formation of malignancy and appear to be tumour specific. Multiple reports have suggested that measurement of the methylation status of the promoter regions of specific genes can aid early detection of cancer, determine prognosis and predict therapy responses. Promising DNA methylation biomarkers include the use of methylated GSTP1 for aiding the early diagnosis of prostate cancer, methylated PITX2 for predicting outcome in lymph node-negative breast cancer patients and methylated MGMT in predicting benefit from alkylating agents in patients with glioblastomas. However, prior to clinical utilisation, these findings require validation in prospective clinical studies. Furthermore, assays for measuring gene methylation need to be standardised, simplified and evaluated in external quality assurance programmes. It is concluded that methylated genes have the potential to provide a new generation of cancer biomarkers.

  18. Models of Hepatocellular Carcinoma and Biomarker Strategy

    Energy Technology Data Exchange (ETDEWEB)

    Bagi, Cedo M., E-mail: cedo.bagi@pfizer.com; Andresen, Catharine J. [Global Science & Technology, PGRD, Pfizer Inc, Groton, CT 06340 (United States)

    2010-07-07

    The overwhelming need to improve preclinical models in oncology has stimulated research efforts to refine and validate robust orthotopic models that closely mimic the disease population and therefore have the potential to better predict clinical outcome with novel therapies. Sophisticated technologies including bioluminescence, contrast enhanced ultrasound imaging, positron emission tomography, computed tomography and magnetic resonance imaging have been added to existing serum- and histology-based biomarkers to assist with patient selection and the design of clinical trials. The rationale for the use of human hepatocellular carcinoma (HCC) cell lines, implementation of xenograft and orthotopic animal models and utilization of available biomarkers have been discussed, providing guidelines to facilitate preclinical research for the development of treatments for HCC patients.

  19. Flavonoids as fruit and vegetable intake biomarkers

    DEFF Research Database (Denmark)

    Krogholm, Kirstine Suszkiewicz

    calculation of the bivariate correlation coefficients is the common approach when using only one reference method. Back in 2002, a strictly controlled dietary intervention study indicated that the sum of 7 different flavonoid aglycones excreted in 24h urine samples potentially could be used as a biomarker...... and cohort studies. The Ph.D. thesis contains four scientific papers. Paper I provides evidence that the sum of 7 flavonoids in 24h urine respond in a linear and sensitive manner to moderate increases in the intake of fruits and vegetables, and thus consolidates that the flavonoids are a valid biomarker...... of fruit and vegetable intakes. In Paper I, the urinary recovery of the 7 flavonoids in morning spot urine (i.e. all urine voids from midnight including the first morning void) was also found to respond to moderate increases in the intake of fruits and vegetables. However, the association was somewhat...

  20. Microparticles as Potential Biomarkers of Cardiovascular Disease

    International Nuclear Information System (INIS)

    França, Carolina Nunes; Izar, Maria Cristina de Oliveira; Amaral, Jônatas Bussador do; Tegani, Daniela Melo; Fonseca, Francisco Antonio Helfenstein

    2015-01-01

    Primary prevention of cardiovascular disease is a choice of great relevance because of its impact on health. Some biomarkers, such as microparticles derived from different cell populations, have been considered useful in the assessment of cardiovascular disease. Microparticles are released by the membrane structures of different cell types upon activation or apoptosis, and are present in the plasma of healthy individuals (in levels considered physiological) and in patients with different pathologies. Many studies have suggested an association between microparticles and different pathological conditions, mainly the relationship with the development of cardiovascular diseases. Moreover, the effects of different lipid-lowering therapies have been described in regard to measurement of microparticles. The studies are still controversial regarding the levels of microparticles that can be considered pathological. In addition, the methodologies used still vary, suggesting the need for standardization of the different protocols applied, aiming at using microparticles as biomarkers in clinical practice

  1. Biomarkers for sepsis: past, present and future

    Directory of Open Access Journals (Sweden)

    Giuseppe Chesi

    2016-12-01

    Full Text Available Sepsis is a complication of severe infection associated with high mortality and open diagnostic issues. Treatment strategies are currently limited and essentially based on prompt recognition, aggressive supportive care and early antibiotic treatment. In the last years, extensive antibiotic use has led to selection, propagation and maintenance of drug-resistant microorganisms. In this context, several biomarkers have been proposed for early identification, etiological definition, risk stratification and improving antibiotic stewardship in septic patient care. Among these molecules, only a few have been translated into clinical practice. In this review, we provided an updated overview of established and developing biomarkers for sepsis, focusing our attention on their pathophysiological profile, advantages, limitations, and appropriate evidence-based use in the management of septic patients.

  2. 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.

  3. Microparticles as Potential Biomarkers of Cardiovascular Disease

    Energy Technology Data Exchange (ETDEWEB)

    França, Carolina Nunes, E-mail: carolufscar24@gmail.com [Universidade Federal de São Paulo - UNIFESP - UNISA, SP, São Paulo (Brazil); Universidade de Santo Amaro - UNISA, SP, São Paulo (Brazil); Izar, Maria Cristina de Oliveira; Amaral, Jônatas Bussador do; Tegani, Daniela Melo; Fonseca, Francisco Antonio Helfenstein [Universidade Federal de São Paulo - UNIFESP - UNISA, SP, São Paulo (Brazil)

    2015-02-15

    Primary prevention of cardiovascular disease is a choice of great relevance because of its impact on health. Some biomarkers, such as microparticles derived from different cell populations, have been considered useful in the assessment of cardiovascular disease. Microparticles are released by the membrane structures of different cell types upon activation or apoptosis, and are present in the plasma of healthy individuals (in levels considered physiological) and in patients with different pathologies. Many studies have suggested an association between microparticles and different pathological conditions, mainly the relationship with the development of cardiovascular diseases. Moreover, the effects of different lipid-lowering therapies have been described in regard to measurement of microparticles. The studies are still controversial regarding the levels of microparticles that can be considered pathological. In addition, the methodologies used still vary, suggesting the need for standardization of the different protocols applied, aiming at using microparticles as biomarkers in clinical practice.

  4. [Inflammatory biomarkers in ischemic acute coronary syndrome].

    Science.gov (United States)

    Domínguez-Rodríguez, Alberto; Abreu-González, Pedro

    2015-10-01

    Diagnosing acute coronary syndrome (ACS) in the emergency department is often a complex process. Inflammatory markers might be useful for the rapid assessment of a patient's overall risk and might also help predict future episodes. The clinical use of these biomarkers could potentially lower the number of emergency visits and help in the prevention of future adverse events. The aim of this review was to evaluate the clinical utility of markers of cardiovascular inflammation in emergency patients with ACS. Based on a critical analysis of a selection of the literature, we concluded that none of the biomarkers of cardiovascular inflammation would at present be useful for stratifying risk in emergency situations, aiding prognosis, or guiding therapy for patients with ACS.

  5. 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.

  6. Metabolite Profiling in the Pursuit of Biomarkers for IVF Outcome: The Case for Metabolomics Studies

    Directory of Open Access Journals (Sweden)

    C. McRae

    2013-01-01

    Full Text Available Background. This paper presents the literature on biomarkers of in vitro fertilisation (IVF outcome, demonstrating the progression of these studies towards metabolite profiling, specifically metabolomics. The need for more, and improved, metabolomics studies in the field of assisted conception is discussed. Methods. Searches were performed on ISI Web of Knowledge SM for literature associated with biomarkers of oocyte and embryo quality, and biomarkers of IVF outcome in embryo culture medium, follicular fluid (FF, and blood plasma in female mammals. Results. Metabolomics in the field of female reproduction is still in its infancy. Metabolomics investigations of embryo culture medium for embryo selection have been the most common, but only within the last five years. Only in 2012 has the first metabolomics investigation of FF for biomarkers of oocyte quality been reported. The only metabolomics studies of human blood plasma in this context have been aimed at identifying women with polycystic ovary syndrome (PCOS. Conclusions. Metabolomics is becoming more established in the field of assisted conception, but the studies performed so far have been preliminary and not all potential applications have yet been explored. With further improved metabolomics studies, the possibility of identifying a method for predicting IVF outcome may become a reality.

  7. Identification of Potential Biomarkers for Antimony Susceptibility ...

    Indian Academy of Sciences (India)

    Identification of Potential Biomarkers for Antimony Susceptibility/Resistance in L. donovani Rentala Madhubala School of Life Sciences Jawaharlal Nehru University New Delhi, India · Slide 2 · Slide 3 · Slide 4 · Slide 5 · Slide 6 · Slide 7 · Slide 8 · Slide 9 · Slide 10 · Slide 11 · Slide 12 · Slide 13 · Slide 14 · Slide 15 · Slide 16.

  8. Biomarkers for Wilms Tumor: a Systematic Review

    Science.gov (United States)

    Cone, Eugene B.; Dalton, Stewart S.; Van Noord, Megan; Tracy, Elizabeth T.; Rice, Henry E.; Routh, Jonathan C.

    2016-01-01

    Purpose Wilms tumor is the most common childhood renal malignancy and the fourth most common childhood cancer. Many biomarkers have been studied but there has been no comprehensive summary. We systematically reviewed the literature on biomarkers in Wilms Tumor with the objective of quantifying the prognostic implication of the presence of individual tumor markers. Methods We searched for English language studies from 1980–2015 performed on children with Wilms Tumor under 18 years old with prognostic data. The protocol was conducted as per PRISMA guidelines. Two reviewers abstracted data in duplicate using a standard evaluation form. We performed descriptive statistics, then calculated relative risks and 95% confidence intervals for markers appearing in multiple level 2 or 3 studies. Results 40 studies were included examining 32 biomarkers in 7381 Wilms patients. Studies had a median of 61 patients with 24 biomarker positive patients per study, and a median follow-up of 68.4 months. Median percent of patients in Stage 1, 2, 3, 4, and 5 were 28.5%, 26.4%, 24.5%, 14.1%, and 1.7%, with 10.2% anaplasia. The strongest negative prognostic association was loss of heterozygosity on 11p15, with a risk of recurrence of 5.00, although loss of heterozygosity on 1p and gain of function on 1q were also strongly linked to increased recurrence (2.93 and 2.86 respectively). Conclusions Several tumor markers are associated with an increased risk of recurrence or a decreased risk of overall survival in Wilms Tumor. These data suggest targets for development of diagnostic tests and potential therapies. PMID:27259655

  9. Bayesian methods for proteomic biomarker development

    Directory of Open Access Journals (Sweden)

    Belinda Hernández

    2015-12-01

    In this review we provide an introduction to Bayesian inference and demonstrate some of the advantages of using a Bayesian framework. We summarize how Bayesian methods have been used previously in proteomics and other areas of bioinformatics. Finally, we describe some popular and emerging Bayesian models from the statistical literature and provide a worked tutorial including code snippets to show how these methods may be applied for the evaluation of proteomic biomarkers.

  10. Fibrosis biomarkers in workers exposed to MWCNTs

    International Nuclear Information System (INIS)

    Fatkhutdinova, Liliya M.; Khaliullin, Timur O.; Vasil'yeva, Olga L.; Zalyalov, Ramil R.; Mustafin, Ilshat G.; Kisin, Elena R.; Birch, M. Eileen; Yanamala, Naveena; Shvedova, Anna A.

    2016-01-01

    Multi-walled carbon nanotubes (MWCNT) with their unique physico-chemical properties offer numerous technological advantages and are projected to drive the next generation of manufacturing growth. As MWCNT have already found utility in different industries including construction, engineering, energy production, space exploration and biomedicine, large quantities of MWCNT may reach the environment and inadvertently lead to human exposure. This necessitates the urgent assessment of their potential health effects in humans. The current study was carried out at NanotechCenter Ltd. Enterprise (Tambov, Russia) where large-scale manufacturing of MWCNT along with relatively high occupational exposure levels was reported. The goal of this small cross-sectional study was to evaluate potential biomarkers during occupational exposure to MWCNT. All air samples were collected at the workplaces from both specific areas and personal breathing zones using filter-based devices to quantitate elemental carbon and perform particle analysis by TEM. Biological fluids of nasal lavage, induced sputum and blood serum were obtained from MWCNT-exposed and non-exposed workers for assessment of inflammatory and fibrotic markers. It was found that exposure to MWCNTs caused significant increase in IL-1β, IL6, TNF-α, inflammatory cytokines and KL-6, a serological biomarker for interstitial lung disease in collected sputum samples. Moreover, the level of TGF-β1 was increased in serum obtained from young exposed workers. Overall, the results from this study revealed accumulation of inflammatory and fibrotic biomarkers in biofluids of workers manufacturing MWCNTs. Therefore, the biomarkers analyzed should be considered for the assessment of health effects of occupational exposure to MWCNT in cross-sectional epidemiological studies. - Highlights: • The effects of MWCNT exposure in humans remain unclear. • We found increased KL-6/TGF-β levels in the biofluids of MWCNT-exposed workers.

  11. Biomarkers as Proxies for Life and Environment

    Science.gov (United States)

    Summons, R. E.

    2006-05-01

    Biomarkers are organic molecules that can be used to trace specific types of organisms or biological processes in contemporary ecosystems, ancient sediments and, potentially, beyond the Earth. Biomarkers offer a means to evaluate Earth's biosphere from its earliest development to the modern day. Hydrocarbons, which are the remains of lipids that once resided in the membranes of ancestral organisms, carry chemical and isotopic clues about the nature of early ecosystems. The hydrocarbon remains of fatty acids, sterols, bacterial triterpenoids and pigments are very recalcitrant substances and can be found in rocks as old as 2.8 billion years. These molecules tell us that the three domains, archaea, bacteria and eukarya that comprise all extant life appeared quite early in Earth's history as did the oxygen-producing photosynthesis that oxidized our atmosphere and made it possible for animal life to evolve and increase in complexity. Pigment-derived biomarkers are especially useful for evaluating paleo-environmental conditions. They occur in rocks from the Archean to the present day and can be especially diagnostic for euxinic conditions. The greatest known mass extinction event occurred at the end of the Permian period and extinguished about 70% of the animals and plants that existed at that time. Much controversy surrounds its cause with many different scenarios having been proposed. An international collaboration has enabled biomarker profiles to be obtained from Permian- Triassic boundary sections in China, Australia, Canada, Tibet and Greenland. These data suggest that euxinic conditions prevailed widely in the oceans for an extended period from the Late Permian and that sulfide toxicity may have been a major factor in the demise of both plant and animal life.

  12. Fibrosis biomarkers in workers exposed to MWCNTs

    Energy Technology Data Exchange (ETDEWEB)

    Fatkhutdinova, Liliya M., E-mail: liliya.fatkhutdinova@gmail.com [Kazan State Medical University, ul. Butlerova 49, Kazan 420012 (Russian Federation); Khaliullin, Timur O., E-mail: Khaliullin.40k@gmail.com [Kazan State Medical University, ul. Butlerova 49, Kazan 420012 (Russian Federation); Department of Physiology & Pharmacology, WVU, Morgantown, WV (United States); Vasil' yeva, Olga L., E-mail: volgaleon@gmail.com [Kazan State Medical University, ul. Butlerova 49, Kazan 420012 (Russian Federation); Zalyalov, Ramil R., E-mail: zalyalov.ramil@gmail.com [Kazan State Medical University, ul. Butlerova 49, Kazan 420012 (Russian Federation); Mustafin, Ilshat G., E-mail: ilshat64@mail.ru [Kazan State Medical University, ul. Butlerova 49, Kazan 420012 (Russian Federation); Kisin, Elena R., E-mail: edk8@cdc.gov [National Institute for Occupational Safety and Health, Morgantown, WV (United States); Birch, M. Eileen, E-mail: mib2@cdc.gov [National Institute for Occupational Safety and Health, Cincinnati, OH (United States); Yanamala, Naveena, E-mail: wqu1@cdc.gov [National Institute for Occupational Safety and Health, Morgantown, WV (United States); Shvedova, Anna A., E-mail: ats1@cdc.gov [National Institute for Occupational Safety and Health, Morgantown, WV (United States); Department of Physiology & Pharmacology, WVU, Morgantown, WV (United States)

    2016-05-15

    Multi-walled carbon nanotubes (MWCNT) with their unique physico-chemical properties offer numerous technological advantages and are projected to drive the next generation of manufacturing growth. As MWCNT have already found utility in different industries including construction, engineering, energy production, space exploration and biomedicine, large quantities of MWCNT may reach the environment and inadvertently lead to human exposure. This necessitates the urgent assessment of their potential health effects in humans. The current study was carried out at NanotechCenter Ltd. Enterprise (Tambov, Russia) where large-scale manufacturing of MWCNT along with relatively high occupational exposure levels was reported. The goal of this small cross-sectional study was to evaluate potential biomarkers during occupational exposure to MWCNT. All air samples were collected at the workplaces from both specific areas and personal breathing zones using filter-based devices to quantitate elemental carbon and perform particle analysis by TEM. Biological fluids of nasal lavage, induced sputum and blood serum were obtained from MWCNT-exposed and non-exposed workers for assessment of inflammatory and fibrotic markers. It was found that exposure to MWCNTs caused significant increase in IL-1β, IL6, TNF-α, inflammatory cytokines and KL-6, a serological biomarker for interstitial lung disease in collected sputum samples. Moreover, the level of TGF-β1 was increased in serum obtained from young exposed workers. Overall, the results from this study revealed accumulation of inflammatory and fibrotic biomarkers in biofluids of workers manufacturing MWCNTs. Therefore, the biomarkers analyzed should be considered for the assessment of health effects of occupational exposure to MWCNT in cross-sectional epidemiological studies. - Highlights: • The effects of MWCNT exposure in humans remain unclear. • We found increased KL-6/TGF-β levels in the biofluids of MWCNT-exposed workers.

  13. Measurement of Soluble Biomarkers by Flow Cytometry

    OpenAIRE

    Antal-Szalm?s, P?ter; Nagy, B?la; Debreceni, Ildik? Beke; Kappelmayer, J?nos

    2013-01-01

    Microparticle based flow cytometric assays for determination of the level of soluble biomarkers are widely used in several research applications and in some diagnostic setups. The major advantages of these multiplex systems are that they can measure a large number of analytes (up to 500) at the same time reducing assay time, costs and sample volume. Most of these assays are based on antigen-antibody interactions and work as traditional immunoassays, but nucleic acid alterations ? by using spe...

