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Sample records for biomarkers predicting clinical

  1. Clinical studies of biomarkers in suicide prediction

    OpenAIRE

    Jokinen, Jussi

    2007-01-01

    Suicide is a major clinical problem in psychiatry and suicidal behaviours can be seen as a nosological entity per se. Predicting suicide is difficult due to its low base-rate and the limited specificity of clinical predictors. Prospective biological studies suggest that dysfunctions in the hypothalamo pituitary adrenal (HPA) axis and the serotonergic system have predictive power for suicide in mood disorders. Suicide attempt is the most robust clinical predictor making suici...

  2. Predictive biomarker discovery through the parallel integration of clinical trial and functional genomics datasets

    DEFF Research Database (Denmark)

    Swanton, C.; Larkin, J.M.; Gerlinger, M.;

    2010-01-01

    RNA screens to identify and validate functionally important genomic or transcriptomic predictive biomarkers of individual drug response in patients. PREDICT's approach to predictive biomarker discovery differs from conventional associative learning approaches, which can be susceptible to the detection of...... European network providing the technological and clinical platform for large-scale functional genomic biomarker discovery. Here we review our current understanding of molecular mechanisms driving resistance to anti-angiogenesis agents, the current limitations of laboratory and clinical trial strategies and...... how the PREDICT consortium will endeavour to identify a new generation of predictive biomarkers....

  3. Predictive biomarkers for personalised anti-cancer drug use: discovery to clinical implementation.

    Science.gov (United States)

    Alymani, Nayef A; Smith, Murray D; Williams, David J; Petty, Russell D

    2010-03-01

    A priority translational research objective in cancer medicine is the discovery of novel therapeutic targets for solid tumours. Ideally, co-discovery of predictive biomarkers occurs in parallel to facilitate clinical development of agents and ultimately personalise clinical use. However, the identification of clinically useful predictive biomarkers for solid tumours has proven challenging with many initially promising biomarkers failing to translate into clinically useful applications. In particular, the 'failure' of a predictive biomarker has often only become apparent at a relatively late stage in investigation. Recently, the field has recognised the need to develop a robust clinical biomarker development methodology to facilitate the process. This review discusses the recent progress in this area focusing on the key stages in the biomarker development process: discovery, validation, qualification and implementation. Concentrating on predictive biomarkers for selecting systemic therapies for individual patients in the clinic, the advances and progress in each of these stages in biomarker development are outlined and the key remaining challenges are discussed. Specific examples are discussed to illustrate the challenges identified and how they have been addressed. Overall, we find that significant progress has been made towards a formalised biomarker developmental process. This holds considerable promise for facilitating the translation of predictive biomarkers from discovery to clinical implementation. Further enhancements could eventually be found through alignment with regulatory processes. PMID:20138504

  4. A combined clinical and biomarker approach to predict diuretic response in acute heart failure

    NARCIS (Netherlands)

    Ter Maaten, Jozine M; Valente, Mattia A E; Metra, Marco; Bruno, Noemi; O'Connor, Christopher M; Ponikowski, Piotr; Teerlink, John R; Cotter, Gad; Davison, Beth; Cleland, John G; Givertz, Michael M; Bloomfield, Daniel M; Dittrich, Howard C; van Veldhuisen, Dirk J; Hillege, Hans L; Damman, Kevin; Voors, Adriaan A

    2015-01-01

    BACKGROUND: Poor diuretic response in acute heart failure is related to poor clinical outcome. The underlying mechanisms and pathophysiology behind diuretic resistance are incompletely understood. We evaluated a combined approach using clinical characteristics and biomarkers to predict diuretic resp

  5. New evidence-based adaptive clinical trial methods for optimally integrating predictive biomarkers into oncology clinical development programs

    Institute of Scientific and Technical Information of China (English)

    Robert A.Beckman; Cong Chen

    2013-01-01

    Predictive biomarkers are important to the future of oncology; they can be used to identify patient populations who will benefit from therapy,increase the value of cancer medicines,and decrease the size and cost of clinical trials while increasing their chance of success.But predictive biomarkers do not always work.When unsuccessful,they add cost,complexity,and time to drug development.This perspective describes phases 2 and 3 development methods that efficiently and adaptively check the ability of a biomarker to predict clinical outcomes.In the end,the biomarker is emphasized to the extent that it can actually predict.

  6. Predictive biomarker discovery through the parallel integration of clinical trial and functional genomics datasets.

    Science.gov (United States)

    Swanton, Charles; Larkin, James M; Gerlinger, Marco; Eklund, Aron C; Howell, Michael; Stamp, Gordon; Downward, Julian; Gore, Martin; Futreal, P Andrew; Escudier, Bernard; Andre, Fabrice; Albiges, Laurence; Beuselinck, Benoit; Oudard, Stephane; Hoffmann, Jens; Gyorffy, Balázs; Torrance, Chris J; Boehme, Karen A; Volkmer, Hansjuergen; Toschi, Luisella; Nicke, Barbara; Beck, Marlene; Szallasi, Zoltan

    2010-01-01

    The European Union multi-disciplinary Personalised RNA interference to Enhance the Delivery of Individualised Cytotoxic and Targeted therapeutics (PREDICT) consortium has recently initiated a framework to accelerate the development of predictive biomarkers of individual patient response to anti-cancer agents. The consortium focuses on the identification of reliable predictive biomarkers to approved agents with anti-angiogenic activity for which no reliable predictive biomarkers exist: sunitinib, a multi-targeted tyrosine kinase inhibitor and everolimus, a mammalian target of rapamycin (mTOR) pathway inhibitor. Through the analysis of tumor tissue derived from pre-operative renal cell carcinoma (RCC) clinical trials, the PREDICT consortium will use established and novel methods to integrate comprehensive tumor-derived genomic data with personalized tumor-derived small hairpin RNA and high-throughput small interfering RNA screens to identify and validate functionally important genomic or transcriptomic predictive biomarkers of individual drug response in patients. PREDICT's approach to predictive biomarker discovery differs from conventional associative learning approaches, which can be susceptible to the detection of chance associations that lead to overestimation of true clinical accuracy. These methods will identify molecular pathways important for survival and growth of RCC cells and particular targets suitable for therapeutic development. Importantly, our results may enable individualized treatment of RCC, reducing ineffective therapy in drug-resistant disease, leading to improved quality of life and higher cost efficiency, which in turn should broaden patient access to beneficial therapeutics, thereby enhancing clinical outcome and cancer survival. The consortium will also establish and consolidate a European network providing the technological and clinical platform for large-scale functional genomic biomarker discovery. Here we review our current understanding

  7. Molecular biomarkers of colorectal cancer: prognostic and predictive tools for clinical practice

    Institute of Scientific and Technical Information of China (English)

    Wei-qin JIANG; Fang-fang FU; Yang-xia LI; Wei-bin WANG; Hao-hao WANG; Hai-ping JIANG; Li-song TENG

    2012-01-01

    Colorectal cancer remains one of the most common types of cancer and leading causes of cancer death worldwide.Although we have made steady progress in chemotherapy and targeted therapy,evidence suggests that the majority of patients undergoing drug therapy experience severe,debilitating,and even lethal adverse drug events which considerably outweigh the benefits.The identification of suitable biomarkers will allow clinicians to deliver the most appropriate drugs to specific patients and spare them ineffective and expensive treatments.Prognostic and predictive biomarkers have been the subjects of many published papers,but few have been widely incorporated into clinical practice.Here,we want to review recent biomarker data related to colorectal cancer,which may have been ready for clinical use.

  8. Biomarkers for predicting clinical response to immunosuppressive therapy in aplastic anemia.

    Science.gov (United States)

    Narita, Atsushi; Kojima, Seiji

    2016-08-01

    The decision to select hematopoietic stem cell transplantation (HSCT) or immunosuppressive therapy (IST) as initial therapy in acquired aplastic anemia (AA) is currently based on patient age and the availability of a human leukocyte antigen (HLA)-matched donor. Although IST is a promising treatment option, the ability to predict its long-term outcomes remains poor due to refractoriness, relapses, and the risk of clonal evolution. Several predictive biomarkers for response to IST have been posited, including age, gender, pre-treatment blood cell counts, cytokines, gene mutations, paroxysmal nocturnal hemoglobinuria (PNH), and telomere length (TL). While previous studies have provided substantial biological insights into the utility of IST, the prognostic power of the reported biomarkers is currently insufficient to contribute to clinical decision making. Recently, a large retrospective analysis proposed the combination of minor PNH clones and TL as an efficient predictor of IST response. Identification of a reliable predictor would provide a useful tool for determining the most appropriate treatment choice for AA patients, including up-front HSCT from HLA-matched unrelated donor. The present review summarizes studies evaluating the utility of biomarkers in predicting the clinical response to IST of patients with AA, and provides a baseline for prospective studies aimed at validating previously reported biomarkers. PMID:27091471

  9. Sputum biomarkers and the prediction of clinical outcomes in patients with cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Theodore G Liou

    Full Text Available Lung function, acute pulmonary exacerbations (APE, and weight are the best clinical predictors of survival in cystic fibrosis (CF; however, underlying mechanisms are incompletely understood. Biomarkers of current disease state predictive of future outcomes might identify mechanisms and provide treatment targets, trial endpoints and objective clinical monitoring tools. Such CF-specific biomarkers have previously been elusive. Using observational and validation cohorts comprising 97 non-transplanted consecutively-recruited adult CF patients at the Intermountain Adult CF Center, University of Utah, we identified biomarkers informative of current disease and predictive of future clinical outcomes. Patients represented the majority of sputum producers. They were recruited March 2004-April 2007 and followed through May 2011. Sputum biomarker concentrations were measured and clinical outcomes meticulously recorded for a median 5.9 (interquartile range 5.0 to 6.6 years to study associations between biomarkers and future APE and time-to-lung transplantation or death. After multivariate modeling, only high mobility group box-1 protein (HMGB-1, mean=5.84 [log ng/ml], standard deviation [SD] =1.75 predicted time-to-first APE (hazard ratio [HR] per log-unit HMGB-1=1.56, p-value=0.005, number of future APE within 5 years (0.338 APE per log-unit HMGB-1, p<0.001 by quasi-Poisson regression and time-to-lung transplantation or death (HR=1.59, p=0.02. At APE onset, sputum granulocyte macrophage colony stimulating factor (GM-CSF, mean 4.8 [log pg/ml], SD=1.26 was significantly associated with APE-associated declines in lung function (-10.8 FEV(1% points per log-unit GM-CSF, p<0.001 by linear regression. Evaluation of validation cohorts produced similar results that passed tests of mutual consistency. In CF sputum, high HMGB-1 predicts incidence and recurrence of APE and survival, plausibly because it mediates long-term airway inflammation. High APE-associated GM

  10. Towards understanding and predicting suicidality in women: biomarkers and clinical risk assessment.

    Science.gov (United States)

    Levey, D F; Niculescu, E M; Le-Niculescu, H; Dainton, H L; Phalen, P L; Ladd, T B; Weber, H; Belanger, E; Graham, D L; Khan, F N; Vanipenta, N P; Stage, E C; Ballew, A; Yard, M; Gelbart, T; Shekhar, A; Schork, N J; Kurian, S M; Sandusky, G E; Salomon, D R; Niculescu, A B

    2016-06-01

    Women are under-represented in research on suicidality to date. Although women have a lower rate of suicide completion than men, due in part to the less-violent methods used, they have a higher rate of suicide attempts. Our group has previously identified genomic (blood gene expression biomarkers) and clinical information (apps) predictors for suicidality in men. We now describe pilot studies in women. We used a powerful within-participant discovery approach to identify genes that change in expression between no suicidal ideation (no SI) and high suicidal ideation (high SI) states (n=12 participants out of a cohort of 51 women psychiatric participants followed longitudinally, with diagnoses of bipolar disorder, depression, schizoaffective disorder and schizophrenia). We then used a Convergent Functional Genomics (CFG) approach to prioritize the candidate biomarkers identified in the discovery step by using all the prior evidence in the field. Next, we validated for suicidal behavior the top-ranked biomarkers for SI, in a demographically matched cohort of women suicide completers from the coroner's office (n=6), by assessing which markers were stepwise changed from no SI to high SI to suicide completers. We then tested the 50 biomarkers that survived Bonferroni correction in the validation step, as well as top increased and decreased biomarkers from the discovery and prioritization steps, in a completely independent test cohort of women psychiatric disorder participants for prediction of SI (n=33) and in a future follow-up cohort of psychiatric disorder participants for prediction of psychiatric hospitalizations due to suicidality (n=24). Additionally, we examined how two clinical instruments in the form of apps, Convergent Functional Information for Suicidality (CFI-S) and Simplified Affective State Scale (SASS), previously tested in men, perform in women. The top CFI-S item distinguishing high SI from no SI states was the chronic stress of social isolation. We

  11. Prognostic and Predictive Biomarkers in Colorectal Cancer. From the Preclinical Setting to Clinical Practice.

    Science.gov (United States)

    Maurel, Joan; Postigo, Antonio

    2015-01-01

    Colorectal cancer (CRC) is the second largest cause of cancer mortality in Western countries, mostly due to metastasis. Understanding the natural history and prognostic factors in patients with metastatic CRC (mCRC) is essential for the optimal design of clinical trials. The main prognostic factors currently used in clinical practice are related to tumor behavior (e.g., white blood counts, levels of lactate dehydrogenase, levels of alkaline phosphatase) disease extension (e.g., presence of extrahepatic spread, number of organs affected) and general functional status (e.g., performance status as defined by the Eastern Cooperative Oncology Group). However, these parameters are not always sufficient to establish appropriate therapeutic strategies. First-line therapy in mCRC combines conventional chemotherapy (CHT) (e.g., FOLFOX, FOLFIRI, CAPOX) with a number of agents targeted to specific signaling pathways (TA) (e.g., panitumumab and cetuximab for cases KRAS/NRAS WT, and bevacizumab). Although the response rate to this combination regime exceeds 50%, progression of the disease is almost universal and only less than 10% of patients are free of disease at 2 years. Current clinical trials with second and third line therapy include new TA, such as tyrosin-kinase receptors inhibitors (MET, HER2, IGF-1R), inhibitors of BRAF, MEK, PI3K, AKT, mTORC, NOTCH and JAK1/JAK2, immunotherapy modulators and check point inhibitors (anti-PD-L1 and anti- PD1). Despite the identification of multiple prognostic and predictive biomarkers and signatures, it is still unclear how expression of many of these biomarkers is modulated by CHT and/or TA, thus potentially affecting response to treatment. In this review we analyzed how certain biomarkers in tumor cells and microenvironment influence the response to new TA and immune-therapies strategies in mCRC pre-treated patients. PMID:26452385

  12. Near-infrared spectroscopy in schizophrenia: A possible biomarker for predicting clinical outcome and treatment response

    Directory of Open Access Journals (Sweden)

    Shinsuke eKoike

    2013-11-01

    Full Text Available Functional near-infrared spectroscopy (fNIRS is a relatively new technique that can measure hemoglobin changes in brain tissues, and its use in psychiatry has been progressing rapidly. Although it has several disadvantages (e.g., relatively low spatial resolution and the possibility of shallow coverage in the depth of brain regions compared with other functional neuroimaging techniques (e.g., functional magnetic resonance imaging and positron emission tomography, fNIRS may be a candidate instrument for clinical use in psychiatry, as it can measure brain activity in naturalistic position easily and noninvasively. fNIRS instruments are also small and work silently, and can be moved almost everywhere including schools and care units. Previous fNIRS studies have shown that patients with schizophrenia have impaired activity and characteristic waveform patterns in the prefrontal cortex during the letter version of the verbal fluency task, and part of these results have been approved as one of the Advanced Medical Technologies as an aid for the differential diagnosis of depressive symptoms by the Ministry of Health, Labor and Welfare of Japan in 2009, which was the first such approval in the field of psychiatry. Moreover, previous studies suggest that the activity in the frontopolar prefrontal cortex is associated with their functions in chronic schizophrenia and is its next candidate biomarker. Future studies aimed at exploring fNIRS differences in various clinical stages, longitudinal changes, drug effects, and variations during different task paradigms will be needed to develop more accurate biomarkers that can be used to aid differential diagnosis, the comprehension of the present condition, the prediction of outcome, and the decision regarding treatment options in schizophrenia. Future fNIRS researches will require standardized measurement procedures, probe settings, analytical methods and tools, manuscript description, and database systems in an

  13. Lipocalin-2 as an Infection-Related Biomarker to Predict Clinical Outcome in Ischemic Stroke

    Science.gov (United States)

    Hochmeister, Sonja; Engel, Odilo; Adzemovic, Milena Z.; Pekar, Thomas; Kendlbacher, Paul; Zeitelhofer, Manuel; Haindl, Michaela; Meisel, Andreas; Fazekas, Franz; Seifert-Held, Thomas

    2016-01-01

    Objectives From previous data in animal models of cerebral ischemia, lipocalin-2 (LCN2), a protein related to neutrophil function and cellular iron homeostasis, is supposed to have a value as a biomarker in ischemic stroke patients. Therefore, we examined LCN2 expression in the ischemic brain in an animal model and measured plasma levels of LCN2 in ischemic stroke patients. Methods In the mouse model of transient middle cerebral artery occlusion (tMCAO), LCN2 expression in the brain was analyzed by immunohistochemistry and correlated to cellular nonheme iron deposition up to 42 days after tMCAO. In human stroke patients, plasma levels of LCN2 were determined one week after ischemic stroke. In addition to established predictive parameters such as age, National Institutes of Health Stroke Scale and thrombolytic therapy, LCN2 was included into linear logistic regression modeling to predict clinical outcome at 90 days after stroke. Results Immunohistochemistry revealed expression of LCN2 in the mouse brain already at one day following tMCAO, and the amount of LCN2 subsequently increased with a maximum at 2 weeks after tMCAO. Accumulation of cellular nonheme iron was detectable one week post tMCAO and continued to increase. In ischemic stroke patients, higher plasma levels of LCN2 were associated with a worse clinical outcome at 90 days and with the occurrence of post-stroke infections. Conclusions LCN2 is expressed in the ischemic brain after temporary experimental ischemia and paralleled by the accumulation of cellular nonheme iron. Plasma levels of LCN2 measured in patients one week after ischemic stroke contribute to the prediction of clinical outcome at 90 days and reflect the systemic response to post-stroke infections. PMID:27152948

  14. Presepsin is an early monitoring biomarker for predicting clinical outcome in patients with sepsis.

    Science.gov (United States)

    Ali, Fahmy T; Ali, Mohamed A M; Elnakeeb, Mostafa M; Bendary, Heba N M

    2016-09-01

    Despite their undoubted helpfulness in diagnosing sepsis, increased blood C-reactive protein (CRP) and procalcitonin (PCT) levels have been described in many noninfectious conditions. Presepsin is a soluble fragment of the cluster of differentiation 14 involved in pathogen recognition by innate immunity. We aimed to investigate the diagnostic and prognostic performance of presepsin in comparison to PCT and CRP in patients presenting with systemic inflammatory response syndrome (SIRS) and suspected sepsis. Seventy-six subjects were enrolled in this study, including 51 patients with SIRS as well as 25 healthy subjects. Plasma presepsin, PCT and CRP levels were serially measured on admission and at days 1, 3, 7 and 15. Presepsin and PCT yielded similar diagnostic accuracy, whereas presepsin performed significantly better than CRP. Presepsin and PCT showed comparable performance for predicting 28-day mortality, and both biomarkers performed significantly better than CRP. In septic patients, presepsin revealed earlier concentration changes over time when compared to PCT and CRP. Presepsin and PCT could differentiate between septic and non-septic patients with comparable accuracy and both biomarkers showed similar performance for predicting 28-day mortality. Early changes in presepsin concentrations might reflect the appropriateness of the therapeutic modality and could be useful for making effective treatment decisions. PMID:27353646

  15. Clinical trial designs for evaluating the medical utility of prognostic and predictive biomarkers in oncology

    OpenAIRE

    Simon, Richard

    2010-01-01

    Physicians need improved tools for selecting treatments for individual patients. Many diagnostic entities hat were traditionally viewed as individual diseases are heterogeneous in their molecular pathogenesis and treatment responsiveness. This results in the treatment of many patients with ineffective drugs, incursion of substantial medical costs for the treatment of patients who do not benefit and the conducting of large clinical trials to identify small, average treatment benefits for heter...

  16. Predicting the severity of acute bronchiolitis in infants: should we use a clinical score or a biomarker?

    Science.gov (United States)

    Amat, Flore; Henquell, Cécile; Verdan, Matthieu; Roszyk, Laurence; Mulliez, Aurélien; Labbé, André

    2014-11-01

    Krebs von den Lungen 6 antigen (KL-6) has been shown to be a useful biomarker of the severity of Respiratory syncytial virus bronchiolitis. To assess the correlation between the clinical severity of acute bronchiolitis, serum KL-6, and the causative viruses, 222 infants with acute bronchiolitis presenting at the Pediatric Emergency Department of Estaing University Hospital, Clermont-Ferrand, France, were prospectively enrolled from October 2011 to May 2012. Disease severity was assessed with a score calculated from oxygen saturation, respiratory rate, and respiratory effort. A nasopharyngeal aspirate was collected to screen for a panel of 20 respiratory viruses. Serum was assessed and compared with a control group of 38 bronchiolitis-free infants. No significant difference in KL-6 levels was found between the children with bronchiolitis (mean 231 IU/mL ± 106) and those without (230 IU/mL ± 102), or between children who were hospitalized or not, or between the types of virus. No correlation was found between serum KL-6 levels and the disease severity score. The absence of Human Rhinovirus was a predictive factor for hospitalization (OR 3.4 [1.4-7.9]; P = 0.006). Older age and a higher oxygen saturation were protective factors (OR 0.65[0.55-0.77]; P < 0.0001 and OR 0.67 [0.54-0.85] P < 0.001, respectively). These results suggest that in infants presenting with bronchiolitis for the first time, clinical outcome depends more on the adaptive capacities of the host than on epithelial dysfunction intensity. Many of the features of bronchiolitis are affected by underlying disease and by treatment. PMID:24374757

  17. Tyrosine kinase inhibitor sunitinib therapy is effective in the treatment of bone metastasis from cancer of unknown primary: Identification of clinical and immunohistochemical biomarkers predicting survival.

    Science.gov (United States)

    Ma, Yifei; Zhou, Wang; He, Shaohui; Xu, Wei; Xiao, Jianru

    2016-09-15

    Bone metastasis from cancer of unknown primary (BMCUP) brings poor survival prognosis and its management remains controversial. Sunitinib (SUTENT) proved effective in many sorts of solid tumors but has never been applied for patients with occult primary cancers, and there is no study to identify sensitive or resistant biomarkers for sunitinib therapy in CUP patients. An analysis was carried out to investigate the efficacy of sunitinib by multivariate survival analysis of 286 patients with BMCUP. We further carried out multivariate analysis to identify histological and clinical biomarkers that could predict sensitivity or resistance for sunitinib therapy. Of the 286 patients included from January 2011 to March 2016, sunitinib therapy proved effective to prolong survival in patients with BMCUP. Sensitive and resistant biomarkers were identified in histological specimen of patients receiving sunitinib therapy. Clinical factors were also identified that predict poor survival prognosis for sunitinib therapy. Sunitinib therapy proved effective to prolong survival in patients with BMCUP. Sensitive markers for sunitinib therapy include KDR positivity and early-developed treatment-induced hypertension. Resistance factors for sunitinib include VEGF positivity, CAIX positivity and squamous cell carcinoma pathology type. Prolonged symptom time and severe weight loss before therapy seemed to be associated with poor survival prognosis for sunitinib therapy. PMID:27164264

  18. Forecasting Cytokine Storms with New Predictive Biomarkers.

    Science.gov (United States)

    Rouce, Rayne H; Heslop, Helen E

    2016-06-01

    T cells genetically modified with CD19 chimeric antigen receptors have produced impressive clinical responses in patients with refractory B-cell malignancies, but therapeutic responses are often accompanied by cytokine release syndrome (CRS), which can cause significant morbidity and mortality. Teachey and colleagues have identified predictive biomarkers for this complication that may allow testing of earlier intervention with agents such as the IL6 receptor blocker tocilizumab to evaluate whether CRS can be ameliorated without jeopardizing clinical responses. Cancer Discov; 6(6); 579-80. ©2016 AACR.See related article by Teachey et al., p. 664. PMID:27261481

  19. A Practical Approach to Aid Physician Interpretation of Clinically Actionable Predictive Biomarker Results in a Multi-Platform Tumor Profiling Service.

    Directory of Open Access Journals (Sweden)

    KennethJosephRussell

    2014-04-01

    Full Text Available Patients in whom the standard of care has failed or who have uncommon tumors for which no standard of care exists are often treated with drugs selected based on the physician’s best guess. The rate of success for this method is generally low. With the advent of fast, affordable tumor profiling technologies, and a growth in the understanding of predictive biomarkers, it is now possible to identify drugs potentially associated with clinical benefit for such patients. We present the Caris approach to evidence-based tumor profiling and two patients with advanced ovarian and prostate cancer in whom standard of care had failed and tumor profiling identified an effective treatment schedule. To establish Caris Molecular Intelligence™ (CMI, over 120,000 clinical publications were screened and graded to characterize the predictive value of biomarkers that form the panel of tests. CMI includes multiple technologies to measure changes in proteins, ribonucleic acid (RNA, and deoxyribonucleic acid (DNA and proprietary software that matches the test results with the published evidence. The CMI results enable physicians to select drugs that are more likely to benefit the patients, avoid drugs that are not likely to work, and find treatment options that otherwise would not be considered. Worldwide, over 60,000 cancer patients have undergone evidence based tumor profiling with CMI. In the cases reported in this article, CMI identified treatments that would not have been routinely used in the respective clinical setting. The clinical outcomes observed help to illustrate the utility of this approach.

  20. Predicting Progression from Mild Cognitive Impairment to Alzheimer's Dementia Using Clinical, MRI, and Plasma Biomarkers via Probabilistic Pattern Classification.

    Directory of Open Access Journals (Sweden)

    Igor O Korolev

    Full Text Available Individuals with mild cognitive impairment (MCI have a substantially increased risk of developing dementia due to Alzheimer's disease (AD. In this study, we developed a multivariate prognostic model for predicting MCI-to-dementia progression at the individual patient level.Using baseline data from 259 MCI patients and a probabilistic, kernel-based pattern classification approach, we trained a classifier to distinguish between patients who progressed to AD-type dementia (n = 139 and those who did not (n = 120 during a three-year follow-up period. More than 750 variables across four data sources were considered as potential predictors of progression. These data sources included risk factors, cognitive and functional assessments, structural magnetic resonance imaging (MRI data, and plasma proteomic data. Predictive utility was assessed using a rigorous cross-validation framework.Cognitive and functional markers were most predictive of progression, while plasma proteomic markers had limited predictive utility. The best performing model incorporated a combination of cognitive/functional markers and morphometric MRI measures and predicted progression with 80% accuracy (83% sensitivity, 76% specificity, AUC = 0.87. Predictors of progression included scores on the Alzheimer's Disease Assessment Scale, Rey Auditory Verbal Learning Test, and Functional Activities Questionnaire, as well as volume/cortical thickness of three brain regions (left hippocampus, middle temporal gyrus, and inferior parietal cortex. Calibration analysis revealed that the model is capable of generating probabilistic predictions that reliably reflect the actual risk of progression. Finally, we found that the predictive accuracy of the model varied with patient demographic, genetic, and clinical characteristics and could be further improved by taking into account the confidence of the predictions.We developed an accurate prognostic model for predicting MCI-to-dementia progression

  1. Clinical risk stratification optimizes value of biomarkers to predict new-onset heart failure in a community-based cohort

    NARCIS (Netherlands)

    Brouwers, Frank P; van Gilst, Wiek H; Damman, Kevin; van den Berg, Maarten P; Gansevoort, Ron T; Bakker, Stephan J L; Hillege, Hans L; van Veldhuisen, Dirk J; van der Harst, Pim; de Boer, Rudolf A

    2014-01-01

    BACKGROUND: We aim to identify and quantify the value of biomarkers for incident new-onset heart failure (HF) in a community-based cohort and subgroups based on cardiovascular risk and evaluate the prognostic value of 13 biomarkers for HF with reduced and preserved ejection fraction. METHODS AND RES

  2. Clinical Risk Stratification Optimizes Value of Biomarkers to Predict New-Onset Heart Failure in a Community-Based Cohort

    NARCIS (Netherlands)

    Brouwers, Frank P.; van Gilst, Wiek H.; Damman, Kevin; van den Berg, Maarten P.; Gansevoort, Ron T.; Bakker, Stephan J. L.; Hillege, Hans L.; van Veldhuisen, Dirk J.; van der Harst, Pim; de Boer, Rudolf A.

    2014-01-01

    Background-We aim to identify and quantify the value of biomarkers for incident new-onset heart failure (HF) in a community-based cohort and subgroups based on cardiovascular risk and evaluate the prognostic value of 13 biomarkers for HF with reduced and preserved ejection fraction. Methods and Resu

  3. Epidemiological and Clinical Baseline Characteristics as Predictive Biomarkers of Response to Anti-VEGF Treatment in Patients with Neovascular AMD

    Directory of Open Access Journals (Sweden)

    Miltiadis K. Tsilimbaris

    2016-01-01

    Full Text Available Purpose. To review the current literature investigating patient response to antivascular endothelial growth factor-A (VEGF therapy in the treatment of neovascular age-related macular degeneration (nAMD and to identify baseline characteristics that might predict response. Method. A literature search of the PubMed database was performed, using the keywords: AMD, anti-VEGF, biomarker, optical coherence tomography, treatment outcome, and predictor. The search was limited to articles published from 2006 to date. Exclusion criteria included phase 1 trials, case reports, studies focusing on indications other than nAMD, and oncology. Results. A total of 1467 articles were identified, of which 845 were excluded. Of the 622 remaining references, 47 met all the search criteria and were included in this review. Conclusion. Several baseline characteristics correlated with anti-VEGF treatment response, including best-corrected visual acuity, age, lesion size, and retinal thickness. The majority of factors were associated with disease duration, suggesting that longer disease duration before treatment results in worse treatment outcomes. This highlights the need for early treatment for patients with nAMD to gain optimal treatment outcomes. Many of the identified baseline characteristics are interconnected and cannot be evaluated in isolation; therefore multivariate analyses will be required to determine any specific relationship with treatment response.

  4. Clinical and biomarker changes in premanifest Huntington disease show trial feasibility: a decade of the PREDICT-HD study

    Directory of Open Access Journals (Sweden)

    Jane S Paulsen

    2014-04-01

    Full Text Available There is growing consensus that intervention and treatment of Huntington disease (HD should occur at the earliest stage possible. Various early-intervention methods for this fatal neurodegenerative disease have been identified, but preventive clinical trials for HD are limited by a lack of knowledge of the natural history of the disease and a dearth of appropriate outcome measures. Objectives of the current study are to document the natural history of premanifest HD progression in the largest cohort ever studied and to develop a battery of imaging and clinical markers of premanifest HD progression that can be used as outcome measures in preventive clinical trials. PREDICT-HD is a 32-site, international, observational study of premanifest HD, with annual examination of 1013 participants with premanifest HD and 301 gene-expansion negative controls between 2001 and 2012. Findings document 39 variables representing imaging, motor, cognitive, functional, and psychiatric domains, showing different rates of decline between premanifest Huntington disease and controls. Required sample size and models of premanifest HD are presented to inform future design of clinical and preclinical research. Preventive clinical trials in premanifest HD with participants who have a medium or high probability of motor onset are calculated to be as resource-effective as those conducted in diagnosed HD and could interrupt disease seven to twelve years earlier. Methods and measures for preventive clinical trials in premanifest HD more than a dozen years from motor onset are also feasible. These findings represent the most thorough documentation of a clinical battery for experimental therapeutics in stages of premanifest HD, the time period for which effective intervention may provide the most positive possible outcome for patients and their families affected by this devastating disease.

  5. The potential role of biomarkers in predicting gestational diabetes.

    Science.gov (United States)

    Brink, Huguette S; van der Lely, Aart Jan; van der Linden, Joke

    2016-09-01

    Gestational diabetes (GD) is a frequent complication during pregnancy and is associated with maternal and neonatal complications. It is suggested that a disturbing environment for the foetus, such as impaired glucose metabolism during intrauterine life, may result in enduring epigenetic changes leading to increased disease risk in adult life. Hence, early prediction of GD is vital. Current risk prediction models are based on maternal and clinical parameters, lacking a strong predictive value. Adipokines are mainly produced by adipocytes and suggested to be a link between obesity and its cardiovascular complications. Various adipokines, including adiponectin, leptin and TNF&, have shown to be dysregulated in GD. This review aims to outline biomarkers potentially associated with the pathophysiology of GD and discuss the role of integrating predictive biomarkers in current clinical risk prediction models, in order to enhance the identification of those at risk. PMID:27492245

  6. Biomarkers of fibrosis and impaired liver function in chronic hepatitis C: how well do they predict clinical outcomes?

    DEFF Research Database (Denmark)

    Peters, L.; Rockstroh, J.K.

    2010-01-01

    levels of the fibrosis marker hyaluronic acid are a strong predictor of clinical complications. A smaller study found hyaluronic acid and two other fibrosis tests, aspartate aminotransferase-to-platelet ratio index (APRI) and Fib-4, to be independent predictors of mortality when included in models with...

  7. Clinical Relevance of Biomarkers of Oxidative Stress

    DEFF Research Database (Denmark)

    Frijhoff, Jeroen; Winyard, Paul G; Zarkovic, Neven;

    2015-01-01

    acids. RECENT ADVANCES: An increased understanding of the biology behind diseases and redox biology has led to more specific and sensitive tools to measure oxidative stress markers, which are very diverse and sometimes very low in abundance. CRITICAL ISSUES: The literature is very heterogeneous...... using nonspecific methods, while specific methodologies are often too sophisticated or laborious for routine clinical use. FUTURE DIRECTIONS: Several markers of oxidative stress still represent a viable biomarker opportunity for clinical use. However, positive findings with currently used biomarkers...... still need to be validated in larger sample sizes and compared with current clinical standards to establish them as clinical diagnostics. It is important to realize that oxidative stress is a nuanced phenomenon that is difficult to characterize, and one biomarker is not necessarily better than others...

  8. 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.

  9. Serial and panel analyses of biomarkers do not improve the prediction of bacteremia compared to one procalcitonin measurement

    NARCIS (Netherlands)

    Tromp, M.; Lansdorp, B.; Bleeker-Rovers, C.P.; Klein Gunnewiek, J.M.; Kullberg, B.J.; Pickkers, P.

    2012-01-01

    Objectives We evaluated the value of a single biomarker, biomarker panels, biomarkers combined with clinical signs of sepsis, and serial determinations of biomarkers in the prediction of bacteremia in patients with sepsis. Methods Adult patients visiting the emergency department because of a susp

  10. Serial and panel analyses of biomarkers do not improve the prediction of bacteremia compared to one procalcitonin measurement.

    NARCIS (Netherlands)

    Tromp, M.; Lansdorp, B.; Bleeker-Rovers, C.P.; Gunnewiek, J.M.; Kullberg, B.J.; Pickkers, P.

    2012-01-01

    OBJECTIVES: We evaluated the value of a single biomarker, biomarker panels, biomarkers combined with clinical signs of sepsis, and serial determinations of biomarkers in the prediction of bacteremia in patients with sepsis. METHODS: Adult patients visiting the emergency department because of a suspe

  11. Clinical Biomarkers for Hypoxia Targeting

    OpenAIRE

    Le, Quynh-Thu; Courter, Don

    2008-01-01

    Tumor hypoxia or a reduction of the tissue oxygen tension is a key microenvironmental factor for tumor progression and treatment resistance in solid tumors. Because hypoxic tumor cells have been demonstrated to be more resistant to ionizing radiation, hypoxia has been a focus of laboratory and clinical research in radiation therapy for many decades. It is believed that proper detection of hypoxic regions would guide treatment options and ultimately improve tumor response. To date, most clinic...

  12. Biomarkers for predicting complete debulking in ovarian cancer

    DEFF Research Database (Denmark)

    Fagö-Olsen, Carsten Lindberg; Ottesen, Bent; Christensen, Ib Jarle; Høgdall, Estrid; Lundvall, Lene; Nedergaard, Lotte; Engelholm, Svend-Aage; Antonsen, Sofie Leisby; Lydolph, Magnus; Høgdall, Claus

    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.......64. CONCLUSION: Our validated model based on biomarkers was unable to predict surgical outcome for patients with ovarian cancer....

  13. Potential biomarkers for the clinical prognosis of severe dengue

    Directory of Open Access Journals (Sweden)

    Mayara Marques Carneiro da Silva

    2013-09-01

    Full Text Available Currently, several assays can confirm acute dengue infection at the point-of-care. However, none of these assays can predict the severity of the disease symptoms. A prognosis test that predicts the likelihood of a dengue patient to develop a severe form of the disease could permit more efficient patient triage and treatment. We hypothesise that mRNA expression of apoptosis and innate immune response-related genes will be differentially regulated during the early stages of dengue and might predict the clinical outcome. Aiming to identify biomarkers for dengue prognosis, we extracted mRNA from the peripheral blood mononuclear cells of mild and severe dengue patients during the febrile stage of the disease to measure the expression levels of selected genes by quantitative polymerase chain reaction. The selected candidate biomarkers were previously identified by our group as differentially expressed in microarray studies. We verified that the mRNA coding for CFD, MAGED1, PSMB9, PRDX4 and FCGR3B were differentially expressed between patients who developed clinical symptoms associated with the mild type of dengue and patients who showed clinical symptoms associated with severe dengue. We suggest that this gene expression panel could putatively serve as biomarkers for the clinical prognosis of dengue haemorrhagic fever.

  14. Clinical Utility of Biomarkers in Localized Prostate Cancer.

    OpenAIRE

    Leapman, MS; Nguyen, HG; Cooperberg, MR

    2016-01-01

    A new generation of prostate cancer (PCa) biomarkers has emerged, including diagnostic serum and urine markers aimed at refining the identification high-grade tumors and tissue-based gene expression assays offering prognostic and predictive clinical information. Such tests seek to improve treatment-related decisions at multiple decision points, including initial diagnosis and following initial primary therapy. In this review, we aim to contextualize the body of evidence surrounding these emer...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    biomarker panels are thus required. There is also a paucity of studies that assess the effect of treatments on novel biomarker panels and determine whether initial treatment-induced changes in novel biomarkers predict changes in long-term renal outcomes. Such studies can not only improve our healthcare but......Diabetic kidney disease occurs in ∼ 25-40% of patients with type 2 diabetes. Given the high risk of progressive renal function loss and end-stage renal disease, early identification of patients with a renal risk is important. Novel biomarkers may aid in improving renal risk stratification. In this...... metabolomics biomarkers. We focus on multiple biomarker panels since the molecular processes of renal disease progression in type 2 diabetes are heterogeneous, rendering it unlikely that a single biomarker significantly adds to clinical risk prediction. A limited number of prospective studies of multiple...

  16. MicroRNA signatures as clinical biomarkers in lung cancer

    Directory of Open Access Journals (Sweden)

    Markou A

    2015-05-01

    Full Text Available Athina Markou, Martha Zavridou, Evi S Lianidou Analysis of Circulating Tumor Cells, Lab of Analytical Chemistry, Department of Chemistry, University of Athens, Athens, Greece Abstract: Even if early lung cancer detection has been recently significantly improved, the invasive nature of current diagnostic procedures, and a relatively high percentage of false positives, is limiting the application of modern detection tools. The discovery and clinical evaluation of novel specific and robust non-invasive biomarkers for diagnosis of lung cancer at an early stage, as well as for better prognosis and prediction of therapy response, is very challenging. MicroRNAs (miRNAs can play an important role in the diagnosis and management of lung cancer patients, as important and reliable biomarkers for cancer detection and prognostic prediction, and even as promising as novel targets for cancer therapy. miRNAs are important in cancer pathogenesis, and deregulation of their expression levels has been detected not only in lung cancer but in many other human tumor types. Numerous studies strongly support the potential of miRNAs as biomarkers in non-small-cell lung cancer, and there is increasing evidence that altered miRNA expression is associated with tumor progression and survival. It is worth mentioning also that detection of miRNAs circulating in plasma or serum has enormous potential, because miRNAs serve as non-invasive biomarkers not only for the diagnosis and prognosis of the disease, but also as novel response and sensitivity predictors for cancer treatment. In this review, we summarize the current findings on the critical role of miRNAs in lung cancer tumorigenesis and highlight their potential as circulating biomarkers in lung cancer. Our review is based on papers that have been published after 2011, and includes the key words “miRNAs” and “lung cancer”. Keywords: non-small-cell lung carcinoma, miRNAs, tumor biomarkers, circulating miRNAs, liquid

  17. Biomarkers of treatment outcome in schizophrenia: Defining a benchmark for clinical significance.

    Science.gov (United States)

    Levine, Stephen Z; Rabinowitz, Jonathan; Uher, Rudolf; Kapur, Shitij

    2015-10-01

    Emerging data from on imaging and genetic studies have generated interest in "clinically significant" biomarkers to predict response and prognosis. What constitutes "clinical significance" and how a biomarker would reach that threshold are unclear. To develop a benchmark we reviewed different approaches for defining "clinical significance" applied in schizophrenia research and identified that an improvement of 15 points on the PANSS Total is considered meaningful in clinical settings. Using this benchmark and we simulated thousands of schizophrenia trials, using characteristics derived from the NEWMEDS database with over 8000 patients with schizophrenia, to the kind of imaging, genetic, and other biomarkers that could attain clinical significance. We plotted the interaction between frequency-of-occurrence, the effect size of biomarkers and their relationship to the clinical significance threshold. Results show that categorical biomarkers are likely to attain clinical significance when they occur in 20-50% of the clinical population, and can predict at least a 8-10 point PANSS scale difference. Genetic markers are likely to have clinical significance when they occur in 20-50% of the population and can predict 7-9 points on the PANSS scale. A marker with a lower frequency or lesser effect size would find it hard to meet clinical significance thresholds for schizophrenia. The assumptions and limitations of this approach are discussed. Compared with standards in the rest of medicine, biomarkers that can attain this benchmark will be cost-effective and are likely to be adopted by clinical systems. PMID:26145487

  18. Translating colorectal cancer genetics into clinically useful biomarkers.

    Science.gov (United States)

    Morley-Bunker, A; Walker, L C; Currie, M J; Pearson, J; Eglinton, T

    2016-08-01

    Colorectal cancer (CRC) is a major health problem worldwide accounting for over a million deaths annually. While many patients with Stage II and III CRC can be cured with combinations of surgery, radiotherapy and chemotherapy, this is morbid costly treatment and a significant proportion will suffer recurrence and eventually die of CRC. Increased understanding of the molecular pathogenesis of CRC has the potential to identify high risk patients and target therapy more appropriately. Despite increased understanding of the molecular events underlying CRC development, established molecular techniques have only produced a limited number of biomarkers suitable for use in routine clinical practice to predict risk, prognosis and response to treatment. Recent rapid technological developments, however, have made genomic sequencing of CRC more economical and efficient, creating potential for the discovery of genetic biomarkers that have greater diagnostic, prognostic and therapeutic capabilities for the management of CRC. This paper reviews the current understanding of the molecular pathogenesis of CRC, and summarizes molecular biomarkers that surgeons will encounter in current clinical use as well as those under development in clinical and preclinical trials. New molecular technologies are reviewed together with their potential impact on the understanding of the molecular pathogenesis of CRC and their potential clinical utility in classification, diagnosis, prognosis and targeting of therapy. PMID:26990814

  19. Plasma biomarkers discriminate clinical forms of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Marta Tejera-Alhambra

    Full Text Available Multiple sclerosis, the most common cause of neurological disability in young population after trauma, represents a significant public health burden. Current challenges associated with management of multiple sclerosis (MS patients stem from the lack of biomarkers that might enable stratification of the different clinical forms of MS and thus prompt treatment for those patients with progressive MS, for whom there is currently no therapy available. In the present work we analyzed a set of thirty different plasma cytokines, chemokines and growth factors present in circulation of 129 MS patients with different clinical forms (relapsing remitting, secondary progressive and primary progressive MS and 53 healthy controls, across two independent cohorts. The set of plasma analytes was quantified with Luminex xMAP technology and their predictive power regarding clinical outcome was evaluated both individually using ROC curves and in combination using logistic regression analysis. Our results from two independent cohorts of MS patients demonstrate that the divergent clinical and histology-based MS forms are associated with distinct profiles of circulating plasma protein biomarkers, with distinct signatures being composed of chemokines and growth/angiogenic factors. With this work, we propose that an evaluation of a set of 4 circulating biomarkers (HGF, Eotaxin/CCL11, EGF and MIP-1β/CCL4 in MS patients might serve as an effective tool in the diagnosis and more personalized therapeutic targeting of MS patients.

  20. Translation of neurological biomarkers to clinically relevant platforms.

    Science.gov (United States)

    Hayes, Ronald L; Robinson, Gillian; Muller, Uwe; Wang, Kevin K W

    2009-01-01

    Like proteomics more generally, neuroproteomics has recently been linked to the discovery of biochemical markers of central nervous system (CNS) injury and disease. Although neuroproteomics has enjoyed considerable success in discovery of candidate biomarkers, there are a number of challenges facing investigators interested in developing clinically useful platforms to assess biomarkers for damage to the CNS. These challenges include intrinsic physiological complications such as the blood-brain barrier. Effective translation of biomarkers to clinical practice also requires development of entirely novel pathways and product development strategies. Drawing from lessons learned from applications of biomarkers to traumatic brain injury, this study outlines major elements of such a pathway. As with other indications, biomarkers can have three major areas of application: (1) drug development; (2) diagnosis and prognosis; (3) patient management. Translation of CNS biomarkers to practical clinical platforms raises a number of integrated elements. Biomarker discovery and initial selection needs to be integrated at the earliest stages with components that will allow systematic prioritization and triage of biomarker candidates. A number of important criteria need to be considered in selecting clinical biomarker candidates. Development of proof of concept assays and their optimization and validation represent an often overlooked feature of biomarker translational research. Initial assay optimization should confirm that assays can detect biomarkers in relevant clinical samples. Since access to human clinical samples is critical to identification of biomarkers relevant to injury and disease as well as for assay development, design of human clinical validation studies is an important component of translational biomarker research platforms. Although these clinical studies share much in common with clinical trials for assessment of drug therapeutic efficacy, there are a number of

  1. Predictive Biomarkers for Bevacizumab in Anti-tumor Therapy

    Directory of Open Access Journals (Sweden)

    Qingqing PAN

    2011-07-01

    Full Text Available Bevacizumab, the monoclonal antibody of vascular endothelial growth factor (VEGF has been applied to the therapy of several neoplasms, but an appropriate biomarker to predict the efficacy has not been found. Those markers can originate from peripheral circulation, tumor tissue and genes. Some researches have found that low level of vascular cell adhesion molecule-1 (VCAM-1, E-selectin, angiopoietin 2 (Ang-2 in circulation or carbonic anhydrase 9 (CA9, CD31-microvessel density (CD31-MVD in tumor tissue can predict better activity of bevacizumab. Moreover, high level of soluble VEGFR2 (sVEGFR2 in circulation or the ratio of phosphorylated-VEGFR2 (p-VEGFR2 and VEGFR2 in tumor tissue increasing has the same predictive function. As to the gene, VEGF-634 CC, VEGF-1498 TT and VEGFR2 H472Q are only related to the side effct. Thus more clinical tirals and basic researches should be performed to find out effective biomarkers in bevacizumab’s therapy.

  2. Integrative EEG biomarkers predict progression to Alzheimer's disease at the MCI stage

    Directory of Open Access Journals (Sweden)

    Simon-Shlomo ePoil

    2013-10-01

    Full Text Available Alzheimer's disease (AD is a devastating disorder of increasing prevalence in modern society. Mild cognitive impairment (MCI is considered a transitional stage between normal aging and AD; however, not all subjects with MCI progress to AD. Prediction of conversion to AD at an early stage would enable an earlier, and potentially more effective, treatment of AD. Electroencephalography (EEG biomarkers would provide a non-invasive and relatively cheap screening tool to predict conversion to AD; however, traditional EEG biomarkers have not been considered accurate enough to be useful in clinical practice. Here, we aim to combine the information from multiple EEG biomarkers into a diagnostic classification index in order to improve the accuracy of predicting conversion from MCI to AD within a two-year period. We followed 86 patients initially diagnosed with MCI for two years during which 25 patients converted to AD. We show that multiple EEG biomarkers mainly related to activity in the beta-frequency range (13–30 Hz can predict conversion from MCI to AD. Importantly, by integrating six EEG biomarkers into a diagnostic index using logistic regression the prediction improved compared with the classification using the individual biomarkers, with a sensitivity of 88% and specificity of 82%, compared with a sensitivity of 64% and specificity of 62% of the best individual biomarker in this index. In order to identify this diagnostic index we developed a data mining approach implemented in the Neurophysiological Biomarker Toolbox (http://www.nbtwiki.net/. We suggest that this approach can be used to identify optimal combinations of biomarkers (integrative biomarkers also in other modalities. Potentially, these integrative biomarkers could be more sensitive to disease progression and response to therapeutic intervention.

  3. Circulating microRNAs as Prognostic and Predictive Biomarkers in Patients with Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Jakob Vasehus Schou

    2016-06-01

    Full Text Available MiRNAs are suggested as promising cancer biomarkers. They are stable and extractable from a variety of clinical tissue specimens (fresh frozen or formalin fixed paraffin embedded tissue and a variety of body fluids (e.g., blood, urine, saliva. However, there are several challenges that need to be solved, considering their potential as biomarkers in cancer, such as lack of consistency between biomarker panels in independent studies due to lack of standardized sample handling and processing, use of inconsistent normalization approaches, and differences in patients populations. Focusing on colorectal cancer (CRC, divergent results regarding circulating miRNAs as prognostic or predictive biomarkers are reported in the literature. In the present review, we summarize the current data on circulating miRNAs as prognostic/predictive biomarkers in patients with localized and metastatic CRC (mCRC.

  4. Rational bases for the use of the Immunoscore in routine clinical settings as a prognostic and predictive biomarker in cancer patients.

    Science.gov (United States)

    Kirilovsky, Amos; Marliot, Florence; El Sissy, Carine; Haicheur, Nacilla; Galon, Jérôme; Pagès, Franck

    2016-08-01

    The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) tumor, nodes, metastasis (TNM) classification system based on tumor features is used for prognosis estimation and treatment recommendations in most cancers. However, the clinical outcome can vary significantly among patients within the same tumor stage and TNM classification does not predict response to therapy. Therefore, many efforts have been focused on the identification of new markers. Multiple tumor cell-based approaches have been proposed but very few have been translated into the clinic. The recent demonstration of the essential role of the immune system in tumor progression has allowed great advances in the understanding of this complex disease and in the design of novel therapies. The analysis of the immune infiltrate by imaging techniques in large patient cohorts highlighted the prognostic impact of the in situ immune cell infiltrate in tumors. Moreover, the characterization of the immune infiltrates (e.g. type, density, distribution within the tumor, phenotype, activation status) in patients treated with checkpoint-blockade strategies could provide information to predict the disease outcome. In colorectal cancer, we have developed a prognostic score ('Immunoscore') that takes into account the distribution of the density of both CD3(+) lymphocytes and CD8(+) cytotoxic T cells in the tumor core and the invasive margin that could outperform TNM staging. Currently, an international retrospective study is under way to validate the Immunoscore prognostic performance in patients with colon cancer. The use of Immunoscore in clinical practice could improve the patients' prognostic assessment and therapeutic management. PMID:27121213

  5. Current status of predictive biomarkers for neoadjuvant therapy in esophageal cancer

    Institute of Scientific and Technical Information of China (English)

    Norihisa; Uemura; Tadashi; Kondo

    2014-01-01

    Neoadjuvant therapy has been proven to be extremely valuable and is widely used for advanced esophageal cancer. However, a significant proportion of treated patients(60%-70%) does not respond well to neoadjuvant treatments and develop severe adverse effects. Therefore, predictive markers for individualization of multimodality treatments are urgently needed in esophageal cancer. Recently, molecular biomarkers that predict the response to neoadjuvant therapy have been explored in multimodal approaches in esophageal cancer and successful examples of biomarker identification have been reported. In this review, promising candidates for predictive molecular biomarkers developed by using multiple molecular approaches are reviewed. Moreover, treatment strategies based on the status of predicted biomarkers are discussed, while considering the international differences in the clinical background. However, in the absence of adequate treatment options related to the results of the biomarker test, the usefulness of these diagnostic tools is limited and new effective therapies for biomarker-identified nonresponders to cancer treatment should be concurrent with the progress of predictive technologies. Further improvement in the prognosis of esophageal cancer patients can be achieved through the introduction of novel therapeutic approaches in clinical practice.

  6. Biomarkers in dementia: clinical utility and new directions

    OpenAIRE

    Ahmed, R. M.; Paterson, R. W.; Warren, J D; Zetterberg, H.; O'Brien, J. T.; Fox, N C; Halliday, G. M.; Schott, J M

    2014-01-01

    Imaging, cerebrospinal fluid (CSF) and blood-based biomarkers have the potential to improve the accuracy by which specific causes of dementia can be diagnosed in vivo, provide insights into the underlying pathophysiology, and may be used as inclusion criteria and outcome measures for clinical trials. While a number of imaging and CSF biomarkers are currently used for each of these purposes, this is an evolving field, with numerous potential biomarkers in varying stages of research and develop...

  7. Prognostic and predictive biomarkers in adult and paediatric gliomas: towards personalised brain tumour treatment

    Directory of Open Access Journals (Sweden)

    KathreenaMaryKurian

    2014-03-01

    Full Text Available It is increasingly clear that both adult and paediatric glial tumour entities represent collections of neoplastic lesions, each with individual pathological molecular events and treatment responses. In this review we discuss the current prognostic biomarkers validated for clinical use or with future clinical validity for gliomas. Accurate prognostication is crucial for managing patients as treatments may be associated with high morbidity and the benefits of high risk interventions must be judged by the treating clinicians. We also review biomarkers with predictive validity which may become clinically relevant with the development of targeted therapies for adult and paediatric gliomas.

  8. Plasma Biomarkers Can Predict Treatment Response in Tuberculosis Patients

    OpenAIRE

    Lee, Meng-Rui; Tsai, Chia-Jung; Wang, Wei-Jie; Chuang, Tzu-Yi; Yang, Chih-Mann; Chang, Lih-Yu; Lin, Ching-Kai; Wang, Jann-Yuan; Shu, Chin-Chong; Lee, Li-Na; Yu, Chong-Jen

    2015-01-01

    Abstract Despite numerous studies, there has been little progress in the use of biomarkers for predicting treatment response in patients with tuberculosis (TB). Patients with culture-confirmed pulmonary TB between 2010 and 2014 were prospectively recruited. Blood samples were taken upon diagnosis and 2 months after the start of standard anti-TB treatment. A pilot study utilizing measurement of TB-antigen-stimulated cytokines was conducted to select potential biomarkers for further testing. Ou...

  9. Xenograft assessment of predictive biomarkers for standard head and neck cancer therapies

    International Nuclear Information System (INIS)

    Head and neck squamous cell carcinoma (HNSCC) remains a challenging cancer to treat with overall 5-year survival on the order of 50–60%. Therefore, predictive biomarkers for this disease would be valuable to provide more effective and individualized therapeutic approaches for these patients. While prognostic biomarkers such as p16 expression correlate with outcome; to date, no predictive biomarkers have been clinically validated for HNSCC. We generated xenografts in immunocompromised mice from six established HNSCC cell lines and evaluated response to cisplatin, cetuximab, and radiation. Tissue microarrays were constructed from pre- and posttreatment tumor samples derived from each xenograft experiment. Quantitative immunohistochemistry was performed using a semiautomated imaging and analysis platform to determine the relative expression of five potential predictive biomarkers: epidermal growth factor receptor (EGFR), phospho-EGFR, phospho-Akt, phospho-ERK, and excision repair cross-complementation group 1 (ERCC1). Biomarker levels were compared between xenografts that were sensitive versus resistant to a specific therapy utilizing a two-sample t-test with equal standard deviations. Indeed the xenografts displayed heterogeneous responses to each treatment, and we linked a number of baseline biomarker levels to response. This included low ERCC1 being associated with cisplatin sensitivity, low phospho-Akt correlated with cetuximab sensitivity, and high total EGFR was related to radiation resistance. Overall, we developed a systematic approach to identifying predictive biomarkers and demonstrated several connections between biomarker levels and treatment response. Despite these promising initial results, this work requires additional preclinical validation, likely involving the use of patient-derived xenografts, prior to moving into the clinical realm for confirmation among patients with HNSCC

  10. DNA Damage in Chronic Kidney Disease: Evaluation of Clinical Biomarkers

    Science.gov (United States)

    Schupp, Nicole; Stopper, Helga; Heidland, August

    2016-01-01

    Patients with chronic kidney disease (CKD) exhibit an increased cancer risk compared to a healthy control population. To be able to estimate the cancer risk of the patients and to assess the impact of interventional therapies thereon, it is of particular interest to measure the patients' burden of genomic damage. Chromosomal abnormalities, reduced DNA repair, and DNA lesions were found indeed in cells of patients with CKD. Biomarkers for DNA damage measurable in easily accessible cells like peripheral blood lymphocytes are chromosomal aberrations, structural DNA lesions, and oxidatively modified DNA bases. In this review the most common methods quantifying the three parameters mentioned above, the cytokinesis-block micronucleus assay, the comet assay, and the quantification of 8-oxo-7,8-dihydro-2′-deoxyguanosine, are evaluated concerning the feasibility of the analysis and regarding the marker's potential to predict clinical outcomes. PMID:27313827

  11. Use of Gene Expression Biomarkers to Predict Suicidality.

    Science.gov (United States)

    Simons, Ries

    2016-07-01

    Since the tragic accident of Germanwings flight 4U9525, there has been discussion about methods to identify and prevent suicidality in pilots. Neurogenetic scientists claim that biomarker tests for suicidality as part of healthcare assessments may lead to early identification of suicidal behavior. In this commentary the value of these gene expression biomarkers for aeromedical purposes is evaluated based on relevant literature. It is concluded that the currently identified biomarkers for suicidality need thorough validation before they can be used. The aeromedical examiner's most important tool is still an anamnesis, in which warning signs of suicidal behavior can be picked up. Simons R. Use of gene expression biomarkers to predict suicidality. Aerosp Med Hum Perform. 2016; 87(7):659-660. PMID:27503048

  12. Evidence that a panel of neurodegeneration biomarkers predicts vasospasm, infarction, and outcome in aneurysmal subarachnoid hemorrhage.

    Directory of Open Access Journals (Sweden)

    Robert Siman

    Full Text Available Biomarkers for neurodegeneration could be early prognostic measures of brain damage and dysfunction in aneurysmal subarachnoid hemorrhage (aSAH with clinical and medical applications. Recently, we developed a new panel of neurodegeneration biomarkers, and report here on their relationships with pathophysiological complications and outcomes following severe aSAH. Fourteen patients provided serial cerebrospinal fluid samples for up to 10 days and were evaluated by ultrasonography, angiography, magnetic resonance imaging, and clinical examination. Functional outcomes were assessed at hospital discharge and 6-9 months thereafter. Eight biomarkers for acute brain damage were quantified: calpain-derived α-spectrin N- and C-terminal fragments (CCSntf and CCSctf, hypophosphorylated neurofilament H,14-3-3 β and ζ, ubiquitin C-terminal hydrolase L1, neuron-specific enolase, and S100β. All 8 biomarkers rose up to 100-fold in a subset of patients. Better than any single biomarker, a set of 6 correlated significantly with cerebral vasospasm, brain infarction, and poor outcome. Furthermore, CSF levels of 14-3-3β, CCSntf, and NSE were early predictors of subsequent moderate-to-severe vasospasm. These data provide evidence that a panel of neurodegeneration biomarkers may predict lasting brain dysfunction and the pathophysiological processes that lead to it following aSAH. The panel may be valuable as surrogate endpoints for controlled clinical evaluation of treatment interventions and for guiding aSAH patient care.