  14. New serum biomarkers for prostate cancer diagnosis

    Science.gov (United States)

    Chadha, Kailash C.; Miller, Austin; Nair, Bindukumar B.; Schwartz, Stanley A.; Trump, Donald L.; Underwood, Willie

    2014-01-01

    Background Prostate-specific antigen (PSA) is currently used as a biomarker for diagnosis and management of prostate cancer (CaP). However, PSA typically lacks the sensitivity and specificity desired of a diagnostic marker. Objective The goal of this study was to identify an additional biomarker or a panel of biomarkers that is more sensitive and specific than PSA in differentiating benign versus malignant prostate disease and/or localized CaP versus metastatic CaP. Methods Concurrent measurements of circulating interleukin-8 (IL-8), Tumor necrosis factor-α (TNF-α) and soluble tumor necrosis factor-α receptors 1 (sTNFR1) were obtained from four groups of men: (1) Controls (2) with elevated prostate-specific antigen with a negative prostate biopsy (elPSA_negBx) (3) with clinically localized CaP and (4) with castration resistant prostate cancer. Results TNF-α Area under the receiver operating characteristic curve (AUC = 0.93) and sTNFR1 (AUC = 0.97) were strong predictors of elPSA_negBx (vs. CaP). The best predictor of elPSA_negBx vs CaP was sTNFR1 and IL-8 combined (AUC = 0.997). The strongest single predictors of localized versus metastatic CaP were TNF-α (AUC = 0.992) and PSA (AUC = 0.963) levels. Conclusions The specificity and sensitivity of a PSA-based CaP diagnosis can be significantly enhanced by concurrent serum measurements of IL-8, TNF-α and sTNFR1. In view of the concerns about the ability of PSA to distinguish clinically relevant CaP from indolent disease, assessment of these biomarkers in the larger cohort is warranted. PMID:25593898

  15. Recent developments in biomarkers in Parkinson disease

    Science.gov (United States)

    Schapira, Anthony H.V.

    2013-01-01

    Purpose of review Parkinson disease is the second most common neurodegenerative disease after Alzheimer disease, and current demographic trends indicate a life-time risk approaching 4% and predict a doubling of prevalence by 2030. Strategies are being developed to apply recent advances in our understanding of the cause of Parkinson disease to the development of biomarkers that will enable the identification of at-risk individuals, enable early diagnosis and reflect the progression of disease. The latter will be particularly important for the testing of disease-modifying therapies. This review summarizes recent advances in Parkinson disease biomarker development. Recent findings Recent reports continue to reflect the application of a variety of clinical, imaging or biochemical measurements, alone or in combination, to general Parkinson disease populations. Probably the most promising is the assay of alpha-synuclein in the diagnosis and evolution of Parkinson disease. At present, detection techniques are still being refined, but once accurate and reproducible assays are available, it will be important to define the relationship of these to early diagnosis and progression. Alpha-synuclein concentrations may also be modulated by certain disease-modifying agents in development and so may represent a measure of their efficacy. It has to be accepted that no single measure currently fulfils all the necessary criteria for a biomarker in Parkinson disease, but combinations of measures are more likely to deliver benefit. Summary The Parkinson disease biomarker field is approaching a stage when certain combinations of clinical, imaging and biochemical measures may identify a proportion of individuals at risk for developing the disease. However, their general applicability may be limited. Attention is now turning to stratification of Parkinson disease into certain at-risk groups defined by genotype. The application of multimodal screening to these populations may be more

  16. INVESTIGATION OF ANTIFUNGAL ACTIVITY OF QUINOLINIUM DERIVATIVES

    Directory of Open Access Journals (Sweden)

    G. A. Alexandrova

    2013-01-01

    Full Text Available Abstract. Antifungal activity (Candida albicans, Candida krusei of some substituted quinolinium derivatives has been investigated. It was established that the most perspective compound for detail investigation of antifungal activity by labeled biomarkers method was N-phenylbenzoquinaldinium tetrafluoroborate.

  17. Salivary pH: A diagnostic biomarker

    Directory of Open Access Journals (Sweden)

    Sharmila Baliga

    2013-01-01

    Full Text Available Objectives: Saliva contains a variety of host defense factors. It influences calculus formation and periodontal disease. Different studies have been done to find exact correlation of salivary biomarkers with periodontal disease. With a multitude of biomarkers and complexities in their determination, the salivary pH may be tried to be used as a quick chairside test. The aim of this study was to analyze the pH of saliva and determine its relevance to the severity of periodontal disease. Study Design: The study population consisted of 300 patients. They were divided into three groups of 100 patients each: Group A had clinically healthy gingiva, Group B who had generalized chronic gingivitis and Group C who had generalized chronic periodontitis. The randomized unstimulated saliva from each patient was collected and pH was tested. Data was analyzed statistically using analysis of variance technique. Results: The salivary pH was more alkaline for patients with generalized chronic gingivitis as compared with the control group (P = 0.001 whereas patients with generalized chronic periodontitis had more acidic pH as compared with the control group (P = 0.001. Conclusion: These results indicate a significant change in the pH depending on the severity of the periodontal condition. The salivary pH shows significant changes and thus relevance to the severity of periodontal disease. Salivary pH may thus be used as a quick chairside diagnostic biomarker.

  18. Salivary pH: A diagnostic biomarker.

    Science.gov (United States)

    Baliga, Sharmila; Muglikar, Sangeeta; Kale, Rahul

    2013-07-01

    Saliva contains a variety of host defense factors. It influences calculus formation and periodontal disease. Different studies have been done to find exact correlation of salivary biomarkers with periodontal disease. With a multitude of biomarkers and complexities in their determination, the salivary pH may be tried to be used as a quick chairside test. The aim of this study was to analyze the pH of saliva and determine its relevance to the severity of periodontal disease. The study population consisted of 300 patients. They were divided into three groups of 100 patients each: Group A had clinically healthy gingiva, Group B who had generalized chronic gingivitis and Group C who had generalized chronic periodontitis. The randomized unstimulated saliva from each patient was collected and pH was tested. Data was analyzed statistically using analysis of variance technique. The salivary pH was more alkaline for patients with generalized chronic gingivitis as compared with the control group (P = 0.001) whereas patients with generalized chronic periodontitis had more acidic pH as compared with the control group (P = 0.001). These results indicate a significant change in the pH depending on the severity of the periodontal condition. The salivary pH shows significant changes and thus relevance to the severity of periodontal disease. Salivary pH may thus be used as a quick chairside diagnostic biomarker.

  19. Plasma biomarker of dietary phytosterol intake.

    Science.gov (United States)

    Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Spearie, Catherine Anderson; Ostlund, Richard E

    2015-01-01

    Dietary phytosterols, plant sterols structurally similar to cholesterol, reduce intestinal cholesterol absorption and have many other potentially beneficial biological effects in humans. Due to limited information on phytosterol levels in foods, however, it is difficult to quantify habitual dietary phytosterol intake (DPI). Therefore, we sought to identify a plasma biomarker of DPI. Data were analyzed from two feeding studies with a total of 38 subjects during 94 dietary periods. DPI was carefully controlled at low, intermediate, and high levels. Plasma levels of phytosterols and cholesterol metabolites were assessed at the end of each diet period. Based on simple ordinary least squares regression analysis, the best biomarker for DPI was the ratio of plasma campesterol to the endogenous cholesterol metabolite 5-α-cholestanol (R2 = 0.785, P 0.600; P phytosterol intake. Conversely, plasma phytosterol levels alone are not ideal biomarkers of DPI because they are confounded by large inter-individual variation in absorption and turnover of non-cholesterol sterols. Further work is needed to assess the relation between non-cholesterol sterol metabolism and associated cholesterol transport in the genesis of coronary heart disease.

  20. Biomarkers and correlative endpoints for immunotherapy trials.

    Science.gov (United States)

    Morse, Michael A; Osada, Takuya; Hobeika, Amy; Patel, Sandip; Lyerly, H Kim

    2013-01-01

    Immunotherapies for lung cancer are reaching phase III clinical trial, but the ultimate success likely will depend on developing biomarkers to guide development and choosing patient populations most likely to benefit. Because the immune response to cancer involves multiple cell types and cytokines, some spatially and temporally separated, it is likely that multiple biomarkers will be required to fully characterize efficacy of the vaccine and predict eventual benefit. Peripheral blood markers of response, such as the ELISPOT assay and cytokine flow cytometry analyses of peripheral blood mononuclear cells following immunotherapy, remain the standard approach, but it is increasingly important to obtain tissue to study the immune response at the site of the tumor. Earlier clinical endpoints such as response rate and progression-free survival do not correlate with overall survival demonstrated for some immunotherapies, suggesting the need to develop other intermediary clinical endpoints. Insofar as all these biomarkers and surrogate endpoints are relevant in multiple malignancies, it may be possible to extrapolate findings to immunotherapy of lung cancer.

  1. Biomarkers for cardiac cachexia: reality or utopia.

    Science.gov (United States)

    Martins, Telma; Vitorino, Rui; Amado, Francisco; Duarte, José Alberto; Ferreira, Rita

    2014-09-25

    Cardiac cachexia is a serious complication of chronic heart failure, characterized by significant weight loss and body wasting. Chronic heart failure-related muscle wasting results from a chronic imbalance in the activation of anabolic or catabolic pathways, caused by a series of immunological, metabolic, and neurohormonal processes. In spite of the high morbidity and mortality associated to this condition, there is no universally accepted definition or specific biomarkers for cardiac cachexia, which makes its diagnosis and treatment difficult. Several hormonal, inflammatory and oxidative stress molecules have been proposed as serological markers of prognosis in cardiac cachexia but with doubtful success. As individual biomarkers may have limited sensitivity and specificity, multimarker strategies involving mediators of the biological processes modulated by cardiac cachexia will strongly contribute for the diagnosis and management of the disease, as well as for the establishment of new therapeutic targets. An integrated analysis of the biomarkers proposed so far for cardiac cachexia is made in the present review, highlighting the biological processes to which they are related. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Curated compendium of human transcriptional biomarker data.

    Science.gov (United States)

    Golightly, Nathan P; Bell, Avery; Bischoff, Anna I; Hollingsworth, Parker D; Piccolo, Stephen R

    2018-04-17

    One important use of genome-wide transcriptional profiles is to identify relationships between transcription levels and patient outcomes. These translational insights can guide the development of biomarkers for clinical application. Data from thousands of translational-biomarker studies have been deposited in public repositories, enabling reuse. However, data-reuse efforts require considerable time and expertise because transcriptional data are generated using heterogeneous profiling technologies, preprocessed using diverse normalization procedures, and annotated in non-standard ways. To address this problem, we curated 45 publicly available, translational-biomarker datasets from a variety of human diseases. To increase the data's utility, we reprocessed the raw expression data using a uniform computational pipeline, addressed quality-control problems, mapped the clinical annotations to a controlled vocabulary, and prepared consistently structured, analysis-ready data files. These data, along with scripts we used to prepare the data, are available in a public repository. We believe these data will be particularly useful to researchers seeking to perform benchmarking studies-for example, to compare and optimize machine-learning algorithms' ability to predict biomedical outcomes.

  3. Urine Exosomes: An Emerging Trove of Biomarkers.

    Science.gov (United States)

    Street, J M; Koritzinsky, E H; Glispie, D M; Star, R A; Yuen, P S T

    Exosomes are released by most cells and can be isolated from all biofluids including urine. Exosomes are small vesicles formed as part of the endosomal pathway that contain cellular material surrounded by a lipid bilayer that can be traced to the plasma membrane. Exosomes are potentially a more targeted source of material for biomarker discovery than unfractionated urine, and provide diagnostic and pathophysiological information without an invasive tissue biopsy. Cytoplasmic contents including protein, mRNA, miRNA, and lipids have all been studied within the exosomal fraction. Many prospective urinary exosomal biomarkers have been successfully identified for a variety of kidney or genitourinary tract conditions; detection of systemic conditions may also be possible. Isolation and analysis of exosomes can be achieved by several approaches, although many require specialized equipment or involve lengthy protocols. The need for timely analysis in the clinical setting has driven considerable innovation with several promising options recently emerging. Consensus on exosome isolation, characterization, and normalization procedures would resolve critical clinical translational bottlenecks for existing candidate exosomal biomarkers and provide a template for additional discovery studies. 2017 Published by Elsevier Inc.

  4. Individual Biomarkers Using Molecular Personalized Medicine Approaches.

    Science.gov (United States)

    Zenner, Hans P

    2017-01-01

    Molecular personalized medicine tries to generate individual predictive biomarkers to assist doctors in their decision making. These are thought to improve the efficacy and lower the toxicity of a treatment. The molecular basis of the desired high-precision prediction is modern "omex" technologies providing high-throughput bioanalytical methods. These include genomics and epigenomics, transcriptomics, proteomics, metabolomics, microbiomics, imaging, and functional analyses. In most cases, producing big data also requires a complex biomathematical analysis. Using molecular personalized medicine, the conventional physician's check of biomarker results may no longer be sufficient. By contrast, the physician may need to cooperate with the biomathematician to achieve the desired prediction on the basis of the analysis of individual big data typically produced by omex technologies. Identification of individual biomarkers using molecular personalized medicine approaches is thought to allow a decision-making for the precise use of a targeted therapy, selecting the successful therapeutic tool from a panel of preexisting drugs or medical products. This should avoid the treatment of nonresponders and responders that produces intolerable unwanted effects. © 2017 S. Karger AG, Basel.

  5. Evaluation of biomarkers for the prediction of pre-eclampsia in women with type 1 diabetes mellitus: A systematic review.

    Science.gov (United States)

    Wotherspoon, Amy C; Young, Ian S; McCance, David R; Holmes, Valerie A

    2016-07-01

    Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality. Women with type 1 diabetes are considered a high-risk group for developing pre-eclampsia. Much research has focused on biomarkers as a means of screening for pre-eclampsia in the general maternal population; however, there is a lack of evidence for women with type 1 diabetes. To undertake a systematic review to identify potential biomarkers for the prediction of pre-eclampsia in women with type 1 diabetes. We searched Medline, EMBASE, Maternity and Infant Care, Scopus, Web of Science and CINAHL SELECTION CRITERIA: Studies were included if they measured biomarkers in blood or urine of women who developed pre-eclampsia and had pre-gestational type 1 diabetes mellitus Data collection and analysis A narrative synthesis was adopted as a meta-analysis could not be performed, due to high study heterogeneity. A total of 72 records were screened, with 21 eligible studies being included in the review. A wide range of biomarkers was investigated and study size varied from 34 to 1258 participants. No single biomarker appeared to be effective in predicting pre-eclampsia; however, glycaemic control was associated with an increased risk while a combination of angiogenic and anti-angiogenic factors seemed to be potentially useful. Limited evidence suggests that combinations of biomarkers may be more effective in predicting pre-eclampsia than single biomarkers. Further research is needed to verify the predictive potential of biomarkers that have been measured in the general maternal population, as many studies exclude women with diabetes preceding pregnancy. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Introduction: biomarkers in neurodevelopment toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Needleman, H.L.

    1987-10-01

    The search for markers of toxicant exposure and effect upon the development of organisms presents a set of challenges that differ in many ways from those encountered in the study of markers in reproduction or pregnancy. These latter two fields specify a relatively narrow set of organs or biological systems. The term development, on the other hand, can apply to any organ system, or to any set of phenomena that changes in an ordered way over time. For this reason the papers presented in the session on development were chosen to narrow the focus to neurodevelopmental markers, as such markers may be altered by neurotoxic exposure. In attempting to meet this task, the authors have been able to select a group of investigators who work at the leading edges of their respective fields of developmental neuroanatomy, neurotoxicology, neuroendocrinology, neuropsychology, and infant development. The notion that toxicants could affect behavior certainly is not new. Recent knowledge that behavioral aberrations can occur at exposures below those which produce organic changes, and that behavioral aberrations can occur at exposures below those which produce organic changes, and that behavioral observation might provide early markers of effect has given rise to two new fields: behavioral toxicology and behavioral teratology.

  7. 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.

  8. 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

  9. Biomarker Production and Preservation on Europa

    Science.gov (United States)

    Buffo, J.; Schmidt, B. E.

    2017-12-01

    Future landing site selection and sampling techniques for Europa will concentrate on locations of high potential biomarker preservation, however it is unclear what the best targets might be. On Europa, the scenario is quite unlike the depositional surface environments of terrestrial planets we've studied thus far-Europa's surface is passively communicating with putative habitable niches below that extend throughout the ice shell, ocean and sea floor. In this work, I approach biomarker production and preservation on Europa based by considering the many hypotheses that govern the its habitability, the processes that occur within the sea floor, ocean, and ice and exchange between them, and the geologic hypotheses for the formation of its various surfaces to establish, what journey through the planet a biomarker might take to arrive, if possible, at the surface where it is accessible to near-term landed missions. The goal of this project is to construct a simple model through which to consider the context for sampled material that will provide us with the ability to identify limitations in our intuition, understanding of the Europan system, our current hypotheses and data, and provide a road map for developing both areas for new research and identifying technology gaps that we must overcome before we can confidently select a landing site or analyze a sample from the near surface of Europa. I first consider the nature of the environment, i.e. at the sea floor interface, the ocean, or ocean-ice interface, in order to establish what the likely "biomarker" could be and then trace its path through the system: downwelling through the shell, mixing through the ocean, and pathways to the surface. Importantly, many models exist for the production of Europa's surface and subsurface geology that could affect the integrity of a putative biomarker. Often we modulate such considerations as a function of the time-scales over which the geologic process occurs, however such processes

  10. A New Biomarker Proxy for Palaeo-pCO2 Reconstruction in Ancient Sediments

    Science.gov (United States)

    Pancost, R. D.; Magness, S.; Maxwell, J. R.

    2001-12-01

    The carbon isotopic composition of marine organic matter has commonly been used in chemostratigraphy or as a proxy for ancient pCO2 levels. Both of these goals require that the source of organic matter be well defined, and in the case of palaeo-pCO2 investigations, the organic matter must be derived ultimately from aquatic photoautotrophs. However, additional sources, including terrestrial biomass, heterotrophs, or bacteria, can also contribute to total organic carbon (TOC). In the past decade, numerous workers have attempted to refine organic carbon isotope records using the isotopic composition of individual compounds (biomarkers) rather than the TOC. The appeal of this approach is that by examining specific biomarkers, a signal diagnostic for photoautotrophic organisms can be obtained. For compound-specific isotope analyses to be most effective, the compounds analysed must have a relatively specific source. Among the most commonly used biomarkers in palaeo-pCO2 investigations are alkenones, long-chain ketones derived exclusively from certain species of haptophyte algae. However, alkenones are absent in rocks older than the Jurassic and either absent or present in low abundances in rocks older than the Miocene. Thus, in older rocks, other biomarkers, including steranes (derived from eukaryotic sterols), phytane (presumably derived from chlorophyll), and n-alkanes (derived from algal macromolecules), are used. Unfortunately, these compounds can have alternative sources and become less reliable as isotopic proxies for photoautotrophs with increasing thermal maturity and complexity of the hydrocarbon distribution. Here we propose the use of a maleimides (1H-pyrrole-2,5-diones) as a new biomarker class for evaluating past changes in photoautotroph carbon isotopic compositions. Maleimides have three key advantages over other biomarkers in ancient rocks. First, they are degradation products of chlorophyll and have no known alternative origins in marine sediments

  11. Cocktail effects on biomarker responses in fish

    Energy Technology Data Exchange (ETDEWEB)

    Celander, Malin C., E-mail: malin.celander@zool.gu.se [University of Gothenburg, Department of Zoology, Box 463, SE-405 30 Gothenburg (Sweden)

    2011-10-15

    One of today's greatest challenges in environmental toxicology is to understand effects of mixture toxicity, commonly referred to as cocktail effects, in humans and in wildlife. Biomarker responses in fish are routinely used to assess exposure of anthropogenic chemicals in the aquatic environment. However, little is known about how cocktail effects affect these biomarker responses. For this reason, there is an obvious risk for misinterpretation of biomarker-data and this can have profound negative effects on stakeholder's decisions and actions, as well as on legislations and remediation-plans initiated in order to reduce exposure to certain chemicals. Besides, chemical safety-levels are traditionally based on experiences from lab-studies with single chemicals, which is unfortunate as a chemical can be more toxic when it is mixed with other chemicals, because of the cocktail effect. This review focuses on pharmacokinetic interactions between different classes of pollutants on detoxification mechanisms and how that affects two commonly used biomarkers in the aquatic environment: (1) induction of cytochrome P450 1A (CYP1A) that is mediated via activation of the arylhydrocarbon receptor (AhR), used to assess exposure to aromatic hydrocarbons; (2) induction of vitellogenin (VTG) that is mediated via activation of the estrogen receptor (ER), used to assess exposure to estrogenic chemicals. These responses can be either directly or indirectly affected by the presence of other classes of pollutants as a result of cocktail effects. For example, chemicals that inhibit the function of key metabolic enzymes and transporter pumps that are involved in elimination of AhR- and ER agonists, can result in bioaccumulation of aromatic hydrocarbons and estrogenic chemicals resulting in increased biomarker responses. This cocktail effect can lead to overestimation of the actual exposure pressure. On the contrary, induction of expression of key metabolic enzymes and transporter

  12. Circulating biomarkers in cancer care: What possible use?

    Directory of Open Access Journals (Sweden)

    Rob J. Jones

    2017-04-01

    Full Text Available The practice of the physician has changed greatly in the last 100 years. Yet, the fundamental role remains constant: it is the physician's function to make a diagnosis, assess prognosis, choose and deliver the most effective treatment and then to assess the adequacy of that treatment (both in terms of effectiveness and safety. Whereas our predecessors were almost entirely reliant on clinical history and examination findings in conducting these assessments, the 21st century physician is aided by a plethora of blood tests, imaging investigations, electrophysiological recordings and morphological and molecular analyses of tissue samples. For many patients, the totality of these newer tests contributes relatively little to their journey, whilst, for some, key tests can dictate the direction of travel and, sometimes, the ultimate destination. Keywords: Prostate, Cancer, Biomarker

  13. Ascorbate and dehydroascorbic acid as reliable biomarkers of oxidative stress

    DEFF Research Database (Denmark)

    Lykkesfeldt, Jens

    2007-01-01

    , the analytical reproducibility was tested by repeated analysis of plasma aliquots from one individual over four years. The plasma was subjected to acidic deproteinization with an equal volume of 10% meta-phosphoric acid containing 2 mM EDTA and analyzed for ascorbate and dehydroascorbic acid by high-performance...... liquid chromatography with coulometric detection. In a parallel experiment, stability of human plasma samples treated as above and stored at -80°C for five years was tested in a cohort of 131 individuals. No degradation or shift in the equilibrium between ascorbate and dehydroascorbic acid was observed......Lack of post-sampling stability of ascorbate and dehydroascorbic acid and failure to block their in vivo equilibrium have lowered their value as biomarkers of oxidative stress and limited the ability to further investigate their possible role in disease prevention. In the present paper...

  14. FDG PET/CT imaging as a biomarker in lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Meignan, Michel; Itti, Emmanuel [Hopitaux Universitaires Henri Mondor, Paris-Est Creteil University, LYSA Imaging, Department of Nuclear Medicine, Creteil (France); Gallamini, Andrea [Nice University, Research, Innovation and Statistic Department, Antoine Lacassagne Cancer Center, Nice (France); Scientific Research Committee, S. Croce Hospital, Cuneo (Italy); Younes, Anas [Memorial Sloan Kettering Cancer Center, Lymphoma Service, New York, NY (United States)

    2015-04-01

    FDG PET/CT has changed the management of FDG-avid lymphoma and is now recommended as the imaging technique of choice for staging and restaging. The need for tailoring therapy to reduce toxicity in patients with a favourable outcome and for improving treatment in those with high-risk factors requires accurate diagnostic methods and a new prognostic algorithm to identify different risk categories. New drugs are used in relapsed/refractory patients. The role of FDG PET/CT as a biomarker in this context is summarized in this review. New trends in FDG metabolic imaging in lymphoma are addressed including metabolic tumour volume measurement at staging and integrative PET which combines PET data with clinical and molecular markers or other imaging techniques. The quantitative approach for response assessment which is under investigation and is used in large ongoing trials is compared with visual criteria. The place of FDG in the era of targeted therapy is discussed. (orig.)

  15. SLEEP phenomena as an early biomarker for Parkinsonism

    DEFF Research Database (Denmark)

    Kempfner, Jacob; Jennum, Poul; Nikolic, Miki

    2013-01-01

    Idiopathic Rapid-Eye-Movement (REM) sleep Behavior Disorder (iRBD) is one of the most potential biomarkers for Parkinson's Disease (PD) and some atypical PD (AP). It is characterized by REM sleep with abnormal high surface EMG (sEMG) activity. Some twitching during REM sleep is normal, but no one...... has defined what normal is, and no well-defined methodology for measuring muscle activity in REM sleep exists. The purpose of this study is to investigate the possibility of detecting abnormal high muscle activity during REM sleep in subjects diagnosed with iRBD. This has been achieved by considering...... the abnormal high muscle activity during REM sleep in iRBD subjects as an outlier detection problem, while exploiting that iRBD muscle activity is more grouped. It was possible to correctly discriminate all iRBD subjects from healthy elderly control subjects and subjects diagnosed with periodic limb movement...

  16. Transcriptomic biomarkers of altered erythropoiesis to detect autologous blood transfusion.

    Science.gov (United States)

    Salamin, Olivier; Mignot, Jonathan; Kuuranne, Tiia; Saugy, Martial; Leuenberger, Nicolas

    2018-03-01

    Autologous blood transfusion is a powerful means of improving performance and remains one of the most challenging methods to detect. Recent investigations have identified 3 candidate reticulocytes genes whose expression was significantly influenced by blood transfusion. Using quantitative reverse transcription polymerase chain reaction as an alternative quantitative method, the present study supports that delta-aminolevulinate synthase 2 (ALAS2), carbonic anhydrase (CA1), and solute carrier family 4 member 1 (SLC4A1) genes are down-regulated post-transfusion. The expression of these genes exhibited stronger correlation with immature reticulocyte fraction than with reticulocytes percentage. Moreover, the repression of reticulocytes' gene expression was more pronounced than the diminution of immature reticulocyte fraction and reticulocyte percentage following blood transfusion. It suggests that the 3 candidate genes are reliable predictors of bone marrow's response to blood transfusion and that they represent potential biomarkers for the detection of this method prohibited in sports. Copyright © 2017 John Wiley & Sons, Ltd.

  17. Can common serum biomarkers predict complicated appendicitis in children?

    Science.gov (United States)

    Zani, Augusto; Teague, Warwick J; Clarke, Simon A; Haddad, Munther J; Khurana, Sanjeev; Tsang, Thomas; Nataraja, Ramesh M

    2017-07-01

    As appendicitis in children can be managed differently according to the severity of the disease, we investigated whether commonly used serum biomarkers on admission could distinguish between simple and complicated appendicitis. Admission white blood cell (WBC), neutrophil (NEU), and C-reactive protein (CRP) levels were analysed by ROC curve, and Kruskal-Wallis and contingency tests. Patients were divided according to age and histology [normal appendix (NA), simple appendicitis (SA), complicated appendicitis (CA)]. Of 1197 children (NA = 186, SA = 685, CA = 326), 7% were 40 mg/L in 58% CA and 37% SA (p 15 × 10 9 /L in 58% CA and 43% SA (p appendicitis in children older than 5 years of age. Early distinction of appendicitis severity using these tests may guide caregivers in the preoperative decision-making process.

  18. 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.

  19. Biomarkers of Aging: From Function to Molecular Biology

    Directory of Open Access Journals (Sweden)

    Karl-Heinz Wagner

    2016-06-01

    Full Text Available Aging is a major risk factor for most chronic diseases and functional impairments. Within a homogeneous age sample there is a considerable variation in the extent of disease and functional impairment risk, revealing a need for valid biomarkers to aid in characterizing the complex aging processes. The identification of biomarkers is further complicated by the diversity of biological living situations, lifestyle activities and medical treatments. Thus, there has been no identification of a single biomarker or gold standard tool that can monitor successful or healthy aging. Within this short review the current knowledge of putative biomarkers is presented, focusing on their application to the major physiological mechanisms affected by the aging process including physical capability, nutritional status, body composition, endocrine and immune function. This review emphasizes molecular and DNA-based biomarkers, as well as recent advances in other biomarkers such as microRNAs, bilirubin or advanced glycation end products.

  20. Analysis of cutin and suberin biomarker patterns in alluvial sedi-ments

    Science.gov (United States)

    Herschbach, Jennifer; Sesterheim, Anna; König, Frauke; Fuchs, Elmar

    2015-04-01

    Cutin and suberin are the primary source of hydrolysable aliphatic lipid polyesters in soil organic matter (SOM). They are known as geochemical biomarkers to estimate the contribution of different plant species and tissues to SOM. Despite their potential as biomarkers, cutin and suberin have received less attention as flood plain sediment biomarkers. The objectives of this study were to investigate the efficiency of cutin and suberin as biomarkers in floodplains. Therefore similarities between the lipid pattern in alluvial sediments and in the actual vegetation were considered. Lipids of plant tissues (roots, twigs, leaves) from different species (reed (e.g. Phalaris arun-diacea), Salix alba, Ulmus laevis and grassland (e.g. Carex spec.)) and of the un-derlying soils and sediments were obtained and investigated at four sites in the nature reserve Knoblauchsaue (Hessen, Germany). The four sampling sites differ not only with respect to their vegetation, but also within their distance to the river Rhine. Cutin and suberin monomers of plants and soils were analysed by alkaline hydrolysis, methylation and acetylation and subsequent gas chromatography-mass spectrometry. Resulting lipid patterns were specific for the appropriate plant species and tissues. However, the traceability of single selected lipids was decreasing alongside the soil profile, with the exception of monomers in softwood floodplain soils. Selected tissue specific lipid ratios showed a higher traceability due to strong attributions of lipid ratios in soils and roots of U. laevis and Carex spec. and in leaves of U. laevis and S. alba. In contrast, there was no accordance between the suberin specific lipid ratios in soils and roots of S. alba and P. arundiacea. The most robust interpretations were afforded when a set of multiple biomarkers (i.e. a combination of free lipid ratios and ratios of hydrolysable lipids) was used to collectively reconstruct the source vegetation of different sediment layers.

  1. The role of novel biomarkers in childhood idiopathic nephrotic syndrome: a narrative review of published evidence

    Directory of Open Access Journals (Sweden)

    Uwaezuoke SN

    2017-06-01

    Full Text Available Samuel N Uwaezuoke Department of Pediatrics, Pediatric Nephrology Firm, University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu, Nigeria Abstract: Two histological subtypes of idiopathic nephrotic syndrome are commonly recognized in children, namely minimal change nephropathy and focal segmental glomerulosclerosis. Children with minimal change nephropathy (the majority of whom are steroid-sensitive and focal segmental glomerulosclerosis (the majority of whom are steroid-resistant require early identification in order to ensure appropriate therapeutic intervention and better outcome. Although renal biopsy and histology remain the ideal diagnostic steps to identify these histological subtypes, reports indicate that serum and urinary biomarkers are now being utilized in the investigation of childhood idiopathic nephrotic syndrome. This paper aims to review the diagnostic and prognostic utility of novel biomarkers in childhood idiopathic nephrotic syndrome and to highlight their role in differentiating steroid-sensitive nephrotic syndrome (SRNS from steroid-resistant nephrotic syndrome (SSNS. Using the terms “idiopathic nephrotic syndrome,” “children,” and “biomarkers” the PubMed database was searched for relevant studies related to the topic. Biomarkers such as adiponectin, neopterin, β2-microglobulin, and N-acetyl-β-D glucosaminidase were reported as diagnostic markers. In addition to neopterin and N-acetyl-β-D glucosaminidase, urine vitamin D-binding protein and α1β-glycoprotein were shown to differentiate SRNS from SSNS while N-acetyl-β-D glucosaminidase and β2-microglobulin could predict steroid responsiveness and renal outcome in SRNS. Although progress has been made in demonstrating the diagnostic and prognostic utility of these biomarkers, their limited availability in most laboratories has precluded a complete paradigm shift from the conventional renal biopsy. Nevertheless, further longitudinal studies are required

  2. Plasma proteomics to identify biomarkers - Application to cardiovascular diseases

    DEFF Research Database (Denmark)

    Beck, Hans Christian; Overgaard, Martin; Melholt Rasmussen, Lars

    2015-01-01

    There is an unmet need for new cardiovascular biomarkers. Despite this only few biomarkers for the diagnosis or screening of cardiovascular diseases have been implemented in the clinic. Thousands of proteins can be analysed in plasma by mass spectrometry-based proteomics technologies. Therefore......, this technology may therefore identify new biomarkers that previously have not been associated with cardiovascular diseases. In this review, we summarize the key challenges and considerations, including strategies, recent discoveries and clinical applications in cardiovascular proteomics that may lead...

  3. The Wide and Complex Field of NAFLD Biomarker Research: Trends

    OpenAIRE

    Wichro, Erika; Macheiner, Tanja; Schmid, Jasmin; Kavsek, Barbara; Sargsyan, Karine

    2014-01-01

    Background. Nonalcoholic fatty liver disease is now acknowledged as a complex public health issue linked to sedentary lifestyle, obesity, and related disorders like type 2 diabetes and metabolic syndrome. Aims. We aimed to retrieve its trends out of the huge amount of published data. Therefore, we conducted an extensive literature search to identify possible biomarker and/or biomarker combinations by retrospectively assessing and evaluating common and novel biomarkers to predict progression a...

  4. Transmembrane amyloid-related proteins in CSF as potential biomarkers for Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Inmaculada eLopez-Font

    2015-06-01

    Full Text Available In the continuing search for new cerebrospinal fluid (CSF biomarkers for Alzheimer’s disease (AD, reasonable candidates are the secretase enzymes involved in the processing of the amyloid precursor protein (APP, as well as the large proteolytic cleavage fragments sAPPα and sAPPβ. The enzymatic activities of some of these secretases, such as BACE1 and TACE, have been investigated as potential AD biomarkers, and it has been assumed that these activities present in human CSF result from the soluble truncated forms of the membrane-bound enzymes. However, we and others recently identified soluble forms of BACE1 and APP in CSF containing the intracellular domains, as well as the multi-pass transmembrane presenilin-1 (PS1 and other subunits of γ-secretase. We also review recent findings that suggest that most of these soluble transmembrane proteins could display self-association properties based on hydrophobic and/or ionic interactions leading to the formation of heteromeric complexes. The oligomerization state of these potential new biomarkers needs to be taken into consideration for assessing their real potential as CSF biomarkers for AD by adequate molecular tools.

  5. Circulating Long Noncoding RNAs as Potential Biomarkers of Sepsis: A Preliminary Study.

    Science.gov (United States)

    Dai, Yu; Liang, Zhixin; Li, Yulin; Li, Chunsun; Chen, Liangan

    2017-11-01

    Long noncoding RNAs (lncRNAs) are becoming promising biomarker candidates in various diseases as assessed via sequencing technologies. Sepsis is a life-threatening disease without ideal biomarkers. The aim of this study was to investigate the expression profile of lncRNAs in the peripheral blood of sepsis patients and to find potential biomarkers of sepsis. A lncRNA expression profile was performed using peripheral blood from three sepsis patients and three healthy volunteers using microarray screening. The differentially expressed lncRNAs were validated by real-time quantitative polymerase chain reaction (qRT-PCR) in a further set of 22 sepsis patients and 22 healthy volunteers. Among 1316 differentially expressed lncRNAs, 771 were downregulated and 545 were upregulated. Results of the qRT-PCR were consistent with the microarray data. lncRNA ENST00000452391.1, uc001vji.1, and uc021zxw.1 were significantly differentially expressed between sepsis patients and healthy volunteers. Moreover, lncRNA ENST00000504301.1 and ENST00000452391.1 were significantly differentially expressed between sepsis survivors and nonsurvivors. The lncRNA expression profile in the peripheral blood of sepsis patients significantly differed from that of healthy volunteers. Circulating lncRNAs may be good candidates for sepsis biomarkers.

  6. Urinary fructose: a potential biomarker for dietary fructose intake in children.

    Science.gov (United States)

    Johner, S A; Libuda, L; Shi, L; Retzlaff, A; Joslowski, G; Remer, T

    2010-11-01

    Recently, urinary fructose and sucrose excretion in 24-h urine have been established experimentally as new biomarkers for dietary sugar intake in adults. Our objective was to investigate 1) whether the fructose biomarker is also applicable in free-living children and 2) for what kind of sugar it is standing for. Intakes of added and total sugar (including additional sugar from fruit and fruit juices) were assessed by 3-day weighed dietary records in 114 healthy prepubertal children; corresponding 24-h urinary fructose excretion was measured photometrically. The associations between dietary sugar intakes and urinary fructose excretion were examined using linear regression models. To determine whether one of the two sugar variables may be better associated with the urinary biomarker, the statistical Pitman's test was used. Added and total sugar correlated significantly with urinary fructose, but the linear regression indicated a weak association between intake of added sugar and urinary log-fructose excretion (β=0.0026, R(2)=0.055, P=0.01). The association between total sugar intake and log-urinary fructose (β=0.0040, R(2)=0.181, Pestimation of total sugar intake than for the estimation of added dietary sugar intake in children. However, as excreted fructose stems almost exclusively from the diet (both from food-intrinsic and added intakes), it can be assumed that urinary fructose represents a potential biomarker for total dietary fructose intake, irrespective of its source.

  7. 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

  8. 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

  9. 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.

  10. Imaging biomarkers as surrogate endpoints for drug development

    International Nuclear Information System (INIS)

    Richter, Wolf S.