  13. Non-Small Cell Lung Cancer beyond Biomarkers: The Evolving Landscape of Clinical Trial Design

    Directory of Open Access Journals (Sweden)

    Anastasios Dimou

    2014-06-01

    Full Text Available The approval of EGFR and ALK directed tyrosine kinase inhibitors materialized the concept of tailoring therapy on the basis of specific biomarkers for treating patients with NSCLC. Research for other biologics, although demonstrating clinical benefit, has been less successful so far for producing biomarkers that predict response. Blocking angiogenesis is the prototype for the agents that belong in the latter group that target specific molecules, yet they are currently approved for relatively unselected groups of patients. In order to meet the goal of personalizing care in the various settings of NSCLC, a wealth of biologics and compounds are currently being tested in clinical trials in different phases of clinical development. In a subset of the relevant studies, a biomarker perspective is appreciated. This review summarizes the clinical rationale of the major ongoing phase II and III NSCLC studies that employ targeting specific molecules with novel agents, as well as innovative strategies, and includes a comparative discussion of the different designs.

  14. From molecular signatures to predictive biomarkers: Modeling disease pathophysiology and drug mechanism of action

    Directory of Open Access Journals (Sweden)

    BerndMayer

    2014-08-01

    Full Text Available Omics profiling significantly expanded the molecular landscape describing clinical phenotypes. Association analysis resulted in first diagnostic and prognostic biomarker signatures entering clinical utility. However, utilizing Omics for deepening our understanding of disease pathophysiology, and further including specific interference with drug mechanism of action on a molecular process level still sees limited added value in the clinical setting. We exemplify a computational workflow for expanding from statistics-based association analysis towards deriving molecular pathway and process models for characterizing phenotypes and drug mechanism of action. Interference analysis on the molecular model level allows identification of predictive biomarker candidates for testing drug response. We discuss this strategy on diabetic nephropathy, a complex clinical phenotype triggered by diabetes and presenting with renal as well as cardiovascular endpoints. A molecular pathway map indicates involvement of multiple molecular mechanisms, and selected biomarker candidates reported as associated with disease progression are identified for specific molecular processes. Selective interference of drug mechanism of action and disease-associated processes is identified for drug classes in clinical use, in turn providing precision medicine hypotheses utilizing predictive biomarkers.

  15. MTR-18 Predictive Biomarkers Of Bevacizumab Response In Recurrent Glioblastoma Patients

    DEFF Research Database (Denmark)

    Urup, Thomas; Michaelsen, Signe Regner; Olsen, Lars Rønn;

    2015-01-01

    Bevacizumab (BEV) plus chemotherapy has shown activity in recurrent glioblastoma (GBM). However, the prognosis varies and only one third of patients have a durable clinical response to BEV combination therapy. Recent findings from a randomized phase-3 study (AVAglio) indicate that patients with the...... evaluate the predictive and prognostic value of GBM subtypes in recurrent GBM patients treated with BEV therapy. The secondary objective was to identify biomarkers able to predict response to BEV therapy in recurrent GBM patients. METHODS: A total of 90 recurrent GBM patients treated with BEV combination...... proneural GBM subtype have a survival benefit when treated with BEV in combination with standard treatment. However, no validated biomarkers able to predict BEV response have been identified and the biology reflecting a clinical BEV response is poorly understood. The primary objective of this study was to...

  16. Idiopathic pulmonary fibrosis biomarkers: clinical utility and a way of understanding disease pathogenesis

    Directory of Open Access Journals (Sweden)

    Flynn M

    2015-05-01

    Full Text Available Matthew Flynn, Elisabeth S Baker, Daniel J Kass Dorothy P and Richard P Simmons Center for Interstitial Lung Disease, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA Abstract: Idiopathic pulmonary fibrosis (IPF is a typically fatal disease that remains incompletely understood despite intense study and the arrival of drugs that may alter the natural history of the disease. Rendering an accurate diagnosis and predicting prognosis remain challenging problems to clinicians. One potential solution to these clinical problems is the identification of IPF biomarkers, easily measured factors that can be employed to predict clinical behavior. Candidate biomarkers have been identified by research in the laboratory on potential culprit cells or genes that may contribute to the pathogenesis of IPF. In this review, we present the current data on a number of well-studied IPF biomarker candidates and their potential role in the pathogenesis of disease. We also establish a framework for evaluating utility of incorporating these IPF biomarkers into clinical practice. Keywords: idiopathic pulmonary fibrosis, usual interstitial pneumonia, biomarker, matrix metalloproteinases

  17. Biomarkers for the prediction of acute ongoing arterial plaque rupture

    Directory of Open Access Journals (Sweden)

    Guo YL

    2013-07-01

    Full Text Available Yuan-Lin Guo, Jian-Jun Li Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China Abstract: Acute coronary syndrome (ACS is the main cause of mortality for coronary artery disease (CAD. Accordingly, earlier detection and diagnosis might be a key point for reducing the mortality in patients with ACS. One promising strategy is biomarker measurement in patients with ACS. Biomarkers are generally considered to be plasma measurements of molecules, proteins, or enzymes that provide independent diagnostic and prognostic values that can reflect underlying disease state and condition, especially repeated measurements. Nowadays, the most widely used biomarkers to identify or predict ACS are high sensitivity C-reactive protein (hs-CRP and high sensitivity troponin T/I (hs-TnT/I. The aim of the present review was principally to summarize recent evidence regarding some new biomarkers by which we could directly predict acute ongoing arterial plaque rupture, which may help to identify at-risk patients earlier than hs-CRP or hs-TnT/I. Keywords: matrix metalloproteinase-9, lipoprotein associated phospholipase A2, myeloperoxidase, soluble lectin-like oxidized low-density lipoprotein receptor-1, pregnancy-associated plasma protein A, placental growth factor, acute coronary syndrome

  18. New and emerging prognostic and predictive genetic biomarkers in B-cell precursor acute lymphoblastic leukemia.

    Science.gov (United States)

    Moorman, Anthony V

    2016-04-01

    Acute lymphoblastic leukemia (ALL) is a heterogeneous disease at the genetic level. Chromosomal abnormalities are used as diagnostic, prognostic and predictive biomarkers to provide subtype, outcome and drug response information. t(12;21)/ETV6-RUNX1and high hyper-diploidy are good-risk prognostic biomarkers whereasKMT2A(MLL) translocations, t(17;19)/TCF3-HLF, haploidy or low hypodiploidy are high-risk biomarkers. t(9;22)/BCR-ABL1patients require targeted treatment (imatinib/dasatinib), whereas iAMP21 patients achieve better outcomes when treated intensively. High-risk genetic biomarkers are four times more prevalent in adults compared to children. The application of genomic technologies to cases without an established abnormality (B-other) reveals copy number alterations which can be used either individually or in combination as prognostic biomarkers. Transcriptome sequencing studies have identified a network of fusion genes involving kinase genes -ABL1,ABL2,PDGFRB,CSF1R,CRLF2,JAK2andEPORIn vitroandin vivostudies along with emerging clinical observations indicate that patients with a kinase-activating aberration may respond to treatment with small molecular inhibitors like imatinib/dasatinib and ruxolitinib. Further work is required to determine the true frequency of these abnormalities across the age spectrum and the optimal way to incorporate such inhibitors into protocols. In conclusion, genetic biomarkers are playing an increasingly important role in the management of patients with ALL. PMID:27033238

  19. Clinical utility of asthma biomarkers: from bench to bedside

    Directory of Open Access Journals (Sweden)

    Vijverberg SJH

    2013-08-01

    Full Text Available Susanne JH Vijverberg,1,2,* Bart Hilvering,2,* Jan AM Raaijmakers,1 Jan-Willem J Lammers,2 Anke-Hilse Maitland-van der Zee,1,* Leo Koenderman2,* 1Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands; 2Department of Respiratory Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands *These authors contributed equally to this work Abstract: Asthma is a chronic disease characterized by airway inflammation, bronchial hyperresponsiveness, and recurrent episodes of reversible airway obstruction. The disease is very heterogeneous in onset, course, and response to treatment, and seems to encompass a broad collection of heterogeneous disease subtypes with different underlying pathophysiological mechanisms. There is a strong need for easily interpreted clinical biomarkers to assess the nature and severity of the disease. Currently available biomarkers for clinical practice – for example markers in bronchial lavage, bronchial biopsies, sputum, or fraction of exhaled nitric oxide (FeNO – are limited due to invasiveness or lack of specificity. The assessment of markers in peripheral blood might be a good alternative to study airway inflammation more specifically, compared to FeNO, and in a less invasive manner, compared to bronchoalveolar lavage, biopsies, or sputum induction. In addition, promising novel biomarkers are discovered in the field of breath metabolomics (eg, volatile organic compounds and (pharmacogenomics. Biomarker research in asthma is increasingly shifting from the assessment of the value of single biomarkers to multidimensional approaches in which the clinical value of a combination of various markers is studied. This could eventually lead to the development of a clinically applicable algorithm composed of various markers and clinical features to phenotype asthma and improve diagnosis and asthma management

  20. Biomarkers in differentiating clinical dengue cases: A prospective cohort study

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    Gary Kim Kuan Low

    2015-12-01

    Full Text Available Objective: To evaluate five biomarkers (neopterin, vascular endothelial growth factor-A, thrombomodulin, soluble vascular cell adhesion molecule 1 and pentraxin 3 in differentiating clinical dengue cases. Methods: A prospective cohort study was conducted whereby the blood samples were obtained at day of presentation and the final diagnosis were obtained at the end of patients’ follow-up. All patients included in the study were 15 years old or older, not pregnant, not infected by dengue previously and did not have cancer, autoimmune or haematological disorder. Median test was performed to compare the biomarker levels. A subgroup Mann-Whitney U test was analysed between severe dengue and non-severe dengue cases. Monte Carlo method was used to estimate the 2-tailed probability (P value for independent variables with unequal number of patients. Results: All biomarkers except thrombomodulin has P value < 0.001 in differentiating among the healthy subjects, non-dengue fever, dengue without warning signs and dengue with warning signs/severe dengue. Subgroup analysis for all the biomarkers between severe dengue and non-severe dengue cases was not statistically significant except vascular endothelial growth factor-A (P < 0.05. Conclusions: Certain biomarkers were able to differentiate the clinical dengue cases. This could be potentially useful in classifying and determining the severity of dengue infected patients in the hospital.

  1. Prognostic and predictive biomarkers: tools in personalized oncology.

    Science.gov (United States)

    Nalejska, Ewelina; Mączyńska, Ewa; Lewandowska, Marzena Anna

    2014-06-01

    Oncology indispensably leads us to personalized medicine, which allows an individual approach to be taken with each patient. Personalized oncology is based on pharmacogenomics and the effect of genetic differences in individuals (germline and somatic) on the way cancer patients respond to chemotherapeutics. Biomarkers detected using molecular biology tools allow the molecular characterization of cancer signatures and provide information relevant for personalized treatment. Biomarkers can be divided into two main subgroups: prognostic and predictive. The aim of the application of prognostic biomarkers, which provide information on the overall cancer outcome in patients, is to facilitate cancer diagnosis, usually with no need for putting invasive methods into use. Predictive biomarkers help to optimize therapy decisions, as they provide information on the likelihood of response to a given chemotherapeutic. Among the prognostic factors that identify patients with different outcome risks (e.g., recurrence of the disease), the following factors can be distinguished: somatic and germline mutations, changes in DNA methylation that lead to the enhancement or suppression of gene expression, the occurrence of elevated levels of microRNA (miRNA) capable of binding specific messenger RNA (mRNA) molecules, which affects gene expression, as well as the presence of circulating tumor cells (CTCs) in blood, which leads to a poor prognosis for the patient. Biomarkers for personalized oncology are used mainly in molecular diagnostics of chronic myeloid leukemia, colon, breast and lung cancer, and recently in melanoma. They are successfully used in the evaluation of the benefits that can be achieved through targeted therapy or in the evaluation of toxic effects of the chemotherapeutic used in the therapy. PMID:24385403

  2. Analytical Aspects of the Implementation of Biomarkers in Clinical Transplantation.

    Science.gov (United States)

    Shipkova, Maria; López, Olga Millán; Picard, Nicolas; Noceti, Ofelia; Sommerer, Claudia; Christians, Uwe; Wieland, Eberhard

    2016-04-01

    In response to the urgent need for new reliable biomarkers to complement the guidance of the immunosuppressive therapy, a huge number of biomarker candidates to be implemented in clinical practice have been introduced to the transplant community. This includes a diverse range of molecules with very different molecular weights, chemical and physical properties, ex vivo stabilities, in vivo kinetic behaviors, and levels of similarity to other molecules, etc. In addition, a large body of different analytical techniques and assay protocols can be used to measure biomarkers. Sometimes, a complex software-based data evaluation is a prerequisite for appropriate interpretation of the results and for their reporting. Although some analytical procedures are of great value for research purposes, they may be too complex for implementation in a clinical setting. Whereas the proof of "fitness for purpose" is appropriate for validation of biomarker assays used in exploratory drug development studies, a higher level of analytical validation must be achieved and eventually advanced analytical performance might be necessary before diagnostic application in transplantation medicine. A high level of consistency of results between laboratories and between methods (if applicable) should be obtained and maintained to make biomarkers effective instruments in support of therapeutic decisions. This overview focuses on preanalytical and analytical aspects to be considered for the implementation of new biomarkers for adjusting immunosuppression in a clinical setting and highlights critical points to be addressed on the way to make them suitable as diagnostic tools. These include but are not limited to appropriate method validation, standardization, education, automation, and commercialization. PMID:26418704

  3. Functional connectivity classification of autism identifies highly predictive brain features but falls short of biomarker standards

    OpenAIRE

    Mark Plitt; Kelly Anne Barnes; Alex Martin

    2015-01-01

    Objectives: Autism spectrum disorders (ASD) are diagnosed based on early-manifesting clinical symptoms, including markedly impaired social communication. We assessed the viability of resting-state functional MRI (rs-fMRI) connectivity measures as diagnostic biomarkers for ASD and investigated which connectivity features are predictive of a diagnosis. Methods: Rs-fMRI scans from 59 high functioning males with ASD and 59 age- and IQ-matched typically developing (TD) males were used to build ...

  4. Elevation in inflammatory serum biomarkers predicts response to trastuzumab-containing therapy.

    Directory of Open Access Journals (Sweden)

    Ahmed A Alkhateeb

    Full Text Available Approximately half of all HER2/neu-overexpressing breast cancer patients do not respond to trastuzumab-containing therapy. Therefore, there remains an urgent and unmet clinical need for the development of predictive biomarkers for trastuzumab response. Recently, several lines of evidence have demonstrated that the inflammatory tumor microenvironment is a major contributor to therapy resistance in breast cancer. In order to explore the predictive value of inflammation in breast cancer patients, we measured the inflammatory biomarkers serum ferritin and C-reactive protein (CRP in 66 patients immediately before undergoing trastuzumab-containing therapy and evaluated their progression-free and overall survival. The elevation in pre-treatment serum ferritin (>250 ng/ml or CRP (>7.25 mg/l was a significant predictor of reduced progression-free survival and shorter overall survival. When patients were stratified based on their serum ferritin and CRP levels, patients with elevation in both inflammatory biomarkers had a markedly poorer response to trastuzumab-containing therapy. Therefore, the elevation in inflammatory serum biomarkers may reflect a pathological state that decreases the clinical efficacy of this therapy. Anti-inflammatory drugs and life-style changes to decrease inflammation in cancer patients should be explored as possible strategies to sensitize patients to anti-cancer therapeutics.

  5. Are Cerebrospinal Fluid Biomarkers Useful in Predicting the Prognosis of Multiple Sclerosis Patients?

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    Salvatore Monaco

    2011-11-01

    Full Text Available Multiple sclerosis (MS is the prototypical inflammatory demyelinating disorder of the central nervous system (CNS. Although many advances have been made in the comprehension of its pathogenesis, the etiology is still unknown. The complexity of MS reflects in the extreme variability of the clinical manifestations and clinical course both between and within patients, in addition to immunopathological mechanisms and response to treatment. Several prognostic factors have been suggested in large scale studies, but predictions in individual cases are difficult to make. Cerebrospinal fluid (CSF biomarkers, such as 14-3-3, tau, and cystatin C are promising sources of prognostic information with a good potential of quantitative measure, sensitivity, and reliability. However, none has shown sufficient reproducibility to be applied in clinical practice. Here we review the current literature addressing the above mentioned biomarkers as MS severity predictors at an early stage.

  6. 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.

  7. Clinical utility of diagnostic guidelines and putative biomarkers in lymphangioleiomyomatosis

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    Chang William YC

    2012-04-01

    Full Text Available Abstract Background Lymphangioleiomyomatosis is a rare disease occurring almost exclusively in women. Diagnosis often requires surgical biopsy and the clinical course varies between patients with no predictors of progression. We evaluated recent diagnostic guidelines, clinical features and serum biomarkers as diagnostic and prognostic tools. Methods Serum vascular endothelial growth factor-D (VEGF-D, angiotensin converting enzyme (ACE, matrix metalloproteinases (MMP -2 and -9, clinical phenotype, thoracic and abdominal computerised tomography, lung function and quality of life were examined in a cohort of 58 patients. 32 healthy female controls had serum biomarkers measured. Results Serum VEGF-D, ACE and total MMP-2 levels were elevated in patients. VEGF-D was the strongest discriminator between patients and controls (median = 1174 vs. 332 pg/ml p  Conclusions Combining ERS criteria and serum VEGF-D reduces the need for lung biopsy in LAM. VEGF-D was associated with lymphatic disease but not lung function.

  8. Mechanism-specific injury biomarkers predict nephrotoxicity early following glyphosate surfactant herbicide (GPSH) poisoning.

    Science.gov (United States)

    Mohamed, Fahim; Endre, Zoltan H; Pickering, John W; Jayamanne, Shaluka; Palangasinghe, Chathura; Shahmy, Seyed; Chathuranga, Umesh; Wijerathna, Thilini; Shihana, Fathima; Gawarammana, Indika; Buckley, Nicholas A

    2016-09-01

    Acute kidney injury (AKI) is common following glyphosate surfactant herbicide (GPSH) self-poisoning. Serum creatinine (sCr) is the most widely used renal biomarker for diagnosis of AKI although a recent study in rats suggested that urinary kidney injury molecule-1 predicted AKI earlier and better after GPSH-induced nephrotoxicity. We explored the utility of a panel of biomarkers to diagnose GPSH-induced nephrotoxicity in humans. In a prospective multi-centre observational study, serial urine and blood samples were collected until discharge and at follow-up. The diagnostic performance of each biomarker at various time points was assessed. AKI was diagnosed using the Acute Kidney Injury Network (AKIN) definitions. The added value of each biomarker to sCr to diagnose AKI was assessed by the integrated discrimination improvement (IDI) metric. Of 90 symptomatic patients, 51% developed AKI and 5 patients who developed AKIN≥2 died. Increased sCr at 8 and 16h predicted moderate to severe AKI and death. None of the 10 urinary biomarkers tested increased above normal range in patients who did not develop AKI or had mild AKI (AKIN1); most of these patients also had only minor clinical toxicity. Absolute concentrations of serum and urinary cystatin C, urinary interleukin-18 (IL-18), Cytochrome C (CytoC) and NGAL increased many fold within 8h in patients who developed AKIN≥2. Maximum 8 and 16h concentrations of these biomarkers showed an excellent diagnostic performance (AUC-ROC ≥0.8) to diagnose AKIN≥2. However, of these biomarkers only uCytoC added value to sCr to diagnose AKI when assessed by IDI metrics. GPSH-induced nephrotoxicity can be diagnosed within 24h by sCr. Increases in uCytoC and uIL-18 confirm GPSH-induces apoptosis and causes mitochondrial toxicity. Use of these biomarkers may help to identify mechanism specific targeted therapies for GPSH nephrotoxicity in clinical trials. PMID:27288352

  9. Multiple biomarkers for mortality prediction in peripheral arterial disease.

    Science.gov (United States)

    Amrock, Stephen M; Weitzman, Michael

    2016-04-01

    Few studies have assessed which biomarkers influence mortality risk among those with peripheral arterial disease (PAD). We analyzed data from 556 individuals identified to have PAD (i.e. ankle-brachial index ⩽0.9) with available measurements of C-reactive protein, the neutrophil-to-lymphocyte ratio (NLR), homocysteine, and the urinary albumin-to-creatinine ratio (UACR) in the 1999-2004 National Health and Nutrition Examination Survey. We investigated whether a combination of these biomarkers improved the prediction of all-cause and cardiovascular mortality beyond conventional risk factors. During follow-up (median, 8.1 years), 277 of 556 participants died; 63 deaths were attributed to cardiovascular disease. After adjusting for conventional risk factors, Cox proportional-hazards models showed the following to be most strongly associated with all-cause mortality (each is followed by the adjusted hazard ratio [HR] per 1 standard deviation increment in the log values): homocysteine (1.31), UACR (1.21), and NLR (1.20). UACR alone significantly predicted cardiovascular mortality (1.53). Persons in the highest quintile of multimarker scores derived from regression coefficients of significant biomarkers had elevated risks of all-cause mortality (adjusted HR, 2.45; 95% CI, 1.66-3.62; p for trend, HR, 2.20; 95% CI, 1.02-4.71; p for trend, 0.053) compared to those in the lowest two quintiles. The addition of continuous multimarker scores to conventional risk factors improved risk stratification of all-cause mortality (integrated discrimination improvement [IDI], 0.162; pcontinuous multimarker score to conventional risk factors improved mortality prediction among patients with PAD. PMID:26762418

  10. Correlation between Circulating Fungal Biomarkers and Clinical Outcome in Invasive Aspergillosis.

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    Dionysios Neofytos

    Full Text Available Objective means are needed to predict and assess clinical response in patients treated for invasive aspergillosis (IA. We examined whether early changes in serum galactomannan (GM and/or β-D-glucan (BDG can predict clinical outcomes. Patients with proven or probable IA were prospectively enrolled, and serial GM and BDG levels and GM optical density indices (GMI were calculated twice weekly for 6 weeks following initiation of standard-of-care antifungal therapy. Changes in these biomarkers during the first 2 and 6 weeks of treatment were analyzed for associations with clinical response and survival at weeks 6 and 12. Among 47 patients with IA, 53.2% (25/47 and 65.9% (27/41 had clinical response by weeks 6 and 12, respectively. Changes in biomarkers during the first 2 weeks were associated with clinical response at 6 weeks (GMI, P = 0.03 and 12 weeks (GM+BDG composite, P = 0.05; GM, P = 0.04; GMI, P = 0.02. Changes in biomarkers during the first 6 weeks were also associated with clinical response at 6 weeks (GM, P = 0.05; GMI, P = 0.03 and 12 weeks (BDG+GM, P = 0.02; GM, P = 0.02; GMI, P = 0.01. Overall survival rates at 6 weeks and 12 weeks were 87.2% (41/47 and 79.1% (34/43, respectively. Decreasing biomarkers in the first 2 weeks were associated with survival at 6 weeks (BDG+GM, P = 0.03; BDG, P = 0.01; GM, P = 0.03 and at 12 weeks (BDG+GM, P = 0.01; BDG, P = 0.03; GM, P = 0.01; GMI, P = 0.007. Similar correlations occurred for biomarkers measured over 6 weeks. Patients with negative baseline GMI and/or persistently negative GMI during the first 2 weeks were more likely to have CR and survival. These results suggest that changes of biomarkers may be informative to predict and/or assess response to therapy and survival in patients treated for IA.

  11. Fit-for-purpose biomarker method validation for application in clinical trials of anticancer drugs

    OpenAIRE

    Cummings, J.; Raynaud, F; Jones, L.; Sugar, R; Dive, C

    2010-01-01

    Clinical development of new anticancer drugs can be compromised by a lack of qualified biomarkers. An indispensable component to successful biomarker qualification is assay validation, which is also a regulatory requirement. In order to foster flexible yet rigorous biomarker method validation, the fit-for-purpose approach has recently been developed. This minireview focuses on many of the basic issues surrounding validation of biomarker assays utilised in clinical trials. It also provides an ...

  12. Primary Sjӧgren's syndrome: Clinical phenotypes, outcome and the development of biomarkers.

    Science.gov (United States)

    Goules, Andreas V; Tzioufas, Athanasios G

    2016-07-01

    Primary Sjӧgren's syndrome (pSS) is a complex autoimmune disease with distinct clinical phenotypes and variable outcomes. The systemic form of the disease is characterized by immune complex mediated manifestations and is complicated by lymphoma as a result of a polyclonal B cell hyperactivity that is evolving into B cell malignancy. In the past decades, well-established clinical and serological markers have been described in the literature to identify high-risk patients and to predict lymphoma development. However, specific biologic treatments have proven ineffective to control the disease. Significant research effort has been made to reveal the major underlying biological events in this subgroup and identify biomarkers for early diagnosis, prognosis and response to treatment. In this review, we summarize the current data for the proposed histological, molecular and genetic biomarkers. PMID:26970487

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

    Science.gov (United States)

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

  14. Plasma sCD14 as a biomarker to predict pulmonary exacerbations in cystic fibrosis.

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    Bradley S Quon

    Full Text Available BACKGROUND: One in four cystic fibrosis (CF patients diagnosed with a pulmonary exacerbation will not recover their baseline lung function despite standard treatment. This highlights the importance of preventing such events. Clinical decision-making can be improved through a simple blood test that predicts individuals at elevated short-term risk of an exacerbation. METHODS: We obtained plasma samples from 30 stable CF patients from the St. Paul's Hospital Adult CF Clinic (Vancouver, Canada. For 15 patients, an additional plasma sample was obtained during an exacerbation. Soluble CD14 (sCD14 and C-reactive protein (CRP were quantified using ELISA kits. Myeloperoxidase (MPO, interleukin(IL-6, IL-1β, monocyte chemoattractant protein-1 (MCP-1, vascular endothelial growth factor (VEGF, and granulocyte colony-stimulating factor (G-CSF were quantified using Luminex™ immunoassays. Stable state biomarker levels were examined in their ability to predict individuals that would experience a pulmonary exacerbation requiring intravenous (IV antibiotics within 4 months. Paired stable and exacerbation plasma biomarker levels were also compared. RESULTS: sCD14 levels were significantly higher in patients that experienced a pulmonary exacerbation requiring IV antibiotics within 4 months (p = 0.001. sCD14 cut-off value of 1450 ng/mL was associated with an area under the curve of 0.91 (95% CI 0.83-0.99 for predicting an exacerbation within 4 months of a stable visit, with a sensitivity of 100% and specificity of 82%. Plasma sCD14 levels were significantly higher during exacerbations than during periods of clinical stability (p = 0.03. CONCLUSIONS: Plasma sCD14 is a promising biomarker for identifying CF patients who will exacerbate within 4 months of a stable visit but requires further study in larger, independent cohorts.

  15. Predicting the outcomes for out-of-hospital cardiac arrest patients using multiple biomarkers and suspension microarray assays

    Science.gov (United States)

    Huang, Chien-Hua; Tsai, Min-Shan; Chien, Kuo-Liong; Chang, Wei-Tien; Wang, Tzung-Dau; Chen, Shyr-Chyr; Ma, Matthew Huei-Ming; Hsu, Hsin-Yun; Chen, Wen-Jone

    2016-01-01

    Predicting the prognosis for cardiac arrest is still challenging. Combining biomarkers from diverse pathophysiological pathways may provide reliable indicators for the severity of injury and predictors of long-term outcomes. We investigated the feasibility of using a multimarker strategy with key independent biomarkers to improve the prediction of outcomes in cardiac arrest. Adult out-of-hospital cardiac arrest patients with sustained return of spontaneous circulation were prospectively enrolled in this study. Blood samples were taken at 2 and 24 hours after cardiac arrest. Suspension microarray assays were used to test 21 different biomarkers. A total of 99 patients were enrolled, 45 of whom survived to hospital discharge. We identified 11 biomarkers that, when combined with clinical variables and factors of APACHE II score and history of arrhythmia, were independent determinants for outcome of in-hospital mortality (concordance = 0.9249, standard error = 0.0779). Three biomarkers combined with APACHE II and age were independent determinants for favorable neurological outcome at hospital discharge (area under the receiver-operator characteristic curve, 0.938; 95% confidence interval, 0.854 ~ 1.0). In conclusion, a systemic multiple biomarker approach using suspension microarray assays can identify independent predictors and model the outcomes of cardiac arrest patients during the post-cardiac arrest period. PMID:27256246

  16. Microaneurysm turnover in the macula is a biomarker for development of clinically significant macular edema in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Ribeiro L

    2013-01-01

    Full Text Available Luisa Ribeiro, Sandrina Nunes, José Cunha-VazAssociation for Innovation and Biomedical Research on Light and Image and Faculty of Medicine, University of Coimbra, Coimbra, PortugalAbstract: The evolution and progression of diabetic retinopathy varies between individuals and does not necessarily progress to vision loss in every patient. However, it is difficult in clinical practice to predict the clinical course and to identify which eyes will develop vision-threatening complications, ie, clinically significant macular edema or proliferative retinopathy. There is a clear need to identify biomarkers of disease progression. Microaneurysm turnover computed automatically in digital color fundus photography images using the RetmarkerDR is a good biomarker for worsening of retinopathy and development of clinically significant macular edema. For long-term prediction (ten years, a microaneurysm formation rate higher than two per year predicts development of clinically significant macular edema. For short-term prediction (2 years, a microaneurysm turnover rate lower than nine indicates that development of clinically significant macular edema is highly unlikely.Keywords: biomarker, diabetes type 2, diabetic retinopathy, microaneurysms, retina

  17. Clinical importance of predicting radiosensitivity

    International Nuclear Information System (INIS)

    Full text: The optimal use of radiation therapy in cancer treatment is hampered by the application of normal tissue tolerance limits that are derived from population averages. Such limits do not reflect the considerable differences in susceptibility to radiation injury that exist among individuals. Development of assays that accurately predicted normal tissue tolerance in individual patients would permit real application of the concept of treatment to tolerance. By adjusting doses upwards or downwards to achieve a uniform probability of complication in each patient, the therapeutic ratio, i e., the probability of an uncomplicated cure, would be increased for the population as a whole. Although the pathogenesis of radiation injury is highly complex, clinical studies have demonstrated a significant correlation between the in vitro radiosensitivity of patients' fibroblasts and their risk of developing late connective tissue type complications of radiotherapy. While such assays lack the precision and practicality to be used clinically, they do establish the principle of prediction of normal tissue tolerance. Newer assays using surrogate endpoints for cell survival and incorporating insights into the effects of radiation on cellular growth, differentiation, senescence and cytokine production are being developed. Such assays may, in the future, be complemented or replaced by molecular and/or cytogenetic probes to derive robust estimates of individual tolerance. The goal of accurate prediction of individual tolerance for clinical use, while not imminent, does seem achievable

  18. Circulating microRNAs as Prognostic and Predictive Biomarkers in Patients with Colorectal Cancer

    OpenAIRE

    Jakob Vasehus Schou; Julia Sidenius Johansen; Dorte Nielsen; Simona Rossi

    2016-01-01

    MiRNAs are suggested as promising cancer biomarkers. They are stable and extractable from a variety of clinical tissue specimens (fresh frozen or formalin fixed paraffin embedded tissue) and a variety of body fluids (e.g., blood, urine, saliva). However, there are several challenges that need to be solved, considering their potential as biomarkers in cancer, such as lack of consistency between biomarker panels in independent studies due to lack of standardized sample handling and processing, ...

  19. Thalamic functional connectivity predicts seizure laterality in individual TLE patients: Application of a biomarker development strategy

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    Daniel S. Barron

    2015-01-01

    No significant differences in functional connection strength in patient and control groups were observed with Mann-Whitney Tests (corrected for multiple comparisons. Notwithstanding the lack of group differences, individual patient difference scores (from control mean connection strength successfully predicted seizure onset zone as shown in ROC curves: discriminant analysis (two-dimensional predicted seizure onset zone with 85% sensitivity and 91% specificity; logistic regression (four-dimensional achieved 86% sensitivity and 100% specificity. The strongest markers in both analyses were left thalamo-hippocampal and right thalamo-entorhinal cortex functional connection strength. Thus, this study shows that thalamic functional connections are sensitive and specific markers of seizure onset laterality in individual temporal lobe epilepsy patients. This study also advances an overall strategy for the programmatic development of neuroimaging biomarkers in clinical and genetic populations: a disease model informed by coordinate-based meta-analysis was used to anatomically constrain individual patient analyses.

  20. Multiple Biomarkers for the Prediction of First Major Cardiovascular Events and Death

    Science.gov (United States)

    Few investigations have evaluated the incremental usefulness of multiple biomarkers from distinct biologic pathways for predicting the risk of cardiovascular events. We measured 10 biomarkers in 3209 participants attending a routine examination cycle of the Framingham Heart Study: the levels of C-r...

  1. Identification of predictive biomarkers of disease state in transition dairy cows.

    Science.gov (United States)

    Hailemariam, D; Mandal, R; Saleem, F; Dunn, S M; Wishart, D S; Ametaj, B N

    2014-05-01

    phosphatidylcholine diacyl C42:6, could be used to discriminate healthy controls from diseased cows 1 wk before parturition. A 3-metabolite plasma biomarker profile was developed that could predict which cows would develop periparturient diseases, up to 4 wk before clinical symptoms appearing, with a sensitivity of 87% and a specificity of 85%. This is the first report showing that periparturient diseases can be predicted in dairy cattle before their development using a multimetabolite biomarker model. Further research is warranted to validate these potential predictive biomarkers. PMID:24630653

  2. Nanomaterial-Based Electrochemical Immunosensors for Clinically Significant Biomarkers

    Directory of Open Access Journals (Sweden)

    Niina J. Ronkainen

    2014-06-01

    Full Text Available Nanotechnology has played a crucial role in the development of biosensors over the past decade. The development, testing, optimization, and validation of new biosensors has become a highly interdisciplinary effort involving experts in chemistry, biology, physics, engineering, and medicine. The sensitivity, the specificity and the reproducibility of biosensors have improved tremendously as a result of incorporating nanomaterials in their design. In general, nanomaterials-based electrochemical immunosensors amplify the sensitivity by facilitating greater loading of the larger sensing surface with biorecognition molecules as well as improving the electrochemical properties of the transducer. The most common types of nanomaterials and their properties will be described. In addition, the utilization of nanomaterials in immunosensors for biomarker detection will be discussed since these biosensors have enormous potential for a myriad of clinical uses. Electrochemical immunosensors provide a specific and simple analytical alternative as evidenced by their brief analysis times, inexpensive instrumentation, lower assay cost as well as good portability and amenability to miniaturization. The role nanomaterials play in biosensors, their ability to improve detection capabilities in low concentration analytes yielding clinically useful data and their impact on other biosensor performance properties will be discussed. Finally, the most common types of electroanalytical detection methods will be briefly touched upon.

  3. Feature Selection Methods for Early Predictive Biomarker Discovery Using Untargeted Metabolomic Data.

    Science.gov (United States)

    Grissa, Dhouha; Pétéra, Mélanie; Brandolini, Marion; Napoli, Amedeo; Comte, Blandine; Pujos-Guillot, Estelle

    2016-01-01

    Untargeted metabolomics is a powerful phenotyping tool for better understanding biological mechanisms involved in human pathology development and identifying early predictive biomarkers. This approach, based on multiple analytical platforms, such as mass spectrometry (MS), chemometrics and bioinformatics, generates massive and complex data that need appropriate analyses to extract the biologically meaningful information. Despite various tools available, it is still a challenge to handle such large and noisy datasets with limited number of individuals without risking overfitting. Moreover, when the objective is focused on the identification of early predictive markers of clinical outcome, few years before occurrence, it becomes essential to use the appropriate algorithms and workflow to be able to discover subtle effects among this large amount of data. In this context, this work consists in studying a workflow describing the general feature selection process, using knowledge discovery and data mining methodologies to propose advanced solutions for predictive biomarker discovery. The strategy was focused on evaluating a combination of numeric-symbolic approaches for feature selection with the objective of obtaining the best combination of metabolites producing an effective and accurate predictive model. Relying first on numerical approaches, and especially on machine learning methods (SVM-RFE, RF, RF-RFE) and on univariate statistical analyses (ANOVA), a comparative study was performed on an original metabolomic dataset and reduced subsets. As resampling method, LOOCV was applied to minimize the risk of overfitting. The best k-features obtained with different scores of importance from the combination of these different approaches were compared and allowed determining the variable stabilities using Formal Concept Analysis. The results revealed the interest of RF-Gini combined with ANOVA for feature selection as these two complementary methods allowed selecting the 48

  4. Merging person-specific bio-markers for predicting oral cancer recurrence through an ontology.

    Science.gov (United States)

    Salvi, Dario; Picone, Marco; Arredondo, María Teresa; Cabrera-Umpierrez, María Fernanda; Esteban, Ángel; Steger, Sebastian; Poli, Tito

    2013-01-01

    One of the major problems related to cancer treatment is its recurrence. Without knowing in advance how likely the cancer will relapse, clinical practice usually recommends adjuvant treatments that have strong side effects. A way to optimize treatments is to predict the recurrence probability by analyzing a set of bio-markers. The NeoMark European project has identified a set of preliminary bio-markers for the case of oral cancer by collecting a large series of data from genomic, imaging, and clinical evidence. This heterogeneous set of data needs a proper representation in order to be stored, computed, and communicated efficiently. Ontologies are often considered the proper mean to integrate biomedical data, for their high level of formality and for the need of interoperable, universally accepted models. This paper presents the NeoMark system and how an ontology has been designed to integrate all its heterogeneous data. The system has been validated in a pilot in which data will populate the ontology and will be made public for further research. PMID:22955869

  5. DNA Repair Biomarkers Predict Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, Brian M., E-mail: bmalexander@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, Massachusetts (United States); Wang Xiaozhe [On-Q-ity, Inc., Waltham, Massachusetts (United States); Niemierko, Andrzej [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Weaver, David T. [On-Q-ity, Inc., Waltham, Massachusetts (United States); Mak, Raymond H. [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Cancer Center, Boston, Massachusetts (United States); Roof, Kevin S. [Southeast Radiation Oncology, Charlotte, North Carolina (United States); Fidias, Panagiotis [Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts (United States); Wain, John [Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts (United States); Choi, Noah C. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2012-05-01

    Purpose: The addition of neoadjuvant chemoradiotherapy prior to surgical resection for esophageal cancer has improved clinical outcomes in some trials. Pathologic complete response (pCR) following neoadjuvant therapy is associated with better clinical outcome in these patients, but only 22% to 40% of patients achieve pCR. Because both chemotherapy and radiotherapy act by inducing DNA damage, we analyzed proteins selected from multiple DNA repair pathways, using quantitative immunohistochemistry coupled with a digital pathology platform, as possible biomarkers of treatment response and clinical outcome. Methods and Materials: We identified 79 patients diagnosed with esophageal cancer between October 1994 and September 2002, with biopsy tissue available, who underwent neoadjuvant chemoradiotherapy prior to surgery at the Massachusetts General Hospital and used their archived, formalin-fixed, paraffin-embedded biopsy samples to create tissue microarrays (TMA). TMA sections were stained using antibodies against proteins in various DNA repair pathways including XPF, FANCD2, PAR, MLH1, PARP1, and phosphorylated MAPKAP kinase 2 (pMK2). Stained TMA slides were evaluated using machine-based image analysis, and scoring incorporated both the intensity and the quantity of positive tumor nuclei. Biomarker scores and clinical data were assessed for correlations with clinical outcome. Results: Higher scores for MLH1 (p = 0.018) and lower scores for FANCD2 (p = 0.037) were associated with pathologic response to neoadjuvant chemoradiation on multivariable analysis. Staining of MLH1, PARP1, XPF, and PAR was associated with recurrence-free survival, and staining of PARP1 and FANCD2 was associated with overall survival on multivariable analysis. Conclusions: DNA repair proteins analyzed by immunohistochemistry may be useful as predictive markers for response to neoadjuvant chemoradiotherapy in patients with esophageal cancer. These results are hypothesis generating and need

  6. DNA Repair Biomarkers Predict Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer

    International Nuclear Information System (INIS)

    Purpose: The addition of neoadjuvant chemoradiotherapy prior to surgical resection for esophageal cancer has improved clinical outcomes in some trials. Pathologic complete response (pCR) following neoadjuvant therapy is associated with better clinical outcome in these patients, but only 22% to 40% of patients achieve pCR. Because both chemotherapy and radiotherapy act by inducing DNA damage, we analyzed proteins selected from multiple DNA repair pathways, using quantitative immunohistochemistry coupled with a digital pathology platform, as possible biomarkers of treatment response and clinical outcome. Methods and Materials: We identified 79 patients diagnosed with esophageal cancer between October 1994 and September 2002, with biopsy tissue available, who underwent neoadjuvant chemoradiotherapy prior to surgery at the Massachusetts General Hospital and used their archived, formalin-fixed, paraffin-embedded biopsy samples to create tissue microarrays (TMA). TMA sections were stained using antibodies against proteins in various DNA repair pathways including XPF, FANCD2, PAR, MLH1, PARP1, and phosphorylated MAPKAP kinase 2 (pMK2). Stained TMA slides were evaluated using machine-based image analysis, and scoring incorporated both the intensity and the quantity of positive tumor nuclei. Biomarker scores and clinical data were assessed for correlations with clinical outcome. Results: Higher scores for MLH1 (p = 0.018) and lower scores for FANCD2 (p = 0.037) were associated with pathologic response to neoadjuvant chemoradiation on multivariable analysis. Staining of MLH1, PARP1, XPF, and PAR was associated with recurrence-free survival, and staining of PARP1 and FANCD2 was associated with overall survival on multivariable analysis. Conclusions: DNA repair proteins analyzed by immunohistochemistry may be useful as predictive markers for response to neoadjuvant chemoradiotherapy in patients with esophageal cancer. These results are hypothesis generating and need

  7. Personalized Circulating Tumor DNA Biomarkers Dynamically Predict Treatment Response and Survival In Gynecologic Cancers.

    Directory of Open Access Journals (Sweden)

    Elena Pereira

    Full Text Available High-grade serous ovarian and endometrial cancers are the most lethal female reproductive tract malignancies worldwide. In part, failure to treat these two aggressive cancers successfully centers on the fact that while the majority of patients are diagnosed based on current surveillance strategies as having a complete clinical response to their primary therapy, nearly half will develop disease recurrence within 18 months and the majority will die from disease recurrence within 5 years. Moreover, no currently used biomarkers or imaging studies can predict outcome following initial treatment. Circulating tumor DNA (ctDNA represents a theoretically powerful biomarker for detecting otherwise occult disease. We therefore explored the use of personalized ctDNA markers as both a surveillance and prognostic biomarker in gynecologic cancers and compared this to current FDA-approved surveillance tools.Tumor and serum samples were collected at time of surgery and then throughout treatment course for 44 patients with gynecologic cancers, representing 22 ovarian cancer cases, 17 uterine cancer cases, one peritoneal, three fallopian tube, and one patient with synchronous fallopian tube and uterine cancer. Patient/tumor-specific mutations were identified using whole-exome and targeted gene sequencing and ctDNA levels quantified using droplet digital PCR. CtDNA was detected in 93.8% of patients for whom probes were designed and levels were highly correlated with CA-125 serum and computed tomography (CT scanning results. In six patients, ctDNA detected the presence of cancer even when CT scanning was negative and, on average, had a predictive lead time of seven months over CT imaging. Most notably, undetectable levels of ctDNA at six months following initial treatment was associated with markedly improved progression free and overall survival.Detection of residual disease in gynecologic, and indeed all cancers, represents a diagnostic dilemma and a potential

  8. Personalized Circulating Tumor DNA Biomarkers Dynamically Predict Treatment Response and Survival In Gynecologic Cancers

    Science.gov (United States)

    Anand, Sanya; Sebra, Robert; Catalina Camacho, Sandra; Garnar-Wortzel, Leopold; Nair, Navya; Moshier, Erin; Wooten, Melissa; Uzilov, Andrew; Chen, Rong; Prasad-Hayes, Monica; Zakashansky, Konstantin; Beddoe, Ann Marie; Schadt, Eric; Dottino, Peter; Martignetti, John A.

    2015-01-01

    Background High-grade serous ovarian and endometrial cancers are the most lethal female reproductive tract malignancies worldwide. In part, failure to treat these two aggressive cancers successfully centers on the fact that while the majority of patients are diagnosed based on current surveillance strategies as having a complete clinical response to their primary therapy, nearly half will develop disease recurrence within 18 months and the majority will die from disease recurrence within 5 years. Moreover, no currently used biomarkers or imaging studies can predict outcome following initial treatment. Circulating tumor DNA (ctDNA) represents a theoretically powerful biomarker for detecting otherwise occult disease. We therefore explored the use of personalized ctDNA markers as both a surveillance and prognostic biomarker in gynecologic cancers and compared this to current FDA-approved surveillance tools. Methods and Findings Tumor and serum samples were collected at time of surgery and then throughout treatment course for 44 patients with gynecologic cancers, representing 22 ovarian cancer cases, 17 uterine cancer cases, one peritoneal, three fallopian tube, and one patient with synchronous fallopian tube and uterine cancer. Patient/tumor-specific mutations were identified using whole-exome and targeted gene sequencing and ctDNA levels quantified using droplet digital PCR. CtDNA was detected in 93.8% of patients for whom probes were designed and levels were highly correlated with CA-125 serum and computed tomography (CT) scanning results. In six patients, ctDNA detected the presence of cancer even when CT scanning was negative and, on average, had a predictive lead time of seven months over CT imaging. Most notably, undetectable levels of ctDNA at six months following initial treatment was associated with markedly improved progression free and overall survival. Conclusions Detection of residual disease in gynecologic, and indeed all cancers, represents a diagnostic

  9. Intensive serial biomarker profiling for the prediction of neutropenic fever in patients with hematologic malignancies undergoing chemotherapy: a pilot study

    Directory of Open Access Journals (Sweden)

    Steven M. Chan

    2014-06-01

    Full Text Available Neutropenic fever (NF is a life-threatening complication of myelosuppressive chemotherapy in patients with hematologic malignancies and triggers the administration of broad-spectrum antimicrobials. The ability to accurately predict NF would permit initiation of antimicrobials earlier in the course of infection with the goal of decreasing morbid complications and progression to septic shock and death. Changes in the blood level of inflammatory biomarkers may precede the occurrence of NF. To identify potential biomarkers for the prediction of NF, we performed serial meas- urements of nine biomarkers [C-reactive protein (CRP, protein C, interleukin (IL-6, IL-8, IL-10, IL-1β, tumor necrosis factor-α, monocyte chemotactic protein-1, and intercellular adhesion molecule-1] using a multiplex ELISA array platform every 6-8 hours in patients undergoing myelosuppressive chemotherapy for hematologic malignancies. We found that the blood levels of IL-6 and CRP increased significantly 24 to 48 hours prior to the onset of fever. In addition, we showed that frequent biomarker monitoring is feasible using a bedside micro sample test device. The results of this pilot study suggest that serial monitoring of IL-6 and CRP levels using a bedside device may be useful in the prediction of NF. Prospective studies involving a larger cohort of patients to validate this observation are warranted. This trial is registered at ClinicalTrials.gov (NCT01144793.

  10. Screening Preoperative Peptide Biomarkers for Predicting Postoperative Myocardial Infarction after Coronary Artery Bypass Grafting

    OpenAIRE

    Zhibin Jiang; Ping Hu; Jianxin Liu; Dianjun Wang; Longyu Jin; Chao Hong

    2014-01-01

    Postoperative myocardial infarction (PMI) is one of the most serious complications of cardiac surgeries. No preoperative biomarker is currently available for predicting PMI after cardiac surgeries. In the present study, we used a phage display peptide library to screen potential preoperative peptide biomarkers for predicting PMI after coronary artery bypass grafting (CABG) surgery. Twenty patients who developed PMI after CABG and 20 age-, sex-, and body mass index-matched patients without PMI...

  11. Noncoding RNAs as potential biomarkers to predict the outcome in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Jin K

    2015-02-01

    Full Text Available Kaizhou Jin,1–3,* Guopei Luo,1–3,* Zhiwen Xiao,1–3 Zuqiang Liu,1–3 Chen Liu,1–3 Shunrong Ji,1–3 Jin Xu,1–3 Liang Liu,1–3 Jiang Long,1–3 Quanxing Ni,1–3 Xianjun Yu1–3 1Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, 2Department of Oncology, Shanghai Medical College, Fudan University, 3Pancreatic Cancer Institute, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Pancreatic ductal adenocarcinoma (PDAC, a common digestive system cancer, is highly malignant and has a poor disease outcome. Currently, all available examination and detection methods cannot accurately predict the clinical outcome. Therefore, it is extremely important to identify novel molecular biomarkers for personalized medication and to significantly improve the overall outcome. The “noncoding RNAs” (ncRNAs are a group of RNAs that do not code for proteins, and they are categorized as structural RNAs and regulatory RNAs. It has been shown that microRNAs and long ncRNAs function as regulatory RNAs to affect the progression of various diseases. Many studies have confirmed a role for ncRNAs in the progression of PDAC during the last few years. Because of the significant role of ncRNAs in PDAC, ncRNA profiling may be used to predict PDAC outcome with high accuracy. This review comprehensively analyzes the value of ncRNAs as potential biomarkers to predict the outcome in PDAC and the possible mechanisms thereof. Keywords: pancreatic ductal adenocarcinoma, microRNA, long noncoding RNA, outcome prediction

  12. Biomarkers of oral premalignant epithelial lesions for clinical application.

    Science.gov (United States)

    Mishra, Rajakishore

    2012-07-01

    Oral cancer is the sixth most common form of cancer worldwide, and the majority of cases occur in India and Southeast Asia. Its major risk factors in the western world include smoking and drinking alcohol, whereas in Asia, it is primarily caused by tobacco/areca nut/betel leaf chewing and/or human papillomavirus (HPV) infections. Little is known about this type of cancer despite recent advances in cancer biology. The generally asymptomatic nature of the early oral lesions causes them to remain undetected in many cases. Thus, the disease progresses substantially before the patients seek treatment and is a major contributing factor to the severity of this disease. Therefore, there is a great need to create awareness for its prevention and early diagnosis. The application of advanced molecular biological and biochemical methodologies to elucidate its biomarkers may aid in early detection; however, much more work must be done for this information to be effectively applied in the clinical setting. This review focuses on the need for systematic diagnoses in the early detection of oral cancer using molecular and biochemical approaches, thereby reducing the number of advanced cases in the chewing tobacco-dominated oral cancer population. PMID:22342569

  13. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: III. The 2014 Biomarker Working Group Report.

    Science.gov (United States)

    Paczesny, Sophie; Hakim, Frances T; Pidala, Joseph; Cooke, Kenneth R; Lathrop, Julia; Griffith, Linda M; Hansen, John; Jagasia, Madan; Miklos, David; Pavletic, Steven; Parkman, Robertson; Russek-Cohen, Estelle; Flowers, Mary E D; Lee, Stephanie; Martin, Paul; Vogelsang, Georgia; Walton, Marc; Schultz, Kirk R

    2015-05-01

    Biology-based markers to confirm or aid in the diagnosis or prognosis of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation or monitor its progression are critically needed to facilitate evaluation of new therapies. Biomarkers have been defined as any characteristic that is objectively measured and evaluated as an indicator of a normal biological or pathogenic process, or of a pharmacologic response to a therapeutic intervention. Applications of biomarkers in chronic GVHD clinical trials or patient management include the following: (1) diagnosis and assessment of chronic GVHD disease activity, including distinguishing irreversible damage from continued disease activity; (2) prognostic risk to develop chronic GVHD; and (3) prediction of response to therapy. Sample collection for chronic GVHD biomarkers studies should be well documented following established quality control guidelines for sample acquisition, processing, preservation, and testing, at intervals that are both calendar and event driven. The consistent therapeutic treatment of subjects and standardized documentation needed to support biomarker studies are most likely to be provided in prospective clinical trials. To date, no chronic GVHD biomarkers have been qualified for use in clinical applications. Since our previous chronic GVHD Biomarkers Working Group report in 2005, an increasing number of chronic GVHD candidate biomarkers are available for further investigation. This paper provides a 4-part framework for biomarker investigations: identification, verification, qualification, and application with terminology based on Food and Drug Administration and European Medicines Agency guidelines. PMID:25644957

  14. Issues on fit-for-purpose validation of a panel of ELISAs for application as biomarkers in clinical trials of anti-Angiogenic drugs

    OpenAIRE

    Brookes, K; Cummings, J; Backen, A; Greystoke, A; Ward, T.; Jayson, G C; Dive, C

    2010-01-01

    Background: Successful introduction of new anticancer agents into the clinic is often hampered by a lack of qualified biomarkers. Studies have been conducted of 17 ELISAs representing a potential panel of pharmacodynamic/predictive biomarkers for drugs targeted to tumour vasculature. Methods: The fit-for-purpose approach to method validation was used. Stability studies were performed using recombinant proteins in surrogate matrices, endogenous analytes in healthy volunteer and cancer patient ...

  15. Levels and types of alcohol biomarkers in DUI and clinic samples for estimating workplace alcohol problems.

    Science.gov (United States)

    Marques, Paul R

    2012-02-01

    Widespread concern about illicit drugs as an aspect of workplace performance potentially diminishes attention on employee alcohol use. Alcohol is the dominant drug contributing to poor job performance; it also accounts for a third of the worldwide public health burden. Evidence from public roadways--a workplace for many--provides an example of work-related risk exposure and performance lapses. In most developed countries, alcohol is involved in 20-35% of fatal crashes; drugs other than alcohol are less prominently involved in fatalities. Alcohol biomarkers can improve detection by extending the timeframe for estimating problematic exposure levels and thereby provide better information for managers. But what levels and which markers are right for the workplace? In this paper, an established high-sensitivity proxy for alcohol-driving risk proclivity is used: an average eight months of failed blood alcohol concentration (BAC) breath tests from alcohol ignition interlock devices. Higher BAC test fail rates are known to presage higher rates of future impaired-driving convictions (driving under the influence; DUI). Drivers in alcohol interlock programmes log 5-7 daily BAC tests; in 12 months, this yields thousands of samples. Also, higher programme entry levels of alcohol biomarkers predict a higher likelihood of failed interlock BAC tests during subsequent months. This paper summarizes the potential of selected biomarkers for workplace screening. Markers include phosphatidylethanol (PEth), percent carbohydrate deficient transferrin (%CDT), gammaglutamyltransferase (GGT), gamma %CDT (γ%CDT), and ethylglucuronide (EtG) in hair. Clinical cut-off levels and median/mean levels of these markers in abstinent people, the general population, DUI drivers, and rehabilitation clinics are summarized for context. PMID:22311827

  16. Thalamic functional connectivity predicts seizure laterality in individual TLE patients: Application of a biomarker development strategy

    Science.gov (United States)

    Barron, Daniel S.; Fox, Peter T.; Pardoe, Heath; Lancaster, Jack; Price, Larry R.; Blackmon, Karen; Berry, Kristen; Cavazos, Jose E.; Kuzniecky, Ruben; Devinsky, Orrin; Thesen, Thomas

    2014-01-01

    Noninvasive markers of brain function could yield biomarkers in many neurological disorders. Disease models constrained by coordinate-based meta-analysis are likely to increase this yield. Here, we evaluate a thalamic model of temporal lobe epilepsy that we proposed in a coordinate-based meta-analysis and extended in a diffusion tractography study of an independent patient population. Specifically, we evaluated whether thalamic functional connectivity (resting-state fMRI-BOLD) with temporal lobe areas can predict seizure onset laterality, as established with intracranial EEG. Twenty-four lesional and non-lesional temporal lobe epilepsy patients were studied. No significant differences in functional connection strength in patient and control groups were observed with Mann-Whitney Tests (corrected for multiple comparisons). Notwithstanding the lack of group differences, individual patient difference scores (from control mean connection strength) successfully predicted seizure onset zone as shown in ROC curves: discriminant analysis (two-dimensional) predicted seizure onset zone with 85% sensitivity and 91% specificity; logistic regression (four-dimensional) achieved 86% sensitivity and 100% specificity. The strongest markers in both analyses were left thalamo-hippocampal and right thalamo-entorhinal cortex functional connection strength. Thus, this study shows that thalamic functional connections are sensitive and specific markers of seizure onset laterality in individual temporal lobe epilepsy patients. This study also advances an overall strategy for the programmatic development of neuroimaging biomarkers in clinical and genetic populations: a disease model informed by coordinate-based meta-analysis was used to anatomically constrain individual patient analyses. PMID:25610790

  17. Continuous Metabolic Monitoring Based on Multi-Analyte Biomarkers to Predict Exhaustion

    OpenAIRE

    Michail Kastellorizios; Burgess, Diane J

    2015-01-01

    This work introduces the concept of multi-analyte biomarkers for continuous metabolic monitoring. The importance of using more than one marker lies in the ability to obtain a holistic understanding of the metabolism. This is showcased for the detection and prediction of exhaustion during intense physical exercise. The findings presented here indicate that when glucose and lactate changes over time are combined into multi-analyte biomarkers, their monitoring trends are more sensitive in the su...

  18. Neuroimaging biomarkers to predict treatment response in schizophrenia: the end of 30 years of solitude?

    Science.gov (United States)

    Dazzan, Paola

    2014-12-01

    Studies that have used structural magnetic resonance imaging (MRI) suggest that individuals with psychoses have brain alterations, particularly in frontal and temporal cortices, and in the white matter tracts that connect them. Furthermore, these studies suggest that brain alterations may be particularly prominent, already at illness onset, in those individuals more likely to have poorer outcomes (eg, higher number of hospital admissions, and poorer symptom remission, level of functioning, and response to the first treatment with antipsychotic drugs). The fact that, even when present, these brain alterations are subtle and distributed in nature, has limited, until now, the utility of MRI in the clinical management of these disorders. More recently, MRI approaches, such as machine learning, have suggested that these neuroanatomical biomarkers can be used for direct clinical benefits. For example, using support vector machine, MRI data obtained at illness onset have been used to predict, with significant accuracy, whether a specific individual is likely to experience a remission of symptoms later on in the course of the illness. Taken together, this evidence suggests that validated, strong neuroanatomical markers could be used not only to inform tailored intervention strategies in a single individual, but also to allow patient stratification in clinical trials for new treatments. PMID:25733954

  19. Evaluation of biomarkers of cell cycle arrest and inflammation in prediction of dialysis or recovery after kidney transplantation.

    Science.gov (United States)

    Pianta, Timothy J; Peake, Philip W; Pickering, John W; Kelleher, Michaela; Buckley, Nicholas A; Endre, Zoltan H

    2015-12-01

    Early prediction of delayed graft function (DGF) after kidney transplantation would facilitate patient management. Cell cycle arrest and inflammation are implicated in the pathogenesis of DGF. We assessed the utility of two novel acute kidney injury (AKI) biomarkers, urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), and five inflammatory markers to predict DGF following deceased-donor kidney transplantation. Serial urine concentrations of TIMP-2 and IGFBP7 were measured immediately after transplantation in 56 recipients along with vascular endothelial growth factor-A (VEGF-A), macrophage migration inhibitory factor (MIF), monocyte chemotactic protein-1 (MCP-1), trefoil factor 3 (TFF3) and chemokine (C-X-C) ligand 16 (CXCL16). Delayed graft function (DGF) was defined as requirement for dialysis within 7 days. Integrated discrimination improvement analysis was used to evaluate whether these biomarkers enhanced prediction of DGF independently of a validated clinical risk prediction model. DGF occurred in 22 patients (39%). At 4 h after kidney reperfusion, the area under the receiver operator characteristic curve (AUC) for VEGF-A was good (AUC > 0.80); for TIMP-2, IGFBP7 and [TIMP-2] × [IGFBP7] fair (AUCs 0.70-0.79); and for MIF, MCP-1, TFF3 and CXCL16 poor (AUC < 0.70). Only TIMP-2 and VEGF significantly enhanced the DGF prediction at 4 and 12 h. The cell cycle arrest marker urinary TIMP-2 and the inflammatory biomarker VEGF-A are potentially useful adjuncts to clinical data for early prediction of DGF. PMID:26174580

  20. Background rhythm frequency and theta power of quantitative EEG analysis: predictive biomarkers for cognitive impairment post-cerebral infarcts.

    Science.gov (United States)

    Song, Yang; Zang, Da-Wei; Jin, Yan-Yu; Wang, Zhi-Jun; Ni, Hong-Yan; Yin, Jian-Zhong; Ji, Dong-Xu

    2015-04-01

    In clinical settings, cerebral infarct is a common disease of older adults, which usually increases the risk of cognitive impairment. This study aims to assess the quantitative electroencephalography (qEEG) as a predictive biomarker for the development of cognitive impairment, post-cerebral infarcts, in subjects from the Department of Neurology. They underwent biennial EEG recording. Cerebral infarct subjects, with follow-up cognitive evaluation, were analyzed for qEEG measures of background rhythm frequency (BRF) and relative δ, θ, α, and β band power. The relationship between cognitive impairment and qEEG, and other possible predictors, was assessed by Cox regression. The results showed that the risk hazard of developing cognitive impairment was 14 times higher for those with low BRF than for those with high BRF (P BRF, and relative power in θ band, are potential predictive biomarkers for cognitive impairment in patients with cerebral infarcts. These biomarkers might be valuable in early prediction of cognitive impairment in patients with cerebral infarcts. PMID:24699438

  1. Predicting total, abdominal, visceral and hepatic adiposity with circulating biomarkers in Caucasian and Japanese American women.

    Directory of Open Access Journals (Sweden)

    Unhee Lim

    Full Text Available BACKGROUND: Characterization of abdominal and intra-abdominal fat requires imaging, and thus is not feasible in large epidemiologic studies. OBJECTIVE: We investigated whether biomarkers may complement anthropometry (body mass index [BMI], waist circumference [WC], and waist-hip ratio [WHR] in predicting the size of the body fat compartments by analyzing blood biomarkers, including adipocytokines, insulin resistance markers, sex steroid hormones, lipids, liver enzymes and gastro-neuropeptides. METHODS: Fasting levels of 58 blood markers were analyzed in 60 healthy, Caucasian or Japanese American postmenopausal women who underwent anthropometric measurements, dual energy X-ray absorptiometry (DXA, and abdominal magnetic resonance imaging. Total, abdominal, visceral and hepatic adiposity were predicted based on anthropometry and the biomarkers using Random Forest models. RESULTS: Total body fat was well predicted by anthropometry alone (R(2 = 0.85, by the 5 best predictors from the biomarker model alone (leptin, leptin-adiponectin ratio [LAR], free estradiol, plasminogen activator inhibitor-1 [PAI1], alanine transaminase [ALT]; R(2 = 0.69, or by combining these 5 biomarkers with anthropometry (R(2 = 0.91. Abdominal adiposity (DXA trunk-to-periphery fat ratio was better predicted by combining the two types of predictors (R(2 = 0.58 than by anthropometry alone (R(2 = 0.53 or the 5 best biomarkers alone (25(OH-vitamin D(3, insulin-like growth factor binding protein-1 [IGFBP1], uric acid, soluble leptin receptor [sLEPR], Coenzyme Q10; R(2 = 0.35. Similarly, visceral fat was slightly better predicted by combining the predictors (R(2 = 0.68 than by anthropometry alone (R(2 = 0.65 or the 5 best biomarker predictors alone (leptin, C-reactive protein [CRP], LAR, lycopene, vitamin D(3; R(2 = 0.58. Percent liver fat was predicted better by the 5 best biomarker predictors (insulin, sex hormone binding globulin [SHBG], LAR, alpha-tocopherol, PAI1; R(2 = 0

  2. Prediction of lung cancer based on serum biomarkers by gene expression programming methods.

    Science.gov (United States)

    Yu, Zhuang; Chen, Xiao-Zheng; Cui, Lian-Hua; Si, Hong-Zong; Lu, Hai-Jiao; Liu, Shi-Hai

    2014-01-01

    In diagnosis of lung cancer, rapid distinction between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) tumors is very important. Serum markers, including lactate dehydrogenase (LDH), C-reactive protein (CRP), carcino-embryonic antigen (CEA), neurone specific enolase (NSE) and Cyfra21-1, are reported to reflect lung cancer characteristics. In this study classification of lung tumors was made based on biomarkers (measured in 120 NSCLC and 60 SCLC patients) by setting up optimal biomarker joint models with a powerful computerized tool - gene expression programming (GEP). GEP is a learning algorithm that combines the advantages of genetic programming (GP) and genetic algorithms (GA). It specifically focuses on relationships between variables in sets of data and then builds models to explain these relationships, and has been successfully used in formula finding and function mining. As a basis for defining a GEP environment for SCLC and NSCLC prediction, three explicit predictive models were constructed. CEA and NSE are frequently- used lung cancer markers in clinical trials, CRP, LDH and Cyfra21-1 have significant meaning in lung cancer, basis on CEA and NSE we set up three GEP models-GEP 1(CEA, NSE, Cyfra21-1), GEP2 (CEA, NSE, LDH), GEP3 (CEA, NSE, CRP). The best classification result of GEP gained when CEA, NSE and Cyfra21-1 were combined: 128 of 135 subjects in the training set and 40 of 45 subjects in the test set were classified correctly, the accuracy rate is 94.8% in training set; on collection of samples for testing, the accuracy rate is 88.9%. With GEP2, the accuracy was significantly decreased by 1.5% and 6.6% in training set and test set, in GEP3 was 0.82% and 4.45% respectively. Serum Cyfra21-1 is a useful and sensitive serum biomarker in discriminating between NSCLC and SCLC. GEP modeling is a promising and excellent tool in diagnosis of lung cancer. PMID:25422226

  3. How to Establish Clinical Prediction Models.

    Science.gov (United States)

    Lee, Yong Ho; Bang, Heejung; Kim, Dae Jung

    2016-03-01

    A clinical prediction model can be applied to several challenging clinical scenarios: screening high-risk individuals for asymptomatic disease, predicting future events such as disease or death, and assisting medical decision-making and health education. Despite the impact of clinical prediction models on practice, prediction modeling is a complex process requiring careful statistical analyses and sound clinical judgement. Although there is no definite consensus on the best methodology for model development and validation, a few recommendations and checklists have been proposed. In this review, we summarize five steps for developing and validating a clinical prediction model: preparation for establishing clinical prediction models; dataset selection; handling variables; model generation; and model evaluation and validation. We also review several studies that detail methods for developing clinical prediction models with comparable examples from real practice. After model development and vigorous validation in relevant settings, possibly with evaluation of utility/usability and fine-tuning, good models can be ready for the use in practice. We anticipate that this framework will revitalize the use of predictive or prognostic research in endocrinology, leading to active applications in real clinical practice. PMID:26996421

  4. Perceived age as clinically useful biomarker of ageing: cohort study

    DEFF Research Database (Denmark)

    Christensen, Kaare; Thinggaard, Mikael; McGue, Matt;

    2009-01-01

    young men, and 11 older women (assessors); 1826 twins aged >or=70. MAIN OUTCOME MEASURES: Assessors: perceived age of twins from photographs. Twins: physical and cognitive tests and molecular biomarker of ageing (leucocyte telomere length). RESULTS: For all three groups of assessors, perceived age was...

  5. Usability of cerebrospinal fluid biomarkers in a tertiary memory clinic

    DEFF Research Database (Denmark)

    Brandt, C.; Bahl, J.C.; Heegaard, N.H.;

    2008-01-01

    AIM: Assays for cerebrospinal fluid (CSF) levels of total tau, phospho-tau protein and beta-amyloid 1-42 have been available for some years. The aim of the study was to assess the usability of these biomarkers in a mixed population of tertiary dementia referral patients in a university-based memory...

  6. Robust Early Pregnancy Prediction of Later Preeclampsia Using Metabolomic Biomarkers.

    LENUS (Irish Health Repository)

    Kenny, Louise C

    2010-09-13

    Preeclampsia is a pregnancy-specific syndrome that causes substantial maternal and fetal morbidity and mortality. The etiology is incompletely understood, and there is no clinically useful screening test. Current metabolomic technologies have allowed the establishment of metabolic signatures of preeclampsia in early pregnancy. Here, a 2-phase discovery\\/validation metabolic profiling study was performed. In the discovery phase, a nested case-control study was designed, using samples obtained at 15±1 weeks\\' gestation from 60 women who subsequently developed preeclampsia and 60 controls taking part in the prospective Screening for Pregnancy Endpoints cohort study. Controls were proportionally population matched for age, ethnicity, and body mass index at booking. Plasma samples were analyzed using ultra performance liquid chromatography-mass spectrometry. A multivariate predictive model combining 14 metabolites gave an odds ratio for developing preeclampsia of 36 (95% CI: 12 to 108), with an area under the receiver operator characteristic curve of 0.94. These findings were then validated using an independent case-control study on plasma obtained at 15±1 weeks from 39 women who subsequently developed preeclampsia and 40 similarly matched controls from a participating center in a different country. The same 14 metabolites produced an odds ratio of 23 (95% CI: 7 to 73) with an area under receiver operator characteristic curve of 0.92. The finding of a consistent discriminatory metabolite signature in early pregnancy plasma preceding the onset of preeclampsia offers insight into disease pathogenesis and offers the tantalizing promise of a robust presymptomatic screening test.

  7. Robust early pregnancy prediction of later preeclampsia using metabolomic biomarkers.

    LENUS (Irish Health Repository)

    Kenny, Louise C

    2012-01-31

    Preeclampsia is a pregnancy-specific syndrome that causes substantial maternal and fetal morbidity and mortality. The etiology is incompletely understood, and there is no clinically useful screening test. Current metabolomic technologies have allowed the establishment of metabolic signatures of preeclampsia in early pregnancy. Here, a 2-phase discovery\\/validation metabolic profiling study was performed. In the discovery phase, a nested case-control study was designed, using samples obtained at 15+\\/-1 weeks\\' gestation from 60 women who subsequently developed preeclampsia and 60 controls taking part in the prospective Screening for Pregnancy Endpoints cohort study. Controls were proportionally population matched for age, ethnicity, and body mass index at booking. Plasma samples were analyzed using ultra performance liquid chromatography-mass spectrometry. A multivariate predictive model combining 14 metabolites gave an odds ratio for developing preeclampsia of 36 (95% CI: 12 to 108), with an area under the receiver operator characteristic curve of 0.94. These findings were then validated using an independent case-control study on plasma obtained at 15+\\/-1 weeks from 39 women who subsequently developed preeclampsia and 40 similarly matched controls from a participating center in a different country. The same 14 metabolites produced an odds ratio of 23 (95% CI: 7 to 73) with an area under receiver operator characteristic curve of 0.92. The finding of a consistent discriminatory metabolite signature in early pregnancy plasma preceding the onset of preeclampsia offers insight into disease pathogenesis and offers the tantalizing promise of a robust presymptomatic screening test.

  8. CSF Biomarkers of Alzheimer’s Disease: Impact on Disease Concept, Diagnosis, and Clinical Trial Design

    OpenAIRE

    Fagan, Anne M.

    2014-01-01

    Data from clinicopathologic and biomarker studies have converged to support the view of Alzheimer’s disease (AD) as a continuum, with pathology developing decades prior to the onset of cognitive symptoms which culminate as dementia at the end stage of the disease. This concept is impacting disease nomenclature, diagnostic criteria, prognostic potential, and clinical trial design. Revisions to diagnostic criteria to incorporate biomarker results have recently been proposed in order to increase...

  9. CAIDE Dementia Risk Score and biomarkers of neurodegeneration in memory clinic patients without dementia.

    Science.gov (United States)

    Enache, Daniela; Solomon, Alina; Cavallin, Lena; Kåreholt, Ingemar; Kramberger, Milica Gregoric; Aarsland, Dag; Kivipelto, Miia; Eriksdotter, Maria; Winblad, Bengt; Jelic, Vesna

    2016-06-01

    The aim of this study was to explore cross-sectional associations between Cardiovascular Risk Factors, Aging and Dementia Study (CAIDE) Dementia Risk Score and dementia-related cerebrospinal fluid and neuroimaging biomarkers in 724 patients without dementia from the Memory Clinic at Karolinska University Hospital, Huddinge, Sweden. We additionally evaluated the score's capacity to predict dementia. Two risk score versions were calculated: one including age, gender, obesity, hyperlipidemia, and hypertension; and one additionally including apolipoprotein E (APOE) ε4 carrier status. Cerebrospinal fluid was analyzed for amyloid β (Aβ), total tau, and phosphorylated tau. Visual assessments of medial temporal lobe atrophy (MTA), global cortical atrophy-frontal subscale, and Fazekas scale for white matter changes (WMC) were performed. Higher CAIDE Dementia Risk Score (version without APOE) was significantly associated with higher total tau, more severe MTA, WMC, and global cortical atrophy-frontal subscale. Higher CAIDE Dementia Risk Score (version with APOE) was associated with reduced Aβ, more severe MTA, and WMC. CAIDE Dementia Risk Score version with APOE seemed to predict dementia better in this memory clinic population with short follow-up than the version without APOE. PMID:27143429

  10. Outcome Prediction in Clinical Treatment Processes.

    Science.gov (United States)

    Huang, Zhengxing; Dong, Wei; Ji, Lei; Duan, Huilong

    2016-01-01

    Clinical outcome prediction, as strong implications for health service delivery of clinical treatment processes (CTPs), is important for both patients and healthcare providers. Prior studies typically use a priori knowledge, such as demographics or patient physical factors, to estimate clinical outcomes at early stages of CTPs (e.g., admission). They lack the ability to deal with temporal evolution of CTPs. In addition, most of the existing studies employ data mining or machine learning methods to generate a prediction model for a specific type of clinical outcome, however, a mathematical model that predicts multiple clinical outcomes simultaneously, has not yet been established. In this study, a hybrid approach is proposed to provide a continuous predictive monitoring service on multiple clinical outcomes. More specifically, a probabilistic topic model is applied to discover underlying treatment patterns of CTPs from electronic medical records. Then, the learned treatment patterns, as low-dimensional features of CTPs, are exploited for clinical outcome prediction across various stages of CTPs based on multi-label classification. The proposal is evaluated to predict three typical classes of clinical outcomes, i.e., length of stay, readmission time, and the type of discharge, using 3492 pieces of patients' medical records of the unstable angina CTP, extracted from a Chinese hospital. The stable model was characterized by 84.9% accuracy and 6.4% hamming-loss with 3 latent treatment patterns discovered from data, which outperforms the benchmark multi-label classification algorithms for clinical outcome prediction. Our study indicates the proposed approach can potentially improve the quality of clinical outcome prediction, and assist physicians to understand the patient conditions, treatment inventions, and clinical outcomes in an integrated view. PMID:26573645

  11. Is Abeta a sufficient Biomarker for monitoring anti-Abeta clinical studies? A critical review.

    Directory of Open Access Journals (Sweden)

    Katharina Zimmermann Schindowski

    2013-07-01

    Full Text Available Amyloid-beta (Aβ in Alzheimer’s disease (AD appeared to be a promising target for disease-modifying therapeutic strategies like passive immunotherapy with anti-Aβ monoclonal antibodies (mAbs. Biochemical markers in cerebrospinal fluid (CSF include alterations of Aβ that allow the diagnosis of AD. Biomarker strategies, such as the levels of Aβ in CSF and plasma, currently play an important role in early clinical trials for AD. Indeed, these strategies have a relevant impact on the outcome of such studies, since the biomarkers are used to monitor the bioactivity of anti-Aβ mAbs. The clinical trials of Solanezumab were mainly based on the readout of Aβ levels in CSF and plasma, whereas those of Bapineuzumab were based on cognition; however, little is known about the mechanisms altering these biomarker levels, and no biomarker has yet been proven to be a successful predictor for AD therapy. In addition, the Aβ biomarkers allow for the determination of free and bound anti-Aβ mAb in order to monitor the available amount of bioactive drug and could give hints to the mechanism of action. In this review, we discuss clinicalbiomarker data and the latest regulatory strategies.

  12. Is abeta a sufficient biomarker for monitoring anti-abeta clinical studies? A critical review.

    Science.gov (United States)

    Moreth, Jens; Mavoungou, Chrystelle; Schindowski, Katharina

    2013-01-01

    Amyloid-beta (Aβ) in Alzheimer's disease (AD) appeared to be a promising target for disease-modifying therapeutic strategies like passive immunotherapy with anti-Aβ monoclonal antibodies (mAbs). Biochemical markers in cerebrospinal fluid (CSF) include alterations of Aβ that allow the diagnosis of AD. Biomarker strategies, such as the levels of Aβ in CSF and plasma, currently play an important role in early clinical trials for AD. Indeed, these strategies have a relevant impact on the outcome of such studies, since the biomarkers are used to monitor the bioactivity of anti-Aβ mAbs. The clinical trials of Solanezumab were mainly based on the readout of Aβ levels in CSF and plasma, whereas those of Bapineuzumab were based on cognition; however, little is known about the mechanisms altering these biomarker levels, and no biomarker has yet been proven to be a successful predictor for AD therapy. In addition, the Aβ biomarkers allow for the determination of free and bound anti-Aβ mAb in order to monitor the available amount of bioactive drug and could give hints to the mechanism of action. In this review, we discuss clinicalbiomarker data and the latest regulatory strategies. PMID:23847530

  13. Biomarkers of respiratory syncytial virus (RSV) infection: specific neutrophil and cytokine levels provide increased accuracy in predicting disease severity.

    Science.gov (United States)

    Brown, Paul M; Schneeberger, Dana L; Piedimonte, Giovanni

    2015-09-01

    Despite fundamental advances in the research on respiratory syncytial virus (RSV) since its initial identification almost 60 years ago, recurring failures in developing vaccines and pharmacologic strategies effective in controlling the infection have allowed RSV to become a leading cause of global infant morbidity and mortality. Indeed, the burden of this infection on families and health care organizations worldwide continues to escalate and its financial costs are growing. Furthermore, strong epidemiologic evidence indicates that early-life lower respiratory tract infections caused by RSV lead to the development of recurrent wheezing and childhood asthma. While some progress has been made in the identification of reliable biomarkers for RSV bronchiolitis, a "one size fits all" biomarker capable of accurately and consistently predicting disease severity and post-acute outcomes has yet to be discovered. Therefore, it is of great importance on a global scale to identify useful biomarkers for this infection that will allow pediatricians to cost-effectively predict the clinical course of the disease, as well as monitor the efficacy of new therapeutic strategies. PMID:26074450

  14. Levels and Types of Alcohol Biomarkers in DUI and Clinic Samples for Estimating Workplace Alcohol Problemsa

    Science.gov (United States)

    Marques, Paul R

    2013-01-01

    Widespread concern about illicit drugs as an aspect of workplace performance potentially diminishes attention on employee alcohol use. Alcohol is the dominant drug contributing to poor job performance; it also accounts for a third of the worldwide public health burden. Evidence from public roadways – a workplace for many – provides an example for work-related risk exposure and performance lapses. In most developed countries, alcohol is involved in 20-35% of fatal crashes; drugs other than alcohol are less prominently involved in fatalities. Alcohol biomarkers can improve detection by extending the timeframe for estimating problematic exposure levels and thereby provide better information for managers. But what levels and which markers are right for the workplace? In this report, an established high-sensitivity proxy for alcohol-driving risk proclivity is used: an average 8 months of failed blood alcohol concentration (BAC) breath tests from alcohol ignition interlock devices. Higher BAC test fail rates are known to presage higher rates of future impaired-driving convictions (DUI). Drivers in alcohol interlock programs log 5-7 daily BAC tests; in 12 months, this yields thousands of samples. Also, higher program entry levels of alcohol biomarkers predict a higher likelihood of failed interlock BAC tests during subsequent months. This report summarizes selected biomarkers’ potential for workplace screening. Markers include phosphatidylethanol (PEth), percent carbohydrate deficient transferrin (%CDT), gammaglutamyltransferase (GGT), gamma %CDT (γ%CDT), and ethylglucuronide (EtG) in hair. Clinical cutoff levels and median/mean levels of these markers in abstinent people, the general population, DUI drivers, and rehabilitation clinics are summarized for context. PMID:22311827

  15. Validation of Novel Biomarkers for Prostate Cancer Progression by the Combination of Bioinformatics, Clinical and Functional Studies

    Science.gov (United States)

    Väänänen, Riina-Minna; Mattsson, Jesse; Li, Yifeng; Tallgrén, Terhi; Tong Ochoa, Natalia; Bjartell, Anders; Åkerfelt, Malin; Taimen, Pekka; Boström, Peter J.

    2016-01-01

    The identification and validation of biomarkers for clinical applications remains an important issue for improving diagnostics and therapy in many diseases, including prostate cancer. Gene expression profiles are routinely applied to identify diagnostic and predictive biomarkers or novel targets for cancer. However, only few predictive markers identified in silico have also been validated for clinical, functional or mechanistic relevance in disease progression. In this study, we have used a broad, bioinformatics-based approach to identify such biomarkers across a spectrum of progression stages, including normal and tumor-adjacent, premalignant, primary and late stage lesions. Bioinformatics data mining combined with clinical validation of biomarkers by sensitive, quantitative reverse-transcription PCR (qRT-PCR), followed by functional evaluation of candidate genes in disease-relevant processes, such as cancer cell proliferation, motility and invasion. From 300 initial candidates, eight genes were selected for validation by several layers of data mining and filtering. For clinical validation, differential mRNA expression of selected genes was measured by qRT-PCR in 197 clinical prostate tissue samples including normal prostate, compared against histologically benign and cancerous tissues. Based on the qRT-PCR results, significantly different mRNA expression was confirmed in normal prostate versus malignant PCa samples (for all eight genes), but also in cancer-adjacent tissues, even in the absence of detectable cancer cells, thus pointing to the possibility of pronounced field effects in prostate lesions. For the validation of the functional properties of these genes, and to demonstrate their putative relevance for disease-relevant processes, siRNA knock-down studies were performed in both 2D and 3D organotypic cell culture models. Silencing of three genes (DLX1, PLA2G7 and RHOU) in the prostate cancer cell lines PC3 and VCaP by siRNA resulted in marked growth arrest

  16. Prognostic Value of Multiple Biomarkers in American Indians Free of Clinically Overt Cardiovascular Disease (From the Strong Heart Study)

    OpenAIRE

    Kizer, Jorge R; Krauser, Daniel G.; Rodeheffer, Richard J.; Burnett, John C.; Okin, Peter M; Roman, Mary J.; Umans, Jason G.; Best, Lyle G.; Lee, Elisa T.; Devereux, Richard B.

    2009-01-01

    Several biomarkers have been documented, singly or jointly, to improve risk prediction, but the extent to which they improve prediction-model performance in populations with high prevalences of obesity and diabetes has not been specifically examined. We sought to evaluate the ability of various biomarkers to improve prediction-model performance for death and major cardiovascular (CVD) events in a high-risk population. The relations of 6 biomarkers with outcome were examined in 823 American In...

  17. Predicting mortality with biomarkers: a population-based prospective cohort study for elderly Costa Ricans

    Directory of Open Access Journals (Sweden)

    Rosero-Bixby Luis

    2012-06-01

    Full Text Available Abstract Background Little is known about adult health and mortality relationships outside high-income nations, partly because few datasets have contained biomarker data in representative populations. Our objective is to determine the prognostic value of biomarkers with respect to total and cardiovascular mortality in an elderly population of a middle-income country, as well as the extent to which they mediate the effects of age and sex on mortality. Methods This is a prospective population-based study in a nationally representative sample of elderly Costa Ricans. Baseline interviews occurred mostly in 2005 and mortality follow-up went through December 2010. Sample size after excluding observations with missing values: 2,313 individuals and 564 deaths. Main outcome: prospective death rate ratios for 22 baseline biomarkers, which were estimated with hazard regression models. Results Biomarkers significantly predict future death above and beyond demographic and self-reported health conditions. The studied biomarkers account for almost half of the effect of age on mortality. However, the sex gap in mortality became several times wider after controlling for biomarkers. The most powerful predictors were simple physical tests: handgrip strength, pulmonary peak flow, and walking speed. Three blood tests also predicted prospective mortality: C-reactive protein (CRP, glycated hemoglobin (HbA1c, and dehydroepiandrosterone sulfate (DHEAS. Strikingly, high blood pressure (BP and high total cholesterol showed little or no predictive power. Anthropometric measures also failed to show significant mortality effects. Conclusions This study adds to the growing evidence that blood markers for CRP, HbA1c, and DHEAS, along with organ-specific functional reserve indicators (handgrip, walking speed, and pulmonary peak flow, are valuable tools for identifying vulnerable elderly. The results also highlight the need to better understand an anomaly noted previously in

  18. Circulating biomarkers for predicting cardiovascular disease risk; a systematic review and comprehensive overview of meta-analyses.

    Directory of Open Access Journals (Sweden)

    Thijs C van Holten

    Full Text Available BACKGROUND: Cardiovascular disease is one of the major causes of death worldwide. Assessing the risk for cardiovascular disease is an important aspect in clinical decision making and setting a therapeutic strategy, and the use of serological biomarkers may improve this. Despite an overwhelming number of studies and meta-analyses on biomarkers and cardiovascular disease, there are no comprehensive studies comparing the relevance of each biomarker. We performed a systematic review of meta-analyses on levels of serological biomarkers for atherothrombosis to compare the relevance of the most commonly studied biomarkers. METHODS AND FINDINGS: Medline and Embase were screened on search terms that were related to "arterial ischemic events" and "meta-analyses". The meta-analyses were sorted by patient groups without pre-existing cardiovascular disease, with cardiovascular disease and heterogeneous groups concerning general populations, groups with and without cardiovascular disease, or miscellaneous. These were subsequently sorted by end-point for cardiovascular disease or stroke and summarized in tables. We have identified 85 relevant full text articles, with 214 meta-analyses. Markers for primary cardiovascular events include, from high to low result: C-reactive protein, fibrinogen, cholesterol, apolipoprotein B, the apolipoprotein A/apolipoprotein B ratio, high density lipoprotein, and vitamin D. Markers for secondary cardiovascular events include, from high to low result: cardiac troponins I and T, C-reactive protein, serum creatinine, and cystatin C. For primary stroke, fibrinogen and serum uric acid are strong risk markers. Limitations reside in that there is no acknowledged search strategy for prognostic studies or meta-analyses. CONCLUSIONS: For primary cardiovascular events, markers with strong predictive potential are mainly associated with lipids. For secondary cardiovascular events, markers are more associated with ischemia. Fibrinogen is a

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

    Directory of Open Access Journals (Sweden)

    Martín Gómez Ravetti

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

  20. The Clinical Impact of Recent Advances in LC-MS for Cancer Biomarker Discovery and Verification

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hui; Shi, Tujin; Qian, Weijun; Liu, Tao; Kagan, Jacob; Srivastava, Sudhir; Smith, Richard D.; Rodland, Karin D.; Camp, David G.

    2016-01-01

    Mass spectrometry-based proteomics has become an indispensable tool in biomedical research with broad applications ranging from fundamental biology, systems biology, and biomarker discovery. Recent advances in LC-MS have made it become a major technology in clinical applications, especially in cancer biomarker discovery and verification. To overcome the challenges associated with the analysis of clinical samples, such as extremely wide dynamic range of protein concentrations in biofluids and the need to perform high throughput and accurate quantification, significant efforts have been devoted to improve the overall performance of LC-MS bases clinical proteomics. In this review, we summarize the recent advances in LC-MS in the aspect of cancer biomarker discovery and quantification, and discuss its potentials, limitations, and future perspectives.

  1. The clinical impact of recent advances in LC-MS for cancer biomarker discovery and verification.

    Science.gov (United States)

    Wang, Hui; Shi, Tujin; Qian, Wei-Jun; Liu, Tao; Kagan, Jacob; Srivastava, Sudhir; Smith, Richard D; Rodland, Karin D; Camp, David G

    2016-01-01

    Mass spectrometry (MS) -based proteomics has become an indispensable tool with broad applications in systems biology and biomedical research. With recent advances in liquid chromatography (LC) and MS instrumentation, LC-MS is making increasingly significant contributions to clinical applications, especially in the area of cancer biomarker discovery and verification. To overcome challenges associated with analyses of clinical samples (for example, a wide dynamic range of protein concentrations in bodily fluids and the need to perform high throughput and accurate quantification of candidate biomarker proteins), significant efforts have been devoted to improve the overall performance of LC-MS-based clinical proteomics platforms. Reviewed here are the recent advances in LC-MS and its applications in cancer biomarker discovery and quantification, along with the potentials, limitations and future perspectives. PMID:26581546

  2. Multiplex assays for biomarker research and clinical application: translational science coming of age.

    Science.gov (United States)

    Fu, Qin; Schoenhoff, Florian S; Savage, William J; Zhang, Pingbo; Van Eyk, Jennifer E

    2010-03-01

    Over the last decade, translational science has come into the focus of academic medicine, and significant intellectual and financial efforts have been made to initiate a multitude of bench-to-bedside projects. The quest for suitable biomarkers that will significantly change clinical practice has become one of the biggest challenges in translational medicine. Quantitative measurement of proteins is a critical step in biomarker discovery. Assessing a large number of potential protein biomarkers in a statistically significant number of samples and controls still constitutes a major technical hurdle. Multiplexed analysis offers significant advantages regarding time, reagent cost, sample requirements and the amount of data that can be generated. The two contemporary approaches in multiplexed and quantitative biomarker validation, antibody-based immunoassays and MS-based multiple (or selected) reaction monitoring, are based on different assay principles and instrument requirements. Both approaches have their own advantages and disadvantages and therefore have complementary roles in the multi-staged biomarker verification and validation process. In this review, we discuss quantitative immunoassay and multiple reaction monitoring/selected reaction monitoring assay principles and development. We also discuss choosing an appropriate platform, judging the performance of assays, obtaining reliable, quantitative results for translational research and clinical applications in the biomarker field. PMID:21137048

  3. Alzheimer's disease biomarkers as outcome measures for clinical trials in MCI

    Science.gov (United States)

    Caroli, Anna; Prestia, Annapaola; Wade, Sara; Chen, Kewei; Ayutyanont, Napatkamon; Landau, Susan M.; Madison, Cindee M.; Haense, Cathleen; Herholz, Karl; Reiman, Eric M.; Jagust, William J.; Frisoni, Giovanni B.

    2014-01-01

    Background Aim of this study was to compare the performance and power of the best-established diagnostic biological markers as outcome measures for clinical trials in patients with mild cognitive impairment (MCI). Methods MRI, FDG-PET markers, and ADAS-COG were compared in terms of effect size and statistical power over different followup periods in two MCI groups, selected from ADNI dataset based on CSF (abnormal CSF Aβ1-42 concentration - ABETA+) or MRI evidence of Alzheimer's Disease (AD) (positivity to hippocampal atrophy - HIPPO+). Biomarkers progression was modeled through mixed effect models. Scaled slope was chosen as measure of effect size. Biomarkers power was estimated using simulation algorithms. Results Seventy-four ABETA+ and 51 HIPPO+ MCI patients were included in the study. Imaging biomarkers of neurodegeneration, especially MR measurements, showed highest performance. For all biomarkers and both MCI groups, power increased with increasing follow-up time, irrespective of biomarker assessment frequency. Conclusions These findings provide information about biomarker enrichment and outcome measurements that could be employed to reduce MCI patient samples and treatment duration in future clinical trials. PMID:25437302

  4. Understanding inflammation in juvenile idiopathic arthritis: How immune biomarkers guide clinical strategies in the systemic onset subtype.

    Science.gov (United States)

    Swart, Joost F; de Roock, Sytze; Prakken, Berent J

    2016-09-01

    The translation of basic insight in immunological mechanisms underlying inflammation into clinical practice of inflammatory diseases is still challenging. Here we describe how-through continuous dialogue between bench and bedside-immunological knowledge translates into tangible clinical use in a complex inflammatory disease, juvenile idiopathic arthritis (JIA). Systemic JIA (sJIA) is an autoinflammatory disease, leading to the very successful use of IL-1 antagonists. Further immunological studies identified new immune markers for diagnosis, prediction of complications, response to and successful withdrawal of therapy. Myeloid related protein (MRP)8, MRP14, S100A12, and Interleukin-18 are already used daily in clinic as markers for active sJIA. For non-sJIA subtypes, HLA-B27, antinuclear-antibodies, rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein are still used for classification, prognosis or active disease. MRP8, MRP14, and S100A12 are now under study for clinical practice. We believe that with biomarkers, algorithms can soon be designed for the individual risk of disease, complications, damage, prediction of response to, and successful withdrawal of therapy. In that way, less time will be lost and less pain will be suffered by the patients. In this review, we describe the current status of immunological biomarkers used in diagnosis and treatment of JIA. PMID:27461267

  5. Clinical update on the use of biomarkers of airway inflammation in the management of asthma

    Directory of Open Access Journals (Sweden)

    Dorscheid DR

    2011-06-01

    Full Text Available SJ Wadsworth1,2, DD Sin1,2, DR Dorscheid1,21UBC James Hogg Research Centre, Providence Heart and Lung Institute, St Paul's Hospital, Vancouver, Canada; 2Department of Medicine, University of British Columbia, British Columbia, CanadaAbstract: Biological markers are already used in the diagnosis and treatment of cardiovascular disease and cancer. Biomarkers have great potential use in the clinic as a noninvasive means to make more accurate diagnoses, monitor disease progression, and create personalized treatment regimes. Asthma is a heterogeneous disease with several different phenotypes, generally triggered by multiple gene-environment interactions. Pulmonary function tests are most often used objectively to confirm the diagnosis. However, airflow obstruction can be variable and thus missed using spirometry. Furthermore, lung function measurements may not reflect the precise underlying pathological processes responsible for different phenotypes. Inhaled corticosteroids and ß2-agonists have been the mainstay of asthma therapy for over 30 years, but the heterogeneity of the disease means not all asthmatics respond to the same treatment. High costs and undesired side effects of drugs also drive the need for better targeted treatment of asthma. Biomarkers have the potential to indicate an individual's disease phenotype and thereby guide clinicians in their decisions regarding treatment. This review focuses on biomarkers of airway inflammation which may help us to identify, monitor, and guide treatment of asthmatics. We discuss biomarkers obtained from multiple physiological sources, including sputum, exhaled gases, exhaled breath condensate, serum, and urine. We discuss the inherent limitations and benefits of using biomarkers in a heterogeneous disease such as asthma. We also discuss how we may modify our study designs to improve the identification and potential use of potential biomarkers in asthma.Keywords: asthma, inflammation, airway

  6. APRIL is a novel clinical chemo-resistance biomarker in colorectal adenocarcinoma identified by gene expression profiling

    International Nuclear Information System (INIS)

    5-Fluorouracil(5FU) and oral analogues, such as capecitabine, remain one of the most useful agents for the treatment of colorectal adenocarcinoma. Low toxicity and convenience of administration facilitate use, however clinical resistance is a major limitation. Investigation has failed to fully explain the molecular mechanisms of resistance and no clinically useful predictive biomarkers for 5FU resistance have been identified. We investigated the molecular mechanisms of clinical 5FU resistance in colorectal adenocarcinoma patients in a prospective biomarker discovery project utilising gene expression profiling. The aim was to identify novel 5FU resistance mechanisms and qualify these as candidate biomarkers and therapeutic targets. Putative treatment specific gene expression changes were identified in a transcriptomics study of rectal adenocarcinomas, biopsied and profiled before and after pre-operative short-course radiotherapy or 5FU based chemo-radiotherapy, using microarrays. Tumour from untreated controls at diagnosis and resection identified treatment-independent gene expression changes. Candidate 5FU chemo-resistant genes were identified by comparison of gene expression data sets from these clinical specimens with gene expression signatures from our previous studies of colorectal cancer cell lines, where parental and daughter lines resistant to 5FU were compared. A colorectal adenocarcinoma tissue microarray (n = 234, resected tumours) was used as an independent set to qualify candidates thus identified. APRIL/TNFSF13 mRNA was significantly upregulated following 5FU based concurrent chemo-radiotherapy and in 5FU resistant colorectal adenocarcinoma cell lines but not in radiotherapy alone treated colorectal adenocarcinomas. Consistent withAPRIL's known function as an autocrine or paracrine secreted molecule, stromal but not tumour cell protein expression by immunohistochemistry was correlated with poor prognosis (p = 0.019) in the independent set

  7. Evidence of accelerated ageing in clinical drug addiction from immune, hepatic and metabolic biomarkers

    OpenAIRE

    Reece Albert

    2007-01-01

    Abstract Background Drug addiction is associated with significant disease and death, but its impact on the ageing process has not been considered. The recent demonstration that many of the items available in routine clinical pathology have applicability as biomarkers of the ageing process implies that routine clinical laboratory parameters would be useful as an initial investigation of this possibility. Methods 12,093 clinical laboratory results 1995–2006 were reviewed. To make the age ranges...

  8. Meta-analysis of clinical prediction models

    NARCIS (Netherlands)

    Debray, T.P.A.

    2013-01-01

    The past decades there has been a clear shift from implicit to explicit diagnosis and prognosis. This includes appreciation of clinical -diagnostic and prognostic- prediction models, which is likely to increase with the introduction of fully computerized patient records. Prediction models aim to pro

  9. FDG-PET as a predictive biomarker for therapy with everolimus in metastatic renal cell cancer

    International Nuclear Information System (INIS)

    The mTOR (mammalian target of rapamycin) inhibitor, everolimus, affects tumor growth by targeting cellular metabolic proliferation pathways and delays renal cell carcinoma (RCC) progression. Preclinical evidence suggests that baseline elevated tumor glucose metabolism as quantified by FDG-PET ([18F] fluorodeoxy-glucose positron emission tomography) may predict antitumor activity. Metastatic RCC (mRCC) patients refractory to vascular endothelial growth factor (VEGF) pathway inhibition were treated with standard dose everolimus. FDG-PET scans were obtained at baseline and 2 weeks; serial computed tomography (CT) scans were obtained at baseline and every 8 weeks. Maximum standardized uptake value (SUVmax) of the most FDG avid lesion, average SUVmax of all measured lesions and their corresponding 2-week relative changes were examined for association with 8-week change in tumor size. A total of 63 patients were enrolled; 50 were evaluable for the primary endpoint of which 48 had both PET scans. Patient characteristics included the following: 36 (72%) clear cell histology and median age 59 (range: 37–80). Median pre- and 2-week treatment average SUVmax were 6.6 (1–17.9) and 4.2 (1–13.9), respectively. Response evaluation criteria in solid tumors (RECIST)-based measurements demonstrated an average change in tumor burden of 0.2% (−32.7% to 35.9%) at 8 weeks. Relative change in average SUVmax was the best predictor of change in tumor burden (all evaluable P = 0.01; clear cell subtype P = 0.02), with modest correlation. Baseline average SUVmax was correlated with overall survival and progression-free survival (PFS) (P = 0.023; 0.020), but not with change in tumor burden. Everolimus therapy decreased SUVs on follow-up PET scans in mRCC patients, but changes were only modestly correlated with changes in tumor size. Thus, clinical use of FDG-PET-based biomarkers is challenged by high variability. In this phase II trial, FDG-PET was explored as a predictive biomarker for

  10. Clinical Use of Cancer Biomarkers in Epithelial Ovarian Cancer

    DEFF Research Database (Denmark)

    Söletormos, Georg; Duffy, Michael J; Othman Abu Hassan, Suher; Verheijen, René H M; Tholander, Bengt; Bast, Robert C; Gaarenstroom, Katja N; Sturgeon, Catharine M; Bonfrer, Johannes M; Petersen, Per Hyltoft; Troonen, Hugo; CarloTorre, Gian; Kanty Kulpa, Jan; Tuxen, Malgorzata K; Molina, Raphael

    2016-01-01

    OBJECTIVE: To present an update of the European Group on Tumor Markers guidelines for serum markers in epithelial ovarian cancer. METHODS: Systematic literature survey from 2008 to 2013. The articles were evaluated by level of evidence and strength of recommendation. RESULTS: Because of its low...... sensitivity (50-62% for early stage epithelial ovarian cancer) and limited specificity (94-98.5%), cancer antigen (CA) 125 (CA125) is not recommended as a screening test in asymptomatic women. The Risk of Malignancy Index, which includes CA125, transvaginal ultrasound, and menopausal status, is recommended...... candidate for secondary cytoreductive surgery. CONCLUSIONS: At present, CA125 remains the most important biomarker for epithelial ovarian cancer, excluding tumors of mucinous origin.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives...

  11. Biomarkers that currently effect clinical practice in lung cancer: EGFR, ALK, MET, ROS-1 and KRAS

    Directory of Open Access Journals (Sweden)

    GrzegorzJanuszKorpanty

    2014-08-01

    Full Text Available Lung cancer remains the most lethal malignancy in the world. Despite improvements in surgical treatment, systemic therapy and radiotherapy, the 5-year survival rate for all patients diagnosed with lung cancer remains between 15-20%. Newer therapeutic strategies rely on specific molecular alterations, or biomarkers, that provide opportunities for a personalized approach to specific patient populations. Classification of lung cancer is becoming increasingly focused on these biomarkers, which renders the term “non-small cell lung” cancer less clinically useful. Non-small cell lung cancer is now recognized as a complex malignancy and its molecular and genomic diversity allows for patient-centered treatment options. Here we review advances in targeted treatment of lung adenocarcinoma with respect to five clinically relevant biomarkers - EGFR, ALK, MET, ROS-1 and KRAS.

  12. Robust Microarray Meta-Analysis Identifies Differentially Expressed Genes for Clinical Prediction

    OpenAIRE

    Phan, John H.; Andrew N. Young; Wang, May D.

    2012-01-01

    Combining multiple microarray datasets increases sample size and leads to improved reproducibility in identification of informative genes and subsequent clinical prediction. Although microarrays have increased the rate of genomic data collection, sample size is still a major issue when identifying informative genetic biomarkers. Because of this, feature selection methods often suffer from false discoveries, resulting in poorly performing predictive models. We develop a simple meta-analysis-ba...

  13. Biomarkers in differentiating clinical dengue cases:A prospective cohort study

    Institute of Scientific and Technical Information of China (English)

    Gary Kim Kuan Low; Seng Chiew Gan; Shu Cheow Ho

    2015-01-01

    Objective:To evaluate five biomarkers (neopterin, vascular endothelial growth factor-A, thrombomodulin, soluble vascular cell adhesion molecule 1 and pentraxin 3) in differentiating clinical dengue cases. Methods:A prospective cohort study was conducted whereby the blood samples were obtained at day of presentation and the final diagnosis were obtained at the end of patients’ follow-up. All patients included in the study were 15 years old or older, not pregnant, not infected by dengue previously and did not have cancer, autoimmune or haematological disorder. Median test was performed to compare the biomarker levels. A subgroup Mann-WhitneyU test was analysed between severe dengue and non-severe dengue cases. Monte Carlo method was used to estimate the 2-tailed probability (P) value for independent variables with unequal number of patients. Results: All biomarkers except thrombomodulin hasPvalue < 0.001 in differentiating among the healthy subjects, non-dengue fever, dengue without warning signs and dengue with warning signs/severe dengue. Subgroup analysis for all the biomarkers between severe dengue and non-severe dengue cases was not statistically significant except vascular endothelial growth factor-A (P < 0.05). Conclusions: Certain biomarkers were able to differentiate the clinical dengue cases. This could be potentially useful in classifying and determining the severity of dengue infected patients in the hospital.

  14. Blood biomarkers are helpful in the prediction of response to chemoradiation in rectal cancer: A prospective, hypothesis driven study on patients with locally advanced rectal cancer

    International Nuclear Information System (INIS)

    Purpose/objective: Chemoradiation (CRT) has been shown to lead to downsizing of an important portion of rectal cancers. In order to tailor treatment at an earlier stage during treatment, predictive models are being developed. Adding blood biomarkers may be attractive for prediction, as they can be collected very easily and determined with excellent reproducibility in clinical practice. The hypothesis of this study was that blood biomarkers related to tumor load, hypoxia and inflammation can help to predict response to CRT in rectal cancer. Material/methods: 295 patients with locally advanced rectal cancer who were planned to undergo CRT were prospectively entered into a biobank protocol ( (NCT01067872)). Blood samples were drawn before start of CRT. Nine biomarkers were selected, based on a previously defined hypothesis, and measured in a standardized way by a certified lab: CEA, CA19-9, LDH, CRP, IL-6, IL-8, CA IX, osteopontin and 25-OH-vitamin D. Outcome was analyzed in two ways: pCR vs. non-pCR and responders (defined as ypT0-2N0) vs. non-responders (all other ypTN stages). Results: 276 patients could be analyzed. 20.7% developed a pCR and 47.1% were classified as responders. In univariate analysis CEA (p = 0.001) and osteopontin (p = 0.012) were significant predictors for pCR. Taking response as outcome CEA (p < 0.001), IL-8 (p < 0.001) and osteopontin (p = 0.004) were significant predictors. In multivariate analysis CEA was the strongest predictor for pCR (OR 0.92, p = 0.019) and CEA and IL-8 predicted for response (OR 0.97, p = 0.029 and OR 0.94, p = 0.036). The model based on biomarkers only had an AUC of 0.65 for pCR and 0.68 for response; the strongest model included clinical data, PET-data and biomarkers and had an AUC of 0.81 for pCR and 0.78 for response. Conclusion: CEA and IL-8 were identified as predictive biomarkers for tumor response and PCR after CRT in rectal cancer. Incorporation of these blood biomarkers leads to an additional accuracy of

  15. Serum activin B concentration as predictive biomarker for ectopic pregnancy.

    Science.gov (United States)

    Dhiman, Pooja; Senthilkumar, G P; Rajendiran, Soundravally; Sivaraman, K; Soundararaghavan, S; Kulandhasamy, Maheshwari

    2016-05-01

    We evaluated the diagnostic accuracy of activin B in discriminating tubal ectopic pregnancy (tEP) from intrauterine miscarriages (IUM), and normal viable intrauterine pregnancy (IUP). We included 28 women with tEP, 31 women with IUM, and 29 normal IUP, confirmed both by clinical examination and ultrasonography. Serum activin B concentration was measured at the time of admission using the ELISA kit. The median serum activin B concentration was found to be significantly decreased in both tEP (p=0.004) and IUM (p=0.022) compared to normal IUP. When compared between tEP and IUM, activin B concentrations did not differ significantly. ROC analysis of activin B and free β-hCG demonstrated AUC of 0.722 and 0.805, respectively to discriminate tEP from viable IUP. The model including both activin B and free β-hCG improved the discriminating potential with greater AUC (0.824), and specificity (93%) than individual one. To discriminate tEP from IUM, activin B, free β-hCG and combination of both performed poorly. We conclude that serum activin B concentration is lower in tubal ectopic pregnancy, and can discriminate it from normal pregnancy with moderate accuracy. It also shows improved diagnostic potential along with free β-hCG, but cannot distinguish tEP from IUM reliably. PMID:26968108

  16. Pre-transplant Evaluation of Donor Urinary Biomarkers can Predict Reduced Graft Function After Deceased Donor Kidney Transplantation

    OpenAIRE

    Koo, Tai Yeon; Jeong, Jong Cheol; Lee, Yonggu; Ko, Kwang-Pil; Lee, Kyoung-Bun; Lee, Sik; Park, Suk Joo; Park, Jae Berm; Han, Miyeon; Lim, Hye Jin; Ahn, Curie; Yang, Jaeseok

    2016-01-01

    Abstract Several recipient biomarkers are reported to predict graft dysfunction, but these are not useful in decision making for the acceptance or allocation of deceased donor kidneys; thus, it is necessary to develop donor biomarkers predictive of graft dysfunction. To address this issue, we prospectively enrolled 94 deceased donors and their 109 recipients who underwent transplantation between 2010 and 2013 at 4 Korean transplantation centers. We investigated the predictive values of donor ...

  17. Innovative biomarkers for predicting type 2 diabetes mellitus: relevance to dietary management of frailty in older adults.

    Science.gov (United States)

    Ikwuobe, John; Bellary, Srikanth; Griffiths, Helen R

    2016-06-01

    Type 2 diabetes mellitus (T2DM) increases in prevalence in the elderly. There is evidence for significant muscle loss and accelerated cognitive impairment in older adults with T2DM; these comorbidities are critical features of frailty. In the early stages of T2DM, insulin sensitivity can be improved by a "healthy" diet. Management of insulin resistance by diet in people over 65 years of age should be carefully re-evaluated because of the risk for falling due to hypoglycaemia. To date, an optimal dietary programme for older adults with insulin resistance and T2DM has not been described. The use of biomarkers to identify those at risk for T2DM will enable clinicians to offer early dietary advice that will delay onset of disease and of frailty. Here we have used an in silico literature search for putative novel biomarkers of T2DM risk and frailty. We suggest that plasma bilirubin, plasma, urinary DPP4-positive microparticles and plasma pigment epithelium-derived factor merit further investigation as predictive biomarkers for T2DM and frailty risk in older adults. Bilirubin is screened routinely in clinical practice. Measurement of specific microparticle frequency in urine is less invasive than a blood sample so is a good choice for biomonitoring. Future studies should investigate whether early dietary changes, such as increased intake of whey protein and micronutrients that improve muscle function and insulin sensitivity, affect biomarkers and can reduce the longer term complication of frailty in people at risk for T2DM. PMID:26897532

  18. Cross-validation of biomarkers for the early differential diagnosis and prognosis of dementia in a clinical setting

    International Nuclear Information System (INIS)

    The aim of this study was to evaluate the supportive role of molecular and structural biomarkers (CSF protein levels, FDG PET and MRI) in the early differential diagnosis of dementia in a large sample of patients with neurodegenerative dementia, and in determining the risk of disease progression in subjects with mild cognitive impairment (MCI). We evaluated the supportive role of CSF Aβ42, t-Tau, p-Tau levels, conventional brain MRI and visual assessment of FDG PET SPM t-maps in the early diagnosis of dementia and the evaluation of MCI progression. Diagnosis based on molecular biomarkers showed the best fit with the final diagnosis at a long follow-up. FDG PET SPM t-maps had the highest diagnostic accuracy in Alzheimer's disease and in the differential diagnosis of non-Alzheimer's disease dementias. The p-tau/Aβ42 ratio was the only CSF biomarker providing a significant classification rate for Alzheimer's disease. An Alzheimer's disease-positive metabolic pattern as shown by FDG PET SPM in MCI was the best predictor of conversion to Alzheimer's disease. In this clinical setting, FDG PET SPM t-maps and the p-tau/Aβ42 ratio improved clinical diagnostic accuracy, supporting the importance of these biomarkers in the emerging diagnostic criteria for Alzheimer's disease dementia. FDG PET using SPM t-maps had the highest predictive value by identifying hypometabolic patterns in different neurodegenerative dementias and normal brain metabolism in MCI, confirming its additional crucial exclusionary role. (orig.)

  19. Cross-validation of biomarkers for the early differential diagnosis and prognosis of dementia in a clinical setting

    Energy Technology Data Exchange (ETDEWEB)

    Perani, Daniela [Vita-Salute San Raffaele University, Milan (Italy); San Raffaele Scientific Institute, Division of Neuroscience, Milan (Italy); San Raffaele Hospital, Nuclear Medicine Unit, Milan (Italy); Cerami, Chiara [Vita-Salute San Raffaele University, Milan (Italy); San Raffaele Scientific Institute, Division of Neuroscience, Milan (Italy); San Raffaele Hospital, Clinical Neuroscience Department, Milan (Italy); Caminiti, Silvia Paola [Vita-Salute San Raffaele University, Milan (Italy); San Raffaele Scientific Institute, Division of Neuroscience, Milan (Italy); Santangelo, Roberto; Coppi, Elisabetta; Ferrari, Laura; Magnani, Giuseppe [San Raffaele Hospital, Department of Neurology, Milan (Italy); Pinto, Patrizia [Papa Giovanni XXIII Hospital, Department of Neurology, Bergamo (Italy); Passerini, Gabriella [Servizio di Medicina di Laboratorio OSR, Milan (Italy); Falini, Andrea [Vita-Salute San Raffaele University, Milan (Italy); San Raffaele Scientific Institute, Division of Neuroscience, Milan (Italy); San Raffaele Hospital, CERMAC - Department of Neuroradiology, Milan (Italy); Iannaccone, Sandro [San Raffaele Hospital, Clinical Neuroscience Department, Milan (Italy); Cappa, Stefano Francesco [San Raffaele Scientific Institute, Division of Neuroscience, Milan (Italy); IUSS Pavia, Pavia (Italy); Comi, Giancarlo [Vita-Salute San Raffaele University, Milan (Italy); San Raffaele Hospital, Department of Neurology, Milan (Italy); Gianolli, Luigi [San Raffaele Hospital, Nuclear Medicine Unit, Milan (Italy)

    2016-03-15

    The aim of this study was to evaluate the supportive role of molecular and structural biomarkers (CSF protein levels, FDG PET and MRI) in the early differential diagnosis of dementia in a large sample of patients with neurodegenerative dementia, and in determining the risk of disease progression in subjects with mild cognitive impairment (MCI). We evaluated the supportive role of CSF Aβ{sub 42}, t-Tau, p-Tau levels, conventional brain MRI and visual assessment of FDG PET SPM t-maps in the early diagnosis of dementia and the evaluation of MCI progression. Diagnosis based on molecular biomarkers showed the best fit with the final diagnosis at a long follow-up. FDG PET SPM t-maps had the highest diagnostic accuracy in Alzheimer's disease and in the differential diagnosis of non-Alzheimer's disease dementias. The p-tau/Aβ{sub 42} ratio was the only CSF biomarker providing a significant classification rate for Alzheimer's disease. An Alzheimer's disease-positive metabolic pattern as shown by FDG PET SPM in MCI was the best predictor of conversion to Alzheimer's disease. In this clinical setting, FDG PET SPM t-maps and the p-tau/Aβ{sub 42} ratio improved clinical diagnostic accuracy, supporting the importance of these biomarkers in the emerging diagnostic criteria for Alzheimer's disease dementia. FDG PET using SPM t-maps had the highest predictive value by identifying hypometabolic patterns in different neurodegenerative dementias and normal brain metabolism in MCI, confirming its additional crucial exclusionary role. (orig.)

  20. Continuous metabolic monitoring based on multi-analyte biomarkers to predict exhaustion.

    Science.gov (United States)

    Kastellorizios, Michail; Burgess, Diane J

    2015-01-01

    This work introduces the concept of multi-analyte biomarkers for continuous metabolic monitoring. The importance of using more than one marker lies in the ability to obtain a holistic understanding of the metabolism. This is showcased for the detection and prediction of exhaustion during intense physical exercise. The findings presented here indicate that when glucose and lactate changes over time are combined into multi-analyte biomarkers, their monitoring trends are more sensitive in the subcutaneous tissue, an implantation-friendly peripheral tissue, compared to the blood. This unexpected observation was confirmed in normal as well as type 1 diabetic rats. This study was designed to be of direct value to continuous monitoring biosensor research, where single analytes are typically monitored. These findings can be implemented in new multi-analyte continuous monitoring technologies for more accurate insulin dosing, as well as for exhaustion prediction studies based on objective data rather than the subject's perception. PMID:26028477

  1. Radiogenomics: predicting clinical normal tissue radiosensitivity

    DEFF Research Database (Denmark)

    Alsner, Jan

    2006-01-01

    Studies on the genetic basis of normal tissue radiosensitivity, or  'radiogenomics', aims at predicting clinical radiosensitivity and optimize treatment from individual genetic profiles. Several studies have now reported links between variations in certain genes related to the biological response...... to radiation injury and risk of normal tissue morbidity in cancer patients treated with radiotherapy. However, after these initial association studies including few genes, we are still far from being able to predict clinical radiosensitivity on an individual level. Recent data from our own studies on...

  2. Mining Clinical Data using Minimal Predictive Rules

    OpenAIRE

    Batal, Iyad; Hauskrecht, Milos

    2010-01-01

    Modern hospitals and health-care institutes collect huge amounts of clinical data. Those who deal with such data know that there is a widening gap between data collection and data comprehension. Thus, it is very important to develop data mining techniques capable of automatically extracting useful knowledge to support clinical decision-making in various diagnostic and patient-management tasks. In this paper, we develop a new framework for rule mining based on minimal predictive rules (MPR). O...

  3. Integration of Known DNA, RNA and Protein Biomarkers Provides Prediction of Anti-TNF Response in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Folkersen, Lasse; Brynedal, Boel; Marcela Diaz-Gallo, Lina;

    2016-01-01

    high-throughput RNA sequencing, DNA genotyping, extensive proteomics and flow cytometry measurements, as well as comprehensive clinical phenotyping. Literature review identified 2 proteins, 52 single-nucleotide polymorphisms (SNPs) and 72 gene-expression biomarkers that had previously been proposed as...... predictors of TNF inhibitor response (∆DAS28-CRP). RESULTS: From these published TNFi biomarkers we found that 2 protein, 2 SNP and 8 mRNA biomarkers could be replicated in the 59 TNF initiating patients. Combining these replicated biomarkers into a single signature we found that we could explain 51% of the...

  4. Cortisol and Inflammatory Biomarkers Predict Poor Treatment Response in First Episode Psychosis

    OpenAIRE

    Mondelli, Valeria; Ciufolini, Simone; Belvederi Murri, Martino; Bonaccorso, Stefania; Di Forti, Marta; Giordano, Annalisa; Marques, Tiago R; Zunszain, Patricia A.; Morgan, Craig; MURRAY, Robin M.; Pariante, Carmine M.; Dazzan, Paola

    2015-01-01

    BACKGROUND: Cortisol and inflammatory markers have been increasingly reported as abnormal at psychosis onset. The main aim of our study was to investigate the ability of these biomarkers to predict treatment response at 12 weeks follow-up in first episode psychosis.METHODS: In a longitudinal study, we collected saliva and blood samples in 68 first episode psychosis patients (and 57 controls) at baseline and assessed response to clinician-led antipsychotic treatment after 12 weeks. Moreover, w...

  5. An Observational Study of Bevacizumab-Induced Hypertension as a Clinical Biomarker of Antitumor Activity

    Science.gov (United States)

    Coriat, Romain; Cabanes, Laure; Ropert, Stanislas; Billemont, Bertrand; Alexandre, Jérôme; Durand, Jean-Philippe; Treluyer, Jean-Marc; Knebelmann, Bertrand; Goldwasser, François

    2011-01-01

    Background. Hypertension is a common toxicity of bevacizumab, but the frequency of assessment of blood pressure and standardized grading remain to be defined. This study aimed to describe the incidence of bevacizumab-induced hypertension and factors associated with its development, then to retrospectively assess its relation with activity. Patients and methods. One hundred nineteen patients with advanced or metastatic non-small cell lung cancer, colorectal cancer, or ovarian cancer receiving bevacizumab (2.5 mg/kg per week) and chemotherapy were eligible for this analysis. Blood pressure was measured at home twice daily according to international guidelines, and graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC), version 3.0, and the European Society of Hypertension (ESH) criteria. Results. Home-based measurements detected significantly more cases of hypertension than in-clinic measurements did, according to the ESH criteria (54.6% versus 24.4%; p < .001) or the NCI-CTC (42.9% versus 22.7%; p = .0015). Very early hypertension (within 42 days, according to the ESH criteria) but not hypertension (occurring at any time during treatment period) was predictive of response (p = .0011 and p = .26, respectively). Conclusions. Our preliminary results indicate that home-based measurement and grading according to the ESH criteria represents a reliable method to detect bevacizumab-induced hypertension. Whether hypertension is a biomarker of bevacizumab activity remains to be determined in a prospective study. PMID:21807768

  6. Identification of a novel prostate cancer biomarker, caveolin-1: Implications and potential clinical benefit

    International Nuclear Information System (INIS)

    While prostate cancer is a common disease in men, it is uncommonly life-threatening. To better understand this phenomenon, tumor biologists have sought to elucidate the mechanisms that contribute to the development of virulent prostate cancer. The recent discovery that caveolin-1 (Cav-1) functions as an important oncogene involved in prostate cancer progression reflects the success of this effort. Cav-1 is a major structural coat protein of caveolae, specialized plasma membrane invaginations involved in multiple cellular functions, including molecular transport, cell adhesion, and signal transduction. Cav-1 is aberrantly overexpressed in human prostate cancer, with higher levels evident in metastatic versus primary sites. Intracellular Cav-1 promotes cell survival through activation of Akt and enhancement of additional growth factor pro-survival pathways. Cav-1 is also secreted as a biologically active molecule that promotes cell survival and angiogenesis within the tumor microenvironment. Secreted Cav-1 can be reproducibly detected in peripheral blood using a sensitive and specific immunoassay. Cav-1 levels distinguish men with prostate cancer from normal controls, and preoperative Cav-1 levels predict which patients are at highest risk for relapse following radical prostatectomy for localized disease. Thus, secreted Cav-1 is a promising biomarker in identifying clinically significant prostate cancer

  7. Clinical relevance of breast cancer-related genes as potential biomarkers for oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Squamous cell carcinoma of the oral cavity (OSCC) is a common cancer form with relatively low 5-year survival rates, due partially to late detection and lack of complementary molecular markers as targets for treatment. Molecular profiling of head and neck cancer has revealed biological similarities with basal-like breast and lung carcinoma. Recently, we showed that 16 genes were consistently altered in invasive breast tumors displaying varying degrees of aggressiveness. To extend our findings from breast cancer to another cancer type with similar characteristics, we performed an integrative analysis of transcriptomic and proteomic data to evaluate the prognostic significance of the 16 putative breast cancer-related biomarkers in OSCC using independent microarray datasets and immunohistochemistry. Predictive models for disease-specific (DSS) and/or overall survival (OS) were calculated for each marker using Cox proportional hazards models. We found that CBX2, SCUBE2, and STK32B protein expression were associated with important clinicopathological features for OSCC (peritumoral inflammatory infiltration, metastatic spread to the cervical lymph nodes, and tumor size). Consequently, SCUBE2 and STK32B are involved in the hedgehog signaling pathway which plays a pivotal role in metastasis and angiogenesis in cancer. In addition, CNTNAP2 and S100A8 protein expression were correlated with DSS and OS, respectively. Taken together, these candidates and the hedgehog signaling pathway may be putative targets for drug development and clinical management of OSCC patients

  8. Quantitative Assessment of Tissue Biomarkers and Construction of a Model to Predict Outcome in Breast Cancer Using Multiple Imputation

    Directory of Open Access Journals (Sweden)

    John W. Emerson

    2009-01-01

    Full Text Available Missing data pose one of the greatest challenges in the rigorous evaluation of biomarkers. The limited availability of specimens with complete clinical annotation and quality biomaterial often leads to underpowered studies. Tissue microarray studies, for example, may be further handicapped by the loss of data points because of unevaluable staining, core loss, or the lack of tumor in the histospot. This paper presents a novel approach to these common problems in the context of a tissue protein biomarker analysis in a cohort of patients with breast cancer. Our analysis develops techniques based on multiple imputation to address the missing value problem. We first select markers using a training cohort, identifying a small subset of protein expression levels that are most useful in predicting patient survival. The best model is obtained by including both protein markers (including COX6C, GATA3, NAT1, and ESR1 and lymph node status. The use of either lymph node status or the four protein expression levels provides similar improvements in goodness-of-fi t, with both significantly better than a baseline clinical model. Using the same multiple imputation strategy, we then validate the results out-of-sample on a larger independent cohort. Our approach of integrating multiple imputation with each stage of the analysis serves as an example that may be replicated or adapted in future studies with missing values.