    2006-01-01

    The employment of biomarkers (including imaging biomarkers, especially PET) in drug development has gained increasing attention during recent years. This has been partly stimulated by the hope that the integration of biomarkers into drug development programmes may be a means to increase the efficiency and effectiveness of the drug development process by early identification of promising drug candidates - thereby counteracting the rising costs of drug development. More importantly, however, the interest in biomarkers for drug development is the logical consequence of recent advances in biosciences and medicine which are leading to target-specific treatments in the framework of ''personalised medicine''. A considerable proportion of target-specific drugs will show effects in subgroups of patients only. Biomarkers are a means to identify potential responders, or patient subgroups at risk for specific side-effects. Biomarkers are used in early drug development in the context of translational medicine to gain information about the drug's potential in different patient groups and disease states. The information obtained at this stage is mainly important for designing subsequent clinical trials and to identify promising drug candidates. Biomarkers in later phases of clinical development may - if properly validated - serve as surrogate endpoints for clinical outcomes. Regulatory agencies in the EU and the USA have facilitated the use of biomarkers early in the development process. The validation of biomarkers as surrogate endpoints is part of FDA's ''critical path initiative''. (orig.)

  11. [Collaborative projects with academia for regulatory science studies on biomarkers].

    Science.gov (United States)

    Saito, Yoshiro; Nakamura, Ryosuke; Maekawa, Keiko

    2014-01-01

    Biomarkers are useful tools to be utilized as indicators/predictors of disease severity and drug responsiveness/safety, and thus are expected to promote efficient drug development and to accelerate proper use of approved drugs. Many academic achievements have been reported, but only a small number of biomarkers are used in clinical trials and drug treatments. Regulatory sciences on biomarkers for their secure development and proper qualification are necessary to facilitate their practical application. We started to collaborate with Tohoku University and Nagoya City University for sample quality, biomarker identification, evaluation of their usage, and making guidances. In this short review, scheme and progress of these projects are introduced.

  12. Breast Cancer Biomarkers Based on Nipple and Fine Needle Aspirates

    National Research Council Canada - National Science Library

    Torosian, Michael

    2000-01-01

    .... These biomarkers include: cytology, DNA index, cell cycle parameters, proliferation index, epidermal growth factor receptor overexpression, p53 and RAS hotspot mutations and hypermethylation of specific gene products...

  13. Haemostatic function and biomarkers of endothelial damage before and after platelet transfusion in patients with acute myeloid leukaemia

    DEFF Research Database (Denmark)

    Larsen, A M; Leinøe, E B; Johansson, P I

    2015-01-01

    and after platelet transfusion in patients with acute myeloid leukaemia. MATERIALS AND METHODS: Blood was sampled before, 1 and 24 h after platelet transfusion. Primary and secondary haemostasis was evaluated by whole blood aggregometry (Multiplate) and thromboelastography (TEG). Endothelial biomarkers (s......OBJECTIVES: The beneficial effect of platelet transfusion on haemostasis is well established, but there is emerging evidence that platelet transfusion induces an inflammatory response in vascular endothelial cells. BACKGROUND: We investigated haemostatic function and endothelial biomarkers before......ICAM-1, syndecan-1, sThrombomodulin, sVE-Cadherin) and platelet activation biomarkers (sCD40L, TGF-beta) were investigated along with haematology/biochemistry analyses. RESULTS: Twenty-two patients were included. Despite continued low platelet counts, platelet transfusion normalised the median values...

  14. Inflammasome Proteins As Biomarkers of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Robert W. Keane

    2018-03-01

    Full Text Available Multiple sclerosis (MS is an autoimmune disease that affects the brain and spinal cord. The inflammasome is a multiprotein complex that contributes to the innate immune response in animal models of MS as well as in patients with the disease. Important to the care of patients with MS is the need for biomarkers that can predict disease onset, disease exacerbation, as well as response to treatment. In this study, we analyzed serum samples from 32 patients with MS and 120 age-matched controls, and provide receiver operator characteristic (ROC curves with associated confidence intervals following analyses of serum samples from patients with MS, most of which had the relapsing-remitting form of the disease, and from healthy unaffected donors, and determine the sensitivity and specificity of inflammasome proteins as biomarkers of MS. We report that caspase-1 (1.662 ± 0.6024 difference between means, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC (407.5 ± 35.79, and interleukin (IL-18 (78.53 + 17.86 were elevated in the serum of MS patients when compared to controls. Interestingly, the levels of IL-1β (−0.5961 ± 0.265 were lower in the MS cohort. Importantly, the area under the curve (AUC for ASC and caspase-1 were 0.9448 and 0.848, respectively. Taken together, these data suggest that ASC and caspase-1 could be potential candidate biomarkers for MS onset.

  15. 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.

  16. Determination of photosynthetic and enzymatic biomarkers sensitivity used to evaluate toxic effects of copper and fludioxonil in alga Scenedesmus obliquus

    International Nuclear Information System (INIS)

    Dewez, David; Geoffroy, Laure; Vernet, Guy; Popovic, Radovan

    2005-01-01

    Modulated PAM fluorometry and Plant Efficiency Analyser methods were used to investigate photosynthetic fluorescence parameters of alga Scenedesmus obliquus exposed to inhibitory effect of fungicides copper sulphate and fludioxonil (N-(4-nitrophenyl)-N'-propyl-uree). The change of those parameters were studied when alga S. obliquus have been exposed during 48 h to different concentrations of fungicides (1, 2 and 3 mg l -1 ). Under the same condition, enzymatic activities of catalase, ascorbate peroxidase, glutathione reductase and glutathione S-transferase were investigated to evaluate antioxidative response to fungicides effects. The change of sensitivity of those parameters was dependent to the mode of fungicide action, their concentration and time of exposure. For copper effects, the most indicative photosynthetic biomarkers were parameters Q N as non-photochemical fluorescence quenching, Q Emax as the proton induced fluorescence quenching and ABS/RC as the antenna size per photosystem II reaction center. Copper induced oxidative stress was indicated by increased activity of catalase serving as the most sensitive and valuable enzymatic biomarker. On the other hand, fludioxonil effect on photosynthetic parameters was very negligible and consequently not very useful as biomarkers. However, fludioxonil induced strong antioxidative activities associated with cytosol enzymes, as we found for catalase, ascorbate peroxidase and glutathione S-transferase activities. By obtained results, we may suggest for the activation of those enzymes to be sensitive and valuable biomarkers of oxidative stress induced by fludioxonil. Determination of biomarkers sensitivity may offer advantages in providing real criteria to use them for ecotoxicological diagnostic studies

  17. The Janus serum bank and biomarkers of cancer

    Directory of Open Access Journals (Sweden)

    Randi Gislefoss

    2009-10-01

    Full Text Available The Janus serum bank, established in 1973, contains sera stored at –25 degrees collected from 330,000 originally healthy individuals. The number of cancer cases have increased from zero in 1973 to more than 50,000 in 2005, including invasive and non-invasive cancers. Information on cases have been obtained by coupling the Janus file against the Norwegian Cancer Registry. The sera have been used in over 70 different cancers research projects, usually in case-control studies and in collaboration with national and international research groups. The type of biomarker analysed include antibodies against Chlamydia, CMV, Epstein Barr virus, HPV and Helicobacter pylori. Leptin, long chain fatty acids, androgens and other hormones, vitamins as well as environmental toxins such as organochlorines are other types of cancer biomarkers investigated. Mutation analyses (BRCA-1 etc have been possible using PCR and the trace amounts of DNA remaining in the sera.Janus serum bank ble etablert i 1973 og inneholder sera lagret ved –25 grader, innsamlet fra 330.000 opprinnelig friske personer. Antall krefttilfeller har steget fra null i 1973 til over 50.000 i år 2005, inkludert både invasiv og ikke-invasiv kreft. Informasjon om kasus er tilgjengelig ved å koble Janus-filene mot Kreftregisterets databaser. Serumprøvene er blitt benyttet i over 70 forskjellige kreftforskningsprosjekter, som oftest i kasus-kontroll studier og i samarbeide med en rekke nasjonale og internasjonale forskningsgrupper. Mange ulike biomarkører på kreft er blitt analysert, bl.a. antistoffer mot Chlamydia, CMV, Epstein Barr virus, HPV og Helicobacter pylori. Leptin, lange fettsyrer, androgener og andre hormoner, vitaminer såvel som miljøgifter av typen organiske klorforbindelser er eksempler på andre kreftbiomarkører som er undersøkt. Det har også vært mulig å gjøre mutasjonsanalyser (BRCA-1 etc ved å bruke PCR til å amplifisere opp den spormengden DNA som finnes i serum.

  18. Biomarkers in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Sin, Don D; Vestbo, Jørgen

    2009-01-01

    Currently, with exception of lung function tests, there are no well validated biomarkers or surrogate endpoints that can be used to establish efficacy of novel drugs for chronic obstructive pulmonary disease (COPD). However, the lung function test is not an ideal surrogate for short-term drug...... trials because it (1) does not provide information regarding disease activity or the underlying pathologic process, (2) cannot separate the various phenotypes of COPD, (3) is not specific for COPD, and (4) is relatively unresponsive to known therapies that prolong survival. Accordingly, there are large...

  19. Exhaled Breath Condensate for Proteomic Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    Sean W. Harshman

    2014-07-01

    Full Text Available Exhaled breath condensate (EBC has been established as a potential source of respiratory biomarkers. Compared to the numerous small molecules identified, the protein content of EBC has remained relatively unstudied due to the methodological and technical difficulties surrounding EBC analysis. In this review, we discuss the proteins identified in EBC, by mass spectrometry, focusing on the significance of those proteins identified. We will also review the limitations surrounding mass spectral EBC protein analysis emphasizing recommendations to enhance EBC protein identifications by mass spectrometry. Finally, we will provide insight into the future directions of the EBC proteomics field.

  20. Metabolomics: beyond biomarkers and towards mechanisms

    Science.gov (United States)

    Johnson, Caroline H.; Ivanisevic, Julijana; Siuzdak, Gary

    2017-01-01

    Metabolomics, which is the profiling of metabolites in biofluids, cells and tissues, is routinely applied as a tool for biomarker discovery. Owing to innovative developments in informatics and analytical technologies, and the integration of orthogonal biological approaches, it is now possible to expand metabolomic analyses to understand the systems-level effects of metabolites. Moreover, because of the inherent sensitivity of metabolomics, subtle alterations in biological pathways can be detected to provide insight into the mechanisms that underlie various physiological conditions and aberrant processes, including diseases. PMID:26979502

  1. Exosomes: the future of biomarkers in medicine.

    Science.gov (United States)

    Properzi, Francesca; Logozzi, Mariantonia; Fais, Stefano

    2013-10-01

    Exosomes are nanovesicles secreted into the extracellular environment upon internal vesicle fusion with the plasma membrane. The molecular content of exosomes is a fingerprint of the releasing cell type and of its status. For this reason, and because they are released in easily accessible body fluids such as blood and urine, they represent a precious biomedical tool. A growing body of evidence suggests that exosomes may be used as biomarkers for the diagnosis and prognosis of malignant tumors. This article focuses on the exploitation of exosomes as diagnostic tools for human tumors and discusses possible applications of the same strategies to other pathologies, such as neurodegenerative diseases.

  2. Cardiac biomarkers in neonatal hypoxic ischaemia.

    LENUS (Irish Health Repository)

    Sweetman, D

    2012-04-01

    Following a perinatal hypoxic-ischaemic insult, term infants commonly develop cardiovascular dysfunction. Troponin-T, troponin-I and brain natriuretic peptide are sensitive indicators of myocardial compromise. The long-term effects of cardiovascular dysfunction on neurodevelopmental outcome following perinatal hypoxic ischaemia remain controversial. Follow-up studies are warranted to ensure optimal cardiac function in adulthood. CONCLUSION: Cardiac biomarkers may improve the diagnosis of myocardial injury, help guide management, estimate mortality risk and may also aid in longterm neurodevelopmental outcome prediction following neonatal hypoxic-ischaemia.

  3. Adiponectin as a routine clinical biomarker.

    Science.gov (United States)

    Kishida, Ken; Funahashi, Tohru; Shimomura, Iichiro

    2014-01-01

    Adiponectin is a protein synthesized and secreted predominantly by adipocytes into the peripheral blood. However, circulating adiponectin level is inversely related with body weight, especially visceral fat accumulation. The mechanism of this paradoxical relation remains obscure. Low circulating adiponectin concentrations (hypoadiponectinemia; osteoporosis, and cancer (endometrial cancer, postmenopausal breast cancer, leukemia, colon cancer, gastric cancer, prostate cancer). On the other hand, hyperadiponectinemia is associated with cardiac, renal and pulmonary diseases. This review article focuses on the significance of adiponectin as a clinical biomarker of obesity-related diseases. Routine measurement of adiponectin in patients with lifestyle-related diseases is highly recommended. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Bayesian additive decision trees of biomarker by treatment interactions for predictive biomarker detection and subgroup identification.

    Science.gov (United States)

    Zhao, Yang; Zheng, Wei; Zhuo, Daisy Y; Lu, Yuefeng; Ma, Xiwen; Liu, Hengchang; Zeng, Zhen; Laird, Glen

    2017-10-11

    Personalized medicine, or tailored therapy, has been an active and important topic in recent medical research. Many methods have been proposed in the literature for predictive biomarker detection and subgroup identification. In this article, we propose a novel decision tree-based approach applicable in randomized clinical trials. We model the prognostic effects of the biomarkers using additive regression trees and the biomarker-by-treatment effect using a single regression tree. Bayesian approach is utilized to periodically revise the split variables and the split rules of the decision trees, which provides a better overall fitting. Gibbs sampler is implemented in the MCMC procedure, which updates the prognostic trees and the interaction tree separately. We use the posterior distribution of the interaction tree to construct the predictive scores of the biomarkers and to identify the subgroup where the treatment is superior to the control. Numerical simulations show that our proposed method performs well under various settings comparing to existing methods. We also demonstrate an application of our method in a real clinical trial.

  5. The Biomarker Knowledge System Informatics Pilot Project Supplement To The Biomarker Development Laboratory at Moffitt (Bedlam) — EDRN Public Portal

    Science.gov (United States)

    The Biomarker Knowledge System Informatics Pilot Project goal will develop network interfaces among databases that contain information about existing clinical populations and biospecimens and data relating to those specimens that are important in biomarker assay validation. This protocol comprises one of two that will comprise the Moffitt participation in the Biomarker Knowledge System Informatics Pilot Project. THIS PROTOCOL (58) is the Sput-Epi Database.

  6. Biomarkers of Necrotising Soft Tissue Infections Aspects of the Innate Immune Response

    DEFF Research Database (Denmark)

    Hansen, Marco Bo

    2017-01-01

    -existent in this group of patients. Instead data regarding biomarkers are extrapolated from the wide and heterogenic group of patients with sepsis, even though the immunological responses are likely to differ because of the large amount of necrotic tissue seen in patients with NSTI. We performed the largest prospective......Necrotising soft tissue infection (NSTI) is a life-threatening and rapidly progressing bacterial infection involving one or more layers of the soft tissue compartments causing necrosis. The amputation and mortality rates remain high despite increased focus on the patients. Timely treatment...... of the innate immune response, which included the investigation of acute-phase proteins, pattern recognition molecules of the lectin complement pathway, and inflammatory cytokines. The objective was to investigate aspects of the innate immune response in patients with NSTI, focusing on biomarkers as prognostic...

  7. Urinary Biomarkers in Relapsing Antineutrophil Cytoplasmic Antibody-associated Vasculitis

    Science.gov (United States)

    Lieberthal, Jason G.; Cuthbertson, David; Carette, Simon; Hoffman, Gary S.; Khalidi, Nader A.; Koening, Curry L.; Langford, Carol A.; Maksimowicz-McKinnon, Kathleen; Seo, Philip; Specks, Ulrich; Ytterberg, Steven R.; Merkel, Peter A.; Monach, Paul A.

    2015-01-01

    Objective Glomerulonephritis (GN) is common in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but tools for early detection of renal involvement are imperfect. We investigated 4 urinary proteins as markers of active renal AAV: alpha-1 acid glycoprotein (AGP), kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein-1 (MCP-1), and neutrophil gelatinase-associated lipocalin (NGAL). Methods Patients with active renal AAV (n = 20), active nonrenal AAV (n = 16), and AAV in longterm remission (n = 14) were identified within a longitudinal cohort. Urinary biomarker concentrations (by ELISA) were normalized for urine creatinine. Marker levels during active AAV were compared to baseline remission levels (from 1–4 visits) for each patient. Areas under receiver-operating characteristic curves (AUC), sensitivities, specificities, and likelihood ratios (LR) comparing disease states were calculated. Results Baseline biomarker levels varied among patients. All 4 markers increased during renal flares (p < 0.05). MCP-1 discriminated best between active renal disease and remission: a 1.3-fold increase in MCP-1 had 94% sensitivity and 89% specificity for active renal disease (AUC = 0.93, positive LR 8.5, negative LR 0.07). Increased MCP-1 also characterized 50% of apparently nonrenal flares. Change in AGP, KIM-1, or NGAL showed more modest ability to distinguish active renal disease from remission (AUC 0.71–0.75). Hematuria was noted in 83% of active renal episodes, but also 43% of nonrenal flares and 25% of remission samples. Conclusion Either urinary MCP-1 is not specific for GN in AAV, or it identifies early GN not detected by standard assessment and thus has potential to improve care. A followup study with kidney biopsy as the gold standard is needed. PMID:23547217

  8. Nitric oxide as a potential biomarker in inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Nesina Avdagić

    2013-02-01

    Full Text Available The aim of this study was to investigate changes in serum nitric oxide (NO concentration in inflammatory bowel diseases (IBD patients and its use as potential biomarker in differential diagnosis of ulcerative colitis (UC and Crohn's disease (CD and in disease activity assessment. In 60 patients of both genders - 30 with ulcerative colitis and 30 with Crohn's disease - and 30 controls serum nitric oxide concentration was determined by measuring nitrite concentration, a stable metabolic product of NO with oxygen. Conversion of nitrates (NO3- to nitrites (NO2- was done with elementary zinc. The nitrite concentration was determined by classic colorimetrical Griess reaction. Median serum NO concentration was statistically different (p=0,0005 between UC patients (15.25 µmol/L; 13.47 - 19.88 µmol/L, CD patients (14.54 µmol/L; 13.03 -16.32 µmol/L and healthy controls (13.29 µmol/L; 12.40 - 13.92 µmol/L. When active UC and CD patients were compared with inactive UC and CD patients respectively a significant difference in serum NO level was found (p=0.0005. With a cut-off level of 17.39 µmol/L NO had a sensitivity of 100% and a specificity of 100% in discriminating between active and inactive UC patients. With cut-off value of 14.01 µmol/L serum NO level had a sensitivity of 88% and a specificity of 69% in distinguishing between patients with active CD and inactive CD. Serum NO concentration is a minimally invasive and rapid tool for discriminating between active and inactive IBD patients and could be used as useful biomarker in monitoring of disease activity in IBD patients.