  9. The potential biomarkers in predicting pathologic response of breast cancer to three different chemotherapy regimens: a case control study

    Directory of Open Access Journals (Sweden)

    Xu Chaoyang

    2009-07-01

    Full Text Available Abstract Background Preoperative chemotherapy (PCT has become the standard of care in locally advanced breast cancer. The identification of patient-specific tumor characteristics that can improve the ability to predict response to therapy would help optimize treatment, improve treatment outcomes, and avoid unnecessary exposure to potential toxicities. This study is to determine whether selected biomarkers could predict pathologic response (PR of breast tumors to three different PCT regimens, and to identify a subset of patients who would benefit from a given type of treatment. Methods 118 patients with primary breast tumor were identified and three PCT regimens including DEC (docetaxel+epirubicin+cyclophosphamide, VFC (vinorelbine/vincristine+5-fluorouracil+cyclophosphamide and EFC (epirubicin+5-fluorouracil+cyclophosphamide were investigated. Expression of steroid receptors, HER2, P-gp, MRP, GST-pi and Topo-II was evaluated by immunohistochemical scoring on tumor tissues obtained before and after PCT. The PR of breast carcinoma was graded according to Sataloff's classification. Chi square test, logistic regression and Cochran-Mantel-Haenszel assay were performed to determine the association between biomarkers and PR, as well as the effectiveness of each regimen on induction of PR. Results There was a clear-cut correlation between the expression of ER and decreased PR to PCT in all three different regimens (p p Conclusion ER is an independent predictive factor for PR to PCT regimens including DEC, VFC and EFC in primary breast tumors, while HER2 is only predictive for DEC regimen. Expression of PgR, Topo-II, P-gp, MRP and GST-pi are not predictive for PR to any PCT regimens investigated. Results obtained in this clinical study may be helpful for the selection of appropriate treatments for breast cancer patients.

  10. 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.

  11. Combining multiple serum biomarkers in tumor diagnosis: A clinical assessment

    OpenAIRE

    Li, Xin; LU, JUN; Ren, Hui; CHEN, TIANJUN; Gao, Lin; DI, LIGAI; SONG, ZHUCUI; Zhang, Ying; Yang, Tian; THAKUR, ASMITANANDA; Zhou, Shu-Feng; Yin, Yanhai; Chen, Mingwei

    2012-01-01

    The present study aimed to assess the diagnostic/prognostic value of various clinical tumor markers, including carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin 19 (CYFRA21-1), α-fetoprotein (AFP), carbohydrate antigen-125 (CA-125), carbohydrate antigen-19.9 (CA-19.9) and ferritin, individually or in combination. The electro-chemiluminescence immunization method was performed to detect the levels of seven tumor markers in 560 cancer patients and 103 healthy subjects f...

  12. The potential biomarkers in predicting pathologic response of breast cancer to three different chemotherapy regimens: a case control study

    International Nuclear Information System (INIS)

    Preoperative chemotherapy (PCT) has become the standard of care in locally advanced breast cancer. The identification of patient-specific tumor characteristics that can improve the ability to predict response to therapy would help optimize treatment, improve treatment outcomes, and avoid unnecessary exposure to potential toxicities. This study is to determine whether selected biomarkers could predict pathologic response (PR) of breast tumors to three different PCT regimens, and to identify a subset of patients who would benefit from a given type of treatment. 118 patients with primary breast tumor were identified and three PCT regimens including DEC (docetaxel+epirubicin+cyclophosphamide), VFC (vinorelbine/vincristine+5-fluorouracil+cyclophosphamide) and EFC (epirubicin+5-fluorouracil+cyclophosphamide) were investigated. Expression of steroid receptors, HER2, P-gp, MRP, GST-pi and Topo-II was evaluated by immunohistochemical scoring on tumor tissues obtained before and after PCT. The PR of breast carcinoma was graded according to Sataloff's classification. Chi square test, logistic regression and Cochran-Mantel-Haenszel assay were performed to determine the association between biomarkers and PR, as well as the effectiveness of each regimen on induction of PR. There was a clear-cut correlation between the expression of ER and decreased PR to PCT in all three different regimens (p < 0.05). HER2 expression is significantly associated with increased PR in DEC regimen (p < 0.05), but not predictive for PR in EFC and VFC groups. No significant correlation was found between biomarkers PgR, Topo-II, P-gp, MRP or GST-pi and PR to any tested PCT regimen. After adjusted by a stratification variable of ER or HER2, DEC regimen was more effective in inducing PR in comparison with VFC and EFC regimens. ER is an independent predictive factor for PR to PCT regimens including DEC, VFC and EFC in primary breast tumors, while HER2 is only predictive for DEC regimen. Expression of

  13. Clinical prediction rule for nonmelanoma skin cancer

    Directory of Open Access Journals (Sweden)

    John Alexander Nova

    2015-01-01

    Full Text Available Background: Skin cancer is the most frequent neoplasia in the world. Even though ultraviolet radiation is the main cause, established prevention campaigns have not proved to be effective for controlling the incidence of this disease. Objective: To develop clinical prediction rules based on medical consultation and a questionnaire to estimate the risk of developing nonmelanoma skin cancer. Methods: This study was developed in several steps. They were: Identifying risk factors that could be possible predictors of nonmelanoma skin cancer; their clinical validation; developing a prediction rule using logistic regression; and collecting information from 962 patients in a case and control design (481 cases and 481 controls. We developed independent prediction rules for basal cell and squamous cell carcinomas. Finally, we evaluated reliability for each of the variables. Results: The variables that made up the final prediction rule were: Family history of skin cancer, history of outdoor work, age, phototypes 1-3 and the presence of poikiloderma of civatte, actinic keratosis and conjunctivitis in band. Prediction rules specificity was 87% for basal cell carcinomas and 92% for squamous cell carcinomas. Inter- and intra-observer reliability was good except for the conjunctivitis in band variable. Conclusions: The prediction rules let us calculate the individual risk of developing basal cell carcinoma and squamous cell carcinoma. This is an economic easy-to-apply tool that could be useful in primary and secondary prevention of skin cancer.

  14. Role of biomarkers in the management of antibiotic therapy: an expert panel review: I – currently available biomarkers for clinical use in acute infections

    Science.gov (United States)

    2013-01-01

    In the context of worldwide increasing antimicrobial resistance, good antimicrobial prescribing in more needed than ever; unfortunately, information available to clinicians often are insufficient to rely on. Biomarkers might provide help for decision-making and improve antibiotic management. The purpose of this expert panel review was to examine currently available literature on the potential role of biomarkers to improve antimicrobial prescribing, by answering three questions: 1) Which are the biomarkers available for this purpose?; 2) What is their potential role in the initiation of antibiotic therapy?; and 3) What is their role in the decision to stop antibiotic therapy? To answer these questions, studies reviewed were limited to recent clinical studies (50) and restricted to controlled trials and meta-analyses for answering questions 2 and 3. With regard to the first question concerning routinely available biomarkers, which might be useful for antibiotic management of acute infections, these are currently limited to C-reactive protein (CRP) and procalcitonin (PCT). Other promising biomarkers that may prove useful in the near future but need to undergo more extensive clinical testing include sTREM-1, suPAR, ProADM, and Presepsin. New approaches to biomarkers of infections include point-of-care testing and genomics. PMID:23837559

  15. MRI texture features as biomarkers to predict MGMT methylation status in glioblastomas

    Science.gov (United States)

    Korfiatis, Panagiotis; Kline, Timothy L.; Coufalova, Lucie; Lachance, Daniel H.; Parney, Ian F.; Carter, Rickey E.; Buckner, Jan C.; Erickson, Bradley J.

    2016-01-01

    Purpose: Imaging biomarker research focuses on discovering relationships between radiological features and histological findings. In glioblastoma patients, methylation of the O6-methylguanine methyltransferase (MGMT) gene promoter is positively correlated with an increased effectiveness of current standard of care. In this paper, the authors investigate texture features as potential imaging biomarkers for capturing the MGMT methylation status of glioblastoma multiforme (GBM) tumors when combined with supervised classification schemes. Methods: A retrospective study of 155 GBM patients with known MGMT methylation status was conducted. Co-occurrence and run length texture features were calculated, and both support vector machines (SVMs) and random forest classifiers were used to predict MGMT methylation status. Results: The best classification system (an SVM-based classifier) had a maximum area under the receiver-operating characteristic (ROC) curve of 0.85 (95% CI: 0.78–0.91) using four texture features (correlation, energy, entropy, and local intensity) originating from the T2-weighted images, yielding at the optimal threshold of the ROC curve, a sensitivity of 0.803 and a specificity of 0.813. Conclusions: Results show that supervised machine learning of MRI texture features can predict MGMT methylation status in preoperative GBM tumors, thus providing a new noninvasive imaging biomarker. PMID:27277032

  16. Inflammatory and repair serum biomarker pattern. Association to clinical outcomes in COPD

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    Pinto-Plata Victor

    2012-08-01

    Full Text Available Abstract Background The relationship between serum biomarkers and clinical expressions of COPD is limited. We planned to further describe this association using markers of inflammation and injury and repair. Methods We studied lung function, comorbidities, exercise tolerance, BODE index, and quality of life in 253 COPD patients and recorded mortality over three years. Serum levels of Interleukins 6,8 and16, tumor necrosis factor alpha (TNF α [inflammatory panel], vascular endothelial growth factor (VEGF, and matrix metalloproteinase 9 (MMP-9 [injury and repair panel] and pulmonary and activation-regulated chemokine (PARC/CCL-18 and monocyte chemotactic protein 1 (MCP-1/CCL2 [chemoattractant panel] were measured. We related the pattern of the biomarker levels to minimal clinically important differences (MCID using a novel visualization method [ObServed Clinical Association Results (OSCAR plot]. Results Levels of the inflammatory markers IL-6, TNF α were higher and those of injury and repair lower (p  Conclusions In COPD, serum biomarkers of inflammation and repair are distinctly associated with important clinical parameters and survival.

  17. Predictive Power Estimation Algorithm (PPEA--a new algorithm to reduce overfitting for genomic biomarker discovery.

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    Jiangang Liu

    Full Text Available Toxicogenomics promises to aid in predicting adverse effects, understanding the mechanisms of drug action or toxicity, and uncovering unexpected or secondary pharmacology. However, modeling adverse effects using high dimensional and high noise genomic data is prone to over-fitting. Models constructed from such data sets often consist of a large number of genes with no obvious functional relevance to the biological effect the model intends to predict that can make it challenging to interpret the modeling results. To address these issues, we developed a novel algorithm, Predictive Power Estimation Algorithm (PPEA, which estimates the predictive power of each individual transcript through an iterative two-way bootstrapping procedure. By repeatedly enforcing that the sample number is larger than the transcript number, in each iteration of modeling and testing, PPEA reduces the potential risk of overfitting. We show with three different cases studies that: (1 PPEA can quickly derive a reliable rank order of predictive power of individual transcripts in a relatively small number of iterations, (2 the top ranked transcripts tend to be functionally related to the phenotype they are intended to predict, (3 using only the most predictive top ranked transcripts greatly facilitates development of multiplex assay such as qRT-PCR as a biomarker, and (4 more importantly, we were able to demonstrate that a small number of genes identified from the top-ranked transcripts are highly predictive of phenotype as their expression changes distinguished adverse from nonadverse effects of compounds in completely independent tests. Thus, we believe that the PPEA model effectively addresses the over-fitting problem and can be used to facilitate genomic biomarker discovery for predictive toxicology and drug responses.

  18. Evaluation of different biomarkers to predict individual radiosensitivity in an inter-laboratory comparison--lessons for future studies.

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    Burkhard Greve

    Full Text Available Radiotherapy is a powerful cure for several types of solid tumours, but its application is often limited because of severe side effects in individual patients. With the aim to find biomarkers capable of predicting normal tissue side reactions we analysed the radiation responses of cells from individual head and neck tumour and breast cancer patients of different clinical radiosensitivity in a multicentric study. Multiple parameters of cellular radiosensitivity were analysed in coded samples of peripheral blood lymphocytes (PBLs and derived lymphoblastoid cell lines (LCLs from 15 clinical radio-hypersensitive tumour patients and compared to age- and sex-matched non-radiosensitive patient controls and 15 lymphoblastoid cell lines from age- and sex- matched healthy controls of the KORA study. Experimental parameters included ionizing radiation (IR-induced cell death (AnnexinV, induction and repair of DNA strand breaks (Comet assay, induction of yH2AX foci (as a result of DNA double strand breaks, and whole genome expression analyses. Considerable inter-individual differences in IR-induced DNA strand breaks and their repair and/or cell death could be detected in primary and immortalised cells with the applied assays. The group of clinically radiosensitive patients was not unequivocally distinguishable from normal responding patients nor were individual overreacting patients in the test system unambiguously identified by two different laboratories. Thus, the in vitro test systems investigated here seem not to be appropriate for a general prediction of clinical reactions during or after radiotherapy due to the experimental variability compared to the small effect of radiation sensitivity. Genome-wide expression analysis however revealed a set of 67 marker genes which were differentially induced 6 h after in vitro-irradiation in lymphocytes from radio-hypersensitive and non-radiosensitive patients. These results warrant future validation in larger

  19. Clinical update on the use of biomarkers of airway inflammation in the management of asthma

    OpenAIRE

    Dorscheid DR; Sin DD; Wadsworth SJ

    2011-01-01

    SJ Wadsworth1,2, DD Sin1,2, DR Dorscheid1,21UBC James Hogg Research Centre, Providence Heart and Lung Institute, St Paul's Hospital, Vancouver, Canada; 2Department of Medicine, University of British Columbia, British Columbia, CanadaAbstract: Biological markers are already used in the diagnosis and treatment of cardiovascular disease and cancer. Biomarkers have great potential use in the clinic as a noninvasive means to make more accurate diagnoses, monitor disease progression, and cr...

  20. Is abeta a sufficient biomarker for monitoring anti-abeta clinical studies? A critical review

    OpenAIRE

    Katharina Zimmermann Schindowski

    2013-01-01

    Amyloid-beta (Aβ) in Alzheimer's disease (AD) appeared to be a promising target for disease-modifying therapeutic strategies like passive immunotherapy with anti-Aβ monoclonal antibodies (mAbs). Biochemical markers in cerebrospinal fluid (CSF) include alterations of Aβ that allow the diagnosis of AD. Biomarker strategies, such as the levels of Aβ in CSF and plasma, currently play an important role in early clinical trials for AD. Indeed, these strategies have a relevant impact on the outcome ...

  1. Analysis of a Urinary Biomarker Panel for Obstructive Nephropathy and Clinical Outcomes

    OpenAIRE

    Yuanyuan Xie; Wei Xue; Xinghua Shao; Xiajing Che; Weijia Xu; Zhaohui Ni; Shan Mou

    2014-01-01

    OBJECTIVES: To follow up renal function changes in patients with obstructive nephropathy and to evaluate the predictive value of biomarker panel in renal prognosis. METHODS: A total of 108 patients with obstructive nephropathy were enrolled in the study; 90 patients completed the follow-up. At multiple time points before and after obstruction resolution, urinary samples were prospectively collected in patients with obstructive nephropathy; the levels of urinary kidney injury molecule-1 (uKIM-...

  2. Clinical Significance of Cerebrovascular Biomarkers and White Matter Tract Integrity in Alzheimer Disease

    OpenAIRE

    Wu, Ming-Kung; Lu, Yan-Ting; Huang, Chi-Wei; Lin, Pin-Hsuan; Chen, Nai-Ching; Lui, Chun-Chung; Chang, Wen-Neng; Lee, Chen-Chang; Chang, Ya-Ting; Chen, Sz-Fan; Chang, Chiung-Chih

    2015-01-01

    Abstract Cerebrovascular risk factors and white matter (WM) damage lead to worse cognitive performance in Alzheimer dementia (AD). This study investigated WM microstructure using diffusion tensor imaging in patients with mild to moderate AD and investigated specific fiber tract involvement with respect to predefined cerebrovascular risk factors and neurobehavioral data prediction cross-sectionally and after 18 months. To identify the primary pathoanatomic relationships of risk biomarkers to f...

  3. Performance of diagnostic biomarkers in predicting liver fibrosis among hepatitis C virus-infected Egyptian children

    Directory of Open Access Journals (Sweden)

    Yasser E Nassef

    2013-11-01

    Full Text Available The aim of the present study was to identify specific markers that mirror liver fibrosis progression as an alternative to biopsy when biopsy is contraindicated, especially in children. After liver biopsies were performed, serum samples from 30 hepatitis C virus (HCV paediatric patients (8-14 years were analysed and compared with samples from 30 healthy subjects. All subjects were tested for the presence of serum anti-HCV antibodies. Direct biomarkers for liver fibrosis, including transforming growth factor-β1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1, hyaluronic acid (HA, procollagen type III amino-terminal peptide (PIIINP and osteopontin (OPN, were measured. The indirect biomarkers aspartate and alanine aminotransferases, albumin and bilirubin were also tested. The results revealed a significant increase in the serum marker levels in HCV-infected children compared with the healthy group, whereas albumin levels exhibited a significant decrease. Significantly higher levels of PIIINP, TIMP-1, OPN and HA were detected in HCV-infected children with moderate to severe fibrosis compared with children with mild fibrosis (p < 0.05. The diagnostic accuracy of these direct biomarkers, represented by sensitivity, specificity and positive predictive value, emphasises the utility of PIIINP, TIMP-1, OPN and HA as indicators of liver fibrosis among HCV-infected children.

  4. Systematic review and meta-analysis of tumor biomarkers in predicting prognosis in esophageal cancer

    International Nuclear Information System (INIS)

    Esophageal cancer (EC) is a frequently occurring cancer with poor prognosis despite combined therapeutic strategies. Many biomarkers have been proposed as predictors of adverse events. We sought to assess the prognostic value of biomarkers in predicting the overall survival of esophageal cancer and to help guide personalized cancer treatment to give patients the best chance at remission. We conducted a systematic review and meta-analysis of the published literature to summarize evidence for the discriminatory ability of prognostic biomarkers for esophageal cancer. Relevant literature was identified using the PubMed database on April 11, 2012, and conformed to the REMARK criteria. The primary endpoint was overall survival and data were synthesized with hazard ratios (HRs). We included 109 studies, exploring 13 different biomarkers, which were subjected to quantitative meta-analysis. Promising markers that emerged for the prediction of overall survival in esophageal squamous cell cancer included VEGF (18 eligible studies, n = 1476, HR = 1.85, 95% CI, 1.55-2.21), cyclin D1 (12 eligible studies, n = 1476, HR = 1.82, 95% CI, 1.50-2.20), Ki-67 (3 eligible studies, n = 308, HR = 1.11, 95% CI, 0.70-1.78) and squamous cell carcinoma antigen (5 eligible studies, n = 700, HR = 1.28, 95% CI, 0.97-1.69); prognostic markers for esophageal adenocarcinoma included COX-2 (2 eligible studies, n = 235, HR = 3.06, 95% CI, 2.01-4.65) and HER-2 (3 eligible studies, n = 291, HR = 2.15, 95% CI, 1.39-3.33); prognostic markers for uncategorized ECs included p21 (9 eligible studies, n = 858, HR = 1.27, 95% CI, 0.75-2.16), p53 (31 eligible studies, n = 2851, HR = 1.34, 95% CI, 1.21-1.48), CRP (8 eligible studies, n = 1382, HR = 2.65, 95% CI, 1.64-4.27) and hemoglobin (5 eligible studies, n = 544, HR = 0.91, 95% CI, 0.83-1.00). Although some modest bias cannot be excluded, this review supports the involvement of biomarkers to be associated with EC overall survival

  5. Biomarkers: evaluation of clinical utility in surveillance and early diagnosis for hepatocellular carcinoma.

    Science.gov (United States)

    Song, Peipei; Tang, Qi; Feng, Xiaobin; Tang, Wei

    2016-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second most common cause of death from cancer worldwide. Strategies to surveil and diagnose HCC in an earlier stage are urgently needed since this is when curable interventions can be offered to achieve long-term disease-free survival. Over the past few decades, research has suggested measuring alpha-fetoprotein (AFP) concentration and performing abdominal ultrasound (US) as part of routine surveillance of HCC every 6 months for high-risk patients, and many HCC guidelines worldwide have also recommended these examinations. Over the past 5 years, however, the role of serum biomarkers in HCC surveillance and diagnosis has diminished due to advances in imaging modalities. AFP was excluded from the surveillance and/or diagnostic criteria in the HCC guidelines published by some Western countries. In Asian countries, serum biomarkers such as AFP, the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-γ-carboxyprothrombin (DCP) are still recommended for HCC surveillance and are being used as an adjunctive diagnostic tool in accordance with HCC guidelines. Moreover, novel biomarkers including Dickkopf-1 (DKK1), midkine (MDK), and microRNA (miRNA) are being studied in this regard. China accounts for 50% of HCC cases worldwide, so identifying biomarkers of HCC is paramount. Recent studies have indicated the clinical utility of simultaneous measurement of AFP and DCP for the early detection of HCC in China. They are predominantly used for cases caused by HBV infection. Additional large-scale prospective studies should be conducted to establish the utility of these biomarkers. PMID:27438343

  6. An Evidence-Based Approach to the Use of Predictive Biomarkers in the Treatment of Non- Small Cell Lung Cancer (NSCLC)

    International Nuclear Information System (INIS)

    Recent advances in the treatment of non-small cell lung cancer (NSCLC) have led to improvements in patient survival and quality of life. It is unclear whether molecular abnormalities associated with NSCLC cell survival, growth and proliferation are useful in predicting treatment benefit. We conducted a systematic review to establish which biomarkers contribute meaningfully to the management of NSCLC. A team of researchers searched PubMed and conference proceedings (ASCO, ESMO, IASLC, USCAP) using MESH terms for NSCLC and randomized trials (RCT), plus keywords for variables of interest. Evidence from multiple RCTs confirmed that histologic subtype is prognostic for survival and predictive of treatment efficacy and/or toxicity in NSCLC. Likewise, activating mutations of the epidermal growth factor receptor (EGFR) are associated with benefit from EGFR tyrosine kinase inhibitors in patients with advanced non-squamous NSCLC and should be assessed routinely. No biomarkers to date reliably predict response to anti-Vascular Endothelial Growth Factor (VEGF) therapies. There are inconsistent data on the role of ERCC1, BRCA, Beta tubulin III, RRM1, K-RAS, or TP-53 in treatment decisions. These tests should not be routinely used in selecting treatment at this time, whereas EML4/ALK translocations predict responses to specific targeted agents, the optimal assessment of this molecular abnormality has yet to be established. Personalized care of patients with NSCLC based on biomarkers is increasingly important to both clinical practice and research

  7. A risk management approach for imaging biomarker-driven clinical trials in oncology.

    Science.gov (United States)

    Liu, Yan; deSouza, Nandita M; Shankar, Lalitha K; Kauczor, Hans-Ulrich; Trattnig, Siegfried; Collette, Sandra; Chiti, Arturo

    2015-12-01

    Imaging has steadily evolved in clinical cancer research as a result of improved conventional imaging methods and the innovation of new functional and molecular imaging techniques. Despite this evolution, the design and data quality derived from imaging within clinical trials are not ideal and gaps exist with paucity of optimised methods, constraints of trial operational support, and scarce resources. Difficulties associated with integrating imaging biomarkers into trials have been neglected compared with inclusion of tissue and blood biomarkers, largely because of inherent challenges in the complexity of imaging technologies, safety issues related to new imaging contrast media, standardisation of image acquisition across multivendor platforms, and various postprocessing options available with advanced software. Ignorance of these pitfalls directly affects the quality of the imaging read-out, leading to trial failure, particularly when imaging is a primary endpoint. Therefore, we propose a practical risk-based framework and recommendations for trials driven by imaging biomarkers, which allow identification of risks at trial initiation to better allocate resources and prioritise key tasks. PMID:26678215

  8. Clinical proteomics for liver disease: a promising approach for discovery of novel biomarkers

    Directory of Open Access Journals (Sweden)

    Tsubouchi Hirohito

    2010-12-01

    Full Text Available Abstract Hepatocellular carcinoma (HCC is the fifth most common cancer and advanced hepatic fibrosis is a major risk factor for HCC. Hepatic fibrosis including liver cirrhosis and HCC are mainly induced by persistent hepatitis B or C virus infection, with approximately 500 million people infected with hepatitis B or C virus worldwide. Furthermore, the number of patients with non-alcoholic fatty liver disease (NAFLD has recently increased and NAFLD can progress to cirrhosis and HCC. These chronic liver diseases are major causes of morbidity and mortality, and the identification of non-invasive biomarkers is important for early diagnosis. Recent advancements in quantitative and large-scale proteomic methods could be used to optimize the clinical application of biomarkers. Early diagnosis of HCC and assessment of the stage of hepatic fibrosis or NAFLD can also contribute to more effective therapeutic interventions and an improve prognosis. Furthermore, advancements of proteomic techniques contribute not only to the discovery of clinically useful biomarkers, but also in clarifying the molecular mechanisms of disease pathogenesis by using body fluids, such as serum, and tissue samples and cultured cells. In this review, we report recent advances in quantitative proteomics and several findings focused on liver diseases, including HCC, NAFLD, hepatic fibrosis and hepatitis B or C virus infections.

  9. Variation in serum biomarkers with sex and female hormonal status: implications for clinical tests.

    Science.gov (United States)

    Ramsey, Jordan M; Cooper, Jason D; Penninx, Brenda W J H; Bahn, Sabine

    2016-01-01

    Few serum biomarker tests are implemented in clinical practice and recent reports raise concerns about poor reproducibility of biomarker studies. Here, we investigated the potential role of sex and female hormonal status in this widespread irreproducibility. We examined 171 serum proteins and small molecules measured in 1,676 participants from the Netherlands Study of Depression and Anxiety. Concentrations of 96 molecules varied with sex and 66 molecules varied between oral contraceptive pill users, postmenopausal females, and females in the follicular and luteal phases of the menstrual cycle (FDR-adjusted p-value oral contraceptive pill use. High accuracy (over 90%) classification tools were developed to label samples with sex and female hormonal status where this information was not collected. PMID:27240929

  10. Soluble urokinase-type plasminogen activator receptor is a novel biomarker predicting acute exacerbation in COPD

    Directory of Open Access Journals (Sweden)

    Gumus A

    2015-02-01

    Full Text Available Aziz Gumus,1 Nejat Altintas,2 Halit Cinarka,1 Aynur Kirbas,3 Muge Haziroglu,1 Mevlut Karatas,1 Unal Sahin1 1Department of Pulmonary Medicine, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey; 2Department of Pulmonary Medicine, School of Medicine, Namik Kemal University, Tekirdag, Turkey; 3Department of Clinical Biochemistry, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey Background: Chronic obstructive pulmonary disease (COPD is a chronic inflammatory condition, and progresses with acute exacerbations. (AE. During AE, levels of acute phase reactants such as C-reactive protein (CRP and inflammatory cells in the circulation increase. Soluble urokinase-type plasminogen activator receptor (suPAR levels increase in acute viral and bacterial infections and in diseases involving chronic inflammation. The purpose of this study was to investigate the effectiveness of suPAR in predicting diagnosis of AE of COPD (AE-COPD and response to treatment. Methods: The study population consisted of 43 patients diagnosed with AE-COPD and 30 healthy controls. suPAR, CRP, and fibrinogen levels were measured on the first day of hospitalization and on the seventh day of treatment. Results: We found that fibrinogen (P<0.001, CRP (P<0.001, and suPAR (P<0.001 were significantly higher in patients with AE-COPD than in healthy controls. Fibrinogen (P<0.001, CRP (P=0.001, and suPAR (P<0.001 were significantly decreased by the seventh day of treatment. However, the area under receiver operator characteristic curve showed that suPAR is superior to CRP and fibrinogen in distinguishing AE-COPD. There was a correlation between fibrinogen, CRP, and suPAR. However, only fibrinogen was a powerful predictor of suPAR in multiple linear regression. In multiple logistic regression, only suPAR and fibrinogen were strong predictors of AE-COPD (P=0.002 and P=0.014, respectively. Serum suPAR was negatively correlated with forced expiratory volume in 1

  11. Plasma specific miRNAs as predictive biomarkers for diagnosis and prognosis of glioma

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    Wang Qiong

    2012-11-01

    Full Text Available Abstract Objective Glioblastoma multiforme (GBM is a highly malignant brain tumor with a poor prognosis. MicroRNAs (miRNAs are a class of small non-coding RNAs, approximately 21–25 nucleotides in length. Recently, some researchers have demonstrated that plasma miRNAs are sensitive and specific biomarkers of various cancers. The primary aim of the study is to investigate whether miRNAs present in the plasma of GBM patients can be used as diagnostic biomarkers and are associated with glioma classification and clinical treatment. Materials and Methods Plasma samples were attained by venipuncture from 50 patients and 10 healthy donors. Plasma levels of miRNAs were determined by real-time quantitative polymerase chain reaction. Results The plasma levels of miR-21, miR-128 and miR-342-3p were significantly altered in GBM patients compared to normal controls and could discriminate glioma from healthy controls with high specificity and sensitivity. However, these three miRNAs were not significantly changed in patients with other brain tumors such as meningioma or pituitary adenoma. Furthermore, the plasma levels of these three miRNAs in GBM patients treated by operation and chemo-radiation almost revived to normal levels. Finally, we also demonstrated that miR-128 and miR-342-3p were positively correlated with histopathological grades of glioma. Conclusions These findings suggest that plasma specific miRNAs have potential use as novel biomarkers of glioma and may be useful in clinical management for glioma patients.

  12. Relative value of diverse brain MRI and blood-based biomarkers for predicting cognitive decline in the elderly

    Science.gov (United States)

    Madsen, Sarah K.; Ver Steeg, Greg; Daianu, Madelaine; Mezher, Adam; Jahanshad, Neda; Nir, Talia M.; Hua, Xue; Gutman, Boris A.; Galstyan, Aram; Thompson, Paul M.

    2016-03-01

    Cognitive decline accompanies many debilitating illnesses, including Alzheimer's disease (AD). In old age, brain tissue loss also occurs along with cognitive decline. Although blood tests are easier to perform than brain MRI, few studies compare brain scans to standard blood tests to see which kinds of information best predict future decline. In 504 older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we first used linear regression to assess the relative value of different types of data to predict cognitive decline, including 196 blood panel biomarkers, 249 MRI biomarkers obtained from the FreeSurfer software, demographics, and the AD-risk gene APOE. A subset of MRI biomarkers was the strongest predictor. There was no specific blood marker that increased predictive accuracy on its own, we found that a novel unsupervised learning method, CorEx, captured weak correlations among blood markers, and the resulting clusters offered unique predictive power.

  13. Evaluation of candidate biomarkers to predict cancer cell sensitivity or resistance to PARP-1 inhibitor treatment

    DEFF Research Database (Denmark)

    Oplustilova, L.; Wolanin, K.; Bartkova, J.;

    2012-01-01

    (ADp-ribose) polymerase-1 (PARP-1), an enzyme critical for repair pathways alternative to HR. While promising, treatment with PARP-1 inhibitors (PARP-1i) faces some hurdles, including (1) acquired resistance, (2) search for other sensitizing, non-BRCA1/2 cancer defects and (3) lack of biomarkers to predict response......Impaired DNA damage response pathways may create vulnerabilities of cancer cells that can be exploited therapeutically. One such selective vulnerability is the sensitivity of BRCA1- or BRCA2-defective tumors (hence defective in DNA repair by homologous recombination, HR) to inhibitors of the poly...... to PARP-1i. Here we addressed these issues using PARP-1i on 20 human cell lines from carcinomas of the breast, prostate, colon, pancreas and ovary. Aberrations of the Mre11-Rad50-Nbs1 (MRN) complex sensitized cancer cells to PARP-1i, while p53 status was less predictive, even in response to PARP-1i...

  14. Toxicogenomic multigene biomarker for predicting the future onset of proximal tubular injury in rats

    International Nuclear Information System (INIS)

    Drug-induced renal tubular injury is a major concern in the preclinical safety evaluation of drug candidates. Toxicogenomics is now a generally accepted tool for identifying chemicals with potential safety problems. The specific aim of the present study was to develop a model for use in predicting the future onset of drug-induced proximal tubular injury following repeated dosing with various nephrotoxicants. In total, 41 nephrotoxic and nonnephrotoxic compounds were used for the present analysis. Male Sprague-Dawley rats were dosed orally or intravenously once daily. Animals were exposed to three different doses (low, middle, and high) of each compound, and kidney tissue was collected at 3, 6, 9, and 24 h after single dosing, and on days 4, 8, 15, and 29 after repeated dosing. Gene expression profiles were generated from kidney total RNA using Affymetrix DNA microarrays. Filter-type gene selection and linear classification algorithms were employed to discriminate future onset of proximal tubular injury. We identified genomic biomarkers for use in future onset prediction using the gene expression profiles determined on day 1, when most of the nephrotoxicants had yet to produce detectable histopathological changes. The model was evaluated using a five-fold cross validation, and achieved a sensitivity of 93% and selectivity of 90% with 19 probes. We also found that the prediction accuracy of the optimized model was substantially higher than that produced by any of the single genomic biomarkers or histopathology. The genes included in our model were primarily involved in DNA replication, cell cycle control, apoptosis, and responses to oxidative stress and chemical stimuli. In summary, our toxicogenomic model is particularly useful for predicting the future onset of proximal tubular injury.

  15. Predicting time to prostate cancer recurrence based on joint models for non-linear longitudinal biomarkers and event time outcomes.

    Science.gov (United States)

    Pauler, Donna K; Finkelstein, Dianne M

    2002-12-30

    Biological markers that are both sensitive and specific for tumour regrowth or metastasis are increasingly becoming available and routinely monitored during the regular follow-up of patients treated for cancer. Obtained by a simple blood test, these markers provide an inexpensive non-invasive means for the early detection of recurrence (or progression). Currently, the longitudinal behaviour of the marker is viewed as an indicator of early disease progression, and is applied by a physician in making clinical decisions. One marker that has been studied for use in both population screening for early disease and for detection of recurrence in prostate cancer patients is PSA. The elevation of PSA levels is known to precede clinically detectable recurrence by 2 to 5 years, and current clinical practice often relies partially on multiple recent rises in PSA to trigger a change in treatment. However, the longitudinal trajectory for individual markers is often non-linear; in many cases there is a decline immediately following radiation therapy or surgery, a plateau during remission, followed by an exponential rise following the recurrence of the cancer. The aim of this article is to determine the multiple aspects of the longitudinal PSA biomarker trajectory that can be most sensitive for predicting time to clinical recurrence. Joint Bayesian models for the longitudinal measures and event times are utilized based on non-linear hierarchical models, implied by unknown change-points, for the longitudinal trajectories, and a Cox proportional hazard model for progression times, with functionals of the longitudinal parameters as covariates in the Cox model. Using Markov chain Monte Carlo sampling schemes, the joint model is fit to longitudinal PSA measures from 676 patients treated at Massachusetts General Hospital between the years 1988 and 1995 with follow-up to 1999. Based on these data, predictive schemes for detecting cancer recurrence in new patients based on their

  16. Clinical predictive factors of pathologic tumor response

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Chi Hwan; Kim, Won Dong; Lee, Sang Jeon; Park, Woo Yoon [Chungbuk National University College of Medicine, Cheongju (Korea, Republic of)

    2012-09-15

    The aim of this study was to identify clinical predictive factors for tumor response after preoperative chemoradiotherapy (CRT) in rectal cancer. The study involved 51 patients who underwent preoperative CRT followed by surgery between January 2005 and February 2012. Radiotherapy was delivered to the whole pelvis at a dose of 45 Gy in 25 fractions, followed by a boost of 5.4 Gy in 3 fractions to the primary tumor with 5 fractions per week. Three different chemotherapy regimens were used. Tumor responses to preoperative CRT were assessed in terms of tumor downstaging and pathologic complete response (ypCR). Statistical analyses were performed to identify clinical factors associated with pathologic tumor response. Tumor downstaging was observed in 28 patients (54.9%), whereas ypCR was observed in 6 patients (11.8%). Multivariate analysis found that predictors of downstaging was pretreatment relative lymphocyte count (p = 0.023) and that none of clinical factors was significantly associated with ypCR. Pretreatment relative lymphocyte count (%) has a significant impact on the pathologic tumor response (tumor downstaging) after preoperative CRT for locally advanced rectal cancer. Enhancement of lymphocyte-mediated immune reactions may improve the effect of preoperative CRT for rectal cancer.

  17. The clinical use of biomarkers as prognostic factors in Ewing sarcoma

    Directory of Open Access Journals (Sweden)

    van Maldegem Annmeik M

    2012-02-01

    Full Text Available Abstract Ewing Sarcoma is the second most common primary bone sarcoma with 900 new diagnoses per year in Europe (EU27. It has a poor survival rate in the face of metastatic disease, with no more than 10% survival of the 35% who develop recurrence. Despite the remaining majority having localised disease, approximately 30% still relapse and die despite salvage therapies. Prognostic factors may identify patients at higher risk that might require differential therapeutic interventions. Aside from phenotypic features, quantitative biomarkers based on biological measurements may help identify tumours that are more aggressive. We audited the research which has been done to identify prognostic biomarkers for Ewing sarcoma in the past 15 years. We identified 86 articles were identified using defined search criteria. A total of 11,625 patients were reported, although this number reflects reanalysis of several cohorts. For phenotypic markers, independent reports suggest that tumour size > 8 cm and the presence of metastasis appeared strong predictors of negative outcome. Good histological response (necrosis > 90% after treatment appeared a significant predictor for a positive outcome. However, data proposing biological biomarkers for practical clinical use remain un-validated with only one secondary report published. Our recommendation is that we can stratify patients according to their stage and using the phenotypic features of metastases, tumour size and histological response. For biological biomarkers, we suggest a number of validating studies including markers for 9p21 locus, heat shock proteins, telomerase related markers, interleukins, tumour necrosis factors, VEGF pathway, lymphocyte count, and a number of other markers including Ki-67.

  18. Thymus and activation-regulated chemokine as a clinical biomarker in atopic dermatitis.

    Science.gov (United States)

    Kataoka, Yoko

    2014-03-01

    Thymus and activation-regulated chemokine (TARC/CCL17) is a member of the T-helper 2 chemokine family. In Japan, serum TARC level has been commercially measured since 2008. After years of experience, we realized that TARC is an extremely useful clinical biomarker for atopic dermatitis (AD) treatment. Usually, physicians conduct a visual examination to determine whether their treatment has been successful; however, the visual examination results may not always be accurate; in such cases, serum TARC levels should be measured to eliminate any ambiguity regarding the treatment outcome. When the waning and waxing of eczema and fluctuations in the serum TARC levels were considered, we frequently found that AD does not follow a natural course but follows non-regulated inflammatory floating caused by insufficient intermittent topical treatment. Serum TARC is a promising biomarker for remission and can be used for accurately monitoring proactive treatment for long-term control. Abnormally high serum TARC levels indicate accelerated pathogenesis of cutaneous inflammation. Rapid normalization and maintaining normal serum TARC levels using appropriate topical treatment is a reasonable strategy for alleviating inflammation without upregulating cytokine expression. Observing serum TARC levels during early intervention for severe infantile AD is worthwhile to determine initial disease activity and evaluate treatment efficacy. Appropriate control of severe early-onset infantile AD is important for improving prognosis of eczema and for preventing food allergies. Additionally, this biomarker is useful for improving patient adherence. Dermatologists will be able to make great progress in treating AD by adopting biomarkers such as TARC for accurately assessing non-visible subclinical disorders. PMID:24628072

  19. Pharmacogenetic potential biomarkers for carbamazepine adverse drug reactions and clinical response.

    Science.gov (United States)

    Jaramillo, Nancy Monroy; Galindo, Ingrid Fricke; Vázquez, Alberto Ortega; Cook, Helgi Jung; LLerena, Adrián; López, Marisol López

    2014-01-01

    Carbamazepine (CBZ) is a first-line widely used anticonvulsant. It has a narrow therapeutic index and exhibits considerable interindividual and interethnic variability in clinical efficacy and adverse drug reactions including potentially life-threatening hypersensitivity reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis. The most important pharmacogenetic finding is related to the association of CBZ-induced hypersensitivity with human leukocyte antigens (HLA class I and II alleles). Moreover, genotyping for HLA-B*15:02 allele is required prior to initiating CBZ in Asians and Asian ancestry patients, demonstrating the usefulness of biomarkers to avoid adverse drug reactions. On the other hand, in order to explain the differences in the clinical response to CBZ, genetic polymorphisms in phase I (CYP3A4, CYP3A5 and EPHX1) and phase II (UGT2B7) metabolising enzymes have been assessed; additionally, the influence of transporters (ABCB1 and ABCC2), receptors (PXR) and other drug targets (voltage- gated Na+ channels) in CBZ clinical response has been evaluated. To date, these studies are controversial and require further investigations to clarify the functional role of these polymorphisms as potential biomarkers in regard to CBZ therapy. PMID:24406279

  20. Investigating Multi-cancer Biomarkers and Their Cross-predictability in the Expression Profiles of Multiple Cancer Types

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    George C. Tseng

    2009-01-01

    Full Text Available Microarray technology has been widely applied to the analysis of many malignancies, however, integrative analyses across multiple studies are rarely investigated. In this study we performed a meta-analysis on the expression profiles of four published studies analyzing organ donor, benign tissues adjacent to tumor and tumor tissues from liver, prostate, lung and bladder samples. We identified 99 distinct multi-cancer biomarkers in the comparison of all three tissues in liver and prostate and 44 in the comparison of normal versus tumor in liver, prostate and lung. The bladder samples appeared to have a different list of biomarkers from the other three cancer types. The identified multi-cancer biomarkers achieved high accuracy similar to using whole genome in the within-cancer-type prediction. They also performed superior than the one using whole genome in inter-cancer-type prediction. To test the validity of the multi-cancer biomarkers, 23 independent prostate cancer samples were evaluated and 96% accuracy was achieved in inter-study prediction from the original prostate, liver and lung cancer data sets respectively. The result suggests that the compact lists of multi-cancer biomarkers are important in cancer development and represent the common signatures of malignancies of multiple cancer types. Pathway analysis revealed important tumorogenesis functional categories.

  1. Human Hippocampal Structure: A Novel Biomarker Predicting Mnemonic Vulnerability to, and Recovery from, Sleep Deprivation.

    Science.gov (United States)

    Saletin, Jared M; Goldstein-Piekarski, Andrea N; Greer, Stephanie M; Stark, Shauna; Stark, Craig E; Walker, Matthew P

    2016-02-24

    Sleep deprivation impairs the formation of new memories. However, marked interindividual variability exists in the degree to which sleep loss compromises learning, the mechanistic reasons for which are unclear. Furthermore, which physiological sleep processes restore learning ability following sleep deprivation are similarly unknown. Here, we demonstrate that the structural morphology of human hippocampal subfields represents one factor determining vulnerability (and conversely, resilience) to the impact of sleep deprivation on memory formation. Moreover, this same measure of brain morphology was further associated with the quality of nonrapid eye movement slow wave oscillations during recovery sleep, and by way of such activity, determined the success of memory restoration. Such findings provide a novel human biomarker of cognitive susceptibility to, and recovery from, sleep deprivation. Moreover, this metric may be of special predictive utility for professions in which memory function is paramount yet insufficient sleep is pervasive (e.g., aviation, military, and medicine). PMID:26911684

  2. A three-protein biomarker panel assessed in diagnostic tissue predicts death from prostate cancer for men with localized disease

    International Nuclear Information System (INIS)

    Only a minority of prostate cancers lead to death. Because no tissue biomarkers of aggressiveness other than Gleason score are available at diagnosis, many nonlethal cancers are treated aggressively. We evaluated whether a panel of biomarkers, associated with a range of disease outcomes in previous studies, could predict death from prostate cancer for men with localized disease. Using a case-only design, subjects were identified from three Australian epidemiological studies. Men who had died of their disease, “cases” (N = 83), were matched to “referents” (N = 232), those who had not died of prostate cancer, using incidence density sampling. Diagnostic tissue was retrieved to assess expression of AZGP1, MUC1, NKX3.1, p53, and PTEN by semiquantitative immunohistochemistry (IHC). Poisson regression was used to estimate mortality rate ratios (MRRs) adjusted for age, Gleason score, and stage and to estimate survival probabilities. Expression of MUC1 and p53 was associated with increased mortality (MRR 2.51, 95% CI 1.14–5.54, P = 0.02 and 3.08, 95% CI 1.41–6.95, P = 0.005, respectively), whereas AZGP1 expression was associated with decreased mortality (MRR 0.44, 95% CI 0.20–0.96, P = 0.04). Analyzing all markers under a combined model indicated that the three markers were independent predictors of prostate cancer death and survival. For men with localized disease at diagnosis, assessment of AZGP1, MUC1, and p53 expression in diagnostic tissue by IHC could potentially improve estimates of risk of dying from prostate cancer based only on Gleason score and clinical stage

  3. Combination of Circulating Tumor Cells with Serum Carcinoembryonic Antigen Enhances Clinical Prediction of Non-Small Cell Lung Cancer

    OpenAIRE

    Xi Chen; Xu Wang; Hua He; Ziling Liu; Ji-Fan Hu; Wei Li

    2015-01-01

    Circulating tumor cells (CTCs) have emerged as a potential biomarker in the diagnosis, prognosis, treatment, and surveillance of lung cancer. However, CTC detection is not only costly, but its sensitivity is also low, thus limiting its usage and the collection of robust data regarding the significance of CTCs in lung cancer. We aimed to seek clinical variables that enhance the prediction of CTCs in patients with non-small cell lung cancer (NSCLC). Clinical samples and pathological data were c...

  4. Mini Review: Circular RNAs as Potential Clinical Biomarkers for Disorders in the Central Nervous System.

    Science.gov (United States)

    Lu, Dan; Xu, An-Ding

    2016-01-01

    Circular RNAs (circRNAs) are a type of non-coding RNAs (ncRNAs), produced in eukaryotic cells during post-transcriptional processes. They are more stable than linear RNAs, and possess spatio-temporal properties. CircRNAs do not distribute equally in the neuronal compartments in the brain, but largely enriched in the synapses. These ncRNA species can be used as potential clinical biomarkers in complex disorders of the central nervous system (CNS), which is supported by recent findings. For example, ciRS-7 was found to be a natural microRNAs sponge for miRNA-7 and regulate Parkinson's disease/Alzheimer's disease-related genes; circPAIP2 is an intron-retaining circRNA which upregulates memory-related parental genes PAIP2 to affect memory development through PABP reactivation. The quantity of circRNAs carry important messages, either when they are inside the cells, or in circulation, or in exosomes released from synaptoneurosomes and endothelial. In addition, small molecules such as microRNAs and microvesicles can pass through the blood-brain barrier (BBB) and get into blood. For clinical applications, the study population needs to be phenotypically well-defined. CircRNAs may be combined with other biomarkers and imaging tools to improve the diagnostic power. PMID:27092176

  5. Predictive and Prognostic Protein Biomarkers in Epithelial Ovarian Cancer: Recommendation for Future Studies

    International Nuclear Information System (INIS)

    Epithelial ovarian cancer is the most lethal gynecological malignancy. Due to its lack of symptoms, this disease is diagnosed at an advanced stage when the cancer has already spread to secondary sites. While initial rates of response to first treatment is >80%, the overall survival rate of patients is extremely low, mainly due to development of drug resistance. To date, there are no reliable clinical factors that can properly stratify patients for suitable chemotherapy strategies. Clinical parameters such as disease stage, tumor grade and residual disease, although helpful in the management of patients after their initial surgery to establish the first line of treatment, are not efficient enough. Accordingly, reliable markers that are independent and complementary to clinical parameters are needed for a better management of these patients. For several years, efforts to identify prognostic factors have focused on molecular markers, with a large number having been investigated. This review aims to present a summary of the recent advances in the identification of molecular biomarkers in ovarian cancer patient tissues, as well as an overview of the need and importance of molecular markers for personalized medicine in ovarian cancer

  6. Predictive and Prognostic Protein Biomarkers in Epithelial Ovarian Cancer: Recommendation for Future Studies

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    Cécile Le Page

    2010-05-01

    Full Text Available Epithelial ovarian cancer is the most lethal gynecological malignancy. Due to its lack of symptoms, this disease is diagnosed at an advanced stage when the cancer has already spread to secondary sites. While initial rates of response to first treatment is >80%, the overall survival rate of patients is extremely low, mainly due to development of drug resistance. To date, there are no reliable clinical factors that can properly stratify patients for suitable chemotherapy strategies. Clinical parameters such as disease stage, tumor grade and residual disease, although helpful in the management of patients after their initial surgery to establish the first line of treatment, are not efficient enough. Accordingly, reliable markers that are independent and complementary to clinical parameters are needed for a better management of these patients. For several years, efforts to identify prognostic factors have focused on molecular markers, with a large number having been investigated. This review aims to present a summary of the recent advances in the identification of molecular biomarkers in ovarian cancer patient tissues, as well as an overview of the need and importance of molecular markers for personalized medicine in ovarian cancer.

  7. Response-driven imaging biomarkers for predicting radiation necrosis of the brain

    International Nuclear Information System (INIS)

    Radiation necrosis is an uncommon but severe adverse effect of brain radiation therapy (RT). Current predictive models based on radiation dose have limited accuracy. We aimed to identify early individual response biomarkers based upon diffusion tensor (DT) imaging and incorporated them into a response model for prediction of radiation necrosis. Twenty-nine patients with glioblastoma received six weeks of intensity modulated RT and concurrent temozolomide. Patients underwent DT-MRI scans before treatment, at three weeks during RT, and one, three, and six months after RT. Cases with radiation necrosis were classified based on generalized equivalent uniform dose (gEUD) of whole brain and DT index early changes in the corpus callosum and its substructures. Significant covariates were used to develop normal tissue complication probability models using binary logistic regression. Seven patients developed radiation necrosis. Percentage changes of radial diffusivity (RD) in the splenium at three weeks during RT and at six months after RT differed significantly between the patients with and without necrosis (p = 0.05 and p = 0.01). Percentage change of RD at three weeks during RT in the 30 Gy dose–volume of the splenium and brain gEUD combined yielded the best-fit logistic regression model. Our findings indicate that early individual response during the course of RT, assessed by radial diffusivity, has the potential to aid the prediction of delayed radiation necrosis, which could provide guidance in dose-escalation trials. (paper)

  8. Understanding and predicting suicidality using a combined genomic and clinical risk assessment approach.

    Science.gov (United States)

    Niculescu, A B; Levey, D F; Phalen, P L; Le-Niculescu, H; Dainton, H D; Jain, N; Belanger, E; James, A; George, S; Weber, H; Graham, D L; Schweitzer, R; Ladd, T B; Learman, R; Niculescu, E M; Vanipenta, N P; Khan, F N; Mullen, J; Shankar, G; Cook, S; Humbert, C; Ballew, A; Yard, M; Gelbart, T; Shekhar, A; Schork, N J; Kurian, S M; Sandusky, G E; Salomon, D R

    2015-11-01

    biomarkers for suicidality. We also identified other potential therapeutic targets or biomarkers for drugs known to mitigate suicidality, such as omega-3 fatty acids, lithium and clozapine. Overall, 14% of the top candidate biomarkers also had evidence for involvement in psychological stress response, and 19% for involvement in programmed cell death/cellular suicide (apoptosis). It may be that in the face of adversity (stress), death mechanisms are turned on at a cellular (apoptosis) and organismal level. Finally, we tested the top increased and decreased biomarkers from the discovery for suicidal ideation (CADM1, CLIP4, DTNA, KIF2C), prioritization with CFG for prior evidence (SAT1, SKA2, SLC4A4), and validation for behavior in suicide completers (IL6, MBP, JUN, KLHDC3) steps in a completely independent test cohort of psychiatric participants for prediction of suicidal ideation (n=108), and in a future follow-up cohort of psychiatric participants (n=157) for prediction of psychiatric hospitalizations due to suicidality. The best individual biomarker across psychiatric diagnoses for predicting suicidal ideation was SLC4A4, with a receiver operating characteristic (ROC) area under the curve (AUC) of 72%. For bipolar disorder in particular, SLC4A4 predicted suicidal ideation with an AUC of 93%, and future hospitalizations with an AUC of 70%. SLC4A4 is involved in brain extracellular space pH regulation. Brain pH has been implicated in the pathophysiology of acute panic attacks. We also describe two new clinical information apps, one for affective state (simplified affective state scale, SASS) and one for suicide risk factors (Convergent Functional Information for Suicide, CFI-S), and how well they predict suicidal ideation across psychiatric diagnoses (AUC of 85% for SASS, AUC of 89% for CFI-S). We hypothesized a priori, based on our previous work, that the integration of the top biomarkers and the clinical information into a universal predictive measure (UP-Suicide) would

  9. Cell-free DNA in Human Follicular Microenvironment: New Prognostic Biomarker to Predict in vitro Fertilization Outcomes.

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    Sabine Traver

    Full Text Available Cell-free DNA (cfDNA fragments, detected in blood and in other biological fluids, are released from apoptotic and/or necrotic cells. CfDNA is currently used as biomarker for the detection of many diseases such as some cancers and gynecological and obstetrics disorders. In this study, we investigated if cfDNA levels in follicular fluid (FF samples from in vitro fertilization (IVF patients, could be related to their ovarian reserve status, controlled ovarian stimulation (COS protocols and IVF outcomes. Therefore, 117 FF samples were collected from women (n = 117 undergoing IVF/Intra-cytoplasmic sperm injection (ICSI procedure and cfDNA concentration was quantified by ALU-quantitative PCR. We found that cfDNA level was significantly higher in FF samples from patients with ovarian reserve disorders (low functional ovarian reserve or polycystic ovary syndrome than from patients with normal ovarian reserve (2.7 ± 2.7 ng/μl versus 1.7 ± 2.3 ng/μl, respectively, p = 0.03. Likewise, FF cfDNA levels were significant more elevated in women who received long ovarian stimulation (> 10 days or high total dose of gonadotropins (≥ 3000 IU/l than in women who received short stimulation duration (7-10 days or total dose of gonadotropins < 3000 IU/l (2.4 ± 2.8 ng/μl versus 1.5 ± 1.9 ng/μl, p = 0.008; 2.2 ± 2.3 ng/μl versus 1.5 ± 2.1 ng/μl, p = 0.01, respectively. Finally, FF cfDNA level was an independent and significant predictive factor for pregnancy outcome (adjusted odds ratio = 0.69 [0.5; 0.96], p = 0.03. In multivariate analysis, the Receiving Operator Curve (ROC analysis showed that the performance of FF cfDNA in predicting clinical pregnancy reached 0.73 [0.66-0.87] with 88% specificity and 60% sensitivity. CfDNA might constitute a promising biomarker of follicular micro-environment quality which could be used to predict IVF prognosis and to enhance female infertility management.

  10. Cell-free DNA in Human Follicular Microenvironment: New Prognostic Biomarker to Predict in vitro Fertilization Outcomes

    Science.gov (United States)

    Mullet, Tiffany; Molinari, Nicolas; Vincens, Claire; Anahory, Tal; Hamamah, Samir

    2015-01-01

    Cell-free DNA (cfDNA) fragments, detected in blood and in other biological fluids, are released from apoptotic and/or necrotic cells. CfDNA is currently used as biomarker for the detection of many diseases such as some cancers and gynecological and obstetrics disorders. In this study, we investigated if cfDNA levels in follicular fluid (FF) samples from in vitro fertilization (IVF) patients, could be related to their ovarian reserve status, controlled ovarian stimulation (COS) protocols and IVF outcomes. Therefore, 117 FF samples were collected from women (n = 117) undergoing IVF/Intra-cytoplasmic sperm injection (ICSI) procedure and cfDNA concentration was quantified by ALU-quantitative PCR. We found that cfDNA level was significantly higher in FF samples from patients with ovarian reserve disorders (low functional ovarian reserve or polycystic ovary syndrome) than from patients with normal ovarian reserve (2.7 ± 2.7 ng/μl versus 1.7 ± 2.3 ng/μl, respectively, p = 0.03). Likewise, FF cfDNA levels were significant more elevated in women who received long ovarian stimulation (> 10 days) or high total dose of gonadotropins (≥ 3000 IU/l) than in women who received short stimulation duration (7–10 days) or total dose of gonadotropins < 3000 IU/l (2.4 ± 2.8 ng/μl versus 1.5 ± 1.9 ng/μl, p = 0.008; 2.2 ± 2.3 ng/μl versus 1.5 ± 2.1 ng/μl, p = 0.01, respectively). Finally, FF cfDNA level was an independent and significant predictive factor for pregnancy outcome (adjusted odds ratio = 0.69 [0.5; 0.96], p = 0.03). In multivariate analysis, the Receiving Operator Curve (ROC) analysis showed that the performance of FF cfDNA in predicting clinical pregnancy reached 0.73 [0.66–0.87] with 88% specificity and 60% sensitivity. CfDNA might constitute a promising biomarker of follicular micro-environment quality which could be used to predict IVF prognosis and to enhance female infertility management. PMID:26288130

  11. Molecular Imaging of Biomarkers in Breast Cancer

    Science.gov (United States)

    Ulaner, Gary A.; Riedl, Chris C.; Dickler, Maura N.; Jhaveri, Komal; Pandit-Taskar, Neeta; Weber, Wolfgang

    2016-01-01

    The success of breast cancer therapy is ultimately defined by clinical endpoints such as survival. It is valuable to have biomarkers that can predict the most efficacious therapies or measure response to therapy early in the course of treatment. Molecular imaging has a promising role in complementing and overcoming some of the limitations of traditional biomarkers by providing the ability to perform noninvasive, repeatable whole-body assessments. The potential advantages of imaging biomarkers are obvious and initial clinical studies have been promising, but proof of clinical utility still requires prospective multicenter clinical trials. PMID:26834103

  12. Clinical value of renal injury biomarkers in diagnosis of chronic kidney disease

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    Cheng-lu ZHANG

    2011-12-01

    Full Text Available Objective To investigate the levels of renal injury biomarkers in patients with chronic kidney disease(CKD and evaluate their clinical significances in diagnosis of CKD.Methods A total of 66 subjects(37 patients with CKD and 29 healthy individuals were involved in this study.Serum blood urea nitrogen(SBUN was determined by Glutamate dehydrogenase method;serum creatinine(SCr and urinary creatinine(UCr were detected by sarcosine oxidase method;serum uric acid(SUA was measured by uricase colorimetry;serum cystatin C(Cys C and urinary microalbumin(UmAlbwere analyzed by immunological transmission turbidimetry;urinary protein(U-PROwas measured by Coomassies Brilliant Blue(CBB assay.The UmAlb and U-PRO levels were expressed in units of mg/mmolUCr.Results The results of independent samples t test indicated that significant differences were found in SBUN,SCr,SUA,Cys C,UmAlb and U-PRO(P < 0.05 between patient group and healthy control group.The evaluation of diagnostic effects showed that the areas under the curve at ROC plot for SBUN,SCr,SUA,Cys C,UmAlb and U-PRO were 0.907,0.912,0.742,0.982,0.984 and 0.991,respectively.Conclusions U-PRO,UmAlb and Cys C are ideal biomarkers,SCr and SBUN come next,SUA is the weakest when the above biomarkers are applied to evaluate the renal injury and its severity of the patients with CKD.

  13. Pre-transplant Evaluation of Donor Urinary Biomarkers can Predict Reduced Graft Function After Deceased Donor Kidney Transplantation.

    Science.gov (United States)

    Koo, Tai Yeon; Jeong, Jong Cheol; Lee, Yonggu; Ko, Kwang-Pil; Lee, Kyoung-Bun; Lee, Sik; Park, Suk Joo; Park, Jae Berm; Han, Miyeon; Lim, Hye Jin; Ahn, Curie; Yang, Jaeseok

    2016-03-01

    Several recipient biomarkers are reported to predict graft dysfunction, but these are not useful in decision making for the acceptance or allocation of deceased donor kidneys; thus, it is necessary to develop donor biomarkers predictive of graft dysfunction. To address this issue, we prospectively enrolled 94 deceased donors and their 109 recipients who underwent transplantation between 2010 and 2013 at 4 Korean transplantation centers. We investigated the predictive values of donor urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and L-type fatty acid binding protein (L-FABP) for reduced graft function (RGF). We also developed a prediction model of RGF using these donor biomarkers. RGF was defined as delayed or slow graft function. Multiple logistic regression analysis was used to generate a prediction model, which was internally validated using a bootstrapping method. Multiple linear regression analysis was used to assess the association of biomarkers with 1-year graft function. Notably, donor urinary NGAL levels were associated with donor AKI (P = 0.014), and donor urinary NGAL and L-FABP were predictive for RGF, with area under the receiver-operating characteristic curves (AUROC) of 0.758 and 0.704 for NGAL and L-FABP, respectively. The best-fit model including donor urinary NGAL, L-FABP, and serum creatinine conveyed a better predictive value for RGF than donor serum creatinine alone (P = 0.02). In addition, we generated a scoring method to predict RGF based on donor urinary NGAL, L-FABP, and serum creatinine levels. Diagnostic performance of the RGF prediction score (AUROC 0.808) was significantly better than that of the DGF calculator (AUROC 0.627) and the kidney donor profile index (AUROC 0.606). Donor urinary L-FABP levels were also predictive of 1-year graft function (P = 0.005). Collectively, these findings suggest donor urinary NGAL and L-FABP to be useful biomarkers for RGF, and support the use of

  14. Differences in abundances of cell-signalling proteins in blood reveal novel biomarkers for early detection of clinical Alzheimer's disease.

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    Mateus Rocha de Paula

    Full Text Available BACKGROUND: In November 2007 a study published in Nature Medicine proposed a simple test based on the abundance of 18 proteins in blood to predict the onset of clinical symptoms of Alzheimer's Disease (AD two to six years before these symptoms manifest. Later, another study, published in PLoS ONE, showed that only five proteins (IL-1, IL-3, EGF, TNF- and G-CSF have overall better prediction accuracy. These classifiers are based on the abundance of 120 proteins. Such values were standardised by a Z-score transformation, which means that their values are relative to the average of all others. METHODOLOGY: The original datasets from the Nature Medicine paper are further studied using methods from combinatorial optimisation and Information Theory. We expand the original dataset by also including all pair-wise differences of z-score values of the original dataset ("metafeatures". Using an exact algorithm to solve the resulting Feature Set problem, used to tackle the feature selection problem, we found signatures that contain either only features, metafeatures or both, and evaluated their predictive performance on the independent test set. CONCLUSIONS: It was possible to show that a specific pattern of cell signalling imbalance in blood plasma has valuable information to distinguish between NDC and AD samples. The obtained signatures were able to predict AD in patients that already had a Mild Cognitive Impairment (MCI with up to 84% of sensitivity, while maintaining also a strong prediction accuracy of 90% on a independent dataset with Non Demented Controls (NDC and AD samples. The novel biomarkers uncovered with this method now confirms ANG-2, IL-11, PDGF-BB, CCL15/MIP-1; and supports the joint measurement of other signalling proteins not previously discussed: GM-CSF, NT-3, IGFBP-2 and VEGF-B.

  15. Prognostic utility of biomarkers in predicting of one-year outcomes in patients with aortic stenosis treated with transcatheter or surgical aortic valve implantation.

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    Jiri Parenica

    Full Text Available OBJECTIVES: The aim of the work was to find biomarkers identifying patients at high risk of adverse clinical outcomes after TAVI and SAVR in addition to currently used predictive model (EuroSCORE. BACKGROUND: There is limited data about the role of biomarkers in predicting prognosis, especially when TAVI is available. METHODS: The multi-biomarker sub-study included 42 consecutive high-risk patients (average age 82.0 years; logistic EuroSCORE 21.0% allocated to TAVI transfemoral and transapical using the Edwards-Sapien valve (n = 29, or SAVR with the Edwards Perimount bioprosthesis (n = 13. Standardized endpoints were prospectively followed during the 12-month follow-up. RESULTS: The clinical outcomes after both TAVI and SAVR were comparable. Malondialdehyde served as the best predictor of a combined endpoint at 1 year with AUC (ROC analysis = 0.872 for TAVI group, resp. 0.765 (p<0.05 for both TAVI and SAVR groups. Increased levels of MDA, matrix metalloproteinase 2, tissue inhibitor of metalloproteinase (TIMP1, ferritin-reducing ability of plasma, homocysteine, cysteine and 8-hydroxy-2-deoxyguanosine were all predictors of the occurrence of combined safety endpoints at 30 days (AUC 0.750-0.948; p<0.05 for all. The addition of MDA to a currently used clinical model (EuroSCORE significantly improved prediction of a combined safety endpoint at 30 days and a combined endpoint (0-365 days by the net reclassification improvement (NRI and the integrated discrimination improvement (IDI (p<0.05. Cystatin C, glutathione, cysteinylglycine, asymmetric dimethylarginine, nitrite/nitrate and MMP9 did not prove to be significant. Total of 14.3% died during 1-year follow-up. CONCLUSION: We identified malondialdehyde, a marker of oxidative stress, as the most promising predictor of adverse outcomes during the 30-day and 1-year follow-up in high-risk patients with symptomatic, severe aortic stenosis treated with TAVI. The development of a clinical

  16. FREE RADICAL-RELATED DISEASES: THE PREDICTIVE VALUE OF BIOMARKERS IN THE UMBILICAL CORD BLOOD

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    S. Perrone

    2013-12-01

    Full Text Available Despite recent advances in preterm newborns healthcare, the incidence of neonatal pathologies and disabilities still remain unacceptable high. The deficiency of antioxidant systems and the high free radicals (FRs production may cause several neonatal diseases, such as Retinopathy of Prematurity (ROP, Bronchopulmonary Dysplasia (BPD, Necrotizing Enterocolitis (NEC, Patent Ductus Arteriosus (PDA, Periventricular Leukomalacia (PVL and Intraventricular Hemorrhage (IVH, representing facets of the ‘Free Radical-Related Diseases’ (FRD. The aim of this study is to verify the association between FRD and blood levels of reliable oxidative stress (OS biomarkers in preterm newborns. We enrolled 178 preterm newborns born consecutively at the General Hospital “Santa Maria alle Scotte” in Siena, between 23 and 34 weeks (30,36±2.97 of gestational age, with birth-weight from 430 to 2890 grams (1453±593. After birth, we evaluated in the cord blood the markers of potential risk of OS (Non Protein-Bound Iron, NPBI and the markers of FR damage (Total Hydroperoxides, TH; Advanced Oxidation Protein Products, AOPP. For each newborn, we assessed the presence or absence of the following diseases, considering as FRD the presence of one at least: ROP, BPD, NEC, PDA, PVL, IVH. The univariate logistic regression showed a significant association between FRD and OS related markers. Risk assessment of FRD was higher in newborns with higher values of each OS marker: respectively TH (OR=1.013, p=0,000, AOPP (OR=1.017, p=0,036, NPBI (OR=1.077, p=0.039. Perinatal OS exposure is linked to the main diseases of prematurity. The evaluation of OS biomarkers in preterm newborns through the analysis of umbilical cord blood, can be useful and predictive for early identification of infants at risk for FRD in order to devise appropriate and timely prevention and treating strategies.

  17. Urinary biomarkers TIMP-2 and IGFBP7 early predict acute kidney injury after major surgery.

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    Ivan Gocze

    Full Text Available To assess the ability of the urinary biomarkers IGFBP7 (insulin-like growth factor-binding protein 7 and TIMP-2 (tissue inhibitor of metalloproteinase 2 to early predict acute kidney injury (AKI in high-risk surgical patients.Postoperative AKI is associated with an increase in short and long-term mortality. Using IGFBP7 and TIMP-2 for early detection of cellular kidney injury, thus allowing the early initiation of renal protection measures, may represent a new concept of evaluating renal function.In this prospective study, urinary [TIMP-2]×[IGFBP7] was measured in surgical patients at high risk for AKI. A predefined cut-off value of [TIMP-2]×[IGFBP7] >0.3 was used for assessing diagnostic accuracy. Perioperative characteristics were evaluated, and ROC analyses as well as logistic regression models of risk assessment were calculated with and without a [TIMP-2]×[IGFBP7] test.107 patients were included in the study, of whom 45 (42% developed AKI. The highest median values of biomarker were detected in septic, transplant and patients after hepatic surgery (1.24 vs 0.45 vs 0.47 ng/l²/1000. The area under receiving operating characteristic curve (AUC for the risk of any AKI was 0.85, for early use of RRT 0.83 and for 28-day mortality 0.77. In a multivariable model with established perioperative risk factors, the [TIMP-2]×[IGFBP7] test was the strongest predictor of AKI and significantly improved the risk assessment (p<0.001.Urinary [TIMP-2]×[IGFBP7] test sufficiently detect patients with risk of AKI after major non-cardiac surgery. Due to its rapid responsiveness it extends the time frame for intervention to prevent development of AKI.

  18. A shrinkage approach for estimating a treatment effect using intermediate biomarker data in clinical trials.

    Science.gov (United States)

    Li, Yun; Taylor, Jeremy M G; Little, Roderick J A

    2011-12-01

    In clinical trials, a biomarker (S ) that is measured after randomization and is strongly associated with the true endpoint (T) can often provide information about T and hence the effect of a treatment (Z ) on T. A useful biomarker can be measured earlier than T and cost less than T. In this article, we consider the use of S as an auxiliary variable and examine the information recovery from using S for estimating the treatment effect on T, when S is completely observed and T is partially observed. In an ideal but often unrealistic setting, when S satisfies Prentice's definition for perfect surrogacy, there is the potential for substantial gain in precision by using data from S to estimate the treatment effect on T. When S is not close to a perfect surrogate, it can provide substantial information only under particular circumstances. We propose to use a targeted shrinkage regression approach that data-adaptively takes advantage of the potential efficiency gain yet avoids the need to make a strong surrogacy assumption. Simulations show that this approach strikes a balance between bias and efficiency gain. Compared with competing methods, it has better mean squared error properties and can achieve substantial efficiency gain, particularly in a common practical setting when S captures much but not all of the treatment effect and the sample size is relatively small. We apply the proposed method to a glaucoma data example. PMID:21627627

  19. [Plasma Biomarkers as Predictive Factors for Advanced Hepatocellular Carcinoma with Sorafenib].

    Science.gov (United States)

    Shiozawa, Kazue; Watanabe, Manabu; Ikehara, Takashi; Matsukiyo, Yasushi; Kogame, Michio; Shinohara, Mie; Kikuchi, Yoshinori; Igarashi, Yoshinori; Sumino, Yasukiyo

    2016-07-01

    We examined plasma biomarkers as predictive factors for advanced hepatocellular carcinoma(ad-HCC)patients treated with sorafenib. We analyzed a-fetoprotein(AFP), AFP-L3, des-g-carboxy prothrombin(DCP), neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio(PLR), and vascular endothelial growth factor(VEGF)before sorafenib therapy, and changes in AFP-L3, NLR, PLR, and VEGF 1 month after sorafenib therapy in 16 patients. High AFP-L3(hazard ratio: 1.058, 95%CI: 1.019-1.098, p=0.003)and high NLR(hazard ratio: 1.475, 95%CI: 1.045-2.082, p=0.027)were significantly associated with poor prognosis in ad-HCC patients treated with sorafenib. There were no significant differences in changes in AFP-L3, NLR, PLR, and VEGF 1 month after sorafenib therapy. We suggest that AFP-L3 and NLR levels before sorafenib therapy in patients with ad-HCC are an important predictive factor for the therapeutic effect of sorafenib and patient survival. PMID:27431630

  20. Predictive biomarkers of preterm delivery in women with ongoing IVF pregnancies.

    Science.gov (United States)

    Kanninen, Tomi T; Sisti, Giovanni; Ramer, Ilana; Goldschlag, Dan; Witkin, Steven S; Spandorfer, Steven D

    2015-11-01

    In vitro fertilization (IVF) pregnancies potentially have a higher rate of preterm delivery (PTD) than do spontaneously conceived gestations, and differences persist following adjustment for multiple gestation, maternal age, and parity. The reasons for this increased susceptibility to PTD remain incompletely elucidated. To identify potential biomarkers predictive of PTD in IVF subjects, we performed a retrospective analysis of multiple markers in sera obtained during early gestation that have been suggested to be associated with peri-implantation events. Sera from 35 women with a preterm birth and 68 women with a term delivery, obtained between 9 and 11 days after embryo transfer, were tested blindly for concentrations of interleukin (IL)-1β, IL-6, IL-13, IL-17, human epididymal protein 4 (HE4), secretory leukocyte protease inhibitor (SLPI), insulin-like growth factor (IGF)-I, IGF-II, IGF binding protein (BP)-1, and interferon-γ. Concentrations of HE4 (p=0.001) and IL-13 (p=0.029) were reduced, and levels of IGF-II (p=0.023) and SLPI (p=0.043) were increased, in women who subsequently delivered preterm. By receiver operator curve analysis, the combination of HE4 and IL-13 levels best predicted the outcome preterm birth. The association between deficiencies in circulating HE4 and IL-13 levels during early pregnancy and subsequent PTD suggest that factors contributing to sub-optimal embryo implantation influence length of gestation in women undergoing IVF. PMID:26232150

  1. 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.

  2. Detection of pathological biomarkers in human clinical samples via amplifying genetic switches and logic gates.

    Science.gov (United States)

    Courbet, Alexis; Endy, Drew; Renard, Eric; Molina, Franck; Bonnet, Jérôme

    2015-05-27

    Whole-cell biosensors have several advantages for the detection of biological substances and have proven to be useful analytical tools. However, several hurdles have limited whole-cell biosensor application in the clinic, primarily their unreliable operation in complex media and low signal-to-noise ratio. We report that bacterial biosensors with genetically encoded digital amplifying genetic switches can detect clinically relevant biomarkers in human urine and serum. These bactosensors perform signal digitization and amplification, multiplexed signal processing with the use of Boolean logic gates, and data storage. In addition, we provide a framework with which to quantify whole-cell biosensor robustness in clinical samples together with a method for easily reprogramming the sensor module for distinct medical detection agendas. Last, we demonstrate that bactosensors can be used to detect pathological glycosuria in urine from diabetic patients. These next-generation whole-cell biosensors with improved computing and amplification capacity could meet clinical requirements and should enable new approaches for medical diagnosis. PMID:26019219

  3. 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.

  4. The Predictive Role of Inflammatory Biomarkers in Atrial Fibrillation as Seen through Neutrophil-Lymphocyte Ratio Mirror

    Directory of Open Access Journals (Sweden)

    Feliciano Chanana Paquissi

    2016-01-01

    Full Text Available Atrial fibrillation (AF is the most common arrhythmia and is responsible for significant disease burden worldwide. Current evidence has suggested that systemic inflammatory response plays a crucial role in the initiation, maintenance, and progression of AF. So, recent efforts have been directed in search of measurable inflammatory biomarkers as additional tools in severity and prognosis assessment of AF. A simple, and easily obtainable, inflammatory marker is the neutrophil-lymphocyte ratio (NLR, which has shown good performance in preliminary studies as a potential prognostic biomarker in patients with AF. In this work, we performed a thorough review of clinical studies that evaluated the role of C-reactive protein (CRP, interleukin-6 (IL-6, and NLR as predictors of outcomes in AF. We gave a particular emphasis on the NLR because it is a simpler, widely available, and inexpensive biomarker.

  5. The Predictive Role of Inflammatory Biomarkers in Atrial Fibrillation as Seen through Neutrophil-Lymphocyte Ratio Mirror.

    Science.gov (United States)

    Paquissi, Feliciano Chanana

    2016-01-01

    Atrial fibrillation (AF) is the most common arrhythmia and is responsible for significant disease burden worldwide. Current evidence has suggested that systemic inflammatory response plays a crucial role in the initiation, maintenance, and progression of AF. So, recent efforts have been directed in search of measurable inflammatory biomarkers as additional tools in severity and prognosis assessment of AF. A simple, and easily obtainable, inflammatory marker is the neutrophil-lymphocyte ratio (NLR), which has shown good performance in preliminary studies as a potential prognostic biomarker in patients with AF. In this work, we performed a thorough review of clinical studies that evaluated the role of C-reactive protein (CRP), interleukin-6 (IL-6), and NLR as predictors of outcomes in AF. We gave a particular emphasis on the NLR because it is a simpler, widely available, and inexpensive biomarker. PMID:27446629

  6. The Predictive Role of Inflammatory Biomarkers in Atrial Fibrillation as Seen through Neutrophil-Lymphocyte Ratio Mirror

    Science.gov (United States)

    2016-01-01

    Atrial fibrillation (AF) is the most common arrhythmia and is responsible for significant disease burden worldwide. Current evidence has suggested that systemic inflammatory response plays a crucial role in the initiation, maintenance, and progression of AF. So, recent efforts have been directed in search of measurable inflammatory biomarkers as additional tools in severity and prognosis assessment of AF. A simple, and easily obtainable, inflammatory marker is the neutrophil-lymphocyte ratio (NLR), which has shown good performance in preliminary studies as a potential prognostic biomarker in patients with AF. In this work, we performed a thorough review of clinical studies that evaluated the role of C-reactive protein (CRP), interleukin-6 (IL-6), and NLR as predictors of outcomes in AF. We gave a particular emphasis on the NLR because it is a simpler, widely available, and inexpensive biomarker. PMID:27446629

  7. Role of biomarkers in predicting CVD risk in the setting of HIV infection?

    DEFF Research Database (Denmark)

    Worm, Signe W; Hsue, Priscilla

    2010-01-01

    with risk of CVD. Biomarkers associated with inflammation such as C-reactive protein and interleukin-6 have been suggested to improve risk stratification among intermediate-risk persons; however, their routine use is not recommended in the general population. Both biomarkers have recently been reported......-infected population and will increase as this population continues to age. Identification of intermediate-risk individuals using biomarkers will be an important tool for clinicians in the future to be able to treat HIV-infected individuals aggressively. Future studies of biomarkers among individuals with HIV...

  8. Tailoring the implementation of new biomarkers based on their added predictive value in subgroups of individuals.

    Directory of Open Access Journals (Sweden)

    A van Giessen

    Full Text Available The value of new biomarkers or imaging tests, when added to a prediction model, is currently evaluated using reclassification measures, such as the net reclassification improvement (NRI. However, these measures only provide an estimate of improved reclassification at population level. We present a straightforward approach to characterize subgroups of reclassified individuals in order to tailor implementation of a new prediction model to individuals expected to benefit from it.In a large Dutch population cohort (n = 21,992 we classified individuals to low (< 5% and high (≥ 5% fatal cardiovascular disease risk by the Framingham risk score (FRS and reclassified them based on the systematic coronary risk evaluation (SCORE. Subsequently, we characterized the reclassified individuals and, in case of heterogeneity, applied cluster analysis to identify and characterize subgroups. These characterizations were used to select individuals expected to benefit from implementation of SCORE.Reclassification after applying SCORE in all individuals resulted in an NRI of 5.00% (95% CI [-0.53%; 11.50%] within the events, 0.06% (95% CI [-0.08%; 0.22%] within the nonevents, and a total NRI of 0.051 (95% CI [-0.004; 0.116]. Among the correctly downward reclassified individuals cluster analysis identified three subgroups. Using the characterizations of the typically correctly reclassified individuals, implementing SCORE only in individuals expected to benefit (n = 2,707,12.3% improved the NRI to 5.32% (95% CI [-0.13%; 12.06%] within the events, 0.24% (95% CI [0.10%; 0.36%] within the nonevents, and a total NRI of 0.055 (95% CI [0.001; 0.123]. Overall, the risk levels for individuals reclassified by tailored implementation of SCORE were more accurate.In our empirical example the presented approach successfully characterized subgroups of reclassified individuals that could be used to improve reclassification and reduce implementation burden. In particular when newly

  9. The Role of Proteomics in Biomarker Development for Improved Patient Diagnosis and Clinical Decision Making in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Claire L. Tonry

    2016-07-01

    Full Text Available Prostate Cancer (PCa is the second most commonly diagnosed cancer in men worldwide. Although increased expression of prostate-specific antigen (PSA is an effective indicator for the recurrence of PCa, its intended use as a screening marker for PCa is of considerable controversy. Recent research efforts in the field of PCa biomarkers have focused on the identification of tissue and fluid-based biomarkers that would be better able to stratify those individuals diagnosed with PCa who (i might best receive no treatment (active surveillance of the disease; (ii would benefit from existing treatments; or (iii those who are likely to succumb to disease recurrence and/or have aggressive disease. The growing demand for better prostate cancer biomarkers has coincided with the development of improved discovery and evaluation technologies for multiplexed measurement of proteins in bio-fluids and tissues. This review aims to (i provide an overview of these technologies as well as describe some of the candidate PCa protein biomarkers that have been discovered using them; (ii address some of the general limitations in the clinical evaluation and validation of protein biomarkers; and (iii make recommendations for strategies that could be adopted to improve the successful development of protein biomarkers to deliver improvements in personalized PCa patient decision making.

  10. Mass spectrometry in biomarker applications: from untargeted discovery to targeted verification, and implications for platform convergence and clinical application

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Richard D.

    2012-03-01

    It is really only in the last ten years that mass spectrometry (MS) has had a truly significant (but still small) impact on biomedical research. Much of this impact can be attributed to proteomics and its more basic applications. Early biomedical applications have included a number of efforts aimed at developing new biomarkers; however, the success of these endeavors to date have been quite modest - essentially confined to preclinical applications - and have often suffered from combinations of immature technology and hubris. Now that MS-based proteomics is reaching adolescence, it is appropriate to ask if and when biomarker-related applications will extend to the clinical realm, and what developments will be essential for this transition. Biomarker development can be described as a multistage process consisting of discovery, qualification, verification, research assay optimization, validation, and commercialization (1). From a MS perspective, it is possible to 'bin' measurements into 1 of 2 categories - those aimed at discovering potential protein biomarkers and those seeking to verify and validate biomarkers. Approaches in both categories generally involve digesting proteins (e.g., with trypsin) as a first step to yield peptides that can be effectively detected and identified with MS. Discovery-based approaches use broad 'unbiased' or 'undirected' measurements that attempt to cover as many proteins as possible in the hope of revealing promising biomarker candidates. A key challenge with this approach stems from the extremely large dynamic range (i.e., relative stoichiometry) of proteins of potential interest in biofluids such as plasma and the expectation that biomarker proteins of the greatest clinical value for many diseases may very well be present at low relative abundances (2). Protein concentrations in plasma extend from approximately 10{sup 10} pg/mL for albumin to approximately 10 pg/mL and below for interleukins and other

  11. Risk stratification in non-ST elevation acute coronary syndromes: Risk scores, biomarkers and clinical judgment

    Directory of Open Access Journals (Sweden)

    David Corcoran

    2015-09-01

    Clinical guidelines recommend an early invasive strategy in higher risk NSTE-ACS. The Global Registry of Acute Coronary Events (GRACE risk score is a validated risk stratification tool which has incremental prognostic value for risk stratification compared with clinical assessment or troponin testing alone. In emergency medicine, there has been a limited adoption of the GRACE score in some countries (e.g. United Kingdom, in part related to a delay in obtaining timely blood biochemistry results. Age makes an exponential contribution to the GRACE score, and on an individual patient basis, the risk of younger patients with a flow-limiting culprit coronary artery lesion may be underestimated. The future incorporation of novel cardiac biomarkers into this diagnostic pathway may allow for earlier treatment stratification. The cost-effectiveness of the new diagnostic pathways based on high-sensitivity troponin and copeptin must also be established. Finally, diagnostic tests and risk scores may optimize patient care but they cannot replace patient-focused good clinical judgment.

  12. MRI texture features as biomarkers to predict MGMT methylation status in glioblastomas

    OpenAIRE

    Korfiatis, Panagiotis; Kline, Timothy L.; Coufalova, Lucie; Lachance, Daniel H.; Parney, Ian F.; Carter, Rickey E.; Buckner, Jan C.; Erickson, Bradley J

    2016-01-01

    Purpose: Imaging biomarker research focuses on discovering relationships between radiological features and histological findings. In glioblastoma patients, methylation of the O6-methylguanine methyltransferase (MGMT) gene promoter is positively correlated with an increased effectiveness of current standard of care. In this paper, the authors investigate texture features as potential imaging biomarkers for capturing the MGMT methylation status of glioblastoma multiforme (GBM) tumors when combi...

  13. Prediction of Cardiovascular Events in Statin-Treated Stable Coronary Patients by Lipid and Nonlipid Biomarkers

    NARCIS (Netherlands)

    B.J. Arsenault; P. Barter; D.A. Demicco; W. Bao; G.M. Preston; J.C. LaRosa; S.M. Grundy; P. Deedwania; H. Greten; N.K. Wenger; J. Shepherd; D.D. Waters; J.J.P. Kastelein

    2010-01-01

    Objectives The aim of this study was to investigate the relationship between lipid and nonlipid biomarker levels achieved during statin therapy and the incidence of major cardiovascular events (MCVEs) in patients with stable coronary heart disease (CHD). Background Several plasma nonlipid biomarkers

  14. Clinical Diagnostic Biomarkers from the Personalization of Computational Models of Cardiac Physiology.

    Science.gov (United States)

    Lamata, Pablo; Cookson, Andrew; Smith, Nic

    2016-01-01

    Computational modelling of the heart is rapidly advancing to the point of clinical utility. However, the difficulty of parameterizing and validating models from clinical data indicates that the routine application of truly predictive models remains a significant challenge. We argue there is significant value in an intermediate step towards prediction. This step is the use of biophysically based models to extract clinically useful information from existing patient data. Specifically in this paper we review methodologies for applying modelling frameworks for this goal in the areas of quantifying cardiac anatomy, estimating myocardial stiffness and optimizing measurements of coronary perfusion. Using these indicative examples of the general overarching approach, we finally discuss the value, ongoing challenges and future potential for applying biophysically based modelling in the clinical context. PMID:26399986

  15. SNPs in genes implicated in radiation response are associated with radiotoxicity and evoke roles as predictive and prognostic biomarkers

    International Nuclear Information System (INIS)

    Biomarkers are needed to individualize cancer radiation treatment. Therefore, we have investigated the association between various risk factors, including single nucleotide polymorphisms (SNPs) in candidate genes and late complications to radiotherapy in our nasopharyngeal cancer patients. A cohort of 155 patients was included. Normal tissue fibrosis was scored using RTOG/EORTC grading system. A total of 45 SNPs in 11 candidate genes (ATM, XRCC1, XRCC3, XRCC4, XRCC5, PRKDC, LIG4, TP53, HDM2, CDKN1A, TGFB1) were genotyped by direct genomic DNA sequencing. Patients with severe fibrosis (cases, G3-4, n = 48) were compared to controls (G0-2, n = 107). Univariate analysis showed significant association (P < 0.05) with radiation complications for 6 SNPs (ATM G/A rs1801516, HDM2 promoter T/G rs2279744 and T/A rs1196333, XRCC1 G/A rs25487, XRCC5 T/C rs1051677 and TGFB1 C/T rs1800469). In addition, Kaplan-Meier analyses have also highlighted significant association between genotypes and length of patients’ follow-up after radiotherapy. Multivariate logistic regression has further sustained these results suggesting predictive and prognostic roles of SNPs. Univariate and multivariate analysis suggest that radiation toxicity in radiotherapy patients are associated with certain SNPs, in genes including HDM2 promoter studied for the 1st time. These results support the use of SNPs as genetic predictive markers for clinical radiosensitivity and evoke a prognostic role for length of patients’ follow-up after radiotherapy

  16. Computational and Empirical Studies Predict Mycobacterium tuberculosis-Specific T Cells as a Biomarker for Infection Outcome.

    Science.gov (United States)

    Marino, Simeone; Gideon, Hannah P; Gong, Chang; Mankad, Shawn; McCrone, John T; Lin, Philana Ling; Linderman, Jennifer J; Flynn, JoAnne L; Kirschner, Denise E

    2016-04-01

    Identifying biomarkers for tuberculosis (TB) is an ongoing challenge in developing immunological correlates of infection outcome and protection. Biomarker discovery is also necessary for aiding design and testing of new treatments and vaccines. To effectively predict biomarkers for infection progression in any disease, including TB, large amounts of experimental data are required to reach statistical power and make accurate predictions. We took a two-pronged approach using both experimental and computational modeling to address this problem. We first collected 200 blood samples over a 2- year period from 28 non-human primates (NHP) infected with a low dose of Mycobacterium tuberculosis. We identified T cells and the cytokines that they were producing (single and multiple) from each sample along with monkey status and infection progression data. Machine learning techniques were used to interrogate the experimental NHP datasets without identifying any potential TB biomarker. In parallel, we used our extensive novel NHP datasets to build and calibrate a multi-organ computational model that combines what is occurring at the site of infection (e.g., lung) at a single granuloma scale with blood level readouts that can be tracked in monkeys and humans. We then generated a large in silico repository of in silico granulomas coupled to lymph node and blood dynamics and developed an in silico tool to scale granuloma level results to a full host scale to identify what best predicts Mycobacterium tuberculosis (Mtb) infection outcomes. The analysis of in silico blood measures identifies Mtb-specific frequencies of effector T cell phenotypes at various time points post infection as promising indicators of infection outcome. We emphasize that pairing wetlab and computational approaches holds great promise to accelerate TB biomarker discovery. PMID:27065304

  17. An overview of children as a special population-Relevance to predictive biomarkers

    International Nuclear Information System (INIS)

    There has been an increasing focus on children as a special population in the fields of toxicology and epidemiology. At the same time, there has been considerable improvement in the technology for defining normal development and pathways of pathogenesis. Increased support of these areas has culminated in stronger research programs and greater professional involvement in addressing the specific challenges of applying new techniques and data to the improvement of children's health. Part of these challenges relates to the ever changing environment of the child. Not only does a child's anatomy, physiology, and metabolism change with time, but their lifestyle and awareness change as well. All of these can have a significant impact on a child's exposure and the potential of that exposure to have an effect on health and development. This paper will provide a brief overview of the susceptibility of the child relative to sensitive developmental life stages, the changing nature of exposure parameters during development, and how these factors can impact the relevance of predictive biomarkers of chemical toxicity in children

  18. Expression profiling of blood samples from an SU5416 Phase III metastatic colorectal cancer clinical trial: a novel strategy for biomarker identification

    Directory of Open Access Journals (Sweden)

    Smolich Beverly D

    2003-02-01

    Full Text Available Abstract Background Microarray-based gene expression profiling is a powerful approach for the identification of molecular biomarkers of disease, particularly in human cancers. Utility of this approach to measure responses to therapy is less well established, in part due to challenges in obtaining serial biopsies. Identification of suitable surrogate tissues will help minimize limitations imposed by those challenges. This study describes an approach used to identify gene expression changes that might serve as surrogate biomarkers of drug activity. Methods Expression profiling using microarrays was applied to peripheral blood mononuclear cell (PBMC samples obtained from patients with advanced colorectal cancer participating in a Phase III clinical trial. The PBMC samples were harvested pre-treatment and at the end of the first 6-week cycle from patients receiving standard of care chemotherapy or standard of care plus SU5416, a vascular endothelial growth factor (VEGF receptor tyrosine kinase (RTK inhibitor. Results from matched pairs of PBMC samples from 23 patients were queried for expression changes that consistently correlated with SU5416 administration. Results Thirteen transcripts met this selection criterion; six were further tested by quantitative RT-PCR analysis of 62 additional samples from this trial and a second SU5416 Phase III trial of similar design. This method confirmed four of these transcripts (CD24, lactoferrin, lipocalin 2, and MMP-9 as potential biomarkers of drug treatment. Discriminant analysis showed that expression profiles of these 4 transcripts could be used to classify patients by treatment arm in a predictive fashion. Conclusions These results establish a foundation for the further exploration of peripheral blood cells as a surrogate system for biomarker analyses in clinical oncology studies.

  19. Expression profiling of blood samples from an SU5416 Phase III metastatic colorectal cancer clinical trial: a novel strategy for biomarker identification

    International Nuclear Information System (INIS)

    Microarray-based gene expression profiling is a powerful approach for the identification of molecular biomarkers of disease, particularly in human cancers. Utility of this approach to measure responses to therapy is less well established, in part due to challenges in obtaining serial biopsies. Identification of suitable surrogate tissues will help minimize limitations imposed by those challenges. This study describes an approach used to identify gene expression changes that might serve as surrogate biomarkers of drug activity. Expression profiling using microarrays was applied to peripheral blood mononuclear cell (PBMC) samples obtained from patients with advanced colorectal cancer participating in a Phase III clinical trial. The PBMC samples were harvested pre-treatment and at the end of the first 6-week cycle from patients receiving standard of care chemotherapy or standard of care plus SU5416, a vascular endothelial growth factor (VEGF) receptor tyrosine kinase (RTK) inhibitor. Results from matched pairs of PBMC samples from 23 patients were queried for expression changes that consistently correlated with SU5416 administration. Thirteen transcripts met this selection criterion; six were further tested by quantitative RT-PCR analysis of 62 additional samples from this trial and a second SU5416 Phase III trial of similar design. This method confirmed four of these transcripts (CD24, lactoferrin, lipocalin 2, and MMP-9) as potential biomarkers of drug treatment. Discriminant analysis showed that expression profiles of these 4 transcripts could be used to classify patients by treatment arm in a predictive fashion. These results establish a foundation for the further exploration of peripheral blood cells as a surrogate system for biomarker analyses in clinical oncology studies

  20. Predicting Alzheimer's disease development: a comparison of cognitive criteria and associated neuroimaging biomarkers

    OpenAIRE

    Callahan, Brandy L.; Ramirez, Joel; Berezuk, Courtney; Duchesne, Simon; Black, Sandra E.; ,

    2015-01-01

    Introduction The definition of “objective cognitive impairment” in current criteria for mild cognitive impairment (MCI) varies considerably between research groups and clinics. This study aims to compare different methods of defining memory impairment to improve prediction models for the development of Alzheimer’s disease (AD) from baseline to 24 months. Methods The sensitivity and specificity of six methods of defining episodic memory impairment (< −1, −1.5 or −2 standard deviations [SD] on ...

  1. CDO1 Promoter Methylation is a Biomarker for Outcome Prediction of Anthracycline Treated, Estrogen Receptor-Positive, Lymph Node-Positive Breast Cancer Patients

    International Nuclear Information System (INIS)

    Various biomarkers for prediction of distant metastasis in lymph-node negative breast cancer have been described; however, predictive biomarkers for patients with lymph-node positive (LNP) disease in the context of distinct systemic therapies are still very much needed. DNA methylation is aberrant in breast cancer and is likely to play a major role in disease progression. In this study, the DNA methylation status of 202 candidate loci was screened to identify those loci that may predict outcome in LNP/estrogen receptor-positive (ER+) breast cancer patients with adjuvant anthracycline-based chemotherapy. Quantitative bisulfite sequencing was used to analyze DNA methylation biomarker candidates in a retrospective cohort of 162 LNP/ER+ breast cancer patients, who received adjuvant anthracycline-based chemotherapy. First, twelve breast cancer specimens were analyzed for all 202 candidate loci to exclude genes that showed no differential methylation. To identify genes that predict distant metastasis, the remaining loci were analyzed in 84 selected cases, including the 12 initial ones. Significant loci were analyzed in the remaining 78 independent cases. Metastasis-free survival analysis was conducted by using Cox regression, time-dependent ROC analysis, and the Kaplan-Meier method. Pairwise multivariate regression analysis was performed by linear Cox Proportional Hazard models, testing the association between methylation scores and clinical parameters with respect to metastasis-free survival. Of the 202 loci analysed, 37 showed some indication of differential DNA methylation among the initial 12 patient samples tested. Of those, 6 loci were associated with outcome in the initial cohort (n = 84, log rank test, p < 0.05). Promoter DNA methylation of cysteine dioxygenase 1 (CDO1) was confirmed in univariate and in pairwise multivariate analysis adjusting for age at surgery, pathological T stage, progesterone receptor status, grade, and endocrine therapy as a strong and

  2. Nomograms for predicting prognostic value of inflammatory biomarkers in colorectal cancer patients after radical resection.

    Science.gov (United States)

    Li, Yaqi; Jia, Huixun; Yu, Wencheng; Xu, Ye; Li, Xinxiang; Li, Qingguo; Cai, Sanjun

    2016-07-01

    Increasing evidence indicates that inflammation plays a vital role in tumorigenesis and progression. However, the prognostic value of inflammatory biomarkers in colorectal cancer (CRC) has not been established. In this study, a retrospective analysis was conducted in patients with CRC in Fudan University Shanghai Cancer Center (FUSCC) between April 1, 2007 and April 30, 2014, and 5,336 patients were identified eligible. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and albumin/globulin ratio (AGR) were analyzed. Kaplan-Meier analysis was used to calculate the 5-year overall survival (OS) and disease-free survival (DFS). Cox regression analysis was performed to assess the prognostic factors. Nomograms were established to predict OS and DFS, and Harrell's concordance index (c-index) was adopted to evaluate prediction accuracy. As results, the 5-year OS was 79.2% and the 5-year DFS was 56.0% in the cohort. Patients were stratified into 2 groups by NLR (≤2.72 and >2.72), PLR (≤219.00 and >219.00), LMR (≤2.83 and >2.83) and AGR ( 2.72, PLR > 219.00, LMR ≤ 2.83 and AGR nomograms on OS and DFS were established according to all significant factors, and c-indexes were 0.765 (95% CI: 0.744-0.785) and 0.735 (95% CI: 0.721-0.749), respectively. Nomograms based on OS and DFS can be recommended as practical models to evaluate prognosis for CRC patients. PMID:26933932

  3. Estimation of biomarkers berberine and gallic acid in polyherbal formulation punarnavashtak kwath and its clinical study for hepatoprotective potential

    OpenAIRE

    Shah V; Doshi D; Shah M; Bhatt P

    2010-01-01

    Punarnavashtak (PN) kwath is a classical Ayurvedic formulation mentioned in Ayurvedic literature "Bhaishyajyaratnavali" for hepatic disorders and asthma. Standardization and clinical trial to support its efficacy are lacking. So, in the present study, standardization of PN kwath was done by using biomarkers, gallic acid and berberine, and its hepatoprotective activity was evaluated by clinical study to rationalise the traditional use of this formulation. PN kwath was standardized by HPTLC (Hi...

  4. Assessment of the translational value of mouse lupus models using clinically relevant biomarkers.

    Science.gov (United States)

    Bender, Andrew T; Wu, Yin; Cao, Qiongfang; Ding, Yueyun; Oestreicher, Judith; Genest, Melinda; Akare, Sandeep; Ishizaka, Sally T; Mackey, Matthew F

    2014-06-01

    Lupus is an autoimmune disease with a poorly understood etiology that manifests with a diverse pathology. This heterogeneity has been a challenge to clinical drug development efforts. A related difficulty is the uncertain translational power of animal models used for evaluating potential drug targets and candidate therapeutics, because it is unlikely that any 1 preclinical model will recapitulate the spectrum of human disease. Therefore, multiple models, along with an understanding of the immune mechanisms that drive them, are necessary if we are to use them to identify valid drug targets and evaluate candidate therapies successfully. To this end, we have characterized several different mouse lupus models and report their differences with respect to biomarkers and symptoms that are representative of the human disease. We compared the pristane-induced mouse lupus disease model using 3 different strains (DBA/1, SJL, BALB/c), and the spontaneous NZB x NZW F1(NZB/W) mouse model. We show that the models differ significantly in their autoantibody profiles, disease manifestations such as nephritis and arthritis, and expression of type I interferon-regulated genes. Similar to the NZB/W model, pristane-induced disease in SJL mice manifests with nephritis and proteinuria, whereas the pristane-treated DBA/1 mice develop arthritis and an interferon-driven gene signature that closely resembles that in human patients. The elucidation of each model's strengths and the identification of translatable biomarkers yields insight for basic lupus research and drug development, and should assist in the proper selection of models for evaluating candidate targets and therapeutic strategies. PMID:24462761

  5. Biomarkers of systemic inflammation and depression and fatigue in moderate clinically stable COPD

    Directory of Open Access Journals (Sweden)

    Singh Dave

    2011-01-01

    Full Text Available Abstract Introduction COPD is an inflammatory disease with major co-morbidities. It has recently been suggested that depression may be the result of systemic inflammation. We aimed to explore the association between systemic inflammation and symptoms of depression and fatigue in patients with mainly moderate and clinically stable COPD using a range of inflammatory biomarkers, 2 depression and 2 fatigue scales. Method We assessed 120 patients with moderate COPD (FEV1% 52, men 62%, age 66. Depression was assessed using the BASDEC and CES-D scales. Fatigue was assessed using the Manchester COPD-fatigue scale (MCFS and the Borg scale before and after 6MWT. We measured systemic TNF-α, CRP, TNF-α-R1, TNF-α-R2 and IL-6. Results A multivariate linear model of all biomarkers showed that TNF-α only had a positive correlation with BASDEC depression score (p = 0.007. TNF-α remained positively correlated with depression (p = 0.024 after further adjusting for TNF-α-R1, TNF-α-R2, 6MWD, FEV1%, and pack-years. Even after adding the MCFS score, body mass and body composition to the model TNF-α was still associated with the BASDEC score (p = 0.044. Furthermore, patients with higher TNF-α level (> 3 pg/ml, n = 7 had higher mean CES-D depression score than the rest of the sample (p = 0.03. Borg fatigue score at baseline were weakly correlated with TNF-α and CRP, and with TNF-α only after 6MWT. Patients with higher TNF-α had more fatigue after 6MWD (p = 0.054. Conclusion This study indicates a possible association between TNF-α and two frequent and major co-morbidities in COPD; i.e., depression and fatigue.

  6. Prediction of fruit and vegetable intake from biomarkers using individual participant data of diet-controlled intervention studies

    DEFF Research Database (Denmark)

    Souverein, Olga W; de Vries, Jeanne H M; Freese, Riitta;

    2015-01-01

    concentrations. Furthermore, a prediction model of fruit and vegetable intake based on these biomarkers and subject characteristics (i.e. age, sex, BMI and smoking status) was established. Data from twelve diet-controlled intervention studies were obtained to develop a prediction model for fruit and vegetable......Fruit and vegetable consumption produces changes in several biomarkers in blood. The present study aimed to examine the dose-response curve between fruit and vegetable consumption and carotenoid (α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein and zeaxanthin), folate and vitamin C...... intake (including and excluding fruit and vegetable juices). The study population in the present individual participant data meta-analysis consisted of 526 men and women. Carotenoid, folate and vitamin C concentrations showed a positive relationship with fruit and vegetable intake. Measures of...

  7. Use of Framingham risk score and new biomarkers to predict cardiovascular mortality in older people: population based observational cohort study

    OpenAIRE

    de Ruijter, Wouter; Westendorp, Rudi G. J.; Assendelft, Willem J J; Wendy P J den Elzen; Anton J M de Craen; le Cessie, Saskia; Gussekloo, Jacobijn

    2009-01-01

    Objectives To investigate the performance of classic risk factors, and of some new biomarkers, in predicting cardiovascular mortality in very old people from the general population with no history of cardiovascular disease. Design The Leiden 85-plus Study (1997-2004) is an observational prospective cohort study with 5 years of follow-up. Setting General population of the city of Leiden, the Netherlands. Participants Population based sample of participants aged 85 years (215 women and 87 men) ...

  8. Combining clinical variables to optimize prediction of antidepressant treatment outcomes.

    Science.gov (United States)

    Iniesta, Raquel; Malki, Karim; Maier, Wolfgang; Rietschel, Marcella; Mors, Ole; Hauser, Joanna; Henigsberg, Neven; Dernovsek, Mojca Zvezdana; Souery, Daniel; Stahl, Daniel; Dobson, Richard; Aitchison, Katherine J; Farmer, Anne; Lewis, Cathryn M; McGuffin, Peter; Uher, Rudolf

    2016-07-01

    The outcome of treatment with antidepressants varies markedly across people with the same diagnosis. A clinically significant prediction of outcomes could spare the frustration of trial and error approach and improve the outcomes of major depressive disorder through individualized treatment selection. It is likely that a combination of multiple predictors is needed to achieve such prediction. We used elastic net regularized regression to optimize prediction of symptom improvement and remission during treatment with escitalopram or nortriptyline and to identify contributing predictors from a range of demographic and clinical variables in 793 adults with major depressive disorder. A combination of demographic and clinical variables, with strong contributions from symptoms of depressed mood, reduced interest, decreased activity, indecisiveness, pessimism and anxiety significantly predicted treatment outcomes, explaining 5-10% of variance in symptom improvement with escitalopram. Similar combinations of variables predicted remission with area under the curve 0.72, explaining approximately 15% of variance (pseudo R(2)) in who achieves remission, with strong contributions from body mass index, appetite, interest-activity symptom dimension and anxious-somatizing depression subtype. Escitalopram-specific outcome prediction was more accurate than generic outcome prediction, and reached effect sizes that were near or above a previously established benchmark for clinical significance. Outcome prediction on the nortriptyline arm did not significantly differ from chance. These results suggest that easily obtained demographic and clinical variables can predict therapeutic response to escitalopram with clinically meaningful accuracy, suggesting a potential for individualized prescription of this antidepressant drug. PMID:27089522

  9. 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 novel...... diagnostic tools for stroke subtypes. METHODS: Ninety-seven stroke patients were prospectively investigated in a multicenter design with blood levels of brain biomarkers S100B, neuron specific enolase (NSE), glial fibrillary acidic protein (GFAP) as well as a coagulation biomarker, activated protein C...... exploratory study indicated that blood levels of biomarkers GFAP and APC-PCI, prior to neuroimaging, may rule out ICH in a mixed stroke population....

  10. ULK1: a promising biomarker in predicting poor prognosis and therapeutic response in human nasopharygeal carcinoma.

    Directory of Open Access Journals (Sweden)

    Miao Yun

    Full Text Available Plenty of studies have established that dysregulation of autophagy plays an essential role in cancer progression. The autophagy-related proteins have been reported to be closely associated with human cancer patients' prognosis. We explored the expression dynamics and prognostic value of autophagy-related protein ULK1 by immunochemistry (IHC method in two independent cohorts of nasopharygeal carcinoma (NPC cases. The X-tile program was applied to determine the optimal cut-off value in the training cohort. This derived cutoff value was then subjected to analysis the association of ULK1 expression with patients' clinical characteristics and survival outcome in the validation cohort and overall cases. High ULK1 expression was closely associated with aggressive clinical feature of NPC patients. Furthermore, high expression of ULK1 was observed more frequently in therapeutic resistant group than that in therapeutic effective group. Our univariate and multivariate analysis also showed that higher ULK1 expression predicted inferior disease-specific survival (DSS (P<0.05. Consequently, a new clinicopathologic prognostic model with 3 poor prognostic factors (ie, ULK1 expression, overall clinical stage and therapeutic response could significantly stratify risk (low, intermediate and high for DSS in NPC patients (P<0.001. These findings provide evidence that, the examination of ULK1 expression by IHC method, could serve as an effective additional tool for predicting therapeutic response and patients' survival outcome in NPC patients.

  11. Trace elements in scalp hair and fingernails as biomarkers in clinical studies

    Directory of Open Access Journals (Sweden)

    Awad Abdalla Momen

    2015-01-01

    Full Text Available Context: There are accumulating evidences that the metabolism of several trace elements might have specific roles in clinical disorders and the pathogenesis of many diseases, such as diabetes mellitus (DM and hypertension (HT. Objectives: To validate the analytical procedure and compare the levels of Cd, Cr, Cu, Pb, and Zn in scalp hair (SH and fingernails (FN of patients. Furthermore, to prove that human tissues such as hair and nails are useful in the studies pertaining to chronic body exposure and good biomarkers in clinical studies. Setting and Design: Inductively coupled plasma optical emission spectroscopy operating conditions were carefully selected and well-optimised in order to maximise the sensitivity for the desired elements and to obtain the best precision and accuracy. Factors affecting analytical and biological variability of the concentrations under study were discussed and carefully optimised. Materials and Methods: Totally, 160 samples of SH and 130 FN were collected from occupants of urban population from different districts adjacent to Taif city, Kingdom of Saudi Arabia. Different analytical procedures were investigated, and the most reliable one was developed and validated. Method Validity: The validity of the method was checked by standard addition method. The recoveries were in the range of 96.2-105.7%. Results: Cd, Cr, Cu, and Pb levels in SH were significantly higher in DM and HT compared to control groups, whereas, Zn was significantly lower. Cd and Pb levels in FN were significantly higher in DM and HT, whereas, Cr and Zn were lower, and Cu was in the same levels as compared to the control group. Conclusion: These findings may be consistent with those obtained in other studies, confirming that the deficiency and efficiency of trace elements play a role in clinical disorders and the pathogenesis of many diseases.

  12. Decorin in human oral cancer: A promising predictive biomarker of S-1 neoadjuvant chemosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Kasamatsu, Atsushi, E-mail: kasamatsua@faculty.chiba-u.jp [Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan); Department of Dentistry and Oral–Maxillofacial Surgery, Chiba University Hospital, Chiba 260-8670 (Japan); Uzawa, Katsuhiro, E-mail: uzawak@faculty.chiba-u.jp [Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan); Department of Dentistry and Oral–Maxillofacial Surgery, Chiba University Hospital, Chiba 260-8670 (Japan); Minakawa, Yasuyuki; Ishige, Shunsaku; Kasama, Hiroki [Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan); Endo-Sakamoto, Yosuke; Ogawara, Katsunori [Department of Dentistry and Oral–Maxillofacial Surgery, Chiba University Hospital, Chiba 260-8670 (Japan); Shiiba, Masashi; Takiguchi, Yuichi [Medical Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan); Tanzawa, Hideki [Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba 260-8670 (Japan); Department of Dentistry and Oral–Maxillofacial Surgery, Chiba University Hospital, Chiba 260-8670 (Japan)

    2015-01-30

    Highlights: • DCN is significantly up-regulated in chemoresistant cancer cell lines. • DCN is a key regulator for chemoresistant mechanisms in vitro and in vivo. • DCN predicts the clinical responses to S-1 NAC for patients with oral cancer. - Abstract: We reported previously that decorin (DCN) is significantly up-regulated in chemoresistant cancer cell lines. DCN is a small leucine-rich proteoglycan that exists and functions in stromal and epithelial cells. Accumulating evidence suggests that DCN affects the biology of several types of cancer by directly/indirectly targeting the signaling molecules involved in cell growth, survival, metastasis, and angiogenesis, however, the molecular mechanisms of DCN in chemoresistance and its clinical relevance are still unknown. Here we assumed that DCN silencing cells increase chemosusceptibility to S-1, consisted of tegafur, prodrug of 5-fluorouracil. We first established DCN knockdown transfectants derived from oral cancer cells for following experiments including chemosusceptibility assay to S-1. In addition to the in vitro data, DCN knockdown zenografting tumors in nude mice demonstrate decreasing cell proliferation and increasing apoptosis with dephosphorylation of AKT after S-1 chemotherapy. We also investigated whether DCN expression predicts the clinical responses of neoadjuvant chemotherapy (NAC) using S-1 (S-1 NAC) for oral cancer patients. Immunohistochemistry data in the preoperative biopsy samples was analyzed to determine the cut-off point for status of DCN expression by receiver operating curve analysis. Interestingly, low DCN expression was observed in five (83%) of six cases with complete responses to S-1 NAC, and in one (10%) case of 10 cases with stable/progressive disease, indicating that S-1 chemosensitivity is dramatically effective in oral cancer patients with low DCN expression compared with high DCN expression. Our findings suggest that DCN is a key regulator for chemoresistant mechanisms, and

  13. Decorin in human oral cancer: A promising predictive biomarker of S-1 neoadjuvant chemosensitivity

    International Nuclear Information System (INIS)

    Highlights: • DCN is significantly up-regulated in chemoresistant cancer cell lines. • DCN is a key regulator for chemoresistant mechanisms in vitro and in vivo. • DCN predicts the clinical responses to S-1 NAC for patients with oral cancer. - Abstract: We reported previously that decorin (DCN) is significantly up-regulated in chemoresistant cancer cell lines. DCN is a small leucine-rich proteoglycan that exists and functions in stromal and epithelial cells. Accumulating evidence suggests that DCN affects the biology of several types of cancer by directly/indirectly targeting the signaling molecules involved in cell growth, survival, metastasis, and angiogenesis, however, the molecular mechanisms of DCN in chemoresistance and its clinical relevance are still unknown. Here we assumed that DCN silencing cells increase chemosusceptibility to S-1, consisted of tegafur, prodrug of 5-fluorouracil. We first established DCN knockdown transfectants derived from oral cancer cells for following experiments including chemosusceptibility assay to S-1. In addition to the in vitro data, DCN knockdown zenografting tumors in nude mice demonstrate decreasing cell proliferation and increasing apoptosis with dephosphorylation of AKT after S-1 chemotherapy. We also investigated whether DCN expression predicts the clinical responses of neoadjuvant chemotherapy (NAC) using S-1 (S-1 NAC) for oral cancer patients. Immunohistochemistry data in the preoperative biopsy samples was analyzed to determine the cut-off point for status of DCN expression by receiver operating curve analysis. Interestingly, low DCN expression was observed in five (83%) of six cases with complete responses to S-1 NAC, and in one (10%) case of 10 cases with stable/progressive disease, indicating that S-1 chemosensitivity is dramatically effective in oral cancer patients with low DCN expression compared with high DCN expression. Our findings suggest that DCN is a key regulator for chemoresistant mechanisms, and

  14. Traumatic brain injury produced by exposure to blasts, a critical problem in current wars: biomarkers, clinical studies, and animal models

    Science.gov (United States)

    Dixon, C. Edward

    2011-06-01

    Traumatic brain injury (TBI) resulting from exposure to blast energy released by Improvised Explosive Devices (IEDs) has been recognized as the "signature injury" of Operation Iraqi Freedom and Operation Enduring Freedom. Repeated exposure to mild blasts may produce subtle deficits that are difficult to detect and quantify. Several techniques have been used to detect subtle brain dysfunction including neuropsychological assessments, computerized function testing and neuroimaging. Another approach is based on measurement of biologic substances (e.g. proteins) that are released into the body after a TBI. Recent studies measuring biomarkers in CSF and serum from patients with severe TBI have demonstrated the diagnostic, prognostic, and monitoring potential. Advancement of the field will require 1) biochemical mining for new biomarker candidates, 2) clinical validation of utility, 3) technical advances for more sensitive, portable detectors, 4) novel statistical approach to evaluate multiple biomarkers, and 5) commercialization. Animal models have been developed to simulate elements of blast-relevant TBI including gas-driven shock tubes to generate pressure waves similar to those produced by explosives. These models can reproduce hallmark clinical neuropathological responses such as neuronal degeneration and inflammation, as well as behavioral impairments. An important application of these models is to screen novel therapies and conduct proteomic, genomic, and lipodomic studies to mine for new biomarker candidates specific to blast relevant TBI.

  15. Trends in qualifying biomarkers in drug safety. Consensus of the 2011 meeting of the Spanish Society of Clinical Pharmacology.

    Directory of Open Access Journals (Sweden)

    José A.G. eAgúndez

    2012-01-01

    Full Text Available In this paper we discuss the consensus view on the use of qualifying biomarkers in drug safety, raised within the frame of the XXIV meeting of the Spanish Society of Clinical Pharmacology held in Málaga (Spain in October, 2011.The widespread use of biomarkers as surrogate endpoints is a goal that scientists have long been pursuing. Thirty years ago, when molecular pharmacogenomics evolved, we anticipated that these genetic biomarkers would soon obviate the routine use of drug therapies in a way that patients should adapt to the therapy rather than the opposite. This expected revolution in routine clinical practice never took place as quickly nor with the intensity as initially expected.The concerted action of operating multicenter networks holds great promise for future studies to identify biomarkers related to drug toxicity and to provide better insight into the underlying pathogenesis. Today some pharmacogenomic advances are already widely accepted, but pharmacogenomics still needs further development to elaborate more precise algorithms and many barriers to implementing individualized medicine exist. We briefly discuss our view about these barriers and we provide suggestions and areas of focus to advance in the field.

  16. A clinical prediction rule for histological chorioamnionitis in preterm newborns.

    Directory of Open Access Journals (Sweden)

    Jasper V Been

    Full Text Available BACKGROUND: Histological chorioamnionitis (HC is an intrauterine inflammatory process highly associated with preterm birth and adverse neonatal outcome. HC is often clinically silent and diagnosed postnatally by placental histology. Earlier identification could facilitate treatment individualisation to improve outcome in preterm newborns. AIM: Develop a clinical prediction rule at birth for HC and HC with fetal involvement (HCF in preterm newborns. METHODS: Clinical data and placental pathology were obtained from singleton preterm newborns (gestational age ≤ 32.0 weeks born at Erasmus UMC Rotterdam from 2001 to 2003 (derivation cohort; n = 216 or Máxima MC Veldhoven from 2009 to 2010 (validation cohort; n = 206. HC and HCF prediction rules were developed with preference for high sensitivity using clinical variables available at birth. RESULTS: HC and HCF were present in 39% and 24% in the derivation cohort and in 44% and 22% in the validation cohort, respectively. HC was predicted with 87% accuracy, yielding an area under ROC curve of 0.95 (95%CI = 0.92-0.98, a positive predictive value of 80% (95%CI = 74-84%, and a negative predictive value of 93% (95%CI = 88-96%. Corresponding figures for HCF were: accuracy 83%, area under ROC curve 0.92 (95%CI = 0.88-0.96, positive predictive value 59% (95%CI = 52-62%, and negative predictive value 97% (95%CI = 93-99%. External validation expectedly resulted in some loss of test performance, preferentially affecting positive predictive rather than negative predictive values. CONCLUSION: Using a clinical prediction rule composed of clinical variables available at birth, HC and HCF could be predicted with good test characteristics in preterm newborns. Further studies should evaluate the clinical value of these rules to guide early treatment individualisation.

  17. Potential Clinical Value of Multiparametric PET in the Prediction of Alzheimer’s Disease Progression

    Science.gov (United States)

    Chen, Xueqi; Zhou, Yun; Wang, Rongfu; Cao, Haoyin; Reid, Savina; Gao, Rui; Han, Dong

    2016-01-01

    Objective To evaluate the potential clinical value of quantitative functional FDG PET and pathological amyloid-β PET with cerebrospinal fluid (CSF) biomarkers and clinical assessments in the prediction of Alzheimer’s disease (AD) progression. Methods We studied 82 subjects for up to 96 months (median = 84 months) in a longitudinal Alzheimer’s Disease Neuroimaging Initiative (ADNI) project. All preprocessed PET images were spatially normalized to standard Montreal Neurologic Institute space. Regions of interest (ROI) were defined on MRI template, and standard uptake values ratios (SUVRs) to the cerebellum for FDG and amyloid-β PET were calculated. Predictive values of single and multiparametric PET biomarkers with and without clinical assessments and CSF biomarkers for AD progression were evaluated using receiver operating characteristic (ROC) analysis and logistic regression model. Results The posterior precuneus and cingulate SUVRs were identified for both FDG and amyloid-β PET in predicating progression in normal controls (NCs) and subjects with mild cognitive impairment (MCI). FDG parietal and lateral temporal SUVRs were suggested for monitoring NCs and MCI group progression, respectively. 18F-AV45 global cortex attained (78.6%, 74.5%, 75.4%) (sensitivity, specificity, accuracy) in predicting NC progression, which is comparable to the 11C-PiB global cortex SUVR’s in predicting MCI to AD. A logistic regression model to combine FDG parietal and posterior precuneus SUVR and Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog) Total Mod was identified in predicating NC progression with (80.0%, 94.9%, 93.9%) (sensitivity, specificity, accuracy). The selected model including FDG posterior cingulate SUVR, ADAS-Cog Total Mod, and Mini-Mental State Exam (MMSE) scores for predicating MCI to AD attained (96.4%, 81.2%, 83.6%) (sensitivity, specificity, accuracy). 11C-PiB medial temporal SUVR with MMSE significantly increased 11C-PiB PET AUC to 0.915 (p<0

  18. Pharmacogenetics : the science of predictive clinical pharmacology

    OpenAIRE

    Fenech, Anthony G; Grech, Godfrey

    2014-01-01

    The study of pharmacogenetics has expanded from what were initially casual family-based clinical drug response observations, to a fully-fledged science with direct therapeutic applications, all within a time-span of less than 60 years. A wide spectrum of polymorphisms, located within several genes, are now recognised to influence the pharmacokinetics and pharmacodynamics of the majority of drugs within our therapeutic armamentarium. This information forms the basis for the new development of ...