  9. Identification of prostate cancer biomarkers in urinary exosomes.

    Science.gov (United States)

    Øverbye, Anders; Skotland, Tore; Koehler, Christian J; Thiede, Bernd; Seierstad, Therese; Berge, Viktor; Sandvig, Kirsten; Llorente, Alicia

    2015-10-06

    Exosomes have recently appeared as a novel source of non-invasive cancer biomarkers since tumour-specific molecules can be found in exosomes isolated from biological fluids. We have here investigated the proteome of urinary exosomes by using mass spectrometry to identify proteins differentially expressed in prostate cancer patients compared to healthy male controls. In total, 15 control and 16 prostate cancer samples of urinary exosomes were analyzed. Importantly, 246 proteins were differentially expressed in the two groups. The majority of these proteins (221) were up-regulated in exosomes from prostate cancer patients. These proteins were analyzed according to specific criteria to create a focus list that contained 37 proteins. At 100% specificity, 17 of these proteins displayed individual sensitivities above 60%. Even though several of these proteins showed high sensitivity and specificity for prostate cancer as individual biomarkers, combining them in a multi-panel test has the potential for full differentiation of prostate cancer from non-disease controls. The highest sensitivity, 94%, was observed for transmembrane protein 256 (TM256; chromosome 17 open reading frame 61). LAMTOR proteins were also distinctly enriched with very high specificity for patient samples. TM256 and LAMTOR1 could be used to augment the sensitivity to 100%. Other prominent proteins were V-type proton ATPase 16 kDa proteolipid subunit (VATL), adipogenesis regulatory factor (ADIRF), and several Rab-class members and proteasomal proteins. In conclusion, this study clearly shows the potential of using urinary exosomes in the diagnosis and clinical management of prostate cancer.

  10. Use of biomarkers in triage of patients with suspected stroke.

    Science.gov (United States)

    Vanni, Simone; Polidori, Gianluca; Pepe, Giuseppe; Chiarlone, Melisenda; Albani, Alberto; Pagnanelli, Adolfo; Grifoni, Stefano

    2011-05-01

    The absence of a rapidly available and sensitive diagnostic test represents an important limitation in the triage of patients with suspected stroke. The aim of the present study was to investigate the triage accuracy of a novel test that measures blood-borne biomarkers (triage stroke panel, TSP) and to compare its accuracy with that of the Cincinnati Prehospital Stroke Scale (CPSS). Consecutive patients with suspected stroke presenting to the Emergency Departments of three Italian hospitals underwent triage by a trained nurse according to the CPSS and had blood drawn for TSP testing. The TSP simultaneously measures four markers (B-type natriuretic peptide, D-dimer, matrix metalloproteinase-9, and S100β) presenting a single composite result, the Multimarker Index (MMX). Stroke diagnosis was established by an expert committee blinded to MMX and CPSS results. There were 155 patients enrolled, 87 (56%) of whom had a final diagnosis of stroke. The area under the receiver operating characteristic (ROC) curve for CPSS was 0.77 (95% confidence interval [CI] 0.70-0.84) and that of MMX was 0.74 (95% CI 0.66-0.82) (p = 0.285). Thus, both tests, when used alone, failed to recognize approximately 25% of strokes. The area under the ROC curve of the combination of the two tests (0.86, 95% CI 0.79-0.91) was significantly greater than that of either single test (p = 0.01 vs. CPSS and p vs. TSP). In an emergency care setting, a panel test using multiple biochemical markers showed triage accuracy similar to that of CPSS. Further studies are needed before biomarkers can be introduced in the clinical work-up of patients with suspected stroke. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. 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.

  12. Biomarkers in volunteers exposed to mobile phone radiation.

    Science.gov (United States)

    Söderqvist, Fredrik; Carlberg, Michael; Hardell, Lennart

    2015-06-01

    For some time it has been investigated whether low-intensity non-thermal microwave radiation from mobile phones adversely affects the mammalian blood-brain barrier (BBB). All such studies except one have been either in vitro or experimental animal studies. The one carried out on humans showed a statistically significant increase in serum transthyretin (TTR) 60 min after finishing of a 30-min microwave exposure session. The aim of the present study was to follow up on the finding of the previous one using a better study design. Using biomarkers analyzed in blood serum before and after the exposure this single blinded randomized counterbalanced study, including 24 healthy subjects aged 18-30 years that all underwent three exposure conditions (SAR(10G)=2 W/kg, SAR(10G)=0.2 W/kg, sham), tested whether microwaves from an 890-MHz phone-like signal give acute effects on the integrity of brain-shielding barriers. Over time, statistically significant variations were found for two of the three biomarkers (TTR; β-trace protein); however, no such difference was found between the different exposure conditions nor was there any interaction between exposure condition and time of blood sampling. In conclusion this study failed to show any acute clinically or statistically significant effect of short term microwave exposure on the serum levels of S100β, TTR and β-trace protein with a follow up limited to two hours. The study was hampered by the fact that all study persons were regular wireless phone users and thus not naïve as to microwave exposure. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Prediction of Chronic Kidney Disease Stage 3 by CKD273, a Urinary Proteomic Biomarker

    DEFF Research Database (Denmark)

    Pontillo, Claudia; Zhang, Zhen-Yu; Schanstra, Joost P

    2017-01-01

    Introduction: CKD273 is a urinary biomarker, which in advanced chronic kidney disease predicts further deterioration. We investigated whether CKD273 can also predict a decline of estimated glomerular filtration rate (eGFR) to ... threshold (P = 0.086). Discussion: In conclusion, while accounting for baseline eGFR, albuminuria, and covariables, CKD273 adds to the prediction of stage 3 chronic kidney disease, at which point intervention remains an achievable therapeutic target....

  14. Development of in Vivo Biomarkers for Progressive Tau Pathology after Traumatic Brain Injury

    Science.gov (United States)

    2016-02-01

    excised after severe brain injury . Experimental neurology 2004;190:192-203. 24. Frost B, Diamond MI. Prion-like mechanisms in neurodegenerative...Brain Injury PRINCIPAL INVESTIGATORs: Marc Diamond, MD CONTRACTING ORGANIZATION: Washington University, St Louis MO 63110 UT Southwestern, Dallas...of in Vivo Biomarkers for Progressive Tau Pathology after Traumatic Brain Injury 5b. GRANT NUMBER W81XWH-13-2-0016 5c. PROGRAM ELEMENT NUMBER 6

  15. 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

  16. Prevalence of prenatal exposure to substances of abuse: questionnaire versus biomarkers

    OpenAIRE

    Chiandetti, Antonella; Hernandez, Gimena; Mercadal-Hally, María; Alvarez, Airam; Andreu-Fernandez, Vicente; Navarro-Tapia, Elisabet; Bastons-Compta, Adriana; Garcia-Algar, Oscar

    2017-01-01

    Alcohol and drugs of abuse consumption in young adults, including women of childbearing age, has experienced significant increase over the past two decades. The use of questionnaires as the only measure to investigate prenatal alcohol and drugs of abuse exposure underestimates the real prevalence of exposure and could mislead to wrong conclusions. Therefore, the aim of this article was to compare reported rates of prenatal alcohol and drugs of abuse consumption with biomarkers of exposure by ...

  17. Alcohol Consumption, Mediating Biomarkers, and Risk of Type 2 Diabetes Among Middle-Aged Women

    OpenAIRE

    Beulens, Joline W.J.; Hendriks, Henk F.J.; Rimm, Eric B.; Hu, Frank B.; Mukamal, Ken J.

    2008-01-01

    OBJECTIVE?The purpose of this study was to investigate whether adiponectin concentrations and biomarkers of inflammation, endothelial dysfunction, and insulin resistance mediate the association between alcohol consumption and diabetes. RESEARCH DESIGN AND METHODS?In a nested case-control study of 705 women with incident diabetes and 787 matched control subjects, we examined the adjusted relationship between baseline alcohol consumption and risk of diabetes before and after adjustment for mark...

  18. A simulation study on estimating biomarker-treatment interaction effects in randomized trials with prognostic variables.

    Science.gov (United States)

    Haller, Bernhard; Ulm, Kurt

    2018-02-20

    To individualize treatment decisions based on patient characteristics, identification of an interaction between a biomarker and treatment is necessary. Often such potential interactions are analysed using data from randomized clinical trials intended for comparison of two treatments. Tests of interactions are often lacking statistical power and we investigated if and how a consideration of further prognostic variables can improve power and decrease the bias of estimated biomarker-treatment interactions in randomized clinical trials with time-to-event outcomes. A simulation study was performed to assess how prognostic factors affect the estimate of the biomarker-treatment interaction for a time-to-event outcome, when different approaches, like ignoring other prognostic factors, including all available covariates or using variable selection strategies, are applied. Different scenarios regarding the proportion of censored observations, the correlation structure between the covariate of interest and further potential prognostic variables, and the strength of the interaction were considered. The simulation study revealed that in a regression model for estimating a biomarker-treatment interaction, the probability of detecting a biomarker-treatment interaction can be increased by including prognostic variables that are associated with the outcome, and that the interaction estimate is biased when relevant prognostic variables are not considered. However, the probability of a false-positive finding increases if too many potential predictors are included or if variable selection is performed inadequately. We recommend undertaking an adequate literature search before data analysis to derive information about potential prognostic variables and to gain power for detecting true interaction effects and pre-specifying analyses to avoid selective reporting and increased false-positive rates.

  19. Search for specific biomarkers of IFNβ bioactivity in patients with multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Sunny Malhotra

    Full Text Available Myxovirus A (MxA, a protein encoded by the MX1 gene with antiviral activity, has proven to be a sensitive measure of IFNβ bioactivity in multiple sclerosis (MS. However, the use of MxA as a biomarker of IFNβ bioactivity has been criticized for the lack of evidence of its role on disease pathogenesis and the clinical response to IFNβ. Here, we aimed to identify specific biomarkers of IFNβ bioactivity in order to compare their gene expression induction by type I IFNs with the MxA, and to investigate their potential role in MS pathogenesis. Gene expression microarrays were performed in PBMC from MS patients who developed neutralizing antibodies (NAB to IFNβ at 12 and/or 24 months of treatment and patients who remained NAB negative. Nine genes followed patterns in gene expression over time similar to the MX1, which was considered the gold standard gene, and were selected for further experiments: IFI6, IFI27, IFI44L, IFIT1, HERC5, LY6E, RSAD2, SIGLEC1, and USP18. In vitro experiments in PBMC from healthy controls revealed specific induction of selected biomarkers by IFNβ but not IFNγ, and several markers, in particular USP18 and HERC5, were shown to be significantly induced at lower IFNβ concentrations and more selective than the MX1 as biomarkers of IFNβ bioactivity. In addition, USP18 expression was deficient in MS patients compared with healthy controls (p = 0.0004. We propose specific biomarkers that may be considered in addition to the MxA to evaluate IFNβ bioactivity, and to further explore their implication in MS pathogenesis.

  20. Plasma amyloid levels within the Alzheimer's process and correlations with central biomarkers.

    Science.gov (United States)

    Hanon, Olivier; Vidal, Jean-Sébastien; Lehmann, Sylvain; Bombois, Stéphanie; Allinquant, Bernadette; Tréluyer, Jean-Marc; Gelé, Patrick; Delmaire, Christine; Blanc, Fredéric; Mangin, Jean-François; Buée, Luc; Touchon, Jacques; Hugon, Jacques; Vellas, Bruno; Galbrun, Evelyne; Benetos, Athanase; Berrut, Gilles; Paillaud, Elèna; Wallon, David; Castelnovo, Giovanni; Volpe-Gillot, Lisette; Paccalin, Marc; Robert, Philippe-Henri; Godefroy, Olivier; Dantoine, Thierry; Camus, Vincent; Belmin, Joël; Vandel, Pierre; Novella, Jean-Luc; Duron, Emmanuelle; Rigaud, Anne-Sophie; Schraen-Maschke, Suzanna; Gabelle, Audrey

    2018-02-17

    Diagnostic relevance of plasma amyloid β (Aβ) for Alzheimer's disease (AD) process yields conflicting results. The objective of the study was to assess plasma levels of Aβ 42 and Aβ 40 in amnestic mild cognitive impairment (MCI), nonamnestic MCI, and AD patients and to investigate relationships between peripheral and central biomarkers. One thousand forty participants (417 amnestic MCI, 122 nonamnestic MCI, and 501 AD) from the Biomarker of AmyLoïd pepTide and AlZheimer's diseAse Risk multicenter prospective study with cognition, plasma, cerebrospinal fluid (CSF), and magnetic resonance imaging assessments were included. Plasma Aβ 1-42 and Aβ 1-40 were lower in AD (36.9 [11.7] and 263 [80] pg/mL) than in amnestic MCI (38.2 [11.9] and 269 [68] pg/mL) than in nonamnestic MCI (39.7 [10.5] and 272 [52] pg/mL), respectively (P = .01 for overall difference between groups for Aβ 1-42 and P = .04 for Aβ 1-40 ). Globally, plasma Aβ 1-42 correlated with age, Mini-Mental State Examination, and APOE ε4 allele. Plasma Aβ 1-42 correlated with all CSF biomarkers in MCI but only with CSF Aβ 42 in AD. Plasma Aβ was associated with cognitive status and CSF biomarkers, suggesting the interest of plasma amyloid biomarkers for diagnosis purpose. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Using surrogate biomarkers to improve measurement error models in nutritional epidemiology

    Science.gov (United States)

    Keogh, Ruth H; White, Ian R; Rodwell, Sheila A

    2013-01-01

    Nutritional epidemiology relies largely on self-reported measures of dietary intake, errors in which give biased estimated diet–disease associations. Self-reported measurements come from questionnaires and food records. Unbiased biomarkers are scarce; however, surrogate biomarkers, which are correlated with intake but not unbiased, can also be useful. It is important to quantify and correct for the effects of measurement error on diet–disease associations. Challenges arise because there is no gold standard, and errors in self-reported measurements are correlated with true intake and each other. We describe an extended model for error in questionnaire, food record, and surrogate biomarker measurements. The focus is on estimating the degree of bias in estimated diet–disease associations due to measurement error. In particular, we propose using sensitivity analyses to assess the impact of changes in values of model parameters which are usually assumed fixed. The methods are motivated by and applied to measures of fruit and vegetable intake from questionnaires, 7-day diet diaries, and surrogate biomarker (plasma vitamin C) from over 25000 participants in the Norfolk cohort of the European Prospective Investigation into Cancer and Nutrition. Our results show that the estimated effects of error in self-reported measurements are highly sensitive to model assumptions, resulting in anything from a large attenuation to a small amplification in the diet–disease association. Commonly made assumptions could result in a large overcorrection for the effects of measurement error. Increased understanding of relationships between potential surrogate biomarkers and true dietary intake is essential for obtaining good estimates of the effects of measurement error in self-reported measurements on observed diet–disease associations. Copyright © 2013 John Wiley & Sons, Ltd. PMID:23553407

  2. The use of plant-specific pyrolysis products as biomarkers in peat deposits

    Science.gov (United States)

    Schellekens, Judith; Bradley, Jonathan A.; Kuyper, Thomas W.; Fraga, Isabel; Pontevedra-Pombal, Xabier; Vidal-Torrado, Pablo; Abbott, Geoffrey D.; Buurman, Peter

    2015-09-01

    Peatlands are archives of environmental change that can be driven by climate and human activity. Proxies for peatland vegetation composition provide records of (local) environmental conditions that can be linked to both autogenic and allogenic factors. Analytical pyrolysis offers a molecular fingerprint of peat, and thereby a suite of environmental proxies. Here we investigate analytical pyrolysis as a method for biomarker analysis. Pyrolysates of 48 peatland plant species were compared, comprising seventeen lichens, three Sphagnum species, four non-Sphagnum mosses, eleven graminoids (Cyperaceae, Juncaceae, Poaceae), five Ericaceae and six species from other families. This resulted in twenty-one potential biomarkers, including new markers for lichens (3-methoxy-5-methylphenol) and graminoids (ferulic acid methyl ester). The potential of the identified biomarkers to reconstruct vegetation composition is discussed according to their depth records in cores from six peatlands from boreal, temperate and tropical biomes. The occurrence of markers for Sphagnum, graminoids and lichens in all six studied peat deposits indicates that they persist in peat of thousands of years old, in different vegetation types and under different conditions. In order to facilitate the quantification of biomarkers from pyrolysates, typically expressed as proportion (%) of the total quantified pyrolysis products, an internal standard (5-α-androstane) was introduced. Depth records of the Sphagnum marker 4-isopropenylphenol from the upper 3 m of a Sphagnum-dominated peat, from samples analysed with and without internal standard showed a strong positive correlation (r2 = 0.72, P use of analytical pyrolysis in biomarker research by avoiding quantification of a high number of products.

  3. Prostate Cancer Imaging and Biomarkers Guiding Safe Selection of Active Surveillance

    Directory of Open Access Journals (Sweden)

    Zachary A. Glaser

    2017-10-01

    Full Text Available BackgroundActive surveillance (AS is a widely adopted strategy to monitor men with low-risk, localized prostate cancer (PCa. Current AS inclusion criteria may misclassify as many as one in four patients. The advent of multiparametric magnetic resonance imaging (mpMRI and novel PCa biomarkers may offer improved risk stratification. We performed a review of recently published literature to characterize emerging evidence in support of these novel modalities.MethodsAn English literature search was conducted on PubMed for available original investigations on localized PCa, AS, imaging, and biomarkers published within the past 3 years. Our Boolean criteria included the following terms: PCa, AS, imaging, biomarker, genetic, genomic, prospective, retrospective, and comparative. The bibliographies and diagnostic modalities of the identified studies were used to expand our search.ResultsOur review identified 222 original studies. Our expanded search yielded 244 studies. Among these, 70 met our inclusion criteria. Evidence suggests mpMRI offers improved detection of clinically significant PCa, and MRI-fusion technology enhances the sensitivity of surveillance biopsies. Multiple studies demonstrate the promise of commercially available screening assays for prediction of AS failure, and several novel biomarkers show promise in this setting.ConclusionIn the era of AS for men with low-risk PCa, improved strategies for proper stratification are needed. mpMRI has dramatically enhanced the detection of clinically significant PCa. The advent of novel biomarkers for prediction of aggressive disease and AS failure has shown some initial promise, but further validation is warranted.

  4. [Diagnosis of acute heart failure and relevance of biomarkers in elderly patients].