  19. Plasma biomarkers of acute GVHD and nonrelapse mortality: predictive value of measurements before GVHD onset and treatment.

    Science.gov (United States)

    McDonald, George B; Tabellini, Laura; Storer, Barry E; Lawler, Richard L; Martin, Paul J; Hansen, John A

    2015-07-01

    We identified plasma biomarkers that presaged outcomes in patients with gastrointestinal graft-versus-host disease (GVHD) by measuring 23 biomarkers in samples collected before initiation of treatment. Six analytes with the greatest accuracy in predicting grade 3-4 GVHD in the first cohort (74 patients) were then tested in a second cohort (76 patients). The same 6 analytes were also tested in samples collected at day 14 ± 3 from 167 patients free of GVHD at the time. Logistic regression and calculation of an area under a receiver-operating characteristic (ROC) curve for each analyte were used to determine associations with outcome. Best models in the GVHD onset and landmark analyses were determined by forward selection. In samples from the second cohort, collected a median of 4 days before start of treatment, levels of TIM3, IL6, and sTNFR1 had utility in predicting development of peak grade 3-4 GVHD (area under ROC curve, 0.88). Plasma ST2 and sTNFR1 predicted nonrelapse mortality within 1 year after transplantation (area under ROC curve, 0.90). In the landmark analysis, plasma TIM3 predicted subsequent grade 3-4 GVHD (area under ROC curve, 0.76). We conclude that plasma levels of TIM3, sTNFR1, ST2, and IL6 are informative in predicting more severe GVHD and nonrelapse mortality. PMID:25987657

  20. Chromosomal aberrations in lymphocytes predict human cancer: a report from the European Study Group on Cytogenetic Biomarkers and Health (ESCH)

    DEFF Research Database (Denmark)

    Hagmar, L; Bonassi, S; Strömberg, U; Brøgger, A; Knudsen, Lisbeth E.; Norppa, H; Reuterwall, C

    1998-01-01

    .35-2.89) was obtained for those with a high CA frequency level, whereas the SMRs for those with medium or low did not noticeably differ from unity. Cox's proportional hazards models gave no evidence that the effect of CAs on total cancer incidence/mortality was modified by gender, age at test, or time since...... test. No association was seen between the SCEs or the MN frequencies and subsequent cancer incidence/mortality. The present study further supports our previous observation on the cancer predictivity of the CA biomarker, which seems to be independent of age at test, gender, and time since test. The risk...... patterns were similar within each national cohort. This result suggests that the frequency of CAs in peripheral blood lymphocytes is a relevant biomarker for cancer risk in humans, reflecting either early biological effects of genotoxic carcinogens or individual cancer susceptibility....

  1. Discovering biomarkers from gene expression data for predicting cancer subgroups using neural networks and relational fuzzy clustering

    Directory of Open Access Journals (Sweden)

    Sharma Animesh

    2007-01-01

    Full Text Available Abstract Background The four heterogeneous childhood cancers, neuroblastoma, non-Hodgkin lymphoma, rhabdomyosarcoma, and Ewing sarcoma present a similar histology of small round blue cell tumor (SRBCT and thus often leads to misdiagnosis. Identification of biomarkers for distinguishing these cancers is a well studied problem. Existing methods typically evaluate each gene separately and do not take into account the nonlinear interaction between genes and the tools that are used to design the diagnostic prediction system. Consequently, more genes are usually identified as necessary for prediction. We propose a general scheme for finding a small set of biomarkers to design a diagnostic system for accurate classification of the cancer subgroups. We use multilayer networks with online gene selection ability and relational fuzzy clustering to identify a small set of biomarkers for accurate classification of the training and blind test cases of a well studied data set. Results Our method discerned just seven biomarkers that precisely categorized the four subgroups of cancer both in training and blind samples. For the same problem, others suggested 19–94 genes. These seven biomarkers include three novel genes (NAB2, LSP1 and EHD1 – not identified by others with distinct class-specific signatures and important role in cancer biology, including cellular proliferation, transendothelial migration and trafficking of MHC class antigens. Interestingly, NAB2 is downregulated in other tumors including Non-Hodgkin lymphoma and Neuroblastoma but we observed moderate to high upregulation in a few cases of Ewing sarcoma and Rabhdomyosarcoma, suggesting that NAB2 might be mutated in these tumors. These genes can discover the subgroups correctly with unsupervised learning, can differentiate non-SRBCT samples and they perform equally well with other machine learning tools including support vector machines. These biomarkers lead to four simple human interpretable

  2. Novel diagnostic biomarkers for prostate cancer

    Directory of Open Access Journals (Sweden)

    Chikezie O. Madu, Yi Lu

    2010-01-01

    Full Text Available Prostate cancer is the most frequently diagnosed malignancy in American men, and a more aggressive form of the disease is particularly prevalent among African Americans. The therapeutic success rate for prostate cancer can be tremendously improved if the disease is diagnosed early. Thus, a successful therapy for this disease depends heavily on the clinical indicators (biomarkers for early detection of the presence and progression of the disease, as well as the prediction after the clinical intervention. However, the current clinical biomarkers for prostate cancer are not ideal as there remains a lack of reliable biomarkers that can specifically distinguish between those patients who should be treated adequately to stop the aggressive form of the disease and those who should avoid overtreatment of the indolent form.A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. A biomarker reveals further information to presently existing clinical and pathological analysis. It facilitates screening and detecting the cancer, monitoring the progression of the disease, and predicting the prognosis and survival after clinical intervention. A biomarker can also be used to evaluate the process of drug development, and, optimally, to improve the efficacy and safety of cancer treatment by enabling physicians to tailor treatment for individual patients. The form of the prostate cancer biomarkers can vary from metabolites and chemical products present in body fluid to genes and proteins in the prostate tissues.Current advances in molecular techniques have provided new tools facilitating the discovery of new biomarkers for prostate cancer. These emerging biomarkers will be beneficial and critical in developing new and clinically reliable indicators that will have a high specificity for the diagnosis and prognosis of

  3. Development and Validation of a Prognostic Model Using Blood Biomarker Information for Prediction of Survival of Non-Small-Cell Lung Cancer Patients Treated With Combined Chemotherapy and Radiation or Radiotherapy Alone (NCT00181519, NCT00573040, and NCT00572325)

    International Nuclear Information System (INIS)

    Purpose: Currently, prediction of survival for non-small-cell lung cancer patients treated with (chemo)radiotherapy is mainly based on clinical factors. The hypothesis of this prospective study was that blood biomarkers related to hypoxia, inflammation, and tumor load would have an added prognostic value for predicting survival. Methods and Materials: Clinical data and blood samples were collected prospectively (NCT00181519, NCT00573040, and NCT00572325) from 106 inoperable non-small-cell lung cancer patients (Stages I-IIIB), treated with curative intent with radiotherapy alone or combined with chemotherapy. Blood biomarkers, including lactate dehydrogenase, C-reactive protein, osteopontin, carbonic anhydrase IX, interleukin (IL) 6, IL-8, carcinoembryonic antigen (CEA), and cytokeratin fragment 21-1, were measured. A multivariate model, built on a large patient population (N = 322) and externally validated, was used as a baseline model. An extended model was created by selecting additional biomarkers. The model's performance was expressed as the area under the curve (AUC) of the receiver operating characteristic and assessed by use of leave-one-out cross validation as well as a validation cohort (n = 52). Results: The baseline model consisted of gender, World Health Organization performance status, forced expiratory volume, number of positive lymph node stations, and gross tumor volume and yielded an AUC of 0.72. The extended model included two additional blood biomarkers (CEA and IL-6) and resulted in a leave-one-out AUC of 0.81. The performance of the extended model was significantly better than the clinical model (p = 0.004). The AUC on the validation cohort was 0.66 and 0.76, respectively. Conclusions: The performance of the prognostic model for survival improved markedly by adding two blood biomarkers: CEA and IL-6.

  4. Estimation of biomarkers berberine and gallic acid in polyherbal formulation punarnavashtak kwath and its clinical study for hepatoprotective potential

    Directory of Open Access Journals (Sweden)

    Shah V

    2010-01-01

    Full Text Available Punarnavashtak (PN kwath is a classical Ayurvedic formulation mentioned in Ayurvedic literature "Bhaishyajyaratnavali" for hepatic disorders and asthma. Standardization and clinical trial to support its efficacy are lacking. So, in the present study, standardization of PN kwath was done by using biomarkers, gallic acid and berberine, and its hepatoprotective activity was evaluated by clinical study to rationalise the traditional use of this formulation. PN kwath was standardized by HPTLC (High performance thin layer chromatography using gallic acid and berberine as biomarkers and was subjected to clinical study. For clinical study patients attending outpatient clinics, with an evidence of liver disease were included in the study. During the study period, patients who fulfilled inclusion criteria were randomly assigned. The recommended dose was 20 ml kwath daily for 8 weeks. All the patients underwent clinical examination and laboratory investigations for liver functions tests before the commencement of therapy. Thereafter, clinical assessments were done after 8 weeks of treatment. The results showed significant changes in liver functions tests [serum glutamate oxaloacetate transaminase (SGOT, serum glutamate pyruvate transaminase (SGPT, alkaline phosphatase (ALP, total bilirubin]. There was no report of adverse effects attributable to this formulation. Our results suggest that PN kwath showed significant hepatoprotective activity. Berberine and gallic acid were found to be 0.08 and 4.9%, respectively. Our results suggest that PN kwath showed significant hepatoprotective activity due to presence of various phytoconstituents and support its traditional uses in liver disorder.

  5. Development of liquid chromatography mass spectrometric methods for quantification of metabolites from cellular level to clinical biomarkers

    OpenAIRE

    Tohmola, Niina

    2015-01-01

    Metabolites are low molecular weight compounds participating in different functions of cellular systems. Metabolites can be used as diagnostic biomarkers for numerous diseases. Liquid chromatography tandem mass spectrometry (LC-MS/MS) is a powerful tool in quantification of metabolites from various sample matrices. Good sensitivity and specificity are the main benefits of the technique. Mass spectrometry is commonly used in industry, drug research and clinical diagnostics. Extensive validatio...

  6. Quantitative Imaging Biomarkers: The Application of Advanced Image Processing and Analysis to Clinical and Preclinical Decision Making

    OpenAIRE

    Prescott, Jeffrey William

    2012-01-01

    The importance of medical imaging for clinical decision making has been steadily increasing over the last four decades. Recently, there has also been an emphasis on medical imaging for preclinical decision making, i.e., for use in pharamaceutical and medical device development. There is also a drive towards quantification of imaging findings by using quantitative imaging biomarkers, which can improve sensitivity, specificity, accuracy and reproducibility of imaged characteristics used for dia...

  7. Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies

    OpenAIRE

    Fedele Vita; Scott Gary K; Wong Linda; Sensinger Kelly; Bowers Jessica; Benz Christopher C; Mattie Michael D; Ginzinger David; Getts Robert; Haqq Chris

    2006-01-01

    Abstract Background Recent studies indicate that microRNAs (miRNAs) are mechanistically involved in the development of various human malignancies, suggesting that they represent a promising new class of cancer biomarkers. However, previously reported methods for measuring miRNA expression consume large amounts of tissue, prohibiting high-throughput miRNA profiling from typically small clinical samples such as excision or core needle biopsies of breast or prostate cancer. Here we describe a no...

  8. Comparing clinical responses and the biomarkers of BDNF and cytokines between subthreshold bipolar disorder and bipolar II disorder

    OpenAIRE

    Tzu-Yun Wang; Sheng-Yu Lee; Shiou-Lan Chen; Yun-Hsuan Chang; Liang-Jen Wang; Po See Chen; Shih-Heng Chen; Chun-Hsien Chu; San-Yuan Huang; Nian-Sheng Tzeng; Chia-Ling Li; Yi-Lun Chung; Tsai-Hsin Hsieh; I Hui Lee; Kao Chin Chen

    2016-01-01

    Patients with subthreshold hypomania (SBP; subthreshold bipolar disorder) were indistinguishable from those with bipolar disorder (BP)-II on clinical bipolar validators, but their analyses lacked biological and pharmacological treatment data. Because inflammation and neuroprogression underlies BP, we hypothesized that cytokines and brain-derived neurotrophic factor (BDNF) are biomarkers for BP. We enrolled 41 drug-naïve patients with SBP and 48 with BP-II undergoing 12 weeks of pharmacologica...

  9. Melanoma biomarkers: Vox clamantis in deserto (Review).

    Science.gov (United States)

    Al-Shaer, Mays; Gollapudi, Divya; Papageorgio, Chris

    2010-05-01

    Detecting malignant melanoma at an early stage, monitoring therapy, predicting recurrence and identifying patients at risk for metastasis continue to be a challenging and demanding objective. The last two decades have witnessed innovations in the field of melanoma biomarkers. However, global agreement concerning monitoring and early detection has yet to be reached. This is a review of the current literature regarding melanoma biomarkers including demographic, clinical, pathological and molecular biomarkers that are produced by melanoma or non-melanoma cells. A number of these biomarkers demonstrate promising results as possible methods for early detection, predicting recurrence and monitoring therapy. Other biomarkers appear to be promising for identifying patients at risk for metastasis. We reviewed the most pertinent information in the field thus far and how this knowledge can impact, or not, the management of melanoma patients prognostically and therapeutically. PMID:22966315

  10. Reporting and Methods in Clinical Prediction Research: A Systematic Review

    OpenAIRE

    Bouwmeester, W; Zuithoff, NP; Mallett, S.; Geerlings, MI; Vergouwe, Y.; Steyerberg, EW; Altman, DG; Moons, KG

    2012-01-01

    Editors' Summary Background There are often times in our lives when we would like to be able to predict the future. Is the stock market going to go up, for example, or will it rain tomorrow? Being able predict future health is also important, both to patients and to physicians, and there is an increasing body of published clinicalprediction research.” Diagnostic prediction research investigates the ability of variables or test results to predict the presence or absence of a specific diagnos...

  11. Clinical Prediction Rules for Physical Therapy Interventions: A Systematic Review

    OpenAIRE

    Beneciuk, Jason M.; Bishop, Mark D; George, Steven Z.

    2009-01-01

    Background and Purpose: Clinical prediction rules (CPRs) involving physical therapy interventions have been published recently. The quality of the studies used to develop the CPRs was not previously considered, a fact that has potential implications for clinical applications and future research. The purpose of this systematic review was to determine the quality of published CPRs developed for physical therapy interventions.

  12. Functional connectivity classification of autism identifies highly predictive brain features but falls short of biomarker standards

    Directory of Open Access Journals (Sweden)

    Mark Plitt

    2015-01-01

    Conclusions: While individuals can be classified as having ASD with statistically significant accuracy from their rs-fMRI scans alone, this method falls short of biomarker standards. Classification methods provided further evidence that ASD functional connectivity is characterized by dysfunction of large-scale functional networks, particularly those involved in social information processing.

  13. Predictive data mining in clinical medicine: Current issues and guidelines

    OpenAIRE

    Bellazzi, Riccado; Zupan, Blaz

    2008-01-01

    BACKGROUND: The widespread availability of new computational methods and tools for data analysis and predictive modeling requires medical informatics researchers and practitioners to systematically select the most appropriate strategy to cope with clinical prediction problems. In particular, the collection of methods known as 'data mining' offers methodological and technical solutions to deal with the analysis of medical data and construction of prediction models. A large variety of these met...

  14. Biomarkers in Barrett's esophagus.

    Science.gov (United States)

    Reid, Brian J; Blount, Patricia L; Rabinovitch, Peter S

    2003-04-01

    This article provides a framework for clinicians who are attempting the difficult task of interpreting the Barrett's biomarker literature with the goal of improving care for their patients. Although many articles. including more that 60 proposed biomarkers, have been published on this subject, only a few describe phase 3 and 4 studies that are of interest to the clinical gastroenterologist (Table 1). For year, dysplasia grade has been the sole means of risk stratification for patients with BE, and it likely will continue to be used in the foreseeable future. The current authors believe that dysplasia classification can be valuable using the team management approach and quality controls described previously. Significant problems, however, have emerged in phase 2 through 4 studies of dysplasia that make it imperative for the Barrett's field to incorporate additional biomarkers as they are validated. These problems include poor reproducibility of dysplasia interpretations, poor predictive value for negative, indefinite, and low-grade dysplasia, and inconsistent results for HGD in different centers, all of which makes it virtually impossible to develop national guidelines for surveillance. Some studies have even suggested that endoscopic biopsy surveillance using dysplasia may not be worthwhile. Currently, flow cytometric tetraploidy and aneuploidy have progressed furthest in biomarker validation (see Table 1). With proper handling, endoscopic biopsy specimens can be shipped to reference laboratories that have the instruments, computer analytic methods, and expertise to reproducibly detect tetraploidy and aneuploidy. The results of phase 4 studies indicate that flow cytometry appears to be useful in detecting a subset of patients who do not have HGD and yet have an increased risk of progression to cancer that cannot be identified by dysplasia grade. For many reasons, the authors anticipate that the number of validated biomarkers will increase substantially in the

  15. Cerebrospinal fluid biomarkers in Alzheimer's and Parkinson's diseases-From pathophysiology to clinical practice.

    Science.gov (United States)

    Blennow, Kaj; Biscetti, Leonardo; Eusebi, Paolo; Parnetti, Lucilla

    2016-06-01

    This review provides an update on the role, development, and validation of CSF biomarkers in the diagnosis and prognosis of Alzheimer's disease and PD. Some recent developments on novel biomarkers are also discussed. We also give an overview of methodological/technical factors still hampering the global validation and standardization of CSF Alzheimer's disease and PD biomarkers. CSF biomarkers have the potential to improve the diagnostic accuracy at the early stages not only for Alzheimer's disease but also for PD. This step is essential in view of the availability of disease-modifying treatments. Our vision for the future is that analyzing biomarker panels on a minute amount of CSF could provide important information on the whole spectrum of the molecular pathogenic events characterizing these neurodegenerative disorders. CSF core biomarkers have already been included in the diagnostic criteria for Alzheimer's disease, and they are also under consideration as tools to monitor the effects of disease-modifying drugs. With respect to PD, their potential for improving diagnostic accuracy in early diagnosis is under intense research, resembling the same path followed for Alzheimer's disease. © 2016 International Parkinson and Movement Disorder Society. PMID:27145480

  16. Epigenetic Biomarkers of Preterm Birth and Its Risk Factors

    OpenAIRE

    Anna K. Knight; Smith, Alicia K.

    2016-01-01

    A biomarker is a biological measure predictive of a normal or pathogenic process or response. Biomarkers are often useful for making clinical decisions and determining treatment course. One area where such biomarkers would be particularly useful is in identifying women at risk for preterm delivery and related pregnancy complications. Neonates born preterm have significant morbidity and mortality, both in the perinatal period and throughout the life course, and identifying women at risk of del...

  17. Validation of New Cancer Biomarkers

    DEFF Research Database (Denmark)

    Duffy, Michael J; Sturgeon, Catherine M; Söletormos, Georg; Barak, Vivian; Molina, Rafael; Hayes, Daniel F; Diamandis, Eleftherios P; Bossuyt, Patrick

    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...

  18. In Search of 'Omics'-Based Biomarkers to Predict Risk of Frailty and Its Consequences in Older Individuals: The FRAILOMIC Initiative.

    Science.gov (United States)

    Erusalimsky, Jorge D; Grillari, Johannes; Grune, Tilman; Jansen-Duerr, Pidder; Lippi, Giuseppe; Sinclair, Alan J; Tegnér, Jesper; Viña, Jose; Durrance-Bagale, Anna; Miñambres, Rebeca; Viegas, Marcelo; Rodríguez-Mañas, Leocadio

    2016-01-01

    An increase in the number of older people experiencing disability and dependence is a critical aspect of the demographic change that will emerge within Europe due to the rise in life expectancy. In this scenario, prevention of these conditions is crucial for the well-being of older citizens and for the sustainability of our healthcare systems. Thus, the diagnosis and management of conditions like frailty, which identifies the people at the highest risk for developing those adverse outcomes, is of critical relevance. Currently, assessment of frailty relies primarily on measuring functional parameters, which have limited clinical utility. In this viewpoint article, we describe the FRAILOMIC Initiative, an international, large-scale, multi-endpoint, community- and clinic-based research study funded by the European Commission. The aim of the study is to develop validated measures, comprising both classic and 'omics-based' laboratory biomarkers, which can predict the risk of frailty, improve the accuracy of its diagnosis in clinical practice and provide a prognostic forecast on the evolution from frailty to disability. The initiative includes eight established cohorts of older adults, encompassing >75,000 subjects, most of whom (∼70%) are aged >65 years. Data on function, nutritional status and exercise habits have been collected, and cardiovascular health has been evaluated at baseline. Subjects will be stratified as 'non-frail' or 'frail' using Fried's definition, all adverse outcomes of interest will be recorded and differentially expressed biomarkers associated with the risk of frailty will be identified. Genomic, proteomic and transcriptomic investigations will be carried out using array-based systems. As circulating microRNAs in plasma have been identified in the context of senescence, ageing and age-associated diseases, a miRNome-wide analysis will also be undertaken to identify a miRNA-based signature of frailty. Blood concentrations of secreted proteins known

  19. Emerging Biomarkers in Glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    McNamara, Mairéad G.; Sahebjam, Solmaz; Mason, Warren P., E-mail: warren.mason@uhn.ca [Pencer Brain Tumor Centre, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario M5G 2M9 (Canada)

    2013-08-22

    Glioblastoma, the most common primary brain tumor, has few available therapies providing significant improvement in survival. Molecular signatures associated with tumor aggressiveness as well as with disease progression and their relation to differences in signaling pathways implicated in gliomagenesis have recently been described. A number of biomarkers which have potential in diagnosis, prognosis and prediction of response to therapy have been identified and along with imaging modalities could contribute to the clinical management of GBM. Molecular biomarkers including O(6)-methlyguanine-DNA-methyltransferase (MGMT) promoter and deoxyribonucleic acid (DNA) methylation, loss of heterozygosity (LOH) of chromosomes 1p and 19q, loss of heterozygosity 10q, isocitrate dehydrogenase (IDH) mutations, epidermal growth factor receptor (EGFR), epidermal growth factor, latrophilin, and 7 transmembrane domain-containing protein 1 on chromosome 1 (ELTD1), vascular endothelial growth factor (VEGF), tumor suppressor protein p53, phosphatase and tensin homolog (PTEN), p16INK4a gene, cytochrome c oxidase (CcO), phospholipid metabolites, telomerase messenger expression (hTERT messenger ribonucleic acid [mRNA]), microRNAs (miRNAs), cancer stem cell markers and imaging modalities as potential biomarkers are discussed. Inclusion of emerging biomarkers in prospective clinical trials is warranted in an effort for more effective personalized therapy in the future.

  20. Relevance of circulating nucleosomes and oncological biomarkers for predicting response to transarterial chemoembolization therapy in liver cancer patients

    Directory of Open Access Journals (Sweden)

    Durner Jürgen

    2011-05-01

    Full Text Available Abstract Background Transarterial chemoembolization (TACE therapy is an effective locoregional treatment in hepatocellular cancer (HCC patients. For early modification of therapy, markers predicting therapy response are urgently required. Methods Here, sera of 50 prospectively and consecutively included HCC patients undergoing 71 TACE therapies were taken before and 3 h, 6 h and 24 h after TACE application to analyze concentrations of circulating nucleosomes, cytokeratin-19 fragments (CYFRA 21-1, alpha fetoprotein (AFP, C-reactive protein (CRP and several liver biomarkers, and to compare these with radiological response to therapy. Results While nucleosomes, CYFRA 21-1, CRP and some liver biomarkers increased already 24 h after TACE, percental changes of nucleosome concentrations before and 24 h after TACE and pre- and posttherapeutic values of AFP, gamma-glutamyl-transferase (GGT and alkaline phosphatase (AP significantly indicated the later therapy response (39 progression versus 32 no progression. In multivariate analysis, nucleosomes (24 h, AP (24 h and TACE number were independent predictive markers. The risk score of this combination model achieved an AUC of 81.8% in receiver operating characteristic (ROC curves and a sensitivity for prediction of non-response to therapy of 41% at 97% specificity, and of 72% at 78% specificity. Conclusion Circulating nucleosomes and liver markers are valuable tools for early estimation of the efficacy of TACE therapy in HCC patients.

  1. Relevance of circulating nucleosomes and oncological biomarkers for predicting response to transarterial chemoembolization therapy in liver cancer patients

    International Nuclear Information System (INIS)

    Transarterial chemoembolization (TACE) therapy is an effective locoregional treatment in hepatocellular cancer (HCC) patients. For early modification of therapy, markers predicting therapy response are urgently required. Here, sera of 50 prospectively and consecutively included HCC patients undergoing 71 TACE therapies were taken before and 3 h, 6 h and 24 h after TACE application to analyze concentrations of circulating nucleosomes, cytokeratin-19 fragments (CYFRA 21-1), alpha fetoprotein (AFP), C-reactive protein (CRP) and several liver biomarkers, and to compare these with radiological response to therapy. While nucleosomes, CYFRA 21-1, CRP and some liver biomarkers increased already 24 h after TACE, percental changes of nucleosome concentrations before and 24 h after TACE and pre- and posttherapeutic values of AFP, gamma-glutamyl-transferase (GGT) and alkaline phosphatase (AP) significantly indicated the later therapy response (39 progression versus 32 no progression). In multivariate analysis, nucleosomes (24 h), AP (24 h) and TACE number were independent predictive markers. The risk score of this combination model achieved an AUC of 81.8% in receiver operating characteristic (ROC) curves and a sensitivity for prediction of non-response to therapy of 41% at 97% specificity, and of 72% at 78% specificity. Circulating nucleosomes and liver markers are valuable tools for early estimation of the efficacy of TACE therapy in HCC patients

  2. Thalamic functional connectivity predicts seizure laterality in individual TLE patients: Application of a biomarker development strategy

    OpenAIRE

    Barron, Daniel S.; Fox, Peter T.; Heath Pardoe; Jack Lancaster; Price, Larry R.; Karen Blackmon; Kristen Berry; Cavazos, Jose E.; Ruben Kuzniecky; Orrin Devinsky; Thomas Thesen

    2014-01-01

    Noninvasive markers of brain function could yield biomarkers in many neurological disorders. Disease models constrained by coordinate-based meta-analysis are likely to increase this yield. Here, we evaluate a thalamic model of temporal lobe epilepsy that we proposed in a coordinate-based meta-analysis and extended in a diffusion tractography study of an independent patient population. Specifically, we evaluated whether thalamic functional connectivity (resting-state fMRI-BOLD) with temporal l...

  3. Plasma-derived Extracellular Vesicles Contain Predictive Biomarkers and Potential Therapeutic Targets for Myocardial Ischemic (MI) Injury.

    Science.gov (United States)

    Cheow, Esther Sok Hwee; Cheng, Woo Chin; Lee, Chuen Neng; de Kleijn, Dominique; Sorokin, Vitaly; Sze, Siu Kwan

    2016-08-01

    Myocardial infarction (MI) triggers a potent inflammatory response via the release of circulatory mediators, including extracellular vesicles (EVs) by damaged cardiac cells, necessary for myocardial healing. Timely repression of inflammatory response are critical to prevent and minimize cardiac tissue injuries, nonetheless, progression in this aspect remains challenging. The ability of EVs to trigger a functional response upon delivery of carried bioactive cargos, have made them clinically attractive diagnostic biomarkers and vectors for therapeutic interventions. Using label-free quantitative proteomics approach, we compared the protein cargo of plasma EVs between patients with MI and from patients with stable angina (NMI). We report, for the first time, the proteomics profiling on 252 EV proteins that were modulated with >1.2-fold after MI. We identified six up-regulated biomarkers with potential for clinical applications; these reflected post-infarct pathways of complement activation (Complement C1q subcomponent subunit A (C1QA), 3.23-fold change, p = 0.012; Complement C5 (C5), 1.27-fold change, p = 0.087), lipoprotein metabolism (Apoliporotein D (APOD), 1.86-fold change, p = 0.033; Apolipoprotein C-III (APOCC3), 2.63-fold change, p = 0.029) and platelet activation (Platelet glycoprotein Ib alpha chain (GP1BA), 9.18-fold change, p p = 0.027). The data have been deposited to the ProteomeXchange with identifier PXD002950. This novel biomarker panel was validated in 43 patients using antibody-based assays (C1QA (p = 0.005); C5 (p = 0.0047), APOD (p = 0.0267); APOC3 (p = 0.0064); GP1BA (p = 0.0031); PPBP (p = 0.0465)). We further present that EV-derived fibrinogen components were paradoxically down-regulated in MI, suggesting that a compensatory mechanism may suppress post-infarct coagulation pathways, indicating potential for therapeutic targeting of this mechanism in MI. Taken together, these data demonstrated that plasma EVs contain novel diagnostic biomarkers

  4. Current status of biomarker research in neurology

    OpenAIRE

    Polivka, Jiri; Krakorova, Kristyna; Peterka, Marek; Topolcan, Ondrej

    2016-01-01

    Neurology is one of the typical disciplines where personalized medicine has been recently becoming an important part of clinical practice. In this article, the brief overview and a number of examples of the use of biomarkers and personalized medicine in neurology are described. The various issues in neurology are described in relation to the personalized medicine and diagnostic, prognostic as well as predictive blood and cerebrospinal fluid biomarkers. Such neurological domains discussed in t...

  5. Melanoma biomarkers: Vox clamantis in deserto (Review)

    OpenAIRE

    AL-SHAER, MAYS; GOLLAPUDI, DIVYA; PAPAGEORGIO, CHRIS

    2010-01-01

    Detecting malignant melanoma at an early stage, monitoring therapy, predicting recurrence and identifying patients at risk for metastasis continue to be a challenging and demanding objective. The last two decades have witnessed innovations in the field of melanoma biomarkers. However, global agreement concerning monitoring and early detection has yet to be reached. This is a review of the current literature regarding melanoma biomarkers including demographic, clinical, pathological and molecu...

  6. Predictive Value of IL-8 for Sepsis and Severe Infections after Burn Injury - A Clinical Study

    Science.gov (United States)

    Kraft, Robert; Herndon, David N; Finnerty, Celeste C; Cox, Robert A; Song, Juquan; Jeschke, Marc G

    2014-01-01

    The inflammatory response induced by burn injury contributes to increased incidence of infections, sepsis, organ failure, and mortality. Thus, monitoring post-burn inflammation is of paramount importance but so far there are no reliable biomarkers available to monitor and/or predict infectious complications after burn. As IL-8 is a major mediator for inflammatory responses, the aim of our study was to determine whether IL-8 expression can be used to predict post-burn sepsis, infections, and mortality other outcomes post-burn. Plasma cytokines, acute phase proteins, constitutive proteins, and hormones were analyzed during the first 60 days post injury from 468 pediatric burn patients. Demographics and clinical outcome variables (length of stay, infection, sepsis, multiorgan failure (MOF), and mortality were recorded. A cut-off level for IL-8 was determined using receiver operating characteristic (ROC) analysis. Statistical significance is set at (p<0.05). ROC analysis identified a cut-off level of 234 pg/ml for IL-8 for survival. Patients were grouped according to their average IL-8 levels relative to this cut off and stratified into high (H) (n=133) and low (L) (n=335) groups. In the L group, regression analysis revealed a significant predictive value of IL-8 to percent of total body surface area (TBSA) burned and incidence of MOF (p<0.001). In the H group IL-8 levels were able to predict sepsis (p<0.002). In the H group, elevated IL-8 was associated with increased inflammatory and acute phase responses compared to the L group (p<0.05). High levels of IL-8 correlated with increased MOF, sepsis, and mortality. These data suggest that serum levels of IL-8 may be a valid biomarker for monitoring sepsis, infections, and mortality in burn patients. PMID:25514427

  7. Selection of disease-specific biomarkers by integrating inflammatory mediators with clinical informatics in AECOPD patients: a preliminary study.

    Science.gov (United States)

    Chen, Hong; Song, Zhenju; Qian, Mengjia; Bai, Chunxue; Wang, Xiangdong

    2012-06-01

    Systemic inflammation is a major factor influencing the outcome and quality of patient with chronic obstructive pulmonary disease (COPD) and acute exacerbations (AECOPD). Because of the inflammatory complexity, a great challenge is still confronted to optimize the identification and validation of disease-specific biomarkers. This study aimed at developing a new protocol of specific biomarker evaluation by integrating proteomic profiles of inflammatory mediators with clinical informatics in AECOPD patients, understand better their function and signal networks. Plasma samples were collected from healthy non-smokers or patients with stable COPD (sCOPD) or AECOPD on days 1 and 3 of the admission and discharging day (day 7-10). Forty chemokines were measured using a chemokine multiplex antibody array. Clinical informatics was achieved by a Digital Evaluation Score System (DESS) for assessing severity of patients. Chemokine data was compared among different groups and its correlation with DESS scores was performed by SPSS software. Of 40 chemokines, 30 showed significant difference between sCOPD patients and healthy controls, 16 between AECOPD patients and controls and 13 between AECOPD patients and both sCOPD and controls, including BTC, IL-9, IL-18Bpa, CCL22,CCL23, CCL25, CCL28, CTACK, LIGHT, MSPa, MCP-3, MCP-4 and OPN. Of them, some had significant correlation with DESS scores. There is a disease-specific profile of inflammatory mediators in COPD and AECOPD patients which may have a potential diagnostics together with clinical informatics of patients. Our preliminary study suggested that integration of proteomics with clinical informatics can be a new way to validate and optimize disease-special biomarkers. PMID:21883889

  8. Prediction of labor induction outcome using different clinical parameters

    OpenAIRE

    Tatić-Stupar Žaklina; Novakov-Mikić Aleksandra; Bogavac Mirjana; Milatović Stevan; Sekulić Slobodan

    2013-01-01

    Introduction. Induction of labor is one of the most common obstetric interventions in contemporary obstetrics. Objective. The aim of the study was to evaluate the clinical and sonographic parameters in prediction of success of labor induction. Methods. The prospective study included 422 women in whom induction of labor was carried out at the Department of Obstetrics and Gynecology of Clinical Centre of Vojvodina. The role of body mass index and age of women...

  9. On-time clinical phenotype prediction based on narrative reports

    OpenAIRE

    Bejan, Cosmin A.; Vanderwende, Lucy; Evans, Heather L.; Wurfel, Mark M.; Yetisgen-Yildiz, Meliha

    2013-01-01

    In this paper we describe a natural language processing system which is able to predict whether or not a patient exhibits a specific phenotype using the information extracted from the narrative reports associated with the patient. Furthermore, the phenotypic annotations from our report dataset were performed at the report level which allows us to perform the prediction of the clinical phenotype at any point in time during the patient hospitalization period. Our experiments indicate that an im...

  10. Milk and blood biomarkers associated to the clinical efficacy of a probiotic for the treatment of infectious mastitis.

    Science.gov (United States)

    Espinosa-Martos, I; Jiménez, E; de Andrés, J; Rodríguez-Alcalá, L M; Tavárez, S; Manzano, S; Fernández, L; Alonso, E; Fontecha, J; Rodríguez, J M

    2016-06-01

    Previous studies have shown the efficacy of oral administration of selected lactobacilli strains to treat mastitis. The objective of this study was to find microbiological, biochemical and/or immunological biomarkers of the probiotic effect. Women with (n=23) and without (n=8) symptoms of mastitis received three daily doses (10(9) cfu) of Lactobacillus salivarius PS2 for 21 days. Samples of milk, blood and urine were collected before and after the probiotic intervention, and screened for a wide spectrum of microbiological, biochemical and immunological parameters. In the mastitis group, L. salivarius PS2 intake led to a reduction in milk bacterial counts, milk and blood leukocyte counts and interleukin (IL)-8 level in milk, an increase in those of immunoglobulin (Ig)E, IgG3, epidermal growth factor and IL-7, a modification of the milk electrolyte profile, and a reduction of some oxidative stress biomarkers. Such biomarkers will be useful in future clinical studies involving a larger cohort. PMID:26925605

  11. An Observational Study of Bevacizumab-Induced Hypertension as a Clinical Biomarker of Antitumor Activity

    OpenAIRE

    Mir, Olivier; Coriat, Romain; Cabanes, Laure; Ropert, Stanislas; Billemont, Bertrand; Alexandre, Jérôme; Durand, Jean-Philippe; Treluyer, Jean-Marc; Knebelmann, Bertrand; Goldwasser, François

    2011-01-01

    The incidence of bevacizumab-induced hypertension and factors associated with its development are described, and its relation with activity is retrospectively assessed. A reliable method for the detection and grading of hypertension is determined and recommendations for further studies aiming to study hypertension as a biomarker for bevacizumab efficacy are established.

  12. Disease-specific dynamic biomarkers selected by integrating inflammatory mediators with clinical informatics in ARDS patients with severe pneumonia.

    Science.gov (United States)

    Chen, Chengshui; Shi, Lin; Li, Yuping; Wang, Xiangdong; Yang, Shuanying

    2016-06-01

    Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that occurs as a result of various risk factors, including either direct or indirect lung injury, and systemic inflammation triggered also by severe pneumonia (SP). SP-ARDS-associated morbidity and mortality remains high also due to the lack of disease-specific biomarkers. The present study aimed at identifying disease-specific biomarkers in SP or SP-ARDS by integrating proteomic profiles of inflammatory mediators with clinical informatics. Plasma was sampled from the healthy as controls or patients with SP infected with bacteria or infection-associated SP-ARDS on the day of admission, day 3, and day 7. About 15 or 52 cytokines showed significant difference between SP and SP-ARDS patients with controls or 13 between SP-ARDS with SP alone and controls, including bone morphogenetic protein-15 (BMP-15), chemokine (C-X-C motif) ligand 16 (CXCL16), chemokine (C-X-C motif) receptor 3 (CXCR3), interleukin-6 (IL-6), protein NOV homolog (NOV/CCN3), glypican 3, insulin-like growth factor binding protein 4 (IGFBP-4), IL-5, IL-5 R alpha, IL-22 BP, leptin, MIP-1d, and orexin B with a significant correlation with Digital Evaluation Score System (DESS) scores. ARDS patients with overexpressed IL-6, CXCL16, or IGFBP-4 had significantly longer hospital stay and higher incidence of secondary infection. We also found higher levels of those mediators were associated with poor survival rates in patients with lung cancer and involved in the process of the epithelial mesenchymal transition of alveolar epithelial cells. Our preliminary study suggested that integration of proteomic profiles with clinical informatics as part of clinical bioinformatics is important to validate and optimize disease-specific and disease-staged biomarkers. PMID:27095254

  13. Potential biomarkers predicting risk of pulmonary hypertension in congenital heart disease: the role of homocysteine and hydrogen sulfide

    Institute of Scientific and Technical Information of China (English)

    Sun Ling; Sun Shuo; Li Yufen; Pan Wei; Xie Yumei; Wang Shushui; Zhang Zhiwei

    2014-01-01

    Background Pulmonary hypertension (PH) is a common complication of congenital heart disease (CHD).Although risk stratification is vital for prognosis and therapeutic guidance,the need for understanding the role of novel biomarkers cannot be overlooked.The aim of the present study was to investigate the changes of homocysteine and hydrogen sulfide levels and find potential biomarkers for early detection and treatment.Methods Between September 2012 and April 2013,we prospectively collected data on 158 pediatric patients with left to right shunt CHD at our institution.Standard right heart catheterizations were performed in all cases.Seventy-seven cases were associated with PH.The levels of homocysteine and hydrogen sulfide were detected with fluorescence polarization immunoassay and a sensitive silver-sulphur electrode,respectively.Enzyme-linked immunosorbent assay was used to determine the expression of methylenetetrahydrofolate reductase (MTHFR),cystathionine β-synthase (CBS),and cystathionine gamma-lyase (CSE).Radioimmunoassays were used to obtain folic acid and vitamin B12 levels.Results The difference in the levels of homocysteine,folic acid,vitamin B12,hydrogen sulfide,as well as the MTHFR and CSE expression between patients with PH and without PH were statistically significant (all P <0.05).Homocysteine had the best sensitivity and specificity to predict PH (P <0.001).Subgroup analysis showed that the levels of homocysteine and hydrogen sulfide,and the expression of CSE and MTHFR between patients with dynamic and obstructive PH were significantly different (all P <0.05).Based on the ROC curve,homocysteine had the best sensitivity and specificity to predict obstructive PH (P=0.032),while CSE had the most significant sensitivity and specificity to predict the dynamic PH (P=0.008).Conclusions Increased levels of homocysteine and decreased levels of hydrogen sulfide were significantly negatively correlated in PH associated with CHD.The underlying mechanism

  14. On-time clinical phenotype prediction based on narrative reports

    Science.gov (United States)

    Bejan, Cosmin A.; Vanderwende, Lucy; Evans, Heather L.; Wurfel, Mark M.; Yetisgen-Yildiz, Meliha

    2013-01-01

    In this paper we describe a natural language processing system which is able to predict whether or not a patient exhibits a specific phenotype using the information extracted from the narrative reports associated with the patient. Furthermore, the phenotypic annotations from our report dataset were performed at the report level which allows us to perform the prediction of the clinical phenotype at any point in time during the patient hospitalization period. Our experiments indicate that an important factor in achieving better results for this problem is to determine how much information to extract from the patient reports in the time interval between the patient admission time and the current prediction time. PMID:24551325

  15. Validation of nanodiamond-extracted CFP-10 antigen as a biomarker in clinical isolates of Mycobacterium tuberculosis complex in broth culture media.

    Science.gov (United States)

    Soo, Po-Chi; Horng, Yu-Tze; Chen, Ai-Ti; Yang, Shih-Chieh; Chang, Kai-Chih; Lee, Jen-Jyh; Peng, Wen-Ping

    2015-09-01

    With detonation nanodiamonds (DNDs) and matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS), we previously identified early secreted cell filtrate protein 10 (CFP-10) as a candidate Mycobacterium tuberculosis complex (MTC) biomarker. The performance of the CFP-10 biomarker was initially evaluated in relatively small mycobacterial samples (n = 42 samples) in our previous study. In this study, we conducted DND MALDI-TOF MS experiments to investigate the specificity and sensitivity of the MTC biomarker with 312 MTC and 52 nontuberculous mycobacteria (NTM) clinical samples. The frequency and intensity of the acquired CFP-10 mass-to-charge (m/z) peaks were checked with a program to validate that the singly and doubly charged CFP-10 antigen can be treated as a MTC biomarker. We confirmed that by detecting the singly charged species of CFP-10 antigen, the sensitivity and the specificity of MTC samples could reach 97.4% and 100% and no CFP-10 biomarker could be found in NTM samples. This indicates with CFP-10 biomarker it is easy to distinguish MTC from NTM. Besides, the observed intensity ratio of singly and doubly charged species of CFP-10 antigen was 3.3 ± 2.6 and the CFP-10 antigen could maintain good signal intensity for a week. Our results suggest that, with the DND MALDI-TOF mass spectrometry approach, CFP-10 antigen can be used as an early diagnosis biomarker in clinical practice. PMID:26071665

  16. Neuromedin U: a candidate biomarker and therapeutic target to predict and overcome resistance to HER-tyrosine kinase inhibitors.

    Science.gov (United States)

    Rani, Sweta; Corcoran, Claire; Shiels, Liam; Germano, Serena; Breslin, Susan; Madden, Stephen; McDermott, Martina S; Browne, Brigid C; O'Donovan, Norma; Crown, John; Gogarty, Martina; Byrne, Annette T; O'Driscoll, Lorraine

    2014-07-15

    Intrinsic and acquired resistance to HER-targeting drugs occurs in a significant proportion of HER2-overexpressing breast cancers. Thus, there remains a need to identify predictive biomarkers that could improve patient selection and circumvent these types of drug resistance. Here, we report the identification of neuromedin U (NmU) as an extracellular biomarker in cells resistant to HER-targeted drugs. NmU overexpression occurred in cells with acquired or innate resistance to lapatinib, trastuzumab, neratinib, and afatinib, all of which displayed a similar trend upon short-term exposure, suggesting NmU induction may be an early response. An analysis of 3,489 cases of breast cancer showed NmU to be associated with poor patient outcome, particularly those with HER2-overexpressing tumors independent of established prognostic indicators. Ectopic overexpression of NmU in drug-sensitive cells conferred resistance to all HER-targeting drugs, whereas RNAi-mediated attenuation sensitized cells exhibiting acquired or innate drug resistance. Mechanistic investigations suggested that NmU acted through HSP27 as partner protein to stabilize HER2 protein levels. We also obtained evidence of functional NmU receptors on HER2-overexpressing cells, with the addition of exogenous NmU eliciting an elevation in HER2 and EGFR expression along with drug resistance. Finally, we found that NmU seemed to function in cell motility, invasion, and anoikis resistance. In vivo studies revealed that NmU attenuation impaired tumor growth and metastasis. Taken together, our results defined NmU as a candidate drug response biomarker for HER2-overexpressing cancers and as a candidate therapeutic target to limit metastatic progression and improve the efficacy of HER-targeted drugs. PMID:24876102

  17. Inconvenient truth: cancer biomarker development by using proteomics.

    Science.gov (United States)

    Kondo, Tadashi

    2014-05-01

    A biomarker is a crucial tool for measuring the progress of disease and the effects of treatment for better clinical outcomes in cancer patients. Diagnostic, predictive, and prognostic biomarkers are required in various clinical settings. The proteome, a functional translation of the genome, is considered a rich source of biomarkers; therefore, sizable time and funding have been spent in proteomics to develop biomarkers. Although significant progress has been made in technologies toward comprehensive protein expression profiling, and many biomarker candidates published, none of the reported biomarkers have proven to be beneficial for cancer patients. The present deceleration in biomarker research can be attributed to technical limitations. Additional efforts are required to further technical progress; however, there are many examples demonstrating that problems in biomarker research are not so much with the technology but in the study design. In the study of biomarkers for early diagnosis, candidates are screened and validated by comparing cases and controls of similar sample size, and the low prevalence of disease is often ignored. Although it is reasonable to take advantage of multiple rather than single biomarkers when studying diverse disease mechanisms, the annotation of individual components of reported multiple biomarkers does not often explain the variety of molecular events underlying the clinical observations. In tissue biomarker studies, the heterogeneity of disease tissues and pathological observations are often not considered, and tissues are homogenized as a whole for protein extraction. In addition to the challenge of technical limitations, the fundamental aspects of biomarker development in a disease study need to be addressed. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge. PMID:23896458

  18. Clinical Prediction Rule of Drug Resistant Epilepsy in Children

    Science.gov (United States)

    Boonluksiri, Pairoj; Visuthibhan, Anannit; Katanyuwong, Kamornwan

    2015-01-01

    Background and Purpose: Clinical prediction rules (CPR) are clinical decision-making tools containing variables such as history, physical examination, diagnostic tests by developing scoring model from potential risk factors. This study is to establish clinical prediction scoring of drug-resistant epilepsy (DRE) in children using clinical manifestationa and only basic electroencephalography (EEG). Methods: Retrospective cohort study was conducted. A total of 308 children with diagnosed epilepsy were recruited. Primary outcome was the incidence of DRE. Independent determinants were patient characteristics, clinical manifestations and electroencephalography. CPR was performed based on multiple logistic regression. Results: The incidence of DRE was 42%. Risk factors were age onset, prior neurological deficits, and abnormal EEG. CPR can be established and stratified the prediction using scores into 3 levels such as low risk (score12) with positive likelihood ratio of 0.5, 1.8 and 12.5 respectively. Conclusions: CPR with scoring risks were stratified into 3 levels. The strongest risk is prior global neurological deficits. PMID:26819940

  19. DNA methylation biomarkers predict progression-free and overall survival of metastatic renal cell cancer (mRCC treated with antiangiogenic therapies.

    Directory of Open Access Journals (Sweden)

    Inga Peters

    Full Text Available VEGF-targeted therapy increases both the progression-free (PFS and overall survival (OS of patients with metastasized renal cell cancer (mRCC. Identification of molecular phenotypes of RCC could improve risk-stratification and the prediction of the clinical disease course. We investigated whether gene-specific DNA hypermethylation can predict PFS and OS among patients undergoing anti-VEGF-based therapy. Primary tumor tissues from 18 patients receiving targeted therapy were examined retrospectively using quantitative methylation-specific PCR analysis of CST6, LAD1, hsa-miR-124-3, and hsa-miR-9-1 CpG islands. PFS and OS were analyzed for first-line and sequential antiangiogenic therapies using the log rank statistics. Sensitivity and specificity were determined for predicting first-line therapy failure. Hypermethylation of CST6 and LAD1 was associated with both a shortened PFS (log rank p = 0.009 and p = 0.004 and OS (p = 0.011 and p = 0.043. The median PFS observed for the high and low methylation groups of CST6 and LAD1 was 2.0 vs.11.4 months. LAD1 methylation had a specificity of 1.0 (95% CI 0.65-1.0 and a sensitivity of 0.73 (95% CI 0.43-0.90 for the prediction of first-line therapy. CST6 and LAD1 methylation are candidate epigenetic biomarkers showing unprecedented association with PFS and OS as well as specificity for the prediction of the response to therapy. DNA methylation markers should be considered for the prospective evaluation of larger patient cohorts in future studies.

  20. Identification of potential serum biomarkers to predict feed efficiency in young pigs.

    Science.gov (United States)

    Grubbs, J K; Dekkers, J C M; Huff-Lonergan, E; Tuggle, C K; Lonergan, S M

    2016-04-01

    Identification of biomarkers for feed efficiency in livestock will aid in the efficient production of high-quality protein to meet the demands of a growing population. The overall objective of this research was to identify biomarkers in serum for swine feed efficiency and to discover pathways affected by divergent selection for residual feed intake (RFI). Serum was collected from young pigs (between 35 and 42 d of age) from 2 lines of pigs that have been genetically selected to be either more efficient (low-RFI) or less efficient (high-RFI). After blood collection, during finishing, pigs from each line were placed on either a low-energy/high-fiber diet or a traditional high-energy/low-fiber diet to test for any diet effects on RFI. Subsets of 6 pigs per line within each diet were used in 3 independent experiments. Pigs with extreme RFI phenotypes from the low-energy/high-fiber diet were used to confirm the results from the first 2 comparisons. Two-dimensional difference in gel electrophoresis and mass spectrometry were used to identify proteins with different abundances between RFI line or finishing diet. Three proteins had consistent and significant ( RFI line differences for both diets: gelsolin, vitronectin, and serine protease inhibitor A3 (serpinA3). Abundance of gelsolin, a protein with roles in actin filament assembly and immune response, was greater in the more efficient low-RFI pigs (9 to 39%). Vitronectin was also more abundant in the low-RFI pigs (39 to 56%) and has known roles in blood homeostasis and may regulate adiposity. SerpinA3 is a member of a very large family of proteins referred to as serine protease inhibitors. A total of 14 spots that were more abundant in the low-RFI line, some at least twice as abundant, were identified as serpinA3. Multiple isoforms of serpinA3 have been reported (serpinA3-1 to serpinA3-4 in pigs and serpinA3-1 to serpinA3-8 in cattle) with serpinA3 having many different functions dependent on isoform. Gelsolin

  1. New concepts and challenges in the clinical translation of cancer preventive therapies: the role of pharmacodynamic biomarkers.

    Science.gov (United States)

    Brown, Karen; Rufini, Alessandro

    2015-01-01

    Implementation of therapeutic cancer prevention strategies has enormous potential for reducing cancer incidence and related mortality. Trials of drugs including tamoxifen and aspirin have led the way in demonstrating proof-of-principle that prevention of breast and colorectal cancer is feasible. Many other compounds ranging from drugs in widespread use for various indications, including metformin, bisphosphonates, and vitamin D, to dietary agents such as the phytochemicals resveratrol and curcumin, show preventive activity against several cancers in preclinical models. Notwithstanding the wealth of opportunities, major challenges have hindered the development process and only a handful of therapies are currently approved for cancer risk reduction. One of the major obstacles to successful clinical translation of promising preventive agents is a lack of pharmacodynamic biomarkers to provide an early read out of biological activity in humans and for optimising doses to take into large scale randomised clinical trials. A further confounding factor is a lack of consideration of clinical pharmacokinetics in the design of preclinical experiments, meaning results are frequently reported from studies that use irrelevant or unachievable concentrations. This article focuses on recent findings from investigations with dietary-derived agents to illustrate how a thorough understanding of the mechanisms of action, using models that mimic the clinical scenario, together with the development of compound-specific accompanying pharmacodynamic biomarkers could accelerate the developmental pipeline for preventive agents and maximise the chances of success in future clinical trials. Moreover, the concept of a bell-shaped dose-response curve for therapeutic cancer prevention is discussed, along with the need to rethink the traditional 'more is better' approach for dose selection. PMID:26635905

  2. An integrated model supporting histological and biometric responses as predictive biomarkers of fish health status

    Energy Technology Data Exchange (ETDEWEB)

    Torres Junior, Audalio Rebelo [Department of Oceanography and Limnology, Federal University of Maranhão (Brazil); Sousa, Débora Batista Pinheiro [Postgraduate Program of Aquatic Resources and Fishery (PPGRAP/UEMA), State University of Maranhão (Brazil); Neta, Raimunda Nonata Fortes Carvalho [Department of Chemistry and Biology, State University of Maranhão (Brazil)

    2014-10-06

    In this work, an experimental system of histological (branchial lesions) biomarkers and biometric data in catfish (Sciades herzbergii) was modeled. The fish were sampled along known pollution areas (S1) and from environmental protect areas (S2) in São Marcos' Bay, Brazil. Gills were fixed in 10% formalin and usual histological techniques were used in the first gill arch right. The lesions were observed by light microscopy. There were no histopathological changes in animals captured at reference site (S1). However, in the catfish collected in the potentially contaminated area (S2) was observed several branchial lesions, such as lifting of the lamellar epithelium, fusion of some secondary lamellae, hypertrophy of epithelial cells and lamellar aneurysm. The analysis using the biometric data showed significant differences, being highest in fish analyzed in the reference area. This approach revealed spatial differences related with biometric patterns and morphological modifications of catfish.

  3. An integrated model supporting histological and biometric responses as predictive biomarkers of fish health status

    International Nuclear Information System (INIS)

    In this work, an experimental system of histological (branchial lesions) biomarkers and biometric data in catfish (Sciades herzbergii) was modeled. The fish were sampled along known pollution areas (S1) and from environmental protect areas (S2) in São Marcos' Bay, Brazil. Gills were fixed in 10% formalin and usual histological techniques were used in the first gill arch right. The lesions were observed by light microscopy. There were no histopathological changes in animals captured at reference site (S1). However, in the catfish collected in the potentially contaminated area (S2) was observed several branchial lesions, such as lifting of the lamellar epithelium, fusion of some secondary lamellae, hypertrophy of epithelial cells and lamellar aneurysm. The analysis using the biometric data showed significant differences, being highest in fish analyzed in the reference area. This approach revealed spatial differences related with biometric patterns and morphological modifications of catfish

  4. Clinical application of biomarkers in colon cancer: studies on apoptosis, proliferation and the immune system

    OpenAIRE

    Zeestraten, Eliane Cornelia Maria

    2014-01-01

    Colon cancer is a major contributor to can- cer-related mortality worldwide. Death from colon cancer occurs in the majority of cases from widespread metastatic disease. Only 15% of stage II colon cancer patients that develop metastasis will benefit from adjuvant chemotherapy, all of them will suffer from treatment-related toxicity. This makes it essential for the clinician to precisely identify the patient cohort at risk for metastasis. Prognostic biomarkers might improve current staging crit...

  5. CLINICAL SIGNIFICANCE AND EFFECTIVENESS OF VARIOUS SERUM BIOMARKERS IN DIAGNOSIS OF MYOCARDIAL INFARCTION

    OpenAIRE

    Harpreet Kaur*, Shalini Gupta, Minni Verma, Kamaljit Singh and Jagmohan Singh

    2013-01-01

    Myocardial infarction (MI) causes significant mortality and morbidity. Timely diagnosis allows clinicians to risk stratify their patients and select appropriate treatment. Biochemical markers play a pivotal role in the diagnosis and management of patients with acute myocardial infarction. The older biomarkers like aspartate transaminase, creatine kinase, lactate dehydrogenase has lost their utility due to lack of specificity and limited sensitivity. This paper reviews the current contribution...

  6. Clinical relevance of different biomarkers in imported plasmodium falciparum malaria in adults: a case control study

    OpenAIRE

    Stauga, Sabine; Hahn, Andreas; Brattig, Norbert W.; Fischer-Herr, Johanna; Baldus, Stephan; Burchard, Gerd D; Cramer, Jakob P.

    2013-01-01

    Background For rapid initiation of anti-malarial treatment and prevention of complications, early diagnosis and risk stratification is important in patients with Plasmodium falciparum malaria. Routine laboratory values do not correlate well with disease severity. The aim of this study was to determine the diagnostic and prognostic value of several biomarkers related to inflammation; endothelial and cardiac dysfunction; coagulation, and haemolysis in imported P. falciparum malaria. Methods In ...

  7. Evaluation and clinical application of ethyl glucuronide and ethyl sulfate as biomarkers for recent alcohol consumption

    OpenAIRE

    Dahl, Helen

    2011-01-01

    In recent years, there has been a growing interest in various biochemical markers for detecting acute and chronic alcohol consumption. Biochemical markers for acute and chronic drinking play important roles in detecting alcohol use, abuse and dependence in hospital settings, work place settings, traffic medicine and in forensic toxicology examinations. The alcohol biomarkers can be distinguished into two main classes: “short-term markers” and “long-term markers”. Short-term mar...

  8. A genomic biomarker signature can predict skin sensitizers using a cell-based in vitro alternative to animal tests

    Directory of Open Access Journals (Sweden)

    Albrekt Ann-Sofie

    2011-08-01

    Full Text Available Abstract Background Allergic contact dermatitis is an inflammatory skin disease that affects a significant proportion of the population. This disease is caused by an adverse immune response towards chemical haptens, and leads to a substantial economic burden for society. Current test of sensitizing chemicals rely on animal experimentation. New legislations on the registration and use of chemicals within pharmaceutical and cosmetic industries have stimulated significant research efforts to develop alternative, human cell-based assays for the prediction of sensitization. The aim is to replace animal experiments with in vitro tests displaying a higher predictive power. Results We have developed a novel cell-based assay for the prediction of sensitizing chemicals. By analyzing the transcriptome of the human cell line MUTZ-3 after 24 h stimulation, using 20 different sensitizing chemicals, 20 non-sensitizing chemicals and vehicle controls, we have identified a biomarker signature of 200 genes with potent discriminatory ability. Using a Support Vector Machine for supervised classification, the prediction performance of the assay revealed an area under the ROC curve of 0.98. In addition, categorizing the chemicals according to the LLNA assay, this gene signature could also predict sensitizing potency. The identified markers are involved in biological pathways with immunological relevant functions, which can shed light on the process of human sensitization. Conclusions A gene signature predicting sensitization, using a human cell line in vitro, has been identified. This simple and robust cell-based assay has the potential to completely replace or drastically reduce the utilization of test systems based on experimental animals. Being based on human biology, the assay is proposed to be more accurate for predicting sensitization in humans, than the traditional animal-based tests.

  9. The potential use of biomarkers in predicting contrast-induced acute kidney injury

    Directory of Open Access Journals (Sweden)

    Andreucci M

    2016-09-01

    Full Text Available Michele Andreucci,1 Teresa Faga,1 Eleonora Riccio,2 Massimo Sabbatini,2 Antonio Pisani,2 Ashour Michael,1 1Department of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, 2Department of Public Health, University of Naples Federico II, Naples, Italy Abstract: Contrast-induced acute kidney injury (CI-AKI is a problem associated with the use of iodinated contrast media, causing kidney dysfunction in patients with preexisting renal failure. It accounts for 12% of all hospital-acquired kidney failure and increases the length of hospitalization, a situation that is worsening with increasing numbers of patients with comorbidities, including those requiring cardiovascular interventional procedures. So far, its diagnosis has relied upon the rise in creatinine levels, which is a late marker of kidney damage and is believed to be inadequate. Therefore, there is an urgent need for biomarkers that can detect CI-AKI sooner and more reliably. In recent years, many new biomarkers have been characterized for AKI, and these are discussed particularly with their use in known CI-AKI models and studies and include neutrophil gelatinase-associated lipocalin, cystatin C (Cys-C, kidney injury molecule-1, interleukin-18, N-acetyl-β-d-glucosaminidase, and L-type fatty acid-binding protein (L-FABP. The potential of miRNA and metabolomic technology is also mentioned. Early detection of CI-AKI may lead to early intervention and therefore improve patient outcome, and in future any one or a combination of several of these markers together with development in technology for their analysis may prove effective in this respect. Keywords: radiocontrast media, acute renal failure, markers, renal injury

  10. Innovative drugs to treat depression: did animal models fail to be predictive or did clinical trials fail to detect effects?

    Science.gov (United States)

    Belzung, Catherine

    2014-04-01

    Over recent decades, encouraging preclinical evidence using rodent models pointed to innovative pharmacological targets to treat major depressive disorder. However, subsequent clinical trials have failed to show convincing results. Two explanations for these rather disappointing results can be put forward, either animal models of psychiatric disorders have failed to predict the clinical effectiveness of treatments or clinical trials have failed to detect the effects of these new drugs. A careful analysis of the literature reveals that both statements are true. Indeed, in some cases, clinical efficacy has been predicted on the basis of inappropriate animal models, although the contrary is also true, as some clinical trials have not targeted the appropriate dose or clinical population. On the one hand, refinement of animal models requires using species that have better homological validity, designing models that rely on experimental manipulations inducing pathological features, and trying to model subtypes of depression. On the other hand, clinical research should consider carefully the results from preclinical studies, in order to study these compounds at the correct dose, in the appropriate psychiatric nosological entity or symptomatology, in relevant subpopulations of patients characterized by specific biomarkers. To achieve these goals, translational research has to strengthen the dialogue between basic and clinical science. PMID:24345817

  11. Classical and Novel Biomarkers for Cardiovascular Risk Prediction in the United States

    OpenAIRE

    Folsom, Aaron R.

    2013-01-01

    Cardiovascular risk prediction models based on classical risk factors identified in epidemiologic cohort studies are useful in primary prevention of cardiovascular disease in individuals. This article briefly reviews aspects of cardiovascular risk prediction in the United States and efforts to evaluate novel risk factors. Even though many novel risk markers have been found to be associated with cardiovascular disease, few appear to improve risk prediction beyond the powerful, classical risk f...

  12. A multimodal approach to investigate biomarkers for psychosis in a clinical setting: the integrative neuroimaging studies in schizophrenia targeting for early intervention and prevention (IN-STEP) project.

    Science.gov (United States)

    Koike, Shinsuke; Takano, Yosuke; Iwashiro, Norichika; Satomura, Yoshihiro; Suga, Motomu; Nagai, Tatsuya; Natsubori, Tatsunobu; Tada, Mariko; Nishimura, Yukika; Yamasaki, Syudo; Takizawa, Ryu; Yahata, Noriaki; Araki, Tsuyoshi; Yamasue, Hidenori; Kasai, Kiyoto

    2013-01-01

    Longitudinal clinical investigations and biological measurements have determined not only progressive brain volumetric and functional changes especially around the onset of psychosis but also the abnormality of developmental pathways based on gene-environment interaction model. However, these studies have contributed little to clinical decisions on their diagnosis and therapeutic choices because of subtle differences between patients and healthy controls. A multi-modal approach may resolve this limitation and is favorable to explore the pathophysiology of psychosis. The integrative neuroimaging studies for schizophrenia targeting early intervention and prevention (IN-STEP) is a research project aimed at exploring the pathophysiological features of the onset of psychosis and investigating possible predictive biomarkers for the clinical treatment of psychosis. Since 2008, we have adopted blood sampling, neurocognitive batteries, neurophysiological assessment, structural imaging, and functional imaging longitudinally for help-seeking ultra-high-risk (UHR) individuals and patients with first-episode psychosis (FEP). Here, we intend to introduce the IN-STEP research study protocol and present preliminary clinical findings. Thirty-seven UHR individuals and 30 patients with FEP participated in this study. Six months later, there was no difference in objective and subjective scores between the groups, which suggests that young people having symptoms and functional deficits should be cared for regardless of their history of psychosis according to their clinical stages. The rate of transition to psychosis was 7.1%, 8.0%, and 35.3% (at 6, 12, and 24months, respectively). Through this research project, we expect to clarify the pathophysiological features around the onset of psychosis and improve the prognosis of psychosis through clinical application. PMID:23219075

  13. Application of cardiovascular disease risk prediction models and the relevance of novel biomarkers to risk stratification in Asian Indians

    Directory of Open Access Journals (Sweden)

    S Kanjilal

    2008-02-01

    Full Text Available S Kanjilal1, VS Rao1, M Mukherjee1, BK Natesha1, KS Renuka1, K Sibi1, SS Iyengar1, Vijay V Kakkar1,21Tata Proteomics and Coagulation Department, Thrombosis Research Institute, Bangalore, Narayana Hrudayalaya Hospital, Bangalore, Karnataka, India; 2Thrombosis Research Institute, London, UKAbstract: The increasing pressure on health resources has led to the emergence of risk assessment as an essential tool in the management of cardiovascular disease (CVD. Concern exists regarding the validity of their generalization to all populations. Existing risk scoring models do not incorporate emerging ‘novel’ risk factors. In this context, the aim of the study was to examine the relevance of British, European, and Framingham predictive CVD risk scores to the asymptomatic high risk Indian population. Blood samples drawn from the participants were analyzed for various ‘traditional’ and ‘novel’ biomarkers, and their CVD risk factor profiling was also done. The Framingham model defined only 5% of the study cohort to be at high risk, which appears to be an underestimation of CVD risk in this genetically predisposed population. These subjects at high risk had significantly elevated levels of lipid, pro-inflammatory, pro-thrombotic, and serological markers. It is more relevant to develop risk predictive scores for application to the Indian population. This study substantiates the argument that alternative approaches to risk stratification are required in order to make them more adaptable and applicable to different populations with varying risk factor and disease patterns.Keywords: atherosclerosis, risk factors, risk score, Framingham, plasma biomarkers

  14. The Reliability and Predictive Ability of a Biomarker of Oxidative DNA Damage on Functional Outcomes after Stroke Rehabilitation

    Directory of Open Access Journals (Sweden)

    Yu-Wei Hsieh

    2014-04-01

    Full Text Available We evaluated the reliability of 8-hydroxy-2'-deoxyguanosine (8-OHdG, and determined its ability to predict functional outcomes in stroke survivors. The rehabilitation effect on 8-OHdG and functional outcomes were also assessed. Sixty-one stroke patients received a 4-week rehabilitation. Urinary 8-OHdG levels were determined by liquid chromatography–tandem mass spectrometry. The test-retest reliability of 8-OHdG was good (interclass correlation coefficient = 0.76. Upper-limb motor function and muscle power determined by the Fugl-Meyer Assessment (FMA and Medical Research Council (MRC scales before rehabilitation showed significant negative correlation with 8-OHdG (r = −0.38, r = −0.30; p < 0.05. After rehabilitation, we found a fair and significant correlation between 8-OHdG and FMA (r = −0.34 and 8-OHdG and pain (r = 0.26, p < 0.05. Baseline 8-OHdG was significantly correlated with post-treatment FMA, MRC, and pain scores (r = −0.34, −0.31, and 0.25; p < 0.05, indicating its ability to predict functional outcomes. 8-OHdG levels were significantly decreased, and functional outcomes were improved after rehabilitation. The exploratory study findings conclude that 8-OHdG is a reliable and promising biomarker of oxidative stress and could be a valid predictor of functional outcomes in patients. Monitoring of behavioral indicators along with biomarkers may have crucial benefits in translational stroke research.

  15. Application of cardiovascular disease risk prediction models and the relevance of novel biomarkers to risk stratification in Asian Indians

    Directory of Open Access Journals (Sweden)

    S Kanjilal

    2008-03-01

    Full Text Available S Kanjilal1, VS Rao1, M Mukherjee1, BK Natesha1, KS Renuka1, K Sibi1, SS Iyengar1, Vijay V Kakkar1,21Tata Proteomics and Coagulation Department, Thrombosis Research Institute, Bangalore, Narayana Hrudayalaya Hospital, Bangalore, Karnataka, India; 2Thrombosis Research Institute, London, UKAbstract: The increasing pressure on health resources has led to the emergence of risk assessment as an essential tool in the management of cardiovascular disease (CVD. Concern exists regarding the validity of their generalization to all populations. Existing risk scoring models do not incorporate emerging ‘novel’ risk factors. In this context, the aim of the study was to examine the relevance of British, European, and Framingham predictive CVD risk scores to the asymptomatic high risk Indian population. Blood samples drawn from the participants were analyzed for various ‘traditional’ and ‘novel’ biomarkers, and their CVD risk factor profiling was also done. The Framingham model defined only 5% of the study cohort to be at high risk, which appears to be an underestimation of CVD risk in this genetically predisposed population. These subjects at high risk had significantly elevated levels of lipid, pro-inflammatory, pro-thrombotic, and serological markers. It is more relevant to develop risk predictive scores for application to the Indian population. This study substantiates the argument that alternative approaches to risk stratification are required in order to make them more adaptable and applicable to different populations with varying risk factor and disease patterns.Keywords: atherosclerosis, risk factors, risk score, Framingham, plasma biomarkers

  16. Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies

    Directory of Open Access Journals (Sweden)

    Fedele Vita

    2006-06-01

    Full Text Available Abstract Background Recent studies indicate that microRNAs (miRNAs are mechanistically involved in the development of various human malignancies, suggesting that they represent a promising new class of cancer biomarkers. However, previously reported methods for measuring miRNA expression consume large amounts of tissue, prohibiting high-throughput miRNA profiling from typically small clinical samples such as excision or core needle biopsies of breast or prostate cancer. Here we describe a novel combination of linear amplification and labeling of miRNA for highly sensitive expression microarray profiling requiring only picogram quantities of purified microRNA. Results Comparison of microarray and qRT-PCR measured miRNA levels from two different prostate cancer cell lines showed concordance between the two platforms (Pearson correlation R2 = 0.81; and extension of the amplification, labeling and microarray platform was successfully demonstrated using clinical core and excision biopsy samples from breast and prostate cancer patients. Unsupervised clustering analysis of the prostate biopsy microarrays separated advanced and metastatic prostate cancers from pooled normal prostatic samples and from a non-malignant precursor lesion. Unsupervised clustering of the breast cancer microarrays significantly distinguished ErbB2-positive/ER-negative, ErbB2-positive/ER-positive, and ErbB2-negative/ER-positive breast cancer phenotypes (Fisher exact test, p = 0.03; as well, supervised analysis of these microarray profiles identified distinct miRNA subsets distinguishing ErbB2-positive from ErbB2-negative and ER-positive from ER-negative breast cancers, independent of other clinically important parameters (patient age; tumor size, node status and proliferation index. Conclusion In sum, these findings demonstrate that optimized high-throughput microRNA expression profiling offers novel biomarker identification from typically small clinical samples such as breast

  17. Serum biomarkers may help predict successful misoprostol management of early pregnancy failure.

    Science.gov (United States)

    Schreiber, Courtney A; Ratcliffe, Sarah J; Quinley, Kelly E; Miller, Carrie; Sammel, Mary D

    2015-06-01

    In order to simplify management of early pregnancy loss, our goal was to elucidate predictors of successful medical management of miscarriage with a single dose of misoprostol. In this secondary analysis of data from a multicenter randomized controlled trial, candidate biomarkers were compared between 49 women with missed abortion who succeeded in passing their pregnancy with a single dose of misoprostol and 46 women who did not pass their pregnancy with a misoprostol single dose. We computed the precision of trophoblastic protein and hormone concentrations to discriminate between women who succeed or fail single dose misoprostol management. We also included demographic factors in our analyses. We found overlap in the concentrations of the individual markers between women who succeeded and failed single-dose misoprostol. However, hCG levels ≥ 4000 mIU/mL and ADAM-12 levels ≥ 2500 pg/mL were independently associated with complete uterine expulsion after one dose of misoprostol in our population. A multivariable logistic model for success included non-Hispanic ethnicity and parity EPF). Further study is warranted. PMID:26051455

  18. A Clinical Prediction Formula for Apnea-Hypopnea Index

    OpenAIRE

    Mustafa Sahin; Cem Bilgen; M. Sezai Tasbakan; Rasit Midilli; Basoglu, Ozen K.

    2014-01-01

    Objectives. There are many studies regarding unnecessary polysomnography (PSG) when obstructive sleep apnea syndrome (OSAS) is suspected. In order to reduce unnecessary PSG, this study aims to predict the apnea-hypopnea index (AHI) via simple clinical data for patients who complain of OSAS symptoms. Method. Demographic, anthropometric, physical examination and laboratory data of a total of 390 patients (290 men, average age 50 ± 11) who were subject to diagnostic PSG were obtained and evaluat...

  19. Predictive and Prognostic Protein Biomarkers in Epithelial Ovarian Cancer: Recommendation for Future Studies

    OpenAIRE

    Le Page, Cécile; David G Huntsman; Provencher, Diane M; Mes-Masson, Anne-Marie

    2010-01-01

    Epithelial ovarian cancer is the most lethal gynecological malignancy. Due to its lack of symptoms, this disease is diagnosed at an advanced stage when the cancer has already spread to secondary sites. While initial rates of response to first treatment is >80%, the overall survival rate of patients is extremely low, mainly due to development of drug resistance. To date, there are no reliable clinical factors that can properly stratify patients for suitable chemotherapy strategies. Clinical pa...

  20. Predictive and Prognostic Protein Biomarkers in Epithelial Ovarian Cancer: Recommendation for Future Studies

    OpenAIRE

    Cécile Le Page; David G Huntsman; Provencher, Diane M; Anne-Marie Mes-Masson

    2010-01-01

    Epithelial ovarian cancer is the most lethal gynecological malignancy. Due to its lack of symptoms, this disease is diagnosed at an advanced stage when the cancer has already spread to secondary sites. While initial rates of response to first treatment is >80%, the overall survival rate of patients is extremely low, mainly due to development of drug resistance. To date, there are no reliable clinical factors that can properly stratify patients for suitable chemotherapy strategies. Clinical...

  1. Cytokines and signaling molecules predict clinical outcomes in sepsis.

    Directory of Open Access Journals (Sweden)

    Christopher D Fjell

    Full Text Available INTRODUCTION: Inflammatory response during sepsis is incompletely understood due to small sample sizes and variable timing of measurements following the onset of symptoms. The vasopressin in septic shock trial (VASST compared the addition of vasopressin to norepinephrine alone in patients with septic shock. During this study plasma was collected and 39 cytokines measured in a 363 patients at both baseline (before treatment and 24 hours. Clinical features relating to both underlying health and the acute organ dysfunction induced by the severe infection were collected during the first 28 days of admission. HYPOTHESIS: Cluster analysis of cytokines identifies subgroups of patients at differing risk of death and organ failure. METHODS: Circulating cytokines and other signaling molecules were measured using a Luminex multi-bead analyte detection system. Hierarchical clustering was performed on plasma values to create patient subgroups. Enrichment analysis identified clinical outcomes significantly different according to these chemically defined patient subgroups. Logistic regression was performed to assess the importance of cytokines for predicting patient subgroups. RESULTS: Plasma levels at baseline produced three subgroups of patients, while 24 hour levels produced two subgroups. Using baseline cytokine data, one subgroup of 47 patients showed a high level of enrichment for severe septic shock, coagulopathy, renal failure, and risk of death. Using data at 24 hours, a larger subgroup of 81 patients that largely encompassed the 47 baseline subgroup patients had a similar enrichment profile. Measurement of two cytokines, IL2 and CSF2 and their product were sufficient to classify patients into these subgroups that defined clinical risks. CONCLUSIONS: A distinct pattern of cytokine levels measured early in the course of sepsis predicts disease outcome. Subpopulations of patients have differing clinical outcomes that can be predicted accurately from

  2. Gamma-Glutamyltransferase: A Predictive Biomarker of Cellular Antioxidant Inadequacy and Disease Risk

    OpenAIRE

    Gerald Koenig; Stephanie Seneff

    2015-01-01

    Gamma-glutamyltransferase (GGT) is a well-established serum marker for alcohol-related liver disease. However, GGT’s predictive utility applies well beyond liver disease: elevated GGT is linked to increased risk to a multitude of diseases and conditions, including cardiovascular disease, diabetes, metabolic syndrome (MetS), and all-cause mortality. The literature from multiple population groups worldwide consistently shows strong predictive power for GGT, even across different gender and ethn...

  3. A putative biomarker signature for clinically effective AKT inhibition: correlation of in vitro, in vivo and clinical data identifies the importance of modulation of the mTORC1 pathway

    Science.gov (United States)

    Cheraghchi-Bashi, Azadeh; Salazar, Jean-Frederic; Gungor, Hatice; Saleem, Azeem; Cunnea, Paula; Rama, Nona; Salinas, Cristian; Mills, Gordon B.; Morris, Shannon R.; Kumar, Rakesh; Gabra, Hani; Stronach, Euan A.

    2015-01-01

    Our identification of dysregulation of the AKT pathway in ovarian cancer as a platinum resistance specific event led to a comprehensive analysis of in vitro, in vivo and clinical behaviour of the AKT inhibitor GSK2141795. Proteomic biomarker signatures correlating with effects of GSK2141795 were developed using in vitro and in vivo models, well characterised for related molecular, phenotypic and imaging endpoints. Signatures were validated in temporally paired biopsies from patients treated with GSK2141795 in a clinical study. GSK2141795 caused growth-arrest as single agent in vitro, enhanced cisplatin-induced apoptosis in vitro and reduced tumour volume in combination with platinum in vivo. GSK2141795 treatment in vitro and in vivo resulted in ~50-90% decrease in phospho-PRAS40 and 20-80% decrease in fluoro-deoxyglucose (FDG) uptake. Proteomic analysis of GSK2141795 in vitro and in vivo identified a signature of pathway inhibition including changes in AKT and p38 phosphorylation and total Bim, IGF1R, AR and YB1 levels. In patient biopsies, prior to treatment with GSK2141795 in a phase 1 clinical trial, this signature was predictive of post-treatment changes in the response marker CA125. Development of this signature represents an opportunity to demonstrate the clinical importance of AKT inhibition for re-sensitisation of platinum resistant ovarian cancer to platinum. PMID:26497682

  4. A putative biomarker signature for clinically effective AKT inhibition: correlation of in vitro, in vivo and clinical data identifies the importance of modulation of the mTORC1 pathway.

    Science.gov (United States)

    Cheraghchi-Bashi, Azadeh; Parker, Christine A; Curry, Ed; Salazar, Jean-Frederic; Gungor, Hatice; Saleem, Azeem; Cunnea, Paula; Rama, Nona; Salinas, Cristian; Mills, Gordon B; Morris, Shannon R; Kumar, Rakesh; Gabra, Hani; Stronach, Euan A

    2015-12-01

    Our identification of dysregulation of the AKT pathway in ovarian cancer as a platinum resistance specific event led to a comprehensive analysis of in vitro, in vivo and clinical behaviour of the AKT inhibitor GSK2141795. Proteomic biomarker signatures correlating with effects of GSK2141795 were developed using in vitro and in vivo models, well characterised for related molecular, phenotypic and imaging endpoints. Signatures were validated in temporally paired biopsies from patients treated with GSK2141795 in a clinical study. GSK2141795 caused growth-arrest as single agent in vitro, enhanced cisplatin-induced apoptosis in vitro and reduced tumour volume in combination with platinum in vivo. GSK2141795 treatment in vitro and in vivo resulted in ~50-90% decrease in phospho-PRAS40 and 20-80% decrease in fluoro-deoxyglucose (FDG) uptake. Proteomic analysis of GSK2141795 in vitro and in vivo identified a signature of pathway inhibition including changes in AKT and p38 phosphorylation and total Bim, IGF1R, AR and YB1 levels. In patient biopsies, prior to treatment with GSK2141795 in a phase 1 clinical trial, this signature was predictive of post-treatment changes in the response marker CA125. Development of this signature represents an opportunity to demonstrate the clinical importance of AKT inhibition for re-sensitisation of platinum resistant ovarian cancer to platinum. PMID:26497682

  5. DNA Topoisomerase I Gene Copy Number and mRNA Expression Assessed as Predictive Biomarkers for Adjuvant Irinotecan in Stage II/III Colon Cancer

    DEFF Research Database (Denmark)

    Nygård, Sune Boris; Vainer, Ben; Nielsen, Signe L;

    2016-01-01

    PURPOSE: Prospective-retrospective assessment of the TOP1 gene copy number and TOP1 mRNA expression as predictive biomarkers for adjuvant irinotecan in stage II/III colon cancer (CC). EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded tissue microarrays were obtained from an adjuvant CC trial...

  6. Identification of CREB3L1 as a Biomarker Predicting Doxorubicin Treatment Outcome.

    Directory of Open Access Journals (Sweden)

    Bray Denard

    Full Text Available Doxorubicin has been shown to inhibit proliferation of cancer cells through proteolytic activation of CREB3L1 (cAMP response element binding protein 3-like 1, a transcription factor synthesized as a membrane-bound precursor. Upon doxorubicin treatment, CREB3L1 is cleaved so that the N-terminal domain of the protein can reach the nucleus where it activates transcription of genes that inhibit cell proliferation. These results suggest that the level of CREB3L1 in cancer cells may determine their sensitivity to doxorubicin.Mice transplanted with 6 lines of renal cell carcinoma (RCC were injected with doxorubicin to observe the effect of the chemotherapy on tumor growth. Immunohistochemistry and bioinformatics analyses were performed to compare CREB3L1 levels in types of cancer known to respond to doxorubicin versus those resistant to doxorubicin.Higher levels of CREB3L1 protein are correlated with increased doxorubicin sensitivity of xenograft RCC tumors (p = 0.017 by Pearson analysis. From patient tumor biopsies we analyzed, CREB3L1 was expressed in 19% of RCC, which is generally resistant to doxorubicin, but in 70% of diffuse large B-cell lymphoma that is sensitive to doxorubicin. Doxorubicin is used as the standard treatment for cancers that express the highest levels of CREB3L1 such as osteosarcoma and malignant fibrous histiocytoma but is not generally used to treat those that express the lowest levels of CREB3L1 such as RCC.Identification of CREB3L1 as the biomarker for doxorubicin sensitivity may markedly improve the doxorubicin response rate by applying doxorubicin only to patients with cancers expressing CREB3L1.

  7. Soluble CD59 is a Novel Biomarker for the Prediction of Obstructive Chronic Lung Allograft Dysfunction After Lung Transplantation.

    Science.gov (United States)

    Budding, Kevin; van de Graaf, Eduard A; Kardol-Hoefnagel, Tineke; Kwakkel-van Erp, Johanna M; Luijk, Bart D; Oudijk, Erik-Jan D; van Kessel, Diana A; Grutters, Jan C; Hack, C Erik; Otten, Henderikus G

    2016-01-01

    CD59 is a complement regulatory protein that inhibits membrane attack complex formation. A soluble form of CD59 (sCD59) is present in various body fluids and is associated with cellular damage after acute myocardial infarction. Lung transplantation (LTx) is the final treatment for end-stage lung diseases, however overall survival is hampered by chronic lung allograft dysfunction development, which presents itself obstructively as the bronchiolitis obliterans syndrome (BOS). We hypothesized that, due to cellular damage and activation during chronic inflammation, sCD59 serum levels can be used as biomarker preceding BOS development. We analyzed sCD59 serum concentrations in 90 LTx patients, of whom 20 developed BOS. We observed that BOS patients exhibited higher sCD59 serum concentrations at the time of diagnosis compared to clinically matched non-BOS patients (p = 0.018). Furthermore, sCD59 titers were elevated at 6 months post-LTx (p = 0.0020), when patients had no BOS-related symptoms. Survival-analysis showed that LTx patients with sCD59 titers ≥400 pg/ml 6 months post-LTx have a significant (p < 0.0001) lower chance of BOS-free survival than patients with titers ≤400 pg/ml, 32% vs. 80% respectively, which was confirmed by multivariate analysis (hazard ratio 6.2, p < 0.0001). We propose that circulating sCD59 levels constitute a novel biomarker to identify patients at risk for BOS following LTx. PMID:27215188

  8. Systematic screening of imaging biomarkers for the Islets of Langerhans, among clinically available positron emission tomography tracers

    International Nuclear Information System (INIS)

    Introduction: Functional imaging could be utilized for visualizing pancreatic islets of Langerhans. Therefore, we present a stepwise algorithm for screening of clinically available positron emission tomography (PET) tracers for their use in imaging of the neuroendocrine pancreas in the context of diabetes. Methods: A stepwise procedure was developed for screening potential islet imaging agents. Suitable PET-tracer candidates were identified by their molecular mechanism of targeting. Clinical abdominal examinations were retrospectively analyzed for pancreatic uptake and retention. The target protein localization in the pancreas was assessed in silico by –omics approaches and the in vitro by binding assays to human pancreatic tissue. Results: Six putative candidates were identified and screened by using the stepwise procedure. Among the tested PET tracers, only [11C]5-Hydroxy-tryptophan passed all steps. The remaining identified candidates were falsified as candidates and discarded following in silico and in vitro screening. Conclusions: Of the six clinically available PET tracers identified, [11C]5-HTP was found to be a promising candidate for beta cell imaging, based on intensity of in vivo pancreatic uptake in humans, and islet specificity as assessed on human pancreatic cell preparations. The flow scheme described herein constitutes a methodology for evaluating putative islet imaging biomarkers among clinically available PET tracers

  9. Proteomic biomarkers predicting lymph node involvement in serum of cervical cancer patients. Limitations of SELDI-TOF MS

    Directory of Open Access Journals (Sweden)

    Van Gorp Toon

    2012-06-01

    Full Text Available Abstract Background Lymph node status is not part of the staging system for cervical cancer, but provides important information for prognosis and treatment. We investigated whether lymph node status can be predicted with proteomic profiling. Material & methods Serum samples of 60 cervical cancer patients (FIGO I/II were obtained before primary treatment. Samples were run through a HPLC depletion column, eliminating the 14 most abundant proteins ubiquitously present in serum. Unbound fractions were concentrated with spin filters. Fractions were spotted onto CM10 and IMAC30 surfaces and analyzed with surface-enhanced laser desorption time of flight (SELDI-TOF mass spectrometry (MS. Unsupervised peak detection and peak clustering was performed using MASDA software. Leave-one-out (LOO validation for weighted Least Squares Support Vector Machines (LSSVM was used for prediction of lymph node involvement. Other outcomes were histological type, lymphvascular space involvement (LVSI and recurrent disease. Results LSSVM models were able to determine LN status with a LOO area under the receiver operating characteristics curve (AUC of 0.95, based on peaks with m/z values 2,698.9, 3,953.2, and 15,254.8. Furthermore, we were able to predict LVSI (AUC 0.81, to predict recurrence (AUC 0.92, and to differentiate between squamous carcinomas and adenocarcinomas (AUC 0.88, between squamous and adenosquamous carcinomas (AUC 0.85, and between adenocarcinomas and adenosquamous carcinomas (AUC 0.94. Conclusions Potential markers related with lymph node involvement were detected, and protein/peptide profiling support differentiation between various subtypes of cervical cancer. However, identification of the potential biomarkers was hampered by the technical limitations of SELDI-TOF MS.

  10. Protein signatures as potential surrogate biomarkers for stratification and prediction of treatment response in chronic myeloid leukemia patients.

    Science.gov (United States)

    Alaiya, Ayodele A; Aljurf, Mahmoud; Shinwari, Zakia; Almohareb, Fahad; Malhan, Hafiz; Alzahrani, Hazzaa; Owaidah, Tarek; Fox, Jonathan; Alsharif, Fahad; Mohamed, Said Y; Rasheed, Walid; Aldawsari, Ghuzayel; Hanbali, Amr; Ahmed, Syed Osman; Chaudhri, Naeem

    2016-09-01

    There is unmet need for prediction of treatment response for chronic myeloid leukemia (CML) patients. The present study aims to identify disease-specific/disease-associated protein biomarkers detectable in bone marrow and peripheral blood for objective prediction of individual's best treatment options and prognostic monitoring of CML patients. Bone marrow plasma (BMP) and peripheral blood plasma (PBP) samples from newly-diagnosed chronic-phase CML patients were subjected to expression-proteomics using quantitative two-dimensional gel electrophoresis (2-DE) and label-free liquid chromatography tandem mass spectrometry (LC-MS/MS). Analysis of 2-DE protein fingerprints preceding therapy commencement accurately predicts 13 individuals that achieved major molecular response (MMR) at 6 months from 12 subjects without MMR (No-MMR). Results were independently validated using LC-MS/MS analysis of BMP and PBP from patients that have more than 24 months followed-up. One hundred and sixty-four and 138 proteins with significant differential expression profiles were identified from PBP and BMP, respectively and only 54 proteins overlap between the two datasets. The protein panels also discriminates accurately patients that stay on imatinib treatment from patients ultimately needing alternative treatment. Among the identified proteins are TYRO3, a member of TAM family of receptor tyrosine kinases (RTKs), the S100A8, and MYC and all of which have been implicated in CML. Our findings indicate analyses of a panel of protein signatures is capable of objective prediction of molecular response and therapy choice for CML patients at diagnosis as 'personalized-medicine-model'. PMID:27573699

  11. Paper Highlight: Biomarker Identified for Predicting Early Prostate Cancer Aggressiveness — Site

    Science.gov (United States)

    A team led by Cory Abate-Shen, Michael Shen, and Andrea Califano at Columbia University found that measuring the expression levels of three genes associated with aging can be used to predict the aggressiveness of seemingly low-risk prostate cancer.

  12. Inflammation biomarkers and mortality prediction in patients with type 2 diabetes (ZODIAC-27)

    NARCIS (Netherlands)

    Landman, Gijs W D; Kleefstra, Nanne; Groenier, Klaas H; Bakker, Stephan J L; Groeneveld, Geert H; Bilo, Henk J G; van Hateren, Kornelis J J

    2016-01-01

    BACKGROUND: C-reactive protein (CRP), procalcitonin (PCT) and pro-adrenomedullin (MR-proADM) are inflammation markers associated with long-term mortality risk. We compared the associations and predictive capacities of CRP, PCT and MR-proADM with cardiovascular and all-cause mortality in patients wit

  13. Predicting clinical outcome from reward circuitry function and white matter structure in behaviorally and emotionally dysregulated youth.

    Science.gov (United States)

    Bertocci, M A; Bebko, G; Versace, A; Fournier, J C; Iyengar, S; Olino, T; Bonar, L; Almeida, J R C; Perlman, S B; Schirda, C; Travis, M J; Gill, M K; Diwadkar, V A; Forbes, E E; Sunshine, J L; Holland, S K; Kowatch, R A; Birmaher, B; Axelson, D; Horwitz, S M; Frazier, T W; Arnold, L E; Fristad, M A; Youngstrom, E A; Findling, R L; Phillips, M L

    2016-09-01

    Behavioral and emotional dysregulation in childhood may be understood as prodromal to adult psychopathology. Additionally, there is a critical need to identify biomarkers reflecting underlying neuropathological processes that predict clinical/behavioral outcomes in youth. We aimed to identify such biomarkers in youth with behavioral and emotional dysregulation in the Longitudinal Assessment of Manic Symptoms (LAMS) study. We examined neuroimaging measures of function and white matter in the whole brain using 80 youth aged 14.0 (s.d.=2.0) from three clinical sites. Linear regression using the LASSO (Least Absolute Shrinkage and Selection Operator) method for variable selection was used to predict severity of future behavioral and emotional dysregulation measured by the Parent General Behavior Inventory-10 Item Mania Scale (PGBI-10M)) at a mean of 14.2 months follow-up after neuroimaging assessment. Neuroimaging measures, together with near-scan PGBI-10M, a score of manic behaviors, depressive behaviors and sex, explained 28% of the variance in follow-up PGBI-10M. Neuroimaging measures alone, after accounting for other identified predictors, explained ~1/3 of the explained variance, in follow-up PGBI-10M. Specifically, greater bilateral cingulum length predicted lower PGBI-10M at follow-up. Greater functional connectivity in parietal-subcortical reward circuitry predicted greater PGBI-10M at follow-up. For the first time, data suggest that multimodal neuroimaging measures of underlying neuropathologic processes account for over a third of the explained variance in clinical outcome in a large sample of behaviorally and emotionally dysregulated youth. This may be an important first step toward identifying neurobiological measures with the potential to act as novel targets for early detection and future therapeutic interventions. PMID:26903272

  14. Predicting clinical outcome from reward circuitry function and white matter structure in behaviorally and emotionally dysregulated youth

    Science.gov (United States)

    Bertocci, Michele A.; Bebko, Genna; Versace, Amelia; Fournier, Jay C.; Iyengar, Satish; Olino, Thomas; Bonar, Lisa; Almeida, Jorge R. C.; Perlman, Susan B.; Schirda, Claudiu; Travis, Michael J.; Gill, Mary Kay; Diwadkar, Vaibhav A.; Forbes, Erika E.; Sunshine, Jeffrey L.; Holland, Scott K; Kowatch, Robert A.; Birmaher, Boris; Axelson, David; Horwitz, Sarah M.; Frazier, Thomas W.; Arnold, L. Eugene; Fristad, Mary. A; Youngstrom, Eric A.; Findling, Robert L.; Phillips, Mary L.

    2015-01-01

    Behavioral and emotional dysregulation in childhood may be understood as prodromal to adult psychopathology. Additionally, there is a critical need to identify biomarkers reflecting underlying neuropathological processes that predict clinical/behavioral outcomes in youth. We aimed to identify such biomarkers in youth with behavioral and emotional dysregulation in the Longitudinal Assessment of Manic Symptoms (LAMS) study. We examined neuroimaging measures of function and white matter in the whole brain using 80 youth aged 14.0(sd=2.0) from 3 clinical sites. Linear regression using the LASSO method for variable selection was used to predict severity of future behavioral and emotional dysregulation [measured by the Parent General Behavior Inventory-10 Item Mania Scale (PGBI-10M)] at a mean of 14.2 months follow-up after neuroimaging assessment. Neuroimaging measures, together with near-scan PGBI-10M, a score of manic behaviors, depressive behaviors, and sex, explained 28% of the variance in follow-up PGBI-10M. Neuroimaging measures alone, after accounting for other identified predictors, explained approximately one-third of the explained variance, in follow-up PGBI-10M. Specifically, greater bilateral cingulum length predicted lower PGBI-10M at follow-up. Greater functional connectivity in parietal-subcortical reward circuitry predicted greater PGBI-10M at follow-up. For the first time, data suggest that multimodal neuroimaging measures of underlying neuropathologic processes account for over a third of the explained variance in clinical outcome in a large sample of behaviorally and emotionally dysregulated youth. This may be an important first step toward identifying neurobiological measures with the potential to act as novel targets for early detection and future therapeutic interventions. PMID:26903272

  15. Serum haptoglobin as a novel molecular biomarker predicting colorectal cancer hepatic metastasis.

    Science.gov (United States)

    Sun, Lichao; Hu, Shusheng; Yu, Long; Guo, Chunguang; Sun, Lixin; Yang, Zhihua; Qi, Jun; Ran, Yuliang

    2016-06-01

    Early detection of liver metastasis is important for improving colorectal cancer (CRC) patient survival. Our previous studies showed haptoglobin was highly expressed in primary CRC tissues, especially in heterochronous metastatic cases. Here, we assessed the potential of serum haptoglobin (sHP) as a biomarker for early detection of CRC liver metastasis by evaluating the sHP in 475 CRC patients and 152 healthy volunteers. In the training set (250 cases), sHP level in CRC-M1 (1773.18 ± 690.25 ng/mL) were significantly increased as compared to in CRC-M0 (1544.37 ± 1497.65 ng/mL) or healthy (917.76 ± 571.59 ng/mL). And the high sHP level was correlated with poor survival. Logistic regression analysis revealed that sHP, serum carcinoembryonic antigen (sCEA) and serum carbohydrate antigen 19.9 (sCA19.9) level were the significant parameters for detecting liver metastasis. In leave-one-out-cross-validation, these three markers resulted in 89.1% sensitivity and 85.8% specificity for hepatic metastasis detection. In an independent test set (225 cases), receiver operating characteristic curve analysis of sHP in CRC liver metastasis showed an area under the curve of 0.735, with a sensitivity of 87.2% and a specificity of 59.9%. Combination of sHP, sCEA and sCA19.9 improved diagnostic accuracy to 0.880, with a sensitivity of 88.5% and a specificity of 87.8%. Silencing of HP by specific shRNA significantly inhibited the LOVO and SW620 cell invasion, and suppressed xenograft tumor invasive growth. In summary, these results demonstrate that sHP is associated with poor prognosis of CRC patients and that HP promotes colorectal cancer cell invasion. sHP combining with sCA19.9 and sCEA may be used as accurate predictors of CRC liver metastasis. PMID:26756179

  16. Advances in multiplexed MRM-based protein biomarker quantitation toward clinical utility.

    Science.gov (United States)

    Percy, Andrew J; Chambers, Andrew G; Yang, Juncong; Hardie, Darryl B; Borchers, Christoph H

    2014-05-01

    Accurate and rapid protein quantitation is essential for screening biomarkers for disease stratification and monitoring, and to validate the hundreds of putative markers in human biofluids, including blood plasma. An analytical method that utilizes stable isotope-labeled standard (SIS) peptides and selected/multiple reaction monitoring-mass spectrometry (SRM/MRM-MS) has emerged as a promising technique for determining protein concentrations. This targeted approach has analytical merit, but its true potential (in terms of sensitivity and multiplexing) has yet to be realized. Described herein is a method that extends the multiplexing ability of the MRM method to enable the quantitation 142 high-to-moderate abundance proteins (from 31mg/mL to 44ng/mL) in undepleted and non-enriched human plasma in a single run. The proteins have been reported to be associated to a wide variety of non-communicable diseases (NCDs), from cardiovascular disease (CVD) to diabetes. The concentrations of these proteins in human plasma are inferred from interference-free peptides functioning as molecular surrogates (2 peptides per protein, on average). A revised data analysis strategy, involving the linear regression equation of normal control plasma, has been instituted to enable the facile application to patient samples, as demonstrated in separate nutrigenomics and CVD studies. The exceptional robustness of the LC/MS platform and the quantitative method, as well as its high throughput, makes the assay suitable for application to patient samples for the verification of a condensed or complete protein panel. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge. PMID:23806606

  17. Discovery of potential prognostic long non-coding RNA biomarkers for predicting the risk of tumor recurrence of breast cancer patients.

    Science.gov (United States)

    Zhou, Meng; Zhong, Lei; Xu, Wanying; Sun, Yifan; Zhang, Zhaoyue; Zhao, Hengqiang; Yang, Lei; Sun, Jie

    2016-01-01

    Deregulation of long non-coding RNAs (lncRNAs) expression has been proven to be involved in the development and progression of cancer. However, expression pattern and prognostic value of lncRNAs in breast cancer recurrence remain unclear. Here, we analyzed lncRNA expression profiles of breast cancer patients who did or did not develop recurrence by repurposing existing microarray datasets from the Gene Expression Omnibus database, and identified 12 differentially expressed lncRNAs that were closely associated with tumor recurrence of breast cancer patients. We constructed a lncRNA-focus molecular signature by the risk scoring method based on the expression levels of 12 relapse-related lncRNAs from the discovery cohort, which classified patients into high-risk and low-risk groups with significantly different recurrence-free survival (HR = 2.72, 95% confidence interval 2.07-3.57; p = 4.8e-13). The 12-lncRNA signature also represented similar prognostic value in two out of three independent validation cohorts. Furthermore, the prognostic power of the 12-lncRNA signature was independent of known clinical prognostic factors in at least two cohorts. Functional analysis suggested that the predicted relapse-related lncRNAs may be involved in known breast cancer-related biological processes and pathways. Our results highlighted the potential of lncRNAs as novel candidate biomarkers to identify breast cancer patients at high risk of tumor recurrence. PMID:27503456

  18. EGFR gene copy number as a predictive biomarker for the treatment of metastatic colorectal cancer with anti-EGFR monoclonal antibodies: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Yang Zu-Yao

    2012-08-01

    Full Text Available Abstract Background Epidermal growth factor receptor gene copy number (EGFR GCN has been heavily investigated as a potential predictive biomarker for the treatment of metastatic colorectal cancer (mCRC with anti-EGFR monoclonal antibodies (MAbs. The objective of this study was to systematically review current evidences on this issue. Methods PubMed, EMBASE, The Cochrane Library, Chinese Biomedical Literature Database, Wanfang Data, and the conference abstracts of American Society of Clinical Oncology and European Society of Medical Oncology were comprehensively searched. Studies that reported the objective response rate (ORR, progression-free survival, and/or overall survival of mCRC patients treated with anti-EGFR MAbs, stratified by EGFR GCN status, were included. The effect measures for binary outcome (response and time-to-event outcomes (progression-free survival and overall survival were risk difference and hazard ratio, respectively. Statistical heterogeneity among the studies was assessed by the Cochran’s Q-test and the I2 statistic. If appropriate, a quantitative synthesis of data from different studies would be conducted with a random-effects model. Results Nineteen eligible studies were identified. The criteria for increased EGFR GCN (GCN+ were highly inconsistent across different studies. The prevalence of GCN + ranged from 6.9% to 88.9%, and the difference in ORR between patients with GCN + and those with non-increased EGFR GCN (GCN- varied from −28% to 84%. Because of the significant heterogeneity, no quantitative synthesis of data was performed. There was a general trend towards higher ORR in patients with GCN+. The difference in ORRs between patients with GCN + and those with GCN- was even greater in KRAS wild-type patients, while in KRAS mutated patients the difference often did not exist. Almost all patients with EGFR amplification responded to the treatment. However, the prevalence of EGFR amplification was

  19. Soluble CD30 in renal transplant recipients: Is it a good biomarker to predict rejection?

    OpenAIRE

    Azarpira Negar; Aghdaie Mahdokht; Malekpour Zahra

    2010-01-01

    It has been suggested that the serum soluble CD30 (sCD30) level may be a poten-tial marker for the prediction of acute allograft rejection in kidney transplant recipients. Therefore, its serum concentrations might offer a promising non-invasive tool to recognize patients with an increased risk for developing an acute graft rejection. We retrospectively correlate pre and post transplant level on post transplant graft survival, incidence of acute rejection and graft function using stored serum ...

  20. Which biomarker predicts benefit from EGFR-TKI treatment for patients with lung cancer?

    OpenAIRE

    Uramoto, H; Mitsudomi, T.

    2007-01-01

    Subsets of patients with non-small cell lung cancer respond remarkably well to small molecule tyrosine kinase inhibitors (TKI) specific for epidermal growth factor receptor (EGFR) such as gefitinib or erlotinib. In 2004, it was found that EGFR mutations occurring in the kinase domain are strongly associated with EGFR-TKI sensitivity. However, subsequent studies revealed that this relationship was not perfect and various predictive markers have been reported. These include EGFR gene copy numbe...

  1. Biomarker-based calibration of retrospective exposure predictions of perfluorooctanoic acid

    OpenAIRE

    Shin, HM; Steenland, K; Ryan, PB; Vieira, VM; Bartell, SM

    2014-01-01

    Estimated historical exposures and serum concentrations of perfluorooctanoic acid (PFOA) have been extensively used in epidemiologic studies that examined associations between PFOA exposures and adverse health outcomes among residents in highly exposed areas in the Mid-Ohio Valley. Using measured serum PFOA levels in 2005-2006, we applied two calibration methods to these retrospective exposure predictions: (1) multiplicative calibration and (2) Bayesian pharmacokinetic calibration with larger...

  2. Biomarker-Based Calibration of Retrospective Exposure Predictions of Perfluorooctanoic Acid

    OpenAIRE

    Shin, Hyeong-Moo; Steenland, Kyle; Ryan, P. Barry; Vieira, Verónica M.; Bartell, Scott M

    2014-01-01

    Estimated historical exposures and serum concentrations of perfluorooctanoic acid (PFOA) have been extensively used in epidemiologic studies that examined associations between PFOA exposures and adverse health outcomes among residents in highly exposed areas in the Mid-Ohio Valley. Using measured serum PFOA levels in 2005–2006, we applied two calibration methods to these retrospective exposure predictions: (1) multiplicative calibration and (2) Bayesian pharmacokinetic calibration with larger...

  3. IGFBP2 is a biomarker for predicting longitudinal deterioration in renal function in type 2 diabetes

    OpenAIRE

    Narayanan, Ram P; Fu, Bo; Heald, Adrian H; Siddals, Kirk W.; Oliver, Robert L.; Hudson, Julie E; Payton, Antony; Anderson, Simon G; White, Anne; Ollier, William E R; Gibson, J Martin

    2012-01-01

    Objective Insulin-like growth factors are implicated in the development of diabetic nephropathy. IGF-binding protein 2 (IGFBP2) and IGF2 are expressed in the kidney, but their associations with diabetic nephropathy are unclear. We therefore tested the hypothesis that circulating levels of IGF2 and IGFBP2 predict longitudinal renal function in individuals with type 2 diabetes. Design and methods IGFBP2 and IGF2 measurements were performed in 436 individuals (263 males) with type 2 diabetes. Li...

  4. Methods and biomarkers for outcome prediction after allogeneic hematopoietic stem cell transplantation

    OpenAIRE

    Sairafi, Darius

    2012-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is a potent immunotherapeutic procedure but its usability is limited by a high risk of serious complications. A prerequisite for timely initiation of preventive measures is the availability of predictive methods. This thesis aims to evaluate techniques that may potentially be used to assess the risk of some of these complications on the individual level. Defective function of the pattern recognition receptor NOD2, due to natural...

  5. 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.

  6. Improving biological relevancy of transcriptional biomarkers experiments by applying the MIQE guidelines to pre-clinical and clinical trials.

    Science.gov (United States)

    Dooms, M; Chango, A; Barbour, E; Pouillart, P; Abdel Nour, A M

    2013-01-01

    The "Minimum Information for the Publication of qPCR Experiments" (MIQE [3]) guidelines are very much targeted at basic research experiments and have to our knowledge not been applied to qPCR assays carried out in the context of clinical trials. This report details the use of the MIQE qPCR app for iPhone (App Store, Apple) to assess the MIQE compliance of one clinical and five pre-clinical trials. This resulted in the need to include 14 modifications that make the guidelines more relevant for the assessment of this special type of application. We also discuss the need for flexibility, since while some parameters increase experimental quality, they also require more reagents and more time, which is not always feasible in a clinical setting. PMID:22910527

  7. The predictive value of plasma biomarkers in discharged heart failure patients: the role of plasma BNP.

    Science.gov (United States)

    Beltrami, Matteo; Palazzuoli, Alberto; Ruocco, Gaetano; Aspromonte, Nadia

    2016-04-01

    To date, heart failure (HF) prognosis is still difficult: symptoms and signs are often non-specific, and poor sensitive indicators for HF severity. Brain natriuretic peptide (BNP) is now included in the current guidelines for HF diagnosis, management and risk assessment because of its high specificity and sensibility. BNP became a first-line exam in HF patients' evaluation at hospital admission together with clinical and chest X-ray. In discharged patients, the prognostic role of BNP is associated with decongestion and its significant reduction compared to admission level appears one of the best outcome predictors. In fact BNP measurement could identify patients with increased risk of adverse events and left ventricular remodeling. Although a single BNP value assay and the absolute value during hospitalization is related to the prognosis, especially at discharge. On the other hand, hormone levels could be influenced by several factors (i.e., renal dysfunction, anemia, age, liver insufficiency, Body Mass Index) independently from systemic and pulmonary congestion. Therefore, a new approach which considers a multimodality strategy including BNP assay among the traditional clinical examination and imaging studies should be routinely encouraged to better define cardiac dysfunction's etiology and severity, as well as to recognize patients at risk of adverse outcome. PMID:26474369

  8. Exome mutation burden predicts clinical outcome in ovarian cancer carrying mutated BRCA1 and BRCA2 genes

    DEFF Research Database (Denmark)

    Birkbak, Nicolai Juul; Kochupurakkal, Bose; Gonzalez-Izarzugaza, Jose Maria;

    2013-01-01

    Reliable biomarkers predicting resistance or sensitivity to anti-cancer therapy are critical for oncologists to select proper therapeutic drugs in individual cancer patients. Ovarian and breast cancer patients carrying germline mutations in BRCA1 or BRCA2 genes are often sensitive to DNA damaging......-type BRCA1 and BRCA2 genes. These results suggest that in cancers with DNA repair deficiency caused by functional BRCA loss, higher versus lower Nmut may reflect the status of deficiency or rescue by alternative mechanism(s) for DNA repair, with lower Nmut predicting for resistance to DNA-damaging drugs in...... drugs and relative to non-mutation carriers present a favorable clinical outcome following therapy. Genome sequencing studies have shown a high number of mutations in the tumor genome in patients carrying BRCA1 or BRCA2 mutations (mBRCA). The present study used exome-sequencing and SNP 6 array data of...

  9. Quantitative imaging biomarker ontology (QIBO) for knowledge representation of biomedical imaging biomarkers.

    Science.gov (United States)

    Buckler, Andrew J; Liu, Tiffany Ting; Savig, Erica; Suzek, Baris E; Ouellette, M; Danagoulian, J; Wernsing, G; Rubin, Daniel L; Paik, David

    2013-08-01

    A widening array of novel imaging biomarkers is being developed using ever more powerful clinical and preclinical imaging modalities. These biomarkers have demonstrated effectiveness in quantifying biological processes as they occur in vivo and in the early prediction of therapeutic outcomes. However, quantitative imaging biomarker data and knowledge are not standardized, representing a critical barrier to accumulating medical knowledge based on quantitative imaging data. We use an ontology to represent, integrate, and harmonize heterogeneous knowledge across the domain of imaging biomarkers. This advances the goal of developing applications to (1) improve precision and recall of storage and retrieval of quantitative imaging-related data using standardized terminology; (2) streamline the discovery and development of novel imaging biomarkers by normalizing knowledge across heterogeneous resources; (3) effectively annotate imaging experiments thus aiding comprehension, re-use, and reproducibility; and (4) provide validation frameworks through rigorous specification as a basis for testable hypotheses and compliance tests. We have developed the Quantitative Imaging Biomarker Ontology (QIBO), which currently consists of 488 terms spanning the following upper classes: experimental subject, biological intervention, imaging agent, imaging instrument, image post-processing algorithm, biological target, indicated biology, and biomarker application. We have demonstrated that QIBO can be used to annotate imaging experiments with standardized terms in the ontology and to generate hypotheses for novel imaging biomarker-disease associations. Our results established the utility of QIBO in enabling integrated analysis of quantitative imaging data. PMID:23589184

  10. Androgen receptor variant-7: an important predictive biomarker in castrate resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Oliver Sartor

    2015-06-01

    Full Text Available The recent manuscript in New England Journal of Medicine by Antonarakis et al. [1] has important clinical implications. This study evaluates mRNA expression of a particular androgen receptor splice variant-7 (AR-V7, in circulating tumor cells (CTCs from metastatic castrate-resistant prostate cancer (mCRPC patients receiving enzalutamide or abiraterone. The findings were striking, none of the 18 patients with detectable AR-V7 in CTCs had prostate-specific antigen (PSA responses. Further, the median time to PSA progression after enzalutamide or abiraterone treatment was only 1.3-1.4 months in AR-V7-positive patients as compared to 5.3-6.1 months in AR-V7 negative patients. AR-V7 in CTCs was also associated with shorter survival.

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

    Directory of Open Access Journals (Sweden)

    Elena Nikolayevna Aleksandrova

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Elena Nikolayevna Aleksandrova

    2014-03-01

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

  13. Formalized prediction of clinically significant prostate cancer: is it possible?

    Institute of Scientific and Technical Information of China (English)

    Carvell T Nguyen; Michael W Kattan

    2012-01-01

    Greater understanding of the biology and epidemiology of prostate cancer in the last several decades have led to significant advances in its management.Prostate cancer is now detected in greater numbers at lower stages of disease and is amenable to multiple forms of efficacious treatment.However,there is a lack of conclusive data demonstrating a definitive mortality benefit from this earlier diagnosis and treatment of prostate cancer.It is likely due to the treatment of a large proportion of indolent cancers that would have had little adverse impact on health or lifespan if left alone.Due to this overtreatment phenomenon,active surveillance with delayed intervention is gaining traction as a viable management approach in contemporary practice.The ability to distinguish clinically insignificant cancers from those with a high risk of progression and/or lethality is critical to the appropriate selection of patients for surveillance protocols versus immediate intervention.This chapter will review the ability of various prediction models,including risk groupings and nomograms,to predict indolent disease and determine their role in the contemporary management of clinically localized prostate cancer.

  14. Prediction of labor induction outcome using different clinical parameters

    Directory of Open Access Journals (Sweden)

    Tatić-Stupar Žaklina

    2013-01-01

    Full Text Available Introduction. Induction of labor is one of the most common obstetric interventions in contemporary obstetrics. Objective. The aim of the study was to evaluate the clinical and sonographic parameters in prediction of success of labor induction. Methods. The prospective study included 422 women in whom induction of labor was carried out at the Department of Obstetrics and Gynecology of Clinical Centre of Vojvodina. The role of body mass index and age of women, parity Bishop score, cervical length measured by transvaginal ultrasound was evaluated in regard of the success of induction, which was considered successful if a vaginal delivery occurred within 24 hours after the onset of induction. Data were statistically analyzed by univariate statistical analysis and Pearson’s χ2 test. Results. Out of 422 women, induction of labor was successful in 356 (84.4%, and it failed in 66 (15.6% cases. The values of Bishop score and cervical length had positive correlation with the success of induction. Conclusion. Bishop score and transvaginal cervical length were both reliable predictors in determining the success of labor induction, as well as parity and BMI. These parameters are mostly complementary, not competitive in prediction of labor induction success.

  15. Improving Biomarker Development and Assessment: Standards for Study Design

    Institute of Scientific and Technical Information of China (English)

    Ziding FENG

    2009-01-01

    Background: The Early Detection Research Network (EDRN), NCI funded and investigator driven, has the mission to evaluate biomarkers for their clinical utilities in cancer risk prediction, diagnosis, early detection, and prognosis. Abundant cancer biomarkers reported in literature yet few are used in clinics. Therefore, the emphasis of the EDRN is biomarker validation. Although schema for a phased approach to development exists and guidelines are available for study reporting, a coherent and comprehensive set of guideline for a definitive biomarker validation study design have not been delineated.Methods: We proposed PROBE study design, Prospective specimen collec-tion and Retrospective Blinded Evaluation, for pivotal definitive evaluation of the accuracy of a classification biomarker. A detailed formulation of all aspects of the design is provided. Four tables itemize aspects that relate to (i) the Clinical Context; (ii) Performance Criteria; (iii) the Biomarker test; and (iv) Study power and termination. Alternative designs and strategies were contrasted to illustrate the merit of PROBE design.Results: The ideas are applied to studies of biomarkers the intended use of which is for disease diagnosis, screening, or prognosis. Two EDRN valida-tion studies (breast cancer and prostate cancer) were used as examples to elucidate PROBE design.Conclusion: Common biases that pervade the biomarker research literaturewould be eliminated if these rigorous standards were followed closely. We urge the adoption of the design as standard of practice for pivotal evaluation of the classification accuracy ofbiomarkers.

  16. Predicting of Effective Dose as Biomarker for Cytotoxicity Using Partial Least Square-Fourier Transform Infrared Spectroscopy (PLS_FTIR)

    Science.gov (United States)

    Zendehdel, Rezvan; Khodakarim, Soheila; H. Shirazi, Farshad

    2015-01-01

    Toxicity bioassays are important tools to determine biological effects of chemical agents on species. The questions remained on, what effects have been imposed on each of the different molecular site of cells by chemical exposure and how to find a pattern for chemical toxicity. To address the questions, HepG2 cell lines were exposed to the different concentrations of cisplatin for 24 hours to result cell mortality in the range of one to one hundred percent. Fourier Transform Infrared spectroscopy (FTIR) has been used in this study to analyze the chemical alterations on HepG2 cell line by cisplatin. Partial least square regression (PLS) analysis was then applied to the FTIR spectrum results to search for a biomarker peak and present the desire cellular effects of cisplatin. The comparison of cellular FTIR spectra after exposure to different concentrations of cisplatin confirmed the binding of cisplatin to DNA through direct interaction of platinum to guanine and thymine bases of DNA. Biochemical Index Spectra (BIS) were defined based on the differences between of normal and cisplatin exposed cells. Information from the BIS was subjected to PLS analysis to trigger any particular relationship between the toxicity spectral response and cisplatin concentration. This approach was capable of predicting the concentration of cisplatin for any particular effects observed in the cellular FTIR spectrum (R2 = 0.968 ± 0.037). Our work supports the promises that, FTIR can demonstrate the trace of toxicity before the cells dies. Finally, PLS of FTIR data directly predicts the effective concentration of chemicals in particular cellular components. PMID:26664386

  17. Soluble CD30 in renal transplant recipients: Is it a good biomarker to predict rejection?

    Directory of Open Access Journals (Sweden)

    Azarpira Negar

    2010-01-01

    Full Text Available It has been suggested that the serum soluble CD30 (sCD30 level may be a poten-tial marker for the prediction of acute allograft rejection in kidney transplant recipients. Therefore, its serum concentrations might offer a promising non-invasive tool to recognize patients with an increased risk for developing an acute graft rejection. We retrospectively correlate pre and post transplant level on post transplant graft survival, incidence of acute rejection and graft function using stored serum samples. Ninety-nine patients were divided in two separate groups: Group A in whom sample collection was done one day before transplantation and Group B where sample collection was done five days after transplantation. Younger recipients (aged less than 20 years had higher sCD30 levels (P= 0.02. There was neither significant difference in the incidence of acute rejection nor incomplete response rate after anti rejection therapy in relation to pre trans-plant or post transplant sCD30. We could not find a significantly inferior graft survival rate in the high sCD30 group. In conclusion, younger patients had higher sCD30 concentrations however no correlation existed between the serum concentrations and occurrence of rejection episodes or graft survival.

  18. Identification of tumor-associated antigens as diagnostic and predictive biomarkers in cancer.

    Science.gov (United States)

    Zhang, Jian-Ying; Looi, Kok Sun; Tan, Eng M

    2009-01-01

    Many studies demonstrated that cancer sera contain antibodies which react with autologous cellular antigens generally known as tumor-associated antigens (TAAs). In our laboratories, the approach used in the identification of TAAs has involved initially examining the sera of cancer patients using extracts of tissue culture cells as source of antigens in Western blotting and by indirect immunofluorescence on whole cells. With these two techniques, we identify sera which have high-titer fluorescent staining or strong signals to cell extracts on Western blotting and subsequently use these sera as probes in immunoscreening cDNA expression libraries, and also in proteomic approaches to isolate and identify targeted antigens which might potentially be involved in malignant transformation. In this manner, several novel TAAs including HCC1, p62, p90, and others have been identified. In extension of these studies, we evaluate the sensitivity and specificity of different antigen-antibody systems as markers in cancer in order to develop "tumor-associated antigen array" systems for cancer diagnosis, cancer prediction, and for following the response of patients to treatment. PMID:19381943

  19. Biomarker case-detection and prediction with potential for functional psychosis screening: development and validation of a model related to biochemistry, sensory neural timing and end organ performance.