    Science.gov (United States)

    Ruiz Ortega, Raúl Antonio; Manzano, Luis; Montero-Pérez-Barquero, Manuel

    2014-03-01

    Diagnosis of acute heart failure (HF) is difficult in elderly patients with multiple comorbidities. Risk scales and classification criteria based exclusively on clinical manifestations, such as the Framingham scales, lack sufficient specificity. In addition to clinical manifestations, diagnosis should be based on two key factors: natriuretic peptides and echocardiographic study. When there is clinical suspicion of acute HF, a normal natriuretic peptide level will rule out this process. When a consistent clinical suspicion is present, an echocardiographic study should also be performed. Diagnosis of HF with preserved ejection fraction (HF/pEF) requires detection of an enlarged left atrium or the presence of parameters of diastolic dysfunction. Elevation of cardiac biomarkers seems to be due to myocardial injury and the compensatory mechanisms of the body against this injury (hormone and inflammatory response and repair mechanisms). Elevation of markers of cardiac damage (troponins and natriuretic peptides) have been shown to be useful both in the diagnosis of acute HF and in prediction of outcome. MMP-2 could be useful in the diagnosis of HF/pEF. In addition to biomarkers with diagnostic value, other biomarkers are helpful in prognosis in the acute phase of HF, such as biomarkers of renal failure (eGFR, cystatin and urea), inflammation (cytokines and CRP), and the cell regeneration marker, galectin-3. A promising idea that is under investigation is the use of panels of biomarkers, which could allow more accurate diagnosis and prognosis of acute HF. Copyright © 2014 Elsevier España, S.L. All rights reserved.

  5. 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

  6. Reproducible cancer biomarker discovery in SELDI-TOF MS using different pre-processing algorithms.

    Directory of Open Access Journals (Sweden)

    Jinfeng Zou

    Full Text Available BACKGROUND: There has been much interest in differentiating diseased and normal samples using biomarkers derived from mass spectrometry (MS studies. However, biomarker identification for specific diseases has been hindered by irreproducibility. Specifically, a peak profile extracted from a dataset for biomarker identification depends on a data pre-processing algorithm. Until now, no widely accepted agreement has been reached. RESULTS: In this paper, we investigated the consistency of biomarker identification using differentially expressed (DE peaks from peak profiles produced by three widely used average spectrum-dependent pre-processing algorithms based on SELDI-TOF MS data for prostate and breast cancers. Our results revealed two important factors that affect the consistency of DE peak identification using different algorithms. One factor is that some DE peaks selected from one peak profile were not detected as peaks in other profiles, and the second factor is that the statistical power of identifying DE peaks in large peak profiles with many peaks may be low due to the large scale of the tests and small number of samples. Furthermore, we demonstrated that the DE peak detection power in large profiles could be improved by the stratified false discovery rate (FDR control approach and that the reproducibility of DE peak detection could thereby be increased. CONCLUSIONS: Comparing and evaluating pre-processing algorithms in terms of reproducibility can elucidate the relationship among different algorithms and also help in selecting a pre-processing algorithm. The DE peaks selected from small peak profiles with few peaks for a dataset tend to be reproducibly detected in large peak profiles, which suggests that a suitable pre-processing algorithm should be able to produce peaks sufficient for identifying useful and reproducible biomarkers.

  7. Kadar Asam Urat Serum sebagai Biomarker Preeklamsi

    Directory of Open Access Journals (Sweden)

    Neli Sumanti

    2013-06-01

    Full Text Available Preeclampsia remains a health problem that becomes one of the causes of maternal deaths besides bleeding and infection. The etiology and pathogenesis of preeclampsia are unclear. Increased serum uric acid levels is seen simultaneously with the increase of blood pressure and occurred before the onset of proteinuria. Therefore, the uric acid can be used as a biomarker. The aim of this study was to analyze the serum uric acid levels between normal and preeclampsia pregnancies. The study was conducted in Dr.Hasan Sadikin Hospital Bandung between March and May 2011, using cross sectional study design. Subjects were 45 inpartu normal pregnant women as control and 44 in partu pregnant women with preeclampsia accordance with inclusion and exclusion criteria. Levels of uric acid in normal pregnancy are 3,43 ±0.14 mg/dL. In this study uric acid levels resulting in cut-off levels of 4,8 mg/dL with a sensitivity value of 93%, and specificity 80%. Conclusions: uric acid levels in at term preeclampsia are higher compared with normal pregnancies. Increased levels of uric acid can be considered as one of biomarkers of preeclampsia, hence the serum uric acid levels used as serial examinations in pregnant women during antenatal care.

  8. Biomarkers and Mechanisms of FANCD2 Function

    Directory of Open Access Journals (Sweden)

    Henning Willers

    2008-01-01

    Full Text Available Genetic or epigenetic inactivation of the pathway formed by the Fanconi anemia (FA and BRCA1 proteins occurs in several cancer types, making the affected tumors potentially hypersensitive to DNA cross-linkers and other chemotherapeutic agents. It has been proposed that the inability of FA/BRCA-defective cells to form subnuclear foci of effector proteins, such as FANCD2, can be used as a biomarker to aid individualization of chemotherapy. We show that FANCD2 inactivation not only renders cells sensitive to cross-links, but also oxidative stress, a common effect of cancer therapeutics. Oxidative stress sensitivity does not correlate with FANCD2 or RAD51 foci formation, but associates with increased γH2AX foci levels and apoptosis. Therefore, FANCD2 may protect cells against cross-links and oxidative stress through distinct mechanisms, consistent with the growing notion that the pathway is not linear. Our data emphasize the need for multiple biomarkers, such as γH2AX, FANCD2, and RAD51, to capture all pathway activities.

  9. Discovering Alzheimer Genetic Biomarkers Using Bayesian Networks

    Directory of Open Access Journals (Sweden)

    Fayroz F. Sherif

    2015-01-01

    Full Text Available Single nucleotide polymorphisms (SNPs contribute most of the genetic variation to the human genome. SNPs associate with many complex and common diseases like Alzheimer’s disease (AD. Discovering SNP biomarkers at different loci can improve early diagnosis and treatment of these diseases. Bayesian network provides a comprehensible and modular framework for representing interactions between genes or single SNPs. Here, different Bayesian network structure learning algorithms have been applied in whole genome sequencing (WGS data for detecting the causal AD SNPs and gene-SNP interactions. We focused on polymorphisms in the top ten genes associated with AD and identified by genome-wide association (GWA studies. New SNP biomarkers were observed to be significantly associated with Alzheimer’s disease. These SNPs are rs7530069, rs113464261, rs114506298, rs73504429, rs7929589, rs76306710, and rs668134. The obtained results demonstrated the effectiveness of using BN for identifying AD causal SNPs with acceptable accuracy. The results guarantee that the SNP set detected by Markov blanket based methods has a strong association with AD disease and achieves better performance than both naïve Bayes and tree augmented naïve Bayes. Minimal augmented Markov blanket reaches accuracy of 66.13% and sensitivity of 88.87% versus 61.58% and 59.43% in naïve Bayes, respectively.

  10. Protein Biomarkers of Periodontitis in Saliva

    Science.gov (United States)

    Taylor, John J.

    2014-01-01

    Periodontitis is a chronic inflammatory condition of the tissues that surround and support the teeth and is initiated by inappropriate and excessive immune responses to bacteria in subgingival dental plaque leading to loss of the integrity of the periodontium, compromised tooth function, and eventually tooth loss. Periodontitis is an economically important disease as it is time-consuming and expensive to treat. Periodontitis has a worldwide prevalence of 5–15% and the prevalence of severe disease in western populations has increased in recent decades. Furthermore, periodontitis is more common in smokers, in obesity, in people with diabetes, and in heart disease patients although the pathogenic processes underpinning these links are, as yet, poorly understood. Diagnosis and monitoring of periodontitis rely on traditional clinical examinations which are inadequate to predict patient susceptibility, disease activity, and response to treatment. Studies of the immunopathogenesis of periodontitis and analysis of mediators in saliva have allowed the identification of many potentially useful biomarkers. Convenient measurement of these biomarkers using chairside analytical devices could form the basis for diagnostic tests which will aid the clinician and the patient in periodontitis management; this review will summarise this field and will identify the experimental, technical, and clinical issues that remain to be addressed before such tests can be implemented. PMID:24944840

  11. Sleep electroencephalography as a biomarker in depression

    Directory of Open Access Journals (Sweden)

    Steiger A

    2015-04-01

    Full Text Available Axel Steiger, Marcel Pawlowski, Mayumi Kimura Max Planck Institute of Psychiatry, Munich, Germany Abstract: The sleep electroencephalogram (EEG provides biomarkers of depression, which may help with diagnosis, prediction of therapy response, and prognosis in the treatment of depression. In patients with depression, characteristic sleep EEG changes include impaired sleep continuity, disinhibition of rapid-eye-movement (REM sleep, and impaired non-REM sleep. Most antidepressants suppress REM sleep in depressed patients, healthy volunteers, and in animal models. REM suppression appears to be an important, but not an absolute requirement, for antidepressive effects of a substance. Enhanced REM density, a measure for frequency of REM, characterizes high-risk probands for affective disorders. REM-sleep changes were also found in animal models of depression. Sleep-EEG variables were shown to predict the response to treatment with antidepressants. Furthermore, certain clusters of sleep EEG variables predicted the course of the disorder for several years. Some of the predicted sleep EEG markers appear to be related to hypothalamic–pituitary–adrenal system activity. Keywords: biomarkers, depression, sleep EEG, antidepressants, prediction, animal models

  12. Barium Titanate Nanoparticles for Biomarker Applications

    International Nuclear Information System (INIS)

    Matar, O; Hondow, N S; Brydson, R M D; Milne, S J; Brown, A P; Posada, O M; Wälti, C; Saunders, M; Murray, C A

    2015-01-01

    A tetragonal crystal structure is required for barium titanate nanoparticles to exhibit the nonlinear optical effect of second harmonic light generation (SHG) for use as a biomarker when illuminated by a near-infrared source. Here we use synchrotron XRD to elucidate the tetragonal phase of commercially purchased tetragonal, cubic and hydrothermally prepared barium titanate (BaTiO 3 ) nanoparticles by peak fitting with reference patterns. The local phase of individual nanoparticles is determined by STEM electron energy loss spectroscopy (EELS), measuring the core-loss O K-edge and the Ti L 3 -edge energy separation of the t 2g , e g peaks. The results show a change in energy separation between the t 2g and e g peak from the surface and core of the particles, suggesting an intraparticle phase mixture of the barium titanate nanoparticles. HAADF-STEM and bright field TEM-EDX show cellular uptake of the hydrothermally prepared BaTiO 3 nanoparticles, highlighting the potential for application as biomarkers. (paper)

  13. Diagnosis of Periodontal Diseases by Biomarkers

    Science.gov (United States)

    Kido, Jun-Ichi; Hino, Mami; Bando, Mika; Hiroshima, Yuka

    Many middle aged and old persons take periodontal diseases that mainly cause teeth loss and result in some systemic diseases. The prevention of periodontal diseases is very important for oral and systemic health, but the present diagnostic examination is not fully objective and suitable. To diagnose periodontal diseases exactly, some biomarkers shown inflammation, tissue degradation and bone resorption, in gingival crevicular fluid (GCF) and saliva are known. We demonstrated that GCF levels of calprotectin, inflammation-related protein, and carboxy-terminal propeptide of type I procollagen, bone metabolism-related protein, were associated with clinical condition of periodontal diseases, and suggested that these proteins may be useful biomarkers for periodontal diseases. Recently, determinations of genes and proteins by using microdevices are studied for diagnosis of some diseases. We detected calprotectin protein by chemiluminescent immunoassay on a microchip and showed the possibility of specific and quantitative detection of calprotectin in a very small amount of GCF. To determine plural markers in GCF by using microdevices contributes to develop accurate, objective diagnostic system of periodontal diseases.

  14. Retinal Layer Abnormalities as Biomarkers of Schizophrenia.

    Science.gov (United States)

    Samani, Niraj N; Proudlock, Frank A; Siram, Vasantha; Suraweera, Chathurie; Hutchinson, Claire; Nelson, Christopher P; Al-Uzri, Mohammed; Gottlob, Irene

    2018-06-06

    Schizophrenia is associated with several brain deficits, as well as visual processing deficits, but clinically useful biomarkers are elusive. We hypothesized that retinal layer changes, noninvasively visualized using spectral-domain optical coherence tomography (SD-OCT), may represent a possible "window" to these abnormalities. A Leica EnvisuTM SD-OCT device was used to obtain high-resolution central foveal B-scans in both eyes of 35 patients with schizophrenia and 50 demographically matched controls. Manual retinal layer segmentation was performed to acquire individual and combined layer thickness measurements in 3 macular regions. Contrast sensitivity was measured at 3 spatial frequencies in a subgroup of each cohort. Differences were compared using adjusted linear models and significantly different layer measures in patients underwent Spearman Rank correlations with contrast sensitivity, quantified symptoms severity, disease duration, and antipsychotic medication dose. Total retinal and photoreceptor complex thickness was reduced in all regions in patients (P layer (P layer (P layer thickness (R = -.47, P = .005). Our novel findings demonstrate considerable retinal layer abnormalities in schizophrenia that are related to clinical features and visual function. With time, SD-OCT could provide easily-measurable biomarkers to facilitate clinical assessment and further our understanding of the disease.

  15. Nutrition and biomarkers in psychiatry : research on micronutrient deficiencies in schizophrenia, the role of the intestine in the hyperserotonemia of autism, and a method for non-hypothesis driven discovery of biomarkers in urine

    NARCIS (Netherlands)

    Kemperman, Ramses Franciscus Jacobus

    2007-01-01

    This thesis describes the study of markers of nutrition and intestinal motility in mental disorders with a focus on schizophrenia and autism, and the development, evaluation and application of a biomarker discovery method for urine. The aim of the thesis is to investigate the role of long-chain

  16. CSF biomarker variability in the Alzheimer's Association quality control program

    NARCIS (Netherlands)

    Mattsson, N.; Andreasson, U.; Persson, S.; Carrillo, M.C.; Collins, S.; Chalbot, S.; Cutler, N.; Dufour-Rainfray, D.; Fagan, A.M.; Heegaard, N.H.H.; Robin Hsiung, G.Y.; Hyman, B.; Iqbal, K.; Lachno, D.R.; Lleo, A.; Lewczuk, P.; Molinuevo, J.L.; Parchi, P.; Regeniter, A.; Rissman, R.; Rosenmann, H.; Sancesario, G.; Schroder, J.; Shaw, L.M.; Teunissen, C.E.; Trojanowski, J.Q.; Vanderstichele, H.; Vandijck, M.; Verbeek, M.M.; Zetterberg, H.; Blennow, K.; Kaser, S.A.; et al.,

    2013-01-01

    BACKGROUND: The cerebrospinal fluid (CSF) biomarkers amyloid beta 1-42, total tau, and phosphorylated tau are used increasingly for Alzheimer's disease (AD) research and patient management. However, there are large variations in biomarker measurements among and within laboratories. METHODS: Data

  17. CSF biomarker variability in the Alzheimer's Association quality control program

    NARCIS (Netherlands)

    Mattsson, N.; Andreasson, U.; Persson, S.; Carrillo, M.C.; Collins, S.; Chalbot, S.; Cutler, N.; Dufour-Rainfray, D.; Fagan, A.M.; Heegaard, N.H.H.; Hsiung, G.Y.R.; Hyman, B.; Iqbal, K.; Lachno, D.R.; Lleo, A.; Lewczuk, P.; Molinuevo, J.L.; Parchi, P.; Regeniter, A.; Rissman, R.; Rosenmann, H.; Sancesario, G.; Schroder, J.; Shaw, L.M.; Teunissen, C.E.; Trojanowski, J.Q.; Vanderstichele, H.; Vandijck, M.; Verbeek, M.M.; Zetterberg, H.; Blennow, K.; Kaser, S.A.

    2013-01-01

    Background: The cerebrospinal fluid (CSF) biomarkers amyloid beta 1-42, total tau, and phosphorylated tau are used increasingly for Alzheimer's disease (AD) research and patient management. However, there are large variations in biomarker measurements among and within laboratories. Methods: Data

  18. Cardiovascular biomarkers and sex: the case for women.

    Science.gov (United States)

    Daniels, Lori B; Maisel, Alan S

    2015-10-01

    Measurement of biomarkers is a critical component of cardiovascular care. Women and men differ in their cardiac physiology and manifestations of cardiovascular disease. Although most cardiovascular biomarkers are used by clinicians without taking sex into account, sex-specific differences in biomarkers clearly exist. Baseline concentrations of many biomarkers (including cardiac troponin, natriuretic peptides, galectin-3, and soluble ST2) differ in men versus women, but these sex-specific differences do not generally translate into a need for differential sex-based cut-off points. Furthermore, most biomarkers are similarly diagnostic and prognostic, regardless of sex. Two potential exceptions are cardiac troponins measured by high-sensitivity assay, and proneurotensin. Troponin levels are lower in women than in men and, with the use of high-sensitivity assays, sex-specific cut-off points might improve the diagnosis of myocardial infarction. Proneurotensin is a novel biomarker that was found to be predictive of incident cardiovascular disease in women, but not men, and was also predictive of incident breast cancer. If confirmed, proneurotensin might be a unique biomarker of disease risk in women. With any biomarker, an understanding of sex-specific differences might improve its use and might also lead to an enhanced understanding of the physiological differences between the hearts of men and women.

  19. Application of bio-marker to study on tumor radiosensitivity

    International Nuclear Information System (INIS)

    Guo Wanfeng; Ding Guirong; Han Liangfu

    2001-01-01

    To definite tumor radiosensitivity is important for applying the schedules of individualization of patient radiotherapy. Many laboratories were carrying on the research which predict the tumor radiosensitivity with one bio-marker or/and multi-bio-marker in various levels. At present has not witnessed the specific bio-marker, but it provides an excellent model for predicting tumor radiosensitivity

  20. Metabolomics as a tool in the identification of dietary biomarkers.

    Science.gov (United States)

    Gibbons, Helena; Brennan, Lorraine

    2017-02-01

    Current dietary assessment methods including FFQ, 24-h recalls and weighed food diaries are associated with many measurement errors. In an attempt to overcome some of these errors, dietary biomarkers have emerged as a complementary approach to these traditional methods. Metabolomics has developed as a key technology for the identification of new dietary biomarkers and to date, metabolomic-based approaches have led to the identification of a number of putative biomarkers. The three approaches generally employed when using metabolomics in dietary biomarker discovery are: (i) acute interventions where participants consume specific amounts of a test food, (ii) cohort studies where metabolic profiles are compared between consumers and non-consumers of a specific food and (iii) the analysis of dietary patterns and metabolic profiles to identify nutritypes and biomarkers. The present review critiques the current literature in terms of the approaches used for dietary biomarker discovery and gives a detailed overview of the currently proposed biomarkers, highlighting steps needed for their full validation. Furthermore, the present review also evaluates areas such as current databases and software tools, which are needed to advance the interpretation of results and therefore enhance the utility of dietary biomarkers in nutrition research.