    Directory of Open Access Journals (Sweden)

    Stephanie eFryar-Williams

    2016-04-01

    Full Text Available The Mental Health Biomarker Project aimed to discover case-predictive biomarkers for functional psychosis. In a retrospective, cross-sectional study, candidate marker results from 67, highly-characterized symptomatic participants were compared with results from 67 gender and age matched controls. Urine samples were analysed for catecholamines, their metabolites and hydroxylpyrolline-2-one, an oxidative stress marker. Blood samples were analyzed for vitamin and trace element cofactors of enzymes in the catecholamine synthesis and metabolism pathways. Cognitive, auditory and visual processing measures were assessed using a simple 45 minute, office-based procedure. Receiver Operating Curve (ROC and Odds Ratio analysis discovered biomarkers for deficits in folate, vitamin D and B6 and elevations in free copper to zinc ratio, catecholamines and the oxidative stress marker. Deficits were discovered in peripheral visual and auditory end-organ function, intra-cerebral auditory and visual processing speed and dichotic-listening performance. 15 ROC biomarker variables were divided into 5 functional domains. Through a repeated ROC process, individual ROC variables, followed by domains and finally the overall 15 set model, were dichotomously scored and tallied for abnormal results upon which it was found that ≥ 3 out of 5 abnormal domains achieved an AUC of 0.952 with a sensitivity of 84 per cent and a specificity of 90 percent. Six additional middle ear biomarkers in a 21 biomarker set increased sensitivity to 94% percent. Fivefold cross-validation yielded a mean sensitivity of 85% for the 15 biomarker set. Non-parametric regression analysis confirmed that ≥ 3 out of 5 abnormally scored domains predicted > 50% risk of case-ness whilst 4 abnormally-scored domains predicted 88% risk of case-ness and 100% diagnostic certainty was reached when all 5 domains were abnormally scored. These findings require validation in prospective cohorts and other mental

  20. Biomarker Case-Detection and Prediction with Potential for Functional Psychosis Screening: Development and Validation of a Model Related to Biochemistry, Sensory Neural Timing and End Organ Performance.

    Science.gov (United States)

    Fryar-Williams, Stephanie; Strobel, Jörg E

    2016-01-01

    The Mental Health Biomarker Project aimed to discover case-predictive biomarkers for functional psychosis. In a retrospective, cross-sectional study, candidate marker results from 67 highly characterized symptomatic participants were compared with results from 67 gender- and age-matched controls. Urine samples were analyzed for catecholamines, their metabolites, and hydroxylpyrolline-2-one, an oxidative stress marker. Blood samples were analyzed for vitamin and trace element cofactors of enzymes in catecholamine synthesis and metabolism pathways. Cognitive, auditory, and visual processing measures were assessed using a simple 45-min, office-based procedure. Receiver operating curve (ROC) and odds ratio analysis discovered biomarkers for deficits in folate, vitamin D and B6 and elevations in free copper to zinc ratio, catecholamines and the oxidative stress marker. Deficits were discovered in peripheral visual and auditory end-organ function, intracerebral auditory and visual processing speed and dichotic listening performance. Fifteen ROC biomarker variables were divided into five functional domains. Through a repeated ROC process, individual ROC variables, followed by domains and finally the overall 15 set model, were dichotomously scored and tallied for abnormal results upon which it was found that ≥3 out of 5 abnormal domains achieved an area under the ROC curve of 0.952 with a sensitivity of 84% and a specificity of 90%. Six additional middle ear biomarkers in a 21 biomarker set increased sensitivity to 94%. Fivefold cross-validation yielded a mean sensitivity of 85% for the 15 biomarker set. Non-parametric regression analysis confirmed that ≥3 out of 5 abnormally scored domains predicted >50% risk of caseness while 4 abnormally scored domains predicted 88% risk of caseness; 100% diagnostic certainty was reached when all 5 domains were abnormally scored. These findings require validation in prospective cohorts and other mental illness states. They have

  1. Lenalidomide and metronomic melphalan for CMML and higher risk MDS: a phase 2 clinical study with biomarkers of angiogenesis.

    Science.gov (United States)

    Buckstein, Rena; Kerbel, Robert; Cheung, Matthew; Shaked, Yuval; Chodirker, Lisa; Lee, Christina R; Lenis, Martha; Davidson, Cindy; Cussen, Mary-Anne; Reis, Marciano; Chesney, Alden; Zhang, Liying; Mamedov, Alexandre; Wells, Richard A

    2014-07-01

    Metronomic, low dose chemotherapy may have anti-angiogenic effects and augment the effects of lenalidomide in MDS and CMML. We evaluated the clinical efficacy, tolerability and anti-angiogenic effects of melphalan 2mg and lenalidomide 10mg for 21 days/28 in CMML (n=12) and higher risk MDS (n=8) patients in a prospective phase II study. The primary endpoint was overall response and secondary endpoints included survival, progression-free survival, toxicity and biomarkers of angiogenesis. The median age was 73 years, 55% were pretreated and transfusion dependent. The overall response rate was 3(15%) of 19 evaluable patients but 25% in CMML and 33% in pCMML. Dose reductions and/or delays were common due to myelosuppression. Transient spikes in circulating endothelial cells that declined below baseline were seen in responders and patients with CMML, suggesting anti-angiogenic activity. In conclusion, lenalidomide and metronomic low dose melphalan demonstrate signals of clinical and possible anti-angiogenic activity in patients with pCMML that require future validation. This trial was registered at clinicaltrial.gov under # NCT00744536. PMID:24819395

  2. Comparing clinical responses and the biomarkers of BDNF and cytokines between subthreshold bipolar disorder and bipolar II disorder.

    Science.gov (United States)

    Wang, Tzu-Yun; Lee, Sheng-Yu; Chen, Shiou-Lan; Chang, Yun-Hsuan; Wang, Liang-Jen; Chen, Po See; Chen, Shih-Heng; Chu, Chun-Hsien; Huang, San-Yuan; Tzeng, Nian-Sheng; Li, Chia-Ling; Chung, Yi-Lun; Hsieh, Tsai-Hsin; Lee, I Hui; Chen, Kao Chin; Yang, Yen Kuang; Hong, Jau-Shyong; Lu, Ru-Band

    2016-01-01

    Patients with subthreshold hypomania (SBP; subthreshold bipolar disorder) were indistinguishable from those with bipolar disorder (BP)-II on clinical bipolar validators, but their analyses lacked biological and pharmacological treatment data. Because inflammation and neuroprogression underlies BP, we hypothesized that cytokines and brain-derived neurotrophic factor (BDNF) are biomarkers for BP. We enrolled 41 drug-naïve patients with SBP and 48 with BP-II undergoing 12 weeks of pharmacological treatment (valproic acid, fluoxetine, risperidone, lorazepam). The Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) were used to evaluate clinical responses at baseline and at weeks 0, 1, 2, 4, 8, and 12. Inflammatory cytokines (tumour necrosis factor [TNF]-α, transforming growth factor [TGF]-β1, interleukin [IL]-6, IL-8 and IL-1β) and BDNF levels were also measured. Mixed models repeated measurement was used to examine the therapeutic effect and changes in BDNF and cytokine levels between the groups. HDRS and YMRS scores significantly (P < 0.001) declined in both groups, the SBP group had significantly lower levels of BDNF (P = 0.005) and TGF-β1 (P = 0.02). Patients with SBP and BP-II respond similarly to treatment, but SBP patients may have different neuroinflammation marker expression. PMID:27270858

  3. Human leukocyte antigen-G overexpression predicts poor clinical outcomes in low-grade gliomas.

    Science.gov (United States)

    Fan, Xing; Wang, Yinyan; Zhang, Chuanbao; Liu, Xing; Qian, Zenghui; Jiang, Tao

    2016-05-15

    Overexpression of human leukocyte antigen-G (HLA-G), a non-classical major histocompatibility complex class-I molecule associated with immunosuppression, has been reported in various human malignancies. In the present study, we examined the role of HLA-G in gliomas. Clinical characteristics, mRNA expression microarrays and follow-up data pertaining to 293 patients with histologically confirmed gliomas were analyzed. The expression levels of HLA-G were compared between different grades of gliomas and correlated with progression-free survival (PFS) and overall survival (OS) to evaluate its prognostic value. We found that HLA-G was overexpressed in gliomas as compared to that in normal brain tissue samples (-1.288±0.265). The highest expression levels were in glioblastomas (GBMs), anaplastic gliomas (AGs) and low-grade gliomas (LGGs), in that order (0.328±0.778, 0.176±0.881, -0.388±0.686, respectively). Significant inter-group differences were observed between low-grade and high-grade glioma tissues (pexpression as compared to other LGG patients (p=0.004, Chi-square test). Significant differences were observed with respect to PFS and OS (p=0.009 and 0.032, log-rank test, for PFS and OS, respectively) between the high- and low-expression subgroups in patients with LGGs. On Cox regression analysis, overexpression of HLA-G appeared to be an independent predictor of clinical outcomes (p=0.007 and 0.026, for PFS and OS, respectively). Our results suggest that HLA-G expression may serve as a potential biomarker for predicting aggressive tumor grades of gliomas and for histological subtype of LGGs. Elevated HLA-G expression could serve as an independent predictor of poor clinical outcomes in patients with low-grade gliomas. PMID:27138095

  4. Predictive Value of IL-8 for Sepsis and Severe Infections after Burn Injury - A Clinical Study

    OpenAIRE

    Kraft, Robert; Herndon, David N; Finnerty, Celeste C.; Cox, Robert A.; Song, Juquan; Jeschke, Marc G.

    2015-01-01

    The inflammatory response induced by burn injury contributes to increased incidence of infections, sepsis, organ failure, and mortality. Thus, monitoring post-burn inflammation is of paramount importance but so far there are no reliable biomarkers available to monitor and/or predict infectious complications after burn. As IL-8 is a major mediator for inflammatory responses, the aim of our study was to determine whether IL-8 expression can be used to predict post-burn sepsis, infections, and m...

  5. Cancer predictive value of cytogenetic markers used in occupational health surveillance programs: a report from an ongoing study by the European Study Group on Cytogenetic Biomarkers and Health

    DEFF Research Database (Denmark)

    Hagmar, L; Bonassi, S; Strömberg, U; Mikoczy, Z; Lando, C; Hansteen, I L; Montagud, A H; Knudsen, Lisbeth E.; Norppa, H; Reuterwall, C; Tinnerberg, H; Brogger, A; Forni, A; Högstedt, B; Lambert, B; Mitelman, F; Nordenson, I; Salomaa, S; Skerfving, S

    1998-01-01

    as biomarkers for genotoxic effects which will result in an enhanced cancer risk. In order to assess this problem, Nordic and Italian cohorts were established, and preliminary results from these two studies indicated a predictive value of CA frequency for cancer risk, whereas no such associations...... were observed for SCE or MN. A collaborative study between the Nordic and Italian research groups, will enable a more thorough evaluation of the cancer predictivity of the cytogenetic endpoints. We here report on the establishment of a joint data base comprising 5271 subjects, examined 1965-1988 for at...... least one cytogenetic biomarker. Totally, 3540 subjects had been examined for CA, 2702 for SCE and 1496 for MN. These cohorts have been followed-up with respect to subsequent cancer mortality or cancer incidence, and the expected values have been calculated from rates derived from the general...

  6. Comparison of Plasma and Urine Biomarker Performance in Acute Kidney Injury.

    Directory of Open Access Journals (Sweden)

    Gunnar Schley

    Full Text Available New renal biomarkers measured in urine promise to increase specificity for risk stratification and early diagnosis of acute kidney injury (AKI but concomitantly may be altered by urine concentration effects and chronic renal insufficiency. This study therefore directly compared the performance of AKI biomarkers in urine and plasma.This single-center, prospective cohort study included 110 unselected adults undergoing cardiac surgery with cardiopulmonary bypass between 2009 and 2010. Plasma and/or urine concentrations of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL, liver fatty acid-binding protein (L-FABP, kidney injury molecule 1 (KIM1, and albumin as well as 15 additional biomarkers in plasma and urine were measured during the perioperative period. The primary outcome was AKI defined by AKIN serum creatinine criteria within 72 hours after surgery.Biomarkers in plasma showed markedly better discriminative performance for preoperative risk stratification and early postoperative (within 24h after surgery detection of AKI than urine biomarkers. Discriminative power of urine biomarkers improved when concentrations were normalized to urinary creatinine, but urine biomarkers had still lower AUC values than plasma biomarkers. Best diagnostic performance 4h after surgery had plasma NGAL (AUC 0.83, cystatin C (0.76, MIG (0.74, and L-FAPB (0.73. Combinations of multiple biomarkers did not improve their diagnostic power. Preoperative clinical scoring systems (EuroSCORE and Cleveland Clinic Foundation Score predicted the risk for AKI (AUC 0.76 and 0.71 and were not inferior to biomarkers. Preexisting chronic kidney disease limited the diagnostic performance of both plasma and urine biomarkers.In our cohort plasma biomarkers had higher discriminative power for risk stratification and early diagnosis of AKI than urine biomarkers. For preoperative risk stratification of AKI clinical models showed similar discriminative performance

  7. Approaching a diagnostic point-of-care test for pediatric tuberculosis through evaluation of immune biomarkers across the clinical disease spectrum

    Science.gov (United States)

    Jenum, Synne; Dhanasekaran, S.; Lodha, Rakesh; Mukherjee, Aparna; Kumar Saini, Deepak; Singh, Sarman; Singh, Varinder; Medigeshi, Guruprasad; Haks, Marielle C.; Ottenhoff, Tom H. M.; Doherty, Timothy Mark; Kabra, Sushil K.; Ritz, Christian; Grewal, Harleen M. S.

    2016-01-01

    The World Health Organization (WHO) calls for an accurate, rapid, and simple point-of-care (POC) test for the diagnosis of pediatric tuberculosis (TB) in order to make progress “Towards Zero Deaths”. Whereas the sensitivity of a POC test based on detection of Mycobacterium tuberculosis (MTB) is likely to have poor sensitivity (70–80% of children have culture-negative disease), host biomarkers reflecting the on-going pathological processes across the spectrum of MTB infection and disease may hold greater promise for this purpose. We analyzed transcriptional immune biomarkers direct ex-vivo and translational biomarkers in MTB-antigen stimulated whole blood in 88 Indian children with intra-thoracic TB aged 6 months to 15 years, and 39 asymptomatic siblings. We identified 12 biomarkers consistently associated with either clinical groups “upstream” towards culture-positive TB on the TB disease spectrum (CD14, FCGR1A, FPR1, MMP9, RAB24, SEC14L1, and TIMP2) or “downstream” towards a decreased likelihood of TB disease (BLR1, CD3E, CD8A, IL7R, and TGFBR2), suggesting a correlation with MTB-related pathology and high relevance to a future POC test for pediatric TB. A biomarker signature consisting of BPI, CD3E, CD14, FPR1, IL4, TGFBR2, TIMP2 and TNFRSF1B separated children with TB from asymptomatic siblings (AUC of 88%). PMID:26725873

  8. Systematic review of clinical prediction tools and prognostic factors in aneurysmal subarachnoid hemorrhage

    OpenAIRE

    Lo, Benjamin W. Y.; Hitoshi Fukuda; Yusuke Nishimura; Forough Farrokhyar; Lehana Thabane; Mitchell A. H. Levine

    2015-01-01

    Background: Clinical prediction tools assist in clinical outcome prediction. They quantify the relative contributions of certain variables and condense information that identifies important indicators or predictors to a targeted condition. This systematic review synthesizes and critically appraises the methodologic quality of studies that derive both clinical predictors and clinical predictor tools used to determine outcome prognosis in patients suffering from aneurysmal subarachnoid hemorrha...

  9. Diagnosing Pulmonary Embolism in Pregnancy: Are Biomarkers and Clinical Predictive Models Useful?

    Science.gov (United States)

    Parilla, Barbara V.; Fournogerakis, Rachel; Archer, Amy; Sulo, Suela; Laurent, Lisa; Lee, Patricia; Chhotani, Benazir; Hesse, Kathleen; Kulstad, Erik

    2016-01-01

    Objective The objective of this study was to evaluate whether trimester-specific D-dimer levels or the modified Wells score (MWS) is a useful risk stratification tool to exclude pregnant women at low risk of pulmonary embolism (PE) from diagnostic imaging. Study Design This is a prospective and retrospective cohort study. Pregnant women who underwent diagnostic imaging for suspected PE were prospectively enrolled. D-dimer serum levels were drawn, and a MWS was assigned. Pregnant women diagnosed with a PE before study launch who underwent diagnostic imaging and had a D-dimer level drawn were also evaluated. Results In this study, 17 patients were diagnosed with a PE and 42 patients had no PE on diagnostic imaging. Sixteen out of 17 patients with a PE versus 11 out of 42 without PE had an abnormal D-dimer level (p = 0.001). Four patients with a PE versus zero without a PE had an abnormal MWS (p = 0.005). The combination of a trimester-specific D-dimer level along with the MWS was abnormal in all 17 patients with a documented PE versus 11/42 (26.2%) patients without a documented PE (p = 0.001). Conclusion A combination of trimester-specific D-dimer levels along with a MWS can be used in pregnancy to triage women into a low-risk category for PE and thereby avoid radiation exposure in a majority of pregnant patients. PMID:27119048

  10. Methylated genes as new cancer biomarkers

    DEFF Research Database (Denmark)

    Brunner, Nils; Duffy, M.J; Napieralski, R.;

    2009-01-01

    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...

  11. Personalization of prostate cancer prevention and therapy: are clinically qualified biomarkers in the horizon?

    OpenAIRE

    Yap Timothy A; Swanton Charles; de Bono Johann S

    2012-01-01

    Abstract Prostate cancer remains the most common malignancy among men and the second leading cause of male cancer-related mortality. Death from this disease is invariably due to resistance to androgen deprivation therapy. Our improved understanding of the biology of prostate cancer has heralded a new era in molecular anticancer drug development, with multiple novel anticancer drugs for castration resistant prostate cancer now entering the clinic. These include the taxane cabazitaxel, the vacc...

  12. Biomarkers of sarcopenia in clinical trials—recommendations from the International Working Group on Sarcopenia

    OpenAIRE

    Cesari, Matteo; Pahor, Marco; Goodpaster, Bret; Hellerstein, Marc; Van Kan, Gabor A.; Anker, Stefan D.; Vrijbloed, J. Willem; Isaac, Maria; Rolland, Yves; M’Rini, Christine; Aubertin-Leheudre, Mylène; Cedarbaum, Jesse M.; Zamboni, Mauro; Sieber, Cornell C.; Laurent, Didier

    2012-01-01

    Sarcopenia, the age-related skeletal muscle decline, is associated with relevant clinical and socioeconomic negative outcomes in older persons. The study of this phenomenon and the development of preventive/therapeutic strategies represent public health priorities. The present document reports the results of a recent meeting of the International Working Group on Sarcopenia (a task force consisting of geriatricians and scientists from academia and industry) held on June 7–8, 2011 in Toulouse (...

  13. Early prediction of acute kidney injury biomarkers after endovascular stent graft repair of aortic aneurysm: a prospective observational study

    OpenAIRE

    Ueta, Kazuyoshi; Watanabe, Michiko; Iguchi, Naoya; Uchiyama, Akinori; Shirakawa, Yukitoshi; Kuratani, Toru; Sawa, Yoshiki; Fujino, Yuji

    2014-01-01

    Background Acute kidney injury (AKI) is a common and serious condition usually detected some time after onset by changes in serum creatinine (sCr). Although stent grafting to repair aortic aneurysms is associated with AKI caused by surgical procedures or the use of contrast agents, early biomarkers for AKI have not been adequately examined in stent graft recipients. We studied biomarkers including urinary neutrophil gelatinase-associated lipocalin (NGAL), blood NGAL, N-acetyl-β-d-glucosaminid...

  14. Improving Clinical Prediction of Bipolar Spectrum Disorders in Youth.

    Science.gov (United States)

    Frazier, Thomas W; Youngstrom, Eric A; Fristad, Mary A; Demeter, Christine; Birmaher, Boris; Kowatch, Robert A; Arnold, L Eugene; Axelson, David; Gill, Mary K; Horwitz, Sarah M; Findling, Robert L

    2014-01-01

    This report evaluates whether classification tree algorithms (CTA) may improve the identification of individuals at risk for bipolar spectrum disorders (BPSD). Analyses used the Longitudinal Assessment of Manic Symptoms (LAMS) cohort (629 youth, 148 with BPSD and 481 without BPSD). Parent ratings of mania symptoms, stressful life events, parenting stress, and parental history of mania were included as risk factors. Comparable overall accuracy was observed for CTA (75.4%) relative to logistic regression (77.6%). However, CTA showed increased sensitivity (0.28 vs. 0.18) at the expense of slightly decreased specificity and positive predictive power. The advantage of CTA algorithms for clinical decision making is demonstrated by the combinations of predictors most useful for altering the probability of BPSD. The 24% sample probability of BPSD was substantially decreased in youth with low screening and baseline parent ratings of mania, negative parental history of mania, and low levels of stressful life events (2%). High screening plus high baseline parent-rated mania nearly doubled the BPSD probability (46%). Future work will benefit from examining additional, powerful predictors, such as alternative data sources (e.g., clinician ratings, neurocognitive test data); these may increase the clinical utility of CTA models further. PMID:25143826

  15. Improving Clinical Prediction of Bipolar Spectrum Disorders in Youth

    Directory of Open Access Journals (Sweden)

    Thomas W. Frazier

    2014-03-01

    Full Text Available This report evaluates whether classification tree algorithms (CTA may improve the identification of individuals at risk for bipolar spectrum disorders (BPSD. Analyses used the Longitudinal Assessment of Manic Symptoms (LAMS cohort (629 youth, 148 with BPSD and 481 without BPSD. Parent ratings of mania symptoms, stressful life events, parenting stress, and parental history of mania were included as risk factors. Comparable overall accuracy was observed for CTA (75.4% relative to logistic regression (77.6%. However, CTA showed increased sensitivity (0.28 vs. 0.18 at the expense of slightly decreased specificity and positive predictive power. The advantage of CTA algorithms for clinical decision making is demonstrated by the combinations of predictors most useful for altering the probability of BPSD. The 24% sample probability of BPSD was substantially decreased in youth with low screening and baseline parent ratings of mania, negative parental history of mania, and low levels of stressful life events (2%. High screening plus high baseline parent-rated mania nearly doubled the BPSD probability (46%. Future work will benefit from examining additional, powerful predictors, such as alternative data sources (e.g., clinician ratings, neurocognitive test data; these may increase the clinical utility of CTA models further.

  16. Possible Biomarkers for the Early Detection of HIV-associated Heart Diseases: A Proteomics and Bioinformatics Prediction

    Directory of Open Access Journals (Sweden)

    Suraiya Rasheed

    2015-01-01

    Full Text Available The frequency of cardiovascular disorders is increasing in HIV-infected individuals despite a significant reduction in the viral load by antiretroviral therapies (ART. Since the CD4+ T-cells are responsible for the viral load as well as immunological responses, we hypothesized that chronic HIV-infection of T-cells produces novel proteins/enzymes that cause cardiac dysfunctions. To identify specific factors that might cause cardiac disorders without the influence of numerous cofactors produced by other pathogenic microorganisms that co-inhabit most HIV-infected individuals, we analyzed genome-wide proteomes of a CD4+ T-cell line at different stages of HIV replication and cell growth over >6 months. Subtractive analyses of several hundred differentially regulated proteins from HIV-infected and uninfected counterpart cells and comparisons with proteins expressed from the same cells after treating with the antiviral drug Zidovudine/AZT and inhibiting virus replication, identified a well-coordinated network of 12 soluble/diffusible proteins in HIV-infected cells. Functional categorization, bioinformatics and statistical analyses of each protein predicted that the expression of cardiac-specific Ca2+ kinase together with multiple Ca2+ release channels causes a sustained overload of Ca2+ in the heart which induces fetal/cardiac myosin heavy chains (MYH6 and MYH7 and a myosin light-chain kinase. Each of these proteins has been shown to cause cardiac stress, arrhythmia, hypertrophic signaling, cardiomyopathy and heart failure (p = 8 × 10−11. Translational studies using the newly discovered proteins produced by HIV infection alone would provide additional biomarkers that could be added to the conventional markers for an early diagnosis and/or development of specific therapeutic interventions for heart diseases in HIV-infected individuals.

  17. Periprocedural myocardial infarction enhances the predictive value of inflammatory biomarkers for patients with obstructive coronary artery disease after implantation of drug-eluting stent

    Directory of Open Access Journals (Sweden)

    Jesika A

    2015-02-01

    Full Text Available Anastasia Jesika,1 Zuo-Ying Hu,2 Jing Kan,3 Shao-Liang Chen2 1Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 3Nanjing Heart Center, Nanjing, People’s Republic of China Objective: The present study aims to clarify the long-term clinical importance of interleukin (IL-6 in predicting major adverse cardiac events (MACE for an entire cohort of patients with coronary artery disease after implantation of a drug-eluting stent (DES, and its interplay with periprocedural myocardial infarction (PMI. Background: The correlation of proinflammatory biomarkers with occurrence of clinical events, including PMI and mortality, is controversial. Methods: IL-6 was measured in 1,991 patients at admission. The participants were then assigned to two groups: IL-6 level ≥9 pg/mL and IL-6 level <9 pg/mL. The primary endpoint was the occurrence of cardiac death or myocardial infarction (MI at year 3 after indexed percutaneous coronary intervention (PCI procedure. Results: The in-hospital rate of the primary endpoint in the IL-6 level ≥9 pg/mL group was 9.1%, statistically significantly different to 6.3% in the IL-6 <9 pg/mL group (P=0.026, mainly driven by the increased rate of MI (9.1% vs 6.1%, P=0.025. Those differences in MI/death and MI was sustained through to the 3-year follow-up (10.9% vs 7.6%, P=0.017 and 10.1% vs 7.5%, P=0.049. At the 3-year follow-up after the assigned procedure, more frequent MI was also the main reason for increased composite MACE between the IL-6 ≥9 pg/mL and IL-6 <9 pg/mL groups (20.7% vs 15.8%, P=0.007. In the IL-6 ≥9 pg/mL group, PMI was strongly correlated with mortality at 1-year through to the 3-year (hazard ratio: 2.96, 95% confidence interval: 1.35–6.49, P=0.005 follow-up after PCI procedure. Conclusion: Elevated preprocedural serum IL-6 level was correlated with death, MI, and MACE

  18. Anti-MOG antibody: The history, clinical phenotype, and pathogenicity of a serum biomarker for demyelination.

    Science.gov (United States)

    Ramanathan, Sudarshini; Dale, Russell C; Brilot, Fabienne

    2016-04-01

    Myelin oligodendrocyte glycoprotein (MOG) is a protein exclusively expressed on the surface of oligodendrocytes and myelin in the central nervous system. MOG has been identified as a putative candidate autoantigen and autoantibody target in demyelination for almost three decades, with extensive literature validating its role in murine models of experimental autoimmune encephalomyelitis. Seminal studies using murine anti-MOG antibodies have highlighted the fact that antibodies that target epitopes of native MOG in its conformational state, rather than linearized or denature`d MOG, are biologically relevant. However, the relevance of anti-MOG antibodies in humans has been difficult to decipher over the years due to varying methods of detection as well as the fact that it was assumed that these antibodies would be clinically associated with multiple sclerosis. There is now international consensus that anti-MOG antibodies are important in both pediatric and adult demyelination, and the clinical association of MOG antibody-associated demyelination has been refined to include acute disseminated encephalomyelitis, relapsing and bilateral optic neuritis, and transverse myelitis. Anti-MOG antibodies are now thought not to be associated with multiple sclerosis in adults. Patients with MOG antibody-associated demyelination appear to have a unique clinical, radiological, and therapeutic profile, which represents a major advance in their diagnosis and management. It is imperative to understand whether anti-MOG antibodies are indeed pathogenic, and if so, their mechanisms of action. As it has become apparent that there are differences in MOG epitope binding between species, translation of animal studies to human demyelination should be analyzed in this context. Further work is required to identify the specific epitope binding sites in human disease and pathogenic mechanisms of anti-MOG antibodies, as well optimal therapeutic strategies to improve prognosis and minimize

  19. 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.

  20. Impact of biomarker development on drug safety assessment

    International Nuclear Information System (INIS)

    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.

  1. Amyloid-β peptides and tau protein as biomarkers in cerebrospinal and interstitial fluid following traumatic brain injury: A review of experimental and clinical studies

    Directory of Open Access Journals (Sweden)

    Parmenion P. Tsitsopoulos

    2013-06-01

    Full Text Available Traumatic brain injury (TBI survivors frequently suffer from life-long deficits in cognitive functions and a reduced quality of life. Axonal injury, observed in most severe TBI patients, results in accumulation of amyloid precursor protein (APP. Post-injury enzymatic cleavage of APP can generate amyloid-β (Aβ peptides, a hallmark finding in Alzheimer’s disease (AD. At autopsy, brains of AD and a subset of TBI victims display some similarities including accumulation of Aβ peptides and neurofibrillary tangles of hyperphosphorylated tau proteins. Most epidemiological evidence suggests a link between TBI and AD, implying that TBI has neurodegenerative sequelae. Aβ peptides and tau may be used as biomarkers in interstitial fluid (ISF using cerebral microdialysis and/or cerebrospinal fluid (CSF following clinical TBI. In the present review, the available clinical and experimental literature on Aβ peptides and tau as potential biomarkers following TBI is comprehensively analyzed. Elevated CSF and ISF tau protein levels have been observed following severe TBI and suggested to correlate with clinical outcome. Although Aβ peptides are produced by normal neuronal metabolism, high levels of long and/or fibrillary Aβ peptides may be neurotoxic. Increased CSF and/or ISF Aβ levels post-injury may be related to neuronal activity and/or the presence of axonal injury. The heterogeneity of animal models, clinical cohorts, analytical techniques and the complexity of TBI in available studies make the clinical value of tau and Aβ as biomarkers uncertain at present. Additionally, the link between early post-injury changes in tau and Aβ peptides and the future risk of developing AD remains unclear. Future studies using e.g. rapid biomarker sampling combined with enhanced analytical techniques and/or novel pharmacological tools could provide additional information on the importance of Aβ peptides and tau protein in both the acute pathophysiology and long

  2. High IFIT1 expression predicts improved clinical outcome, and IFIT1 along with MGMT more accurately predicts prognosis in newly diagnosed glioblastoma.

    Science.gov (United States)

    Zhang, Jin-Feng; Chen, Yao; Lin, Guo-Shi; Zhang, Jian-Dong; Tang, Wen-Long; Huang, Jian-Huang; Chen, Jin-Shou; Wang, Xing-Fu; Lin, Zhi-Xiong

    2016-06-01

    Interferon-induced protein with tetratricopeptide repeat 1 (IFIT1) plays a key role in growth suppression and apoptosis promotion in cancer cells. Interferon was reported to induce the expression of IFIT1 and inhibit the expression of O-6-methylguanine-DNA methyltransferase (MGMT).This study aimed to investigate the expression of IFIT1, the correlation between IFIT1 and MGMT, and their impact on the clinical outcome in newly diagnosed glioblastoma. The expression of IFIT1 and MGMT and their correlation were investigated in the tumor tissues from 70 patients with newly diagnosed glioblastoma. The effects on progression-free survival and overall survival were evaluated. Of 70 cases, 57 (81.4%) tissue samples showed high expression of IFIT1 by immunostaining. The χ(2) test indicated that the expression of IFIT1 and MGMT was negatively correlated (r = -0.288, P = .016). Univariate and multivariate analyses confirmed high IFIT1 expression as a favorable prognostic indicator for progression-free survival (P = .005 and .017) and overall survival (P = .001 and .001), respectively. Patients with 2 favorable factors (high IFIT1 and low MGMT) had an improved prognosis as compared with others. The results demonstrated significantly increased expression of IFIT1 in newly diagnosed glioblastoma tissue. The negative correlation between IFIT1 and MGMT expression may be triggered by interferon. High IFIT1 can be a predictive biomarker of favorable clinical outcome, and IFIT1 along with MGMT more accurately predicts prognosis in newly diagnosed glioblastoma. PMID:26980050

  3. Di-22:6-bis(monoacylglycerol)phosphate: A clinical biomarker of drug-induced phospholipidosis for drug development and safety assessment

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Nanjun; Tengstrand, Elizabeth A.; Chourb, Lisa; Hsieh, Frank Y., E-mail: frank.hsieh@nextcea.com

    2014-09-15

    The inability to routinely monitor drug-induced phospholipidosis (DIPL) presents a challenge in pharmaceutical drug development and in the clinic. Several nonclinical studies have shown di-docosahexaenoyl (22:6) bis(monoacylglycerol) phosphate (di-22:6-BMP) to be a reliable biomarker of tissue DIPL that can be monitored in the plasma/serum and urine. The aim of this study was to show the relevance of di-22:6-BMP as a DIPL biomarker for drug development and safety assessment in humans. DIPL shares many similarities with the inherited lysosomal storage disorder Niemann–Pick type C (NPC) disease. DIPL and NPC result in similar changes in lysosomal function and cholesterol status that lead to the accumulation of multi-lamellar bodies (myeloid bodies) in cells and tissues. To validate di-22:6-BMP as a biomarker of DIPL for clinical studies, NPC patients and healthy donors were classified by receiver operator curve analysis based on urinary di-22:6-BMP concentrations. By showing 96.7-specificity and 100-sensitivity to identify NPC disease, di-22:6-BMP can be used to assess DIPL in human studies. The mean concentration of di-22:6-BMP in the urine of NPC patients was 51.4-fold (p ≤ 0.05) above the healthy baseline range. Additionally, baseline levels of di-22:6-BMP were assessed in healthy non-medicated laboratory animals (rats, mice, dogs, and monkeys) and human subjects to define normal reference ranges for nonclinical/clinical studies. The baseline ranges of di-22:6-BMP in the plasma, serum, and urine of humans and laboratory animals were species dependent. The results of this study support the role of di-22:6-BMP as a biomarker of DIPL for pharmaceutical drug development and health care settings. - Highlights: • A reliable biomarker of drug-induced phospholipidosis (DIPL) is needed for humans. • Di-22:6-BMP is specific/sensitive for DIPL in animals as published in literatures. • The di-22:6-BMP biomarker can be validated for humans via NPC patients. • DIPL

  4. Di-22:6-bis(monoacylglycerol)phosphate: A clinical biomarker of drug-induced phospholipidosis for drug development and safety assessment

    International Nuclear Information System (INIS)

    The inability to routinely monitor drug-induced phospholipidosis (DIPL) presents a challenge in pharmaceutical drug development and in the clinic. Several nonclinical studies have shown di-docosahexaenoyl (22:6) bis(monoacylglycerol) phosphate (di-22:6-BMP) to be a reliable biomarker of tissue DIPL that can be monitored in the plasma/serum and urine. The aim of this study was to show the relevance of di-22:6-BMP as a DIPL biomarker for drug development and safety assessment in humans. DIPL shares many similarities with the inherited lysosomal storage disorder Niemann–Pick type C (NPC) disease. DIPL and NPC result in similar changes in lysosomal function and cholesterol status that lead to the accumulation of multi-lamellar bodies (myeloid bodies) in cells and tissues. To validate di-22:6-BMP as a biomarker of DIPL for clinical studies, NPC patients and healthy donors were classified by receiver operator curve analysis based on urinary di-22:6-BMP concentrations. By showing 96.7-specificity and 100-sensitivity to identify NPC disease, di-22:6-BMP can be used to assess DIPL in human studies. The mean concentration of di-22:6-BMP in the urine of NPC patients was 51.4-fold (p ≤ 0.05) above the healthy baseline range. Additionally, baseline levels of di-22:6-BMP were assessed in healthy non-medicated laboratory animals (rats, mice, dogs, and monkeys) and human subjects to define normal reference ranges for nonclinical/clinical studies. The baseline ranges of di-22:6-BMP in the plasma, serum, and urine of humans and laboratory animals were species dependent. The results of this study support the role of di-22:6-BMP as a biomarker of DIPL for pharmaceutical drug development and health care settings. - Highlights: • A reliable biomarker of drug-induced phospholipidosis (DIPL) is needed for humans. • Di-22:6-BMP is specific/sensitive for DIPL in animals as published in literatures. • The di-22:6-BMP biomarker can be validated for humans via NPC patients. • DIPL

  5. Advances in the development of biomarkers for epilepsy.

    Science.gov (United States)

    Pitkänen, Asla; Löscher, Wolfgang; Vezzani, Annamaria; Becker, Albert J; Simonato, Michele; Lukasiuk, Katarzyna; Gröhn, Olli; Bankstahl, Jens P; Friedman, Alon; Aronica, Eleonora; Gorter, Jan A; Ravizza, Teresa; Sisodiya, Sanjay M; Kokaia, Merab; Beck, Heinz

    2016-07-01

    Over 50 million people worldwide have epilepsy. In nearly 30% of these cases, epilepsy remains unsatisfactorily controlled despite the availability of over 20 antiepileptic drugs. Moreover, no treatments exist to prevent the development of epilepsy in those at risk, despite an increasing understanding of the underlying molecular and cellular pathways. One of the major factors that have impeded rapid progress in these areas is the complex and multifactorial nature of epilepsy, and its heterogeneity. Therefore, the vision of developing targeted treatments for epilepsy relies upon the development of biomarkers that allow individually tailored treatment. Biomarkers for epilepsy typically fall into two broad categories: diagnostic biomarkers, which provide information on the clinical status of, and potentially the sensitivity to, specific treatments, and prognostic biomarkers, which allow prediction of future clinical features, such as the speed of progression, severity of epilepsy, development of comorbidities, or prediction of remission or cure. Prognostic biomarkers are of particular importance because they could be used to identify which patients will develop epilepsy and which might benefit from preventive treatments. Biomarker research faces several challenges; however, biomarkers could substantially improve the management of people with epilepsy and could lead to prevention in the right person at the right time, rather than just symptomatic treatment. PMID:27302363

  6. Inflammation as a predictive biomarker for response to omega-3 fatty acids in major depressive disorder: a proof-of-concept study.

    Science.gov (United States)

    Rapaport, M H; Nierenberg, A A; Schettler, P J; Kinkead, B; Cardoos, A; Walker, R; Mischoulon, D

    2016-01-01

    This study explores whether inflammatory biomarkers act as moderators of clinical response to omega-3 (n-3) fatty acids in subjects with major depressive disorder (MDD). One hundred fifty-five subjects with Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) MDD, a baseline 17-item Hamilton Depression Rating Scale (HAM-D-17) score ⩾ 15 and baseline biomarker data (interleukin (IL)-1ra, IL-6, high-sensitivity C-reactive protein (hs-CRP), leptin and adiponectin) were randomized between 18 May 2006 and 30 June 2011 to 8 weeks of double-blind treatment with eicosapentaenoic acid (EPA)-enriched n-3 1060 mg day(-1), docosahexaenoic acid (DHA)-enriched n-3 900 mg day(-1) or placebo. Outcomes were determined using mixed model repeated measures analysis for 'high' and 'low' inflammation groups based on individual and combined biomarkers. Results are presented in terms of standardized treatment effect size (ES) for change in HAM-D-17 from baseline to treatment week 8. Although overall treatment group differences were negligible (ES=-0.13 to +0.04), subjects with any 'high' inflammation improved more on EPA than placebo (ES=-0.39) or DHA (ES=-0.60) and less on DHA than placebo (ES=+0.21); furthermore, EPA-placebo separation increased with increasing numbers of markers of high inflammation. Subjects randomized to EPA with 'high' IL-1ra or hs-CRP or low adiponectin ('high' inflammation) had medium ES decreases in HAM-D-17 scores vs subjects 'low' on these biomarkers. Subjects with 'high' hs-CRP, IL-6 or leptin were less placebo-responsive than subjects with low levels of these biomarkers (medium to large ES differences). Employing multiple markers of inflammation facilitated identification of a more homogeneous cohort of subjects with MDD responding to EPA vs placebo in our cohort. Studies are needed to replicate and extend this proof-of-concept work. PMID:25802980

  7. A large multi-centre European study validates high-sensitivity C-reactive protein (hsCRP) as a clinical biomarker for the diagnosis of diabetes subtypes

    DEFF Research Database (Denmark)

    Thanabalasingham, G.; Shah, N.; Vaxillaire, M.; Hansen, T.; Tuomi, T.; Gasperikova, D.; Szopa, M.; Tjora, E.; James, T. J.; Kokko, P.; Loiseleur, F.; Andersson, E.; Gaget, S.; Isomaa, B.; Nowak, N.; Raeder, H.; Stanik, J.; Njolstad, P. R.; Malecki, M. T.; Klimes, I.; Groop, L.; Pedersen, O.; Froguel, P.; McCarthy, M. I.; Gloyn, A. L.; Owen, K. R.

    2011-01-01

    An accurate molecular diagnosis of diabetes subtype confers clinical benefits; however, many individuals with monogenic diabetes remain undiagnosed. Biomarkers could help to prioritise patients for genetic investigation. We recently demonstrated that high-sensitivity C-reactive protein (hsCRP......) levels are lower in UK patients with hepatocyte nuclear factor 1 alpha (HNF1A)-MODY than in other diabetes subtypes. In this large multi-centre study we aimed to assess the clinical validity of hsCRP as a diagnostic biomarker, examine the genotype-phenotype relationship and compare different hsCRP assays....... High-sensitivity CRP levels were analysed in individuals with HNF1A-MODY (n = 457), glucokinase (GCK)-MODY (n = 404), hepatocyte nuclear factor 4 alpha (HNF4A)-MODY (n = 54) and type 2 diabetes (n = 582) from seven European centres. Three common assays for hsCRP analysis were evaluated. We excluded 121...

  8. A systematic review of studies comparing diagnostic clinical prediction rules with clinical judgment.

    Directory of Open Access Journals (Sweden)

    Sharon Sanders

    Full Text Available Diagnostic clinical prediction rules (CPRs are developed to improve diagnosis or decrease diagnostic testing. Whether, and in what situations diagnostic CPRs improve upon clinical judgment is unclear.We searched MEDLINE, Embase and CINAHL, with supplementary citation and reference checking for studies comparing CPRs and clinical judgment against a current objective reference standard. We report 1 the proportion of study participants classified as not having disease who hence may avoid further testing and or treatment and 2 the proportion, among those classified as not having disease, who do (missed diagnoses by both approaches. 31 studies of 13 medical conditions were included, with 46 comparisons between CPRs and clinical judgment. In 2 comparisons (4%, CPRs reduced the proportion of missed diagnoses, but this was offset by classifying a larger proportion of study participants as having disease (more false positives. In 36 comparisons (78% the proportion of diagnoses missed by CPRs and clinical judgment was similar, and in 9 of these, the CPRs classified a larger proportion of participants as not having disease (fewer false positives. In 8 comparisons (17% the proportion of diagnoses missed by the CPRs was greater. This was offset by classifying a smaller proportion of participants as having the disease (fewer false positives in 2 comparisons. There were no comparisons where the CPR missed a smaller proportion of diagnoses than clinical judgment and classified more participants as not having the disease. The design of the included studies allows evaluation of CPRs when their results are applied independently of clinical judgment. The performance of CPRs, when implemented by clinicians as a support to their judgment may be different.In the limited studies to date, CPRs are rarely superior to clinical judgment and there is generally a trade-off between the proportion classified as not having disease and the proportion of missed diagnoses

  9. A Novel Biomarker Panel Examining Response to Gemcitabine with or without Erlotinib for Pancreatic Cancer Therapy in NCIC Clinical Trials Group PA.3.

    Directory of Open Access Journals (Sweden)

    David B Shultz

    Full Text Available NCIC Clinical Trials Group PA.3 was a randomized control trial that demonstrated improved overall survival (OS in patients receiving erlotinib in addition to gemcitabine for locally advanced or metastatic pancreatic cancer. Prior to therapy, patients had plasma samples drawn for future study. We sought to identify biomarkers within these samples.Using the proximity ligation assay (PLA, a probe panel was built from commercially available antibodies for 35 key proteins selected from a global genetic analysis of pancreatic cancers, and used to quantify protein levels in 20 uL of patient plasma. To determine if any of these proteins levels independently associated with OS, univariate and mulitbaraible Cox models were used. In addition, we examined the associations between biomarker expression and disease stage at diagnosis using Fisher's exact test. The correlation between Erlotinib sensitivity and each biomarkers was assessed using a test of interaction between treatment and biomarker.Of the 569 eligible patients, 480 had samples available for study. Samples were randomly allocated into training (251 and validation sets (229. Among all patients, elevated levels of interleukin-8 (IL-8, carcinoembryonic antigen (CEA, hypoxia-inducible factor 1-alpha (HIF-1 alpha, and interleukin-6 were independently associated with lower OS, while IL-8, CEA, platelet-derived growth factor receptor alpha and mucin-1 were associated with metastatic disease. Patients with elevated levels of receptor tyrosine-protein kinase erbB-2 (HER2 expression had improved OS when treated with erlotinib compared to placebo. In conclusion, PLA is a powerful tool for identifying biomarkers from archived, small volume serum samples. These data may be useful to stratify patient outcomes regardless of therapeutic intervention.ClinicalTrials.gov NCT00040183.

  10. Clinical implications of hypoxia biomarker expression in head and neck squamous cell carcinoma: a systematic review

    International Nuclear Information System (INIS)

    Awareness increases that the tumor biology influences treatment outcome and prognosis in cancer. Tumor hypoxia is thought to decrease sensitivity to radiotherapy and some forms of chemotherapy. Presence of hypoxia may be assessed by investigating expression of endogenous markers of hypoxia (EMH) using immunohistochemistry (IHC). In this systematic review we investigated the effect of EMH expression on local control and survival according to treatment modality in head and neck cancer (head and neck squamous cell carcinoma [HNSCC]). A search was performed in MEDLINE and EMBASE. Studies were eligible for inclusion that described EMH expression in relation to outcome in HNSCC patients. Quality was assessed using the Quality in Prognosis Studies (QUIPS) tool. Hazard ratios for locoregional control and survival were extracted. Forty studies of adequate quality were included. HIF-1a, HIF-2a, CA-IX, GLUT-1, and OPN were identified as the best described EMHs. With exception of HIF-2a, all EMHs were significantly related to adverse outcome in multiple studies, especially in studies where patients underwent single-modality treatment. Positive expression was often correlated with adverse clinical characteristics, including disease stage and differentiation grade. In summary, EMH expression was common in HNSCC patients and negatively influenced their prognosis. Future studies should investigate the effect of hypoxia-modified treatment schedules in patients with high In summary, EMH expression. These may include ARCON, treatment with nimorazole, or novel targeted therapies directed at hypoxic tissue. Also, the feasibility of surgical removal of the hypoxic tumor volume prior to radiotherapy should be investigated

  11. Clinical Use of the Urine Biomarker [TIMP-2] × [IGFBP7] for Acute Kidney Injury Risk Assessment.

    Science.gov (United States)

    Vijayan, Anitha; Faubel, Sarah; Askenazi, David J; Cerda, Jorge; Fissell, William H; Heung, Michael; Humphreys, Benjamin D; Koyner, Jay L; Liu, Kathleen D; Mour, Girish; Nolin, Thomas D; Bihorac, Azra

    2016-07-01

    Acute kidney injury (AKI) is a serious complication, commonly occurring in the critically ill population, with devastating short- and long-term consequences. Despite standardization of the definition and staging of AKI, early recognition remains challenging given that serum creatinine level is a marker, albeit imperfect, of kidney function and not kidney injury. Furthermore, the delay in increase in serum creatinine level after loss of glomerular filtration also prevents timely detection of decreased kidney function in patients with AKI. During the past decade, numerous clinical investigations have evaluated the utility of several biomarkers in the early diagnosis and risk stratification of AKI. In 2014, the US Food and Drug Administration approved the marketing of a test based on the combination of urine concentrations of tissue inhibitor of metalloproteinase 2 and insulin-like growth factor binding protein 7 ([TIMP-2] × [IGFBP7]) to determine whether certain critically ill patients are at risk for developing moderate to severe AKI. The optimal role of this biomarker in the diagnosis, management, and prognosis of AKI in different clinical settings requires further clarification. In this perspective, we summarize the biological actions of these 2 cell-cycle arrest biomarkers and present important considerations regarding the clinical application, interpretation, and limitations of this novel test for the early detection of AKI. PMID:26948834

  12. Biomarkers and Surrogate Endpoints for Normal-Tissue Effects of Radiation Therapy: The Importance of Dose-Volume Effects

    International Nuclear Information System (INIS)

    Biomarkers are of interest for predicting or monitoring normal tissue toxicity of radiation therapy. Advances in molecular radiobiology provide novel leads in the search for normal tissue biomarkers with sufficient sensitivity and specificity to become clinically useful. This article reviews examples of studies of biomarkers as predictive markers, as response markers, or as surrogate endpoints for radiation side effects. Single nucleotide polymorphisms are briefly discussed in the context of candidate gene and genomewide association studies. The importance of adjusting for radiation dose distribution in normal tissue biomarker studies is underlined. Finally, research priorities in this field are identified and discussed.

  13. Cefditoren versus levofloxacin in patients with exacerbations of chronic bronchitis: serum inflammatory biomarkers, clinical efficacy, and microbiological eradication

    Directory of Open Access Journals (Sweden)

    Blasi F

    2013-02-01

    Full Text Available Francesco Blasi, Paolo Tarsia, Marco Mantero, Letizia C Morlacchi, Federico PifferDepartment of Pathophysiology and Transplantation, University of Milan, IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Milan, ItalyBackground: The aim of this open-label, randomized, parallel-group pilot study was to evaluate the efficacy of cefditoren pivoxil and levofloxacin in terms of speed of reduction in inflammatory parameters, clinical recovery, and microbiological eradication.Methods: Forty eligible patients with acute exacerbation of chronic bronchitis (AECB were randomized to receive cefditoren 200 mg twice a day for 5 days (n = 20 or levofloxacin 500 mg once daily for 7 days (n = 20.Results: The inflammatory parameters which were significantly reduced at test-of-cure with respect to visit 1 were Krebs von den Lundgen-6 (KL-6 and interleukin-6. KL-6 decreased both in the overall study population (from 19 ± 11 UI/mL to 6 ± 8 UI/mL, P = 0.000 and in the cefditoren (from 19 ± 13 UI/mL to 8 ± 10 UI/mL, P = 0.006 and levofloxacin (from 19 ± 10 UI/mL to 5 ± 5 UI/mL, P = 0.000 arms. Similarly, interleukin-6 decreased both in the overall study population (from 13.35 ± 16.41 pg/mL to 3 ± 4.7 pg/mL, P = 0.000 and in the cefditoren (from 15.90 ± 19.54 pg/mL to 4.13 ± 6.42 pg/mL, P = 0.015 and levofloxacin (from 10.80 ± 12.55 pg/mL to 1.87 ± 1.16 pg/mL, P = 0.003 arms. At the end of treatment (test-of-cure, 6–9 days after drug initiation, the clinical success rate in the overall study population was 78%; the clinical cure rate was 80% in the cefditoren arm and 75% in the levofloxacin arm. Globally, bacteriological eradication at test-of-cure was obtained in 85% of the overall study population. Both treatments were well tolerated.Conclusion: Cefditoren represents a valid option in the treatment of mild to moderately severe cases of AECB in the outpatient care setting. Moreover, the use of this cephalosporin is associated with a significant

  14. Whole blood defensin mRNA expression is a predictive biomarker of docetaxel response in castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Kohli M

    2015-07-01

    Full Text Available Manish Kohli,1 Charles YF Young,2 Donald J Tindall,2 Debashis Nandy,1 Kyle M McKenzie,3 Graham H Bevan,4 Krishna Vanaja Donkena5 1Department of Oncology, 2Department of Urology, 3Department of Geriatric Medicine, Mayo Clinic, Rochester, MN, 4University of Rochester Medical Center, Rochester, NY, 5Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA Abstract: This study tested the potential of circulating RNA-based signals as predictive biomarkers for docetaxel response in patients with metastatic castration-resistant prostate cancer (CRPC. RNA was analyzed in blood from six CRPC patients by whole-transcriptome sequencing (total RNA-sequencing before and after docetaxel treatment using the Illumina’s HiSeq platform. Targeted RNA capture and sequencing was performed in an independent cohort of ten patients with CRPC matching the discovery cohort to confirm differential expression of the genes. Response to docetaxel was defined on the basis of prostate-specific antigen levels and imaging criteria. Two-way analysis of variance was used to compare differential gene expression in patients classified as responders versus nonresponders before and after docetaxel treatment. Thirty-four genes with two-fold differentially expressed transcripts in responders versus nonresponders were selected from total RNA-sequencing for further validation. Targeted RNA capture and sequencing showed that 13/34 genes were differentially expressed in responders. Alpha defensin genes DEFA1, DEFA1B, and DEFA3 exhibited significantly higher expression in responder patients compared with nonresponder patients before administration of chemotherapy (fold change >2.5. In addition, post-docetaxel treatment significantly increased transcript levels of these defensin genes in responders (fold change >2.8. Our results reveal that patients with higher defensin RNA transcripts in blood respond well to docetaxel therapy. We suggest that monitoring DEFA1, DEFA1B, and DEFA3

  15. Biomarkers in the Management of Difficult Asthma.

    Science.gov (United States)

    Schleich, Florence; Sophie, Demarche; Renaud, Louis

    2016-01-01

    Difficult asthma is a heterogeneous disease of the airways including various types of bronchial inflammation and various degrees of airway remodeling. Therapeutic response of severe asthmatics can be predicted by the use of biomarkers of Type2-high or Type2-low inflammation. Based on sputum cell analysis, four inflammatory phenotypes have been described. As induced sputum is timeconsuming and expensive technique, surrogate biomarkers are useful in clinical practice. Eosinophilic phenotype is likely to reflect ongoing adaptive immunity in response to allergen. Several biomarkers of eosinophilic asthma are easily available in clinical practice (blood eosinophils, serum IgE, exhaled nitric oxyde, serum periostin). Neutrophilic asthma is thought to reflect innate immune system activation in response to pollutants or infectious agents while paucigranulocytic asthma is thought to be not inflammatory and characterized by smooth muscle dysfunction. We currently lack of user-friendly biomarkers of neutrophilic asthma and airway remodeling. In this review, we summarize the biomarkers available for the management of difficult asthma. PMID:26467509

  16. Biomarkers for wound healing and their evaluation.

    Science.gov (United States)

    Patel, S; Maheshwari, A; Chandra, A

    2016-01-01

    A biological marker (biomarker) is a substance used as an indicator of biological state. Advances in genomics, proteomics and molecular pathology have generated many candidate biomarkers with potential clinical value. Research has identified several cellular events and mediators associated with wound healing that can serve as biomarkers. Macrophages, neutrophils, fibroblasts and platelets release cytokines molecules including TNF-α, interleukins (ILs) and growth factors, of which platelet-derived growth factor (PDGF) holds the greatest importance. As a result, various white cells and connective tissue cells release both matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs). Studies have demonstrated that IL-1, IL-6, and MMPs, levels above normal, and an abnormally high MMP/TIMP ratio are often present in non-healing wounds. Clinical examination of wounds for these mediators could predict which wounds will heal and which will not, suggesting use of these chemicals as biomarkers of wound healing. There is also evidence that the application of growth factors like PDGF will alleviate the recuperating process of chronic, non-healing wounds. Finding a specific biomarker for wound healing status would be a breakthrough in this field and helping treat impaired wound healing. PMID:26762498

  17. ECG dispersion mapping predicts clinical deterioration, measured by increase in the Simple Clinical Score.

    LENUS (Irish Health Repository)

    Kellett, J

    2012-01-01

    Objective: ECG dispersion mapping (ECG-DM) is a novel technique that reports abnormal ECG microalternations. We report the ability of ECG-DM to predict clinical deterioration of acutely ill medical patients, as measured by an increase in the Simple Clinical Score (SCS) the day after admission to hospital. Methods: 453 acutely ill medical patients (mean age 69.7 +\\/- 14.0 years) had the SCS recorded and ECGDM performed immediately after admission to hospital. Results: 46 patients had an SCS increase 20.8 +\\/- 7.6 hours after admission. Abnormal micro-alternations during left ventricular re-polarization had the highest association with SCS increase (p=0.0005). Logistic regression showed that only nursing home residence and abnormal micro-alternations during re-polarization of the left ventricle were independent predictors of SCS increase with an odds ratio of 2.84 and 3.01, respectively. Conclusion: ECG-DM changes during left ventricular re-polarization are independent predictors of clinical deterioration the day after hospital admission.

  18. Biomarkers of drug-induced vascular injury

    International Nuclear Information System (INIS)

    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

  19. Biomarkers and surrogate endpoints in kidney disease.

    Science.gov (United States)

    Hartung, Erum A

    2016-03-01

    Kidney disease and its related comorbidities impose a large public health burden. Despite this, the number of clinical trials in nephrology lags behind many other fields. An important factor contributing to the relatively slow pace of nephrology trials is that existing clinical endpoints have significant limitations. "Hard" endpoints for chronic kidney disease, such as progression to end-stage renal disease, may not be reached for decades. Traditional biomarkers, such as serum creatinine in acute kidney injury, may lack sensitivity and predictive value. Finding new biomarkers to serve as surrogate endpoints is therefore an important priority in kidney disease research and may help to accelerate nephrology clinical trials. In this paper, I first review key concepts related to the selection of clinical trial endpoints and discuss statistical and regulatory considerations related to the evaluation of biomarkers as surrogate endpoints. This is followed by a discussion of the challenges and opportunities in developing novel biomarkers and surrogate endpoints in three major areas of nephrology research: acute kidney injury, chronic kidney disease, and autosomal dominant polycystic kidney disease. PMID:25980469

  20. Proteomic analysis identifies galectin-1 as a predictive biomarker for relapsed/refractory disease in classical Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Kamper, Peter; Ludvigsen, Maja; Bendix, Knud;

    2011-01-01

    Considerable effort has been spent identifying prognostic biomarkers in classic Hodgkin lymphoma (cHL). The aim of our study was to search for possible prognostic parameters in advanced-stage cHL using a proteomics-based strategy. A total of 14 cHL pretreatment tissue samples from younger, advanc...

  1. Prediction of fruit and vegetable intake from biomarkers using individual participant data of diet-controlled intervention studies

    NARCIS (Netherlands)

    Souverein, O.W.; Vries, J.H.M. de; Freese, R.; Watzl, B.; Bub, A.; Miller, E.R., III; Castenmiller, J.J.M.; Pasman, W.J.; Hof, K. van het; Chopra, M.; Karlsen, A.; Dragsted, L.O.; Winkels, R.; Itsiopoulos, C.; Brazionis, L.; O'Dea, K.; Loo-Bouwman, C.A. van; Naber, T.H.J.; Voet, H. van der; Boshuizen, H.C.

    2015-01-01

    Fruit and vegetable consumption produces changes in several biomarkers in blood. The present study aimed to examine the dose-response curve between fruit and vegetable consumption and carotenoid (α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein and zeaxanthin), folate and vitamin C concentr

  2. Heritability and clinical determinants of serum indoxyl sulfate and p-cresyl sulfate, candidate biomarkers of the human microbiome enterotype.

    Directory of Open Access Journals (Sweden)

    Liesbeth Viaene

    Full Text Available BACKGROUND: Indoxyl sulfate and p-cresyl sulfate are unique microbial co-metabolites. Both co-metabolites have been involved in the pathogenesis of accelerated cardiovascular disease and renal disease progression. Available evidence suggests that indoxyl sulfate and p-cresyl sulfate may be considered candidate biomarkers of the human enterotype and may help to explain the link between diet and cardiovascular disease burden. OBJECTIVE AND DESIGN: Information on clinical determinants and heritability of indoxyl sulfate and p-cresyl sulfate serum is non-existing. To clarify this issue, the authors determined serum levels of indoxyl sulfate and p-cresyl sulfate in 773 individuals, recruited in the frame of the Flemish Study on Environment, Genes and Health Outcomes (FLEMENGHO study. RESULTS: Serum levels of indoxyl sulfate and p-cresyl sulfate amounted to 3.1 (2.4-4.3 and 13.0 (7.4-21.5 μM, respectively. Regression analysis identified renal function, age and sex as independent determinants of both co-metabolites. Both serum indoxyl sulfate (h2 = 0.17 and p-cresyl sulfate (h2 = 0.18 concentrations showed moderate but significant heritability after adjustment for covariables, with significant genetic and environmental correlations for both co-metabolites. LIMITATIONS: Family studies cannot provide conclusive evidence for a genetic contribution, as confounding by shared environmental effects can never be excluded. CONCLUSIONS: The heritability of indoxyl sulfate and p-cresyl sulfate is moderate. Besides genetic host factors and environmental factors, also renal function, sex and age influence the serum levels of these co-metabolites.

  3. Personalized Medicine and Oncology Practice Guidelines: A Case Study of Contemporary Biomarkers in Colorectal Cancer

    OpenAIRE

    Kelley, Robin K; Van Bebber, Stephanie L; Phillips, Kathryn A; Venook, Alan P.

    2011-01-01

    Predictive and prognostic biomarkers offer a potential means to personalize cancer medicine, although many reach the marketplace before they have been validated, and their adoption is often hindered by variable clinical evidence. Because of this variability in supporting evidence, clinical practice guidelines formulated by panels of subspecialty experts may be particularly important in guiding stakeholders