  1. Oxidative stress biomarkers in Oreochromis niloticus as early ...

    African Journals Online (AJOL)

    2018-04-10

    Apr 10, 2018 ... warning signals in assessing pollution from acid mine drainage and ... fish species Oreochromis niloticus as a bio-indicator organism in active ... Key water quality parameters, including ... Biomarkers can provide early warning of potential higher- ...... CT (2001) The use of biomarkers in Ecological Risk.

  2. The future of blood-based biomarkers for Alzheimer's disease

    DEFF Research Database (Denmark)

    Henriksen, Kim; O'Bryant, Sid E; Hampel, Harald

    2014-01-01

    Treatment of Alzheimer's disease (AD) is significantly hampered by the lack of easily accessible biomarkers that can detect disease presence and predict disease risk reliably. Fluid biomarkers of AD currently provide indications of disease stage; however, they are not robust predictors of disease...

  3. 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.

  4. Multiomics Data Triangulation for Asthma Candidate Biomarkers and Precision Medicine.

    Science.gov (United States)

    Pecak, Matija; Korošec, Peter; Kunej, Tanja

    2018-06-01

    Asthma is a common complex disorder and has been subject to intensive omics research for disease susceptibility and therapeutic innovation. Candidate biomarkers of asthma and its precision treatment demand that they stand the test of multiomics data triangulation before they can be prioritized for clinical applications. We classified the biomarkers of asthma after a search of the literature and based on whether or not a given biomarker candidate is reported in multiple omics platforms and methodologies, using PubMed and Web of Science, we identified omics studies of asthma conducted on diverse platforms using keywords, such as asthma, genomics, metabolomics, and epigenomics. We extracted data about asthma candidate biomarkers from 73 articles and developed a catalog of 190 potential asthma biomarkers (167 human, 23 animal data), comprising DNA loci, transcripts, proteins, metabolites, epimutations, and noncoding RNAs. The data were sorted according to 13 omics types: genomics, epigenomics, transcriptomics, proteomics, interactomics, metabolomics, ncRNAomics, glycomics, lipidomics, environmental omics, pharmacogenomics, phenomics, and integrative omics. Importantly, we found that 10 candidate biomarkers were apparent in at least two or more omics levels, thus promising potential for further biomarker research and development and precision medicine applications. This multiomics catalog reported herein for the first time contributes to future decision-making on prioritization of biomarkers and validation efforts for precision medicine in asthma. The findings may also facilitate meta-analyses and integrative omics studies in the future.

  5. Biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy

    DEFF Research Database (Denmark)

    Stenvang, Jan; Kümler, Iben; Nygård, Sune Boris

    2013-01-01

    -standard chemotherapeutic drug will be relatively low in such a patient cohort it is a pre-requisite that such testing is based on predictive biomarkers. This review describes our strategy of biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy, taking the repurposing of topoisomerase I (Top1...

  6. Salivary proteomic and genomic biomarkers for primary Sjogren's syndrome

    NARCIS (Netherlands)

    Hu, Shen; Wang, Jianghua; Leong, Sonya; Xie, Yongming; Yu, Tianwei; Zhou, Hui; Henry, Sharon; Vissink, Arjan; Pijpe, Justin; Kallenberg, Cees; Elashoff, David; Loo, Joseph A.; Wong, David T.

    2007-01-01

    Objective. To identify a panel of protein and messenger RNA (mRNA) biomarkers in human whole saliva (WS) that may be used in the detection of primary Sjogren's syndrome (SS). Methods. Mass spectrometry and expression microarray profiling were used to identify candidate protein and mRNA, biomarkers

  7. A tuberculosis biomarker database: the key to novel TB diagnostics

    Directory of Open Access Journals (Sweden)

    Seda Yerlikaya

    2017-03-01

    Full Text Available New diagnostic innovations for tuberculosis (TB, including point-of-care solutions, are critical to reach the goals of the End TB Strategy. However, despite decades of research, numerous reports on new biomarker candidates, and significant investment, no well-performing, simple and rapid TB diagnostic test is yet available on the market, and the search for accurate, non-DNA biomarkers remains a priority. To help overcome this ‘biomarker pipeline problem’, FIND and partners are working on the development of a well-curated and user-friendly TB biomarker database. The web-based database will enable the dynamic tracking of evidence surrounding biomarker candidates in relation to target product profiles (TPPs for needed TB diagnostics. It will be able to accommodate raw datasets and facilitate the verification of promising biomarker candidates and the identification of novel biomarker combinations. As such, the database will simplify data and knowledge sharing, empower collaboration, help in the coordination of efforts and allocation of resources, streamline the verification and validation of biomarker candidates, and ultimately lead to an accelerated translation into clinically useful tools.

  8. Biomarkers in Prodromal Parkinson Disease: a Qualitative Review.

    Science.gov (United States)

    Cooper, Christine A; Chahine, Lama M

    2016-11-01

    Over the past several years, the concept of prodromal Parkinson disease (PD) has been increasingly recognized. This term refers to individuals who do not fulfill motor diagnostic criteria for PD, but who have clinical, genetic, or biomarker characteristics suggesting risk of developing PD in the future. Clinical diagnosis of prodromal PD has low specificity, prompting the need for objective biomarkers with higher specificity. In this qualitative review, we discuss objectively defined putative biomarkers for PD and prodromal PD. We searched Pubmed and Embase for articles pertaining to objective biomarkers for PD and their application in prodromal cohorts. Articles were selected based on relevance and methodology. Objective biomarkers of demonstrated utility in prodromal PD include ligand-based imaging and transcranial sonography. Development of serum, cerebrospinal fluid, and tissue-based biomarkers is underway, but their application in prodromal PD has yet to meaningfully occur. Combining objective biomarkers with clinical or genetic prodromal features increases the sensitivity and specificity for identifying prodromal PD. Several objective biomarkers for prodromal PD show promise but require further study, including their application to and validation in prodromal cohorts followed longitudinally. Accurate identification of prodromal PD will likely require a multimodal approach. (JINS, 2016, 22, 956-967).

  9. 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 ...

  10. Salivary proteomic and genomic biomarkers for primary Sjogren's syndrome

    NARCIS (Netherlands)

    Hu, Shen; Wang, Jianghua; Leong, Sonya; Xie, Yongming; Yu, Tianwei; Zhou, Hui; Henry, Sharon; Vissink, Arjan; Pijpe, Justin; Kallenberg, Cees; Elashoff, David; Loo, Joseph A.; Wong, David T.

    Objective. To identify a panel of protein and messenger RNA (mRNA) biomarkers in human whole saliva (WS) that may be used in the detection of primary Sjogren's syndrome (SS). Methods. Mass spectrometry and expression microarray profiling were used to identify candidate protein and mRNA, biomarkers

  11. Engineered gold nanoparticles for identification of novel ovarian biomarkers

    Science.gov (United States)

    Giri, Karuna

    Ovarian cancer is a leading cause of cancer related death among women in the US and worldwide. The disease has a high mortality rate due to limited tools available that can diagnose ovarian cancer at an early stage and the lack of effective treatments for disease free survival at late stages. Identification of proteins specifically expressed/overexpressed in ovarian cancer could lead to identification of novel diagnostic biomarkers and therapeutic targets that improve patient outcomes. In this regard, mass spectrometry is a powerful tool to probe the proteome of a cancer cell. It can aid discovery of proteins important for the pathophysiology of ovarian cancer. These proteins in turn could serve as diagnostic and treatment biomarkers of the disease. However, a limitation of mass spectrometry based proteomic analyses is that the technique lacks sensitivity and is biased against detection of low abundance proteins. With current approaches to biomarker discovery, we may therefore be overlooking candidate proteins that are important for ovarian cancer. This study presents a new approach to enrich low abundance proteins and subsequently detect them with mass spectrometry. Gold nanoparticles (AuNPs) and functionalization of their surfaces provide an excellent opportunity to capture and enrich low abundance proteins. First, the study focused on conducting an extensive investigation of the time evolution of nanoparticle-protein interaction and understanding drivers of protein attachment on nanoparticle surface. The adsorption of proteins to AuNPs was found to be highly dynamic with multiple attachment and detachment events which decreased over time. Initially, electrostatic forces played an important role in protein binding and structurally flexible proteins such as those involved in RNA processing were more likely to bind to AuNPs. More importantly, the feasibility and success of protein enrichment by AuNPs was evaluated. The AuNPs based approach was able to detect

  12. Novel biomarkers for prediabetes, diabetes, and associated complications

    Science.gov (United States)

    Dorcely, Brenda; Katz, Karin; Jagannathan, Ram; Chiang, Stephanie S; Oluwadare, Babajide; Goldberg, Ira J; Bergman, Michael

    2017-01-01

    The number of individuals with prediabetes is expected to grow substantially and estimated to globally affect 482 million people by 2040. Therefore, effective methods for diagnosing prediabetes will be required to reduce the risk of progressing to diabetes and its complications. The current biomarkers, glycated hemoglobin (HbA1c), fructosamine, and glycated albumin have limitations including moderate sensitivity and specificity and are inaccurate in certain clinical conditions. Therefore, identification of additional biomarkers is being explored recognizing that any single biomarker will also likely have inherent limitations. Therefore, combining several biomarkers may more precisely identify those at high risk for developing prediabetes and subsequent progression to diabetes. This review describes recently identified biomarkers and their potential utility for addressing the burgeoning epidemic of dysglycemic disorders. PMID:28860833

  13. Biomarkers of acute lung injury: worth their salt?

    Directory of Open Access Journals (Sweden)

    Proudfoot Alastair G

    2011-12-01

    Full Text Available Abstract The validation of biomarkers has become a key goal of translational biomedical research. The purpose of this article is to discuss the role of biomarkers in the management of acute lung injury (ALI and related research. Biomarkers should be sensitive and specific indicators of clinically important processes and should change in a relevant timeframe to affect recruitment to trials or clinical management. We do not believe that they necessarily need to reflect pathogenic processes. We critically examined current strategies used to identify biomarkers and which, owing to expedience, have been dominated by reanalysis of blood derived markers from large multicenter Phase 3 studies. Combining new and existing validated biomarkers with physiological and other data may add predictive power and facilitate the development of important aids to research and therapy.

  14. 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.

  15. The New Digital Divide For Digital BioMarkers.

    Science.gov (United States)

    Torous, John; Rodriguez, Jorge; Powell, Adam

    2017-09-01

    As smartphone and sensors continue to become more ubiquitous across the world, digital biomarkers have emerged as a scalable and practical tool to explore disease states and advance health. But as the digital divide of access and ownership begins to fade, a new digital divide is emerging. Who are the types of people that own smartphones or smart watches, who are the types of people that download health apps or partake in digital biomarker studies, and who are the types of people that are actually active with digital biomarkers apps and sensors - the people providing the high quality and longitudinal data that this field is being founded upon? Understanding the people behind digital biomarkers, the very people this emerging field aims to help, may actually be the real challenge as well as opportunity for digital biomarkers.

  16. Target biomarker profile for the clinical management of paracetamol overdose

    Science.gov (United States)

    Vliegenthart, A D Bastiaan; Antoine, Daniel J; Dear, James W

    2015-01-01

    Paracetamol (acetaminophen) overdose is one of the most common causes of acute liver injury in the Western world. To improve patient care and reduce pressure on already stretched health care providers new biomarkers are needed that identify or exclude liver injury soon after an overdose of paracetamol is ingested. This review highlights the current state of paracetamol poisoning management and how novel biomarkers could improve patient care and save healthcare providers money. Based on the widely used concept of defining a target product profile, a target biomarker profile is proposed that identifies desirable and acceptable key properties for a biomarker in development to enable the improved treatment of this patient population. The current biomarker candidates, with improved hepatic specificity and based on the fundamental mechanistic basis of paracetamol-induced liver injury, are reviewed and their performance compared with our target profile. PMID:26076366

  17. Potential Peripheral Biomarkers for the Diagnosis of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Seema Patel

    2011-01-01

    Full Text Available Advances in the discovery of a peripheral biomarker for the diagnosis of Alzheimer's would provide a way to better detect the onset of this debilitating disease in a manner that is both noninvasive and universally available. This paper examines the current approaches that are being used to discover potential biomarker candidates available in the periphery. The search for a peripheral biomarker that could be utilized diagnostically has resulted in an extensive amount of studies that employ several biological approaches, including the assessment of tissues, genomics, proteomics, epigenetics, and metabolomics. Although a definitive biomarker has yet to be confirmed, advances in the understanding of the mechanisms of the disease and major susceptibility factors have been uncovered and reveal promising possibilities for the future discovery of a useful biomarker.

  18. Biomarker assessment and molecular testing for prognostication in breast cancer.

    Science.gov (United States)

    Kos, Zuzana; Dabbs, David J

    2016-01-01

    Current treatment of breast cancer incorporates clinical, pathological and molecular data. Oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) define prognosis and identify tumours for targeted therapy, and remain the sole established single-molecule biomarkers defining the minimum breast cancer pathology data set. Ki67 remains one of the most promising yet controversial biomarkers in breast cancer, implemented routinely in some, but not all, pathology departments. Beyond the single-molecule biomarkers, a host of multigene expression tests have been developed to interrogate the driver pathways and biology of individual breast cancers to predict clinical outcome more accurately. A minority of these assays have entered into clinical practice. This review focuses on the established biomarkers of ER, PR and HER2, the controversial but clinically implemented biomarker Ki67 and the currently marketed gene expression signatures. © 2015 John Wiley & Sons Ltd.

  19. 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

  20. A Systematic Review of the Diagnostic and Prognostic Value of Urinary Protein Biomarkers in Urothelial Bladder Cancer

    Science.gov (United States)

    D’Costa, Jamie J.; Goldsmith, James C.; Wilson, Jayne S.; Bryan, Richard T.; Ward, Douglas G.

    2016-01-01

    For over 80 years, cystoscopy has remained the gold-standard for detecting tumours of the urinary bladder. Since bladder tumours have a tendency to recur and progress, many patients are subjected to repeated cystoscopies during long-term surveillance, with the procedure being both unpleasant for the patient and expensive for healthcare providers. The identification and validation of bladder tumour specific molecular markers in urine could enable tumour detection and reduce reliance on cystoscopy, and numerous classes of biomarkers have been studied. Proteins represent the most intensively studied class of biomolecule in this setting. As an aid to researchers searching for better urinary biomarkers, we report a comprehensive systematic review of the literature and a searchable database of proteins that have been investigated to date. Our objective was to classify these proteins as: 1) those with robustly characterised sensitivity and specificity for bladder cancer detection; 2) those that show potential but further investigation is required; 3) those unlikely to warrant further investigation; and 4) those investigated as prognostic markers. This work should help to prioritise certain biomarkers for rigorous validation, whilst preventing wasted effort on proteins that have shown no association whatsoever with the disease, or only modest biomarker performance despite large-scale efforts at validation. PMID:27500198

  1. Inflammatory biomarkers, physical activity, waist circumference, and risk of future coronary heart disease in healthy men and women

    NARCIS (Netherlands)

    Rana, Jamal S.; Arsenault, Benoit J.; Després, Jean-Pierre; Côté, Mélanie; Talmud, Philippa J.; Ninio, Ewa; Wouter Jukema, J.; Wareham, Nicholas J.; Kastelein, John J. P.; Khaw, Kay-Tee; Boekholdt, S. Matthijs

    2011-01-01

    The aim of this study was to determine the contribution of physical activity and abdominal obesity to the variation in inflammatory biomarkers and incident coronary heart disease (CHD) in a European population. In a prospective case-control study nested in the European Prospective Investigation into

  2. Exhaled hydrogen peroxide in chronic obstructive pulmonary disease : an analysis of its applicability as a non-invasive biomarker

    NARCIS (Netherlands)

    Beurden, Wendy Johanna Cornelia van

    2003-01-01

    Several non-invasive biomarkers have been used to investigate the pathophysiology, treatment and prognosis of COPD. However, for most markers there is no standardized procedure and few randomised studies have been performed with COPD patients. We have developed an efficient, sensitive and

  3. A dietary biomarker approach captures compliance and cardiometabolic effects of a healthy nordic diet in individuals with metabolic syndrome

    DEFF Research Database (Denmark)

    Marklund, Matti; Magnusdottir, Ola K; Rosqvist, Fredrik

    2014-01-01

    Assessment of compliance with dietary interventions is necessary to understand the observed magnitude of the health effects of the diet per se. To avoid reporting bias, different dietary biomarkers (DBs) could be used instead of self-reported data. However, few studies investigated a combination ...

  4. Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and Alzheimer disease

    Science.gov (United States)

    Our aim was to investigate the contribution of biomarkers of glucose homeostasis (adiponectin, glucose, glycated albumin, and insulin levels) and inflammation (high-sensitivity C-reactive protein and lipoprotein-associated phospholipase A(2) levels) to the risk of developing Alzheimer disease (AD) a...

  5. Biomarker analysis of American toad (Anaxyrus americanus) and grey tree frog (Hyla versicolor) tadpoles following exposure to atrazine.

    Science.gov (United States)

    The objective of the current study was to use a biomarker-based approach to investigate the influence of atrazine exposure on American toad (Anaxyrus americanus) and grey tree frog (Hyla versicolor) tadpoles. Atrazine is one of the most frequently detected herbicides in environme...

  6. Prospective evaluation of biomarkers for prediction of quality of life in community-acquired pneumonia.

    Science.gov (United States)

    Nickler, Manuela; Schaffner, Daniela; Christ-Crain, Mirjam; Ottiger, Manuel; Thomann, Robert; Hoess, Claus; Henzen, Christoph; Mueller, Beat; Schuetz, Philipp

    2016-11-01

    Most clinical research investigated prognostic biomarkers for their ability to predict cardiovascular events or mortality. It is unknown whether biomarkers allow prediction of quality of life (QoL) after survival of the acute event. Herein, we investigated the prognostic potential of well-established inflammatory/cardiovascular blood biomarkers including white blood cells (WBC), C-reactive protein (CRP), procalcitonin (PCT), pro-adrenomedullin (proADM) and pro-atrial natriuretic peptide (proANP) in regard to a decline in QoL in a well-defined cohort of patients with community-acquired pneumonia (CAP). Within this secondary analysis including 753 patients with a final inpatient diagnosis of CAP from a multicenter trial, we investigated associations between admission biomarker levels and decline in QoL assessed by the EQ-5D health questionnaire from admission to day 30 and after 6 years. Admission proADM and proANP levels significantly predicted decline of the weighted EQ-5D index after 30 days (n=753) with adjusted odds ratios (ORs) of 2.0 ([95% CI 1.1-3.8]; p=0.027) and 3.7 ([95% CI 2.2-6.0]; pscale (VAS). Initial WBC, PCT and CRP values did not well predict QoL at any time point. ProADM and proANP accurately predict short- and long-term decline in QoL across most dimensions in CAP patients. It will be interesting to reveal underlying physiopathology in future studies.

  7. 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

  8. Early biomarkers of joint damage in rheumatoid and psoriatic arthritis.

    LENUS (Irish Health Repository)

    Mc Ardle, Angela

    2015-01-01

    Joint destruction, as evidenced by radiographic findings, is a significant problem for patients suffering from rheumatoid arthritis and psoriatic arthritis. Inherently irreversible and frequently progressive, the process of joint damage begins at and even before the clinical onset of disease. However, rheumatoid and psoriatic arthropathies are heterogeneous in nature and not all patients progress to joint damage. It is therefore important to identify patients susceptible to joint destruction in order to initiate more aggressive treatment as soon as possible and thereby potentially prevent irreversible joint damage. At the same time, the high cost and potential side effects associated with aggressive treatment mean it is also important not to over treat patients and especially those who, even if left untreated, would not progress to joint destruction. It is therefore clear that a protein biomarker signature that could predict joint damage at an early stage would support more informed clinical decisions on the most appropriate treatment regimens for individual patients. Although many candidate biomarkers for rheumatoid and psoriatic arthritis have been reported in the literature, relatively few have reached clinical use and as a consequence the number of prognostic biomarkers used in rheumatology has remained relatively static for several years. It has become evident that a significant challenge in the transition of biomarker candidates to clinical diagnostic assays lies in the development of suitably robust biomarker assays, especially multiplexed assays, and their clinical validation in appropriate patient sample cohorts. Recent developments in mass spectrometry-based targeted quantitative protein measurements have transformed our ability to rapidly develop multiplexed protein biomarker assays. These advances are likely to have a significant impact on the validation of biomarkers in the future. In this review, we have comprehensively compiled a list of candidate

  9. Blood-Based Biomarker Candidates of Cerebral Amyloid Using PiB PET in Non-Demented Elderly

    Science.gov (United States)

    Westwood, Sarah; Leoni, Emanuela; Hye, Abdul; Lynham, Steven; Khondoker, Mizanur R.; Ashton, Nicholas J.; Kiddle, Steven J.; Baird, Alison L.; Sainz-Fuertes, Ricardo; Leung, Rufina; Graf, John; Hehir, Cristina Tan; Baker, David; Cereda, Cristina; Bazenet, Chantal; Ward, Malcolm; Thambisetty, Madhav; Lovestone, Simon

    2018-01-01

    Increasingly, clinical trials for Alzheimer’s disease (AD) are being conducted earlier in the disease phase and with biomarker confirmation using in vivo amyloid PET imaging or CSF tau and Aβ measures to quantify pathology. However, making such a pre-clinical AD diagnosis is relatively costly and the screening failure rate is likely to be high. Having a blood-based marker that would reduce such costs and accelerate clinical trials through identifying potential participants with likely pre-clinical AD would be a substantial advance. In order to seek such a candidate biomarker, discovery phase proteomic analyses using 2DGE and gel-free LC-MS/MS for high and low molecular weight analytes were conducted on longitudinal plasma samples collected over a 12-year period from non-demented older individuals who exhibited a range of 11C-PiB PET measures of amyloid load. We then sought to extend our discovery findings by investigating whether our candidate biomarkers were also associated with brain amyloid burden in disease, in an independent cohort. Seven plasma proteins, including A2M, Apo-A1, and multiple complement proteins, were identified as pre-clinical biomarkers of amyloid burden and were consistent across three time points (p biomarker signature indicative of AD pathology at a stage long before the onset of clinical disease manifestation. As in previous studies, acute phase reactants and inflammatory markers dominate this signature. PMID:27031486

  10. The study of protein biomarkers to understand the biochemical processes underlying beef color development in young bulls.

    Science.gov (United States)

    Gagaoua, Mohammed; Terlouw, E M Claudia; Picard, Brigitte

    2017-12-01

    This study investigates relationships between 21 biomarkers and meat color traits of Longissimus thoracis muscles of young Aberdeen Angus and Limousin bulls. The relationships found allowed to propose metabolic processes underlying meat color. The color coordinates were related with several biomarkers. The relationships were in some cases breed-dependent and the variability explained in the regression models varied between 31 and 56%. The correlations between biomarkers and color parameters were sometimes opposite between breeds. The PCA using the 21 biomarkers and the instrumental color coordinates showed that these variables discriminated efficiently between the two studied breeds. Results are coherent with earlier studies on other beef breeds showing that several proteins belonging to different but partly related biological pathways involved in muscle contraction, metabolism, heat stress and apoptosis are related to beef color. The results suggest that in future, biomarkers may be used to classify meat cuts sampled early post-mortem according to their forthcoming color. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. New Insights into the Evolution of the Human Diet from Faecal Biomarker Analysis in Wild Chimpanzee and Gorilla Faeces.

    Directory of Open Access Journals (Sweden)

    Ainara Sistiaga

    Full Text Available Our understanding of early human diets is based on reconstructed biomechanics of hominin jaws, bone and teeth isotopic data, tooth wear patterns, lithic, taphonomic and zooarchaeological data, which do not provide information about the relative amounts of different types of foods that contributed most to early human diets. Faecal biomarkers are proving to be a valuable tool in identifying relative proportions of plant and animal tissues in Palaeolithic diets. A limiting factor in the application of the faecal biomarker approach is the striking absence of data related to the occurrence of faecal biomarkers in non-human primate faeces. In this study we explored the nature and proportions of sterols and stanols excreted by our closest living relatives. This investigation reports the first faecal biomarker data for wild chimpanzee (Pan troglodytes and mountain gorilla (Gorilla beringei. Our results suggest that the chemometric analysis of faecal biomarkers is a useful tool for distinguishing between NHP and human faecal matter, and hence, it could provide information for palaeodietary research and early human diets.

  12. New Insights into the Evolution of the Human Diet from Faecal Biomarker Analysis in Wild Chimpanzee and Gorilla Faeces.

    Science.gov (United States)

    Sistiaga, Ainara; Wrangham, Richard; Rothman, Jessica M; Summons, Roger E

    2015-01-01

    Our understanding of early human diets is based on reconstructed biomechanics of hominin jaws, bone and teeth isotopic data, tooth wear patterns, lithic, taphonomic and zooarchaeological data, which do not provide information about the relative amounts of different types of foods that contributed most to early human diets. Faecal biomarkers are proving to be a valuable tool in identifying relative proportions of plant and animal tissues in Palaeolithic diets. A limiting factor in the application of the faecal biomarker approach is the striking absence of data related to the occurrence of faecal biomarkers in non-human primate faeces. In this study we explored the nature and proportions of sterols and stanols excreted by our closest living relatives. This investigation reports the first faecal biomarker data for wild chimpanzee (Pan troglodytes) and mountain gorilla (Gorilla beringei). Our results suggest that the chemometric analysis of faecal biomarkers is a useful tool for distinguishing between NHP and human faecal matter, and hence, it could provide information for palaeodietary research and early human diets.

  13. Biomarker responses and contamination levels in the clam Ruditapes philippinarum for biomonitoring the Lagoon of Venice (Italy).

    Science.gov (United States)

    Matozzo, Valerio; Binelli, Andrea; Parolini, Marco; Locatello, Lisa; Marin, Maria Gabriella

    2010-03-01

    A multibiomarker approach was used to assess effects of environmental contaminants in the clam Ruditapes philippinarum from the Lagoon of Venice. Bivalves were collected in 8 sites of the Lagoon (Campalto, Marghera, Palude del Monte, Valle di Brenta, Cà Roman, San Servolo, Fusina and Canale Dese), differently influenced by both anthropogenic impact and natural conditions. The following biomarkers were chosen: total haemocyte count and lysozyme activity in cell-free haemolymph as immunomarkers, acetylcholinesterase activity in gills as a biomarker of exposure to neurotoxic compounds, vitellogenin-like protein levels in both digestive gland and cell-free haemolymph as a biomarker of exposure to estrogenic compounds, and survival-in-air widely used to evaluate general stress conditions in clams. In addition, polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), 1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT) and its breakdown products (DDE, DDD), hexachlorobenzene (HCB) and hexachlorocyclohexane (HCH) were measured in clams. Results demonstrated that the integrated approach between biomarkers and chemical analyses in R. philippinarum is a useful tool in biomonitoring the Lagoon of Venice. The biomarker responses suggested quite similar contamination levels in the entire Lagoon, although the relative impact of differing classes of pollutants changed among sites according to potential sources, as chemical analyses demonstrated. Overall, among the sampling sites investigated, Palude del Monte can represent an environmental risk area, bearing in mind its peculiar use for clam culture.

  14. Biomarkers of general stress in mussels as common indicators for marine biomonitoring programmes in Europe: The ICON experience.

    Science.gov (United States)

    Martínez-Gómez, Concepción; Robinson, Craig David; Burgeot, Thierry; Gubbins, Matt; Halldorsson, Halldor P; Albentosa, Marina; Bignell, John P; Hylland, Ketil; Vethaak, A Dick

    2017-03-01

    This study investigated whether general stress biomarkers in mussels can be applied as common first-tier biomarkers in regional biomonitoring programmes in the North Sea (including Iceland) and western Mediterranean Sea. Stress on Stress (SoS) and lysosomal membrane stability (LMS) biomarkers were analysed in resident mussels (Mytilus sp.) from 8 coastal sites and in transplanted mussels (Mytilus galloprovincialis) from two Spanish Mediterranean coastal sites. The assessment of results, as input to pollution monitoring strategies, was performed jointly for LMS and SoS data from the two regions. Contaminant body burden of the mussels was compared with biomarker results. The results demonstrated that these two general and non-expensive stress biomarkers in mussel can be applied throughout European waters, providing a cost-effective and harmonised approach to screen contaminant-related biological effects within the framework of wide-scale pollution biomonitoring programmes, such as that proposed by the European Union, i.e. the Marine Strategy Framework Directive. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Biomarkers of cadmium and arsenic interactions

    International Nuclear Information System (INIS)

    Nordberg, G.F.; Jin, T.; Hong, F.; Zhang, A.; Buchet, J.P.; Bernard, A.

    2005-01-01

    Advances in proteomics have led to the identification of sensitive urinary biomarkers of renal dysfunction that are increasingly used in toxicology and epidemiology. Recent animal data show that combined exposure to inorganic arsenic (As) and cadmium (Cd) gives rise to more pronounced renal toxicity than exposure to each of the agents alone. In order to examine if similar interaction occurs in humans, renal dysfunction was studied in population groups (619 persons in total) residing in two metal contaminated areas in China: mainly a Cd contaminated area in Zhejiang province (Z-area) and mainly a As contaminated area in Guizhou province (G-area). Nearby control areas without excessive metal exposure were also included. Measurements of urinary β 2 -microglobulin (UB2MG), N-acetyl-β-glucosaminidase (UNAG), retinol binding protein (URBP) and albumin (UALB) were used as markers of renal dysfunction. Urinary Cd (UCd) and total As (UTAs) were analyzed by graphite-furnace atomic absorption spectrometry. Urinary inorganic As and its mono- and di-methylated metabolites (UIAs) were determined by Hydride generation. Results. As expected, the highest UCd values occurred in Z-area (Geometric mean, GM 11.6 μg/g crea) while the highest UTAs values occurred in G-area (GM = 288 μg/g crea). Statistically significant increases compared to the respective control area were present both for UTAs, UCd and for UB2MG, UNAG and UALB in Z-area as well as in G-area. UIAs was determined only in Z area. In G-area, there was a clear dose-response pattern both in relation to UTAs and UCd for each of the biomarkers of renal dysfunction. An interaction effect between As and Cd was demonstrated at higher levels of a combined exposure to As and Cd enhancing the effect on the kidney. In Z-area an increased prevalence of B2MG-uria, NAG-uria and ALB-uria was found in relation to UCd, but no relationship to UTAs was found. A statistically significant relationship between UIAs and UB2MG was found among

  16. Proteomic biomarkers for ovarian cancer risk in women with polycystic ovary syndrome: a systematic review and biomarker database integration.

    Science.gov (United States)

    Galazis, Nicolas; Olaleye, Olalekan; Haoula, Zeina; Layfield, Robert; Atiomo, William

    2012-12-01

    To review and identify possible biomarkers for ovarian cancer (OC) in women with polycystic ovary syndrome (PCOS). Systematic literature searches of MEDLINE, EMBASE, and Cochrane using the search terms "proteomics," "proteomic," and "ovarian cancer" or "ovarian carcinoma." Proteomic biomarkers for OC were then integrated with an updated previously published database of all proteomic biomarkers identified to date in patients with PCOS. Academic department of obstetrics and gynecology in the United Kingdom. A total of 180 women identified in the six studies. Tissue samples from women with OC vs. tissue samples from women without OC. Proteomic biomarkers, proteomic technique used, and methodologic quality score. A panel of six biomarkers was overexpressed both in women with OC and in women with PCOS. These biomarkers include calreticulin, fibrinogen-γ, superoxide dismutase, vimentin, malate dehydrogenase, and lamin B2. These biomarkers could help improve our understanding of the links between PCOS and OC and could potentially be used to identify subgroups of women with PCOS at increased risk of OC. More studies are required to further evaluate the role these biomarkers play in women with PCOS and OC. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  17. Investigational Approaches for Mesothelioma

    International Nuclear Information System (INIS)

    Surmont, Veerle F.; Thiel, Eric R. E. van; Vermaelen, Karim; Meerbeeck, Jan P. van

    2011-01-01

    Malignant pleural mesothelioma (MPM) is a rare, aggressive tumor with a poor prognosis. In view of the poor survival benefit from first-line chemotherapy and the lack of subsequent effective treatment options, there is a strong need for the development of more effective treatment approaches for patients with MPM. This review will provide a comprehensive state of the art of new investigational approaches for mesothelioma. In an introductory section, the etiology, epidemiology, natural history, and standard of care treatment for MPM will be discussed. This review provide an update of the major clinical trials that impact mesothelioma treatment, discuss the impact of novel therapeutics, and provide perspective on where the clinical research in mesothelioma is moving. The evidence was collected by a systematic analysis of the literature (2000–2011) using the databases Medline (National Library of Medicine, USA), Embase (Elsevier, Netherlands), Cochrane Library (Great Britain), National Guideline Clearinghouse (USA), HTA Database (International Network of Agencies for Health Technology Assessment – INAHTA), NIH database (USA), International Pleural Mesothelioma Program – WHOLIS (WHO Database), with the following keywords and filters: mesothelioma, guidelines, treatment, surgery, chemotherapy, radiotherapy, review, investigational, drugs. Currently different targeted therapies and biologicals are under investigation for MPM. It is important that the molecular biologic research should first focus on mesothelioma-specific pathways and biomarkers in order to have more effective treatment options for this disease. The use of array technology will be certainly an implicit gain in the identification of new potential prognostic or biomarkers or important pathways in the MPM pathogenesis. Probably a central mesothelioma virtual tissue bank may contribute to the ultimate goal to identify druggable targets and to develop personalized treatment for the MPM patients.

  18. Investigational approaches for mesothelioma

    Directory of Open Access Journals (Sweden)

    Veerle F Surmont

    2011-08-01

    Full Text Available MPM is a rare, aggressive tumour with a poor prognosis. In view of the poor survival benefit from first-line chemotherapy and the lack of subsequent effective treatment options, there is a strong need for the development of more effective treatment approaches for patients with MPM. This review will provide a comprehensive state of the art of new investigational approaches for mesothelioma. In an introductory section, the aetiology, epidemiology, natural history and standard of care treatment for MPM will be discussed. This review provide an update of the major clinical trials that impact mesothelioma treatment, discuss the impact of novel therapeutics and provide perspective on where the clinical research in mesothelioma is moving.The evidence was collected by a systematic analysis of the literature (2000–2011 using the databases Medline (National Library of Medicine, USA, Embase (Elsevier, Netherlands, Cochrane Library (Great Britain, National Guideline Clearinghouse (USA, HTA Database (International Network of Agencies for Health Technology Assessment – INAHTA, NIH database (USA, International Pleural Mesothelioma Program – WHOLIS (WHO Database , with the following keywords and filters: mesothelioma, guidelines, treatment, surgery, chemotherapy, radiotherapy, review, investigational, drugsCurrently different targeted therapies and biologicals are under investigation for MPM. It is important that the molecular biologic research should first focus on mesothelioma-specific pathways and biomarkers in order to have more effective treatment options for this disease. The use of array technology will be certainly an implicit gain in the identification of new potential prognostic or biomarkers or important pathways in the MPM pathogenesis. Probably a central mesothelioma virtual tissue bank may contribute to the ultimate goal to identify druggable targets and to develop personalized treatment for the MPM patients.

  19. An OMIC biomarker detection algorithm TriVote and its application in methylomic biomarker detection.

    Science.gov (United States)

    Xu, Cheng; Liu, Jiamei; Yang, Weifeng; Shu, Yayun; Wei, Zhipeng; Zheng, Weiwei; Feng, Xin; Zhou, Fengfeng

    2018-04-01

    Transcriptomic and methylomic patterns represent two major OMIC data sources impacted by both inheritable genetic information and environmental factors, and have been widely used as disease diagnosis and prognosis biomarkers. Modern transcriptomic and methylomic profiling technologies detect the status of tens of thousands or even millions of probing residues in the human genome, and introduce a major computational challenge for the existing feature selection algorithms. This study proposes a three-step feature selection algorithm, TriVote, to detect a subset of transcriptomic or methylomic residues with highly accurate binary classification performance. TriVote outperforms both filter and wrapper feature selection algorithms with both higher classification accuracy and smaller feature number on 17 transcriptomes and two methylomes. Biological functions of the methylome biomarkers detected by TriVote were discussed for their disease associations. An easy-to-use Python package is also released to facilitate the further applications.

  20. Symptoms and biomarkers associated with celiac disease

    DEFF Research Database (Denmark)

    Kårhus, Line L; Thuesen, Betina H; Rumessen, Juri J.

    2016-01-01

    OBJECTIVES: To identify possible early predictors (symptoms and biomarkers) of celiac disease, compare symptoms before and after screening, and evaluate the diagnostic efficacy of serologic screening for celiac disease in an adult Danish population. METHODS: This cross-sectional population......-positive individuals 19 months after the clinical evaluation to obtain information on their symptoms and their experience with participation in the screening. RESULTS: Before screening, participants subsequently diagnosed with celiac disease did not differ from the rest of the population with respect to symptoms...... with having been diagnosed and 71% felt better on a gluten-free diet. CONCLUSION: There were no differences in the prevalence of symptoms between participants with and without screening-detected celiac disease, confirming that risk stratification in a general population by symptoms is difficult. The majority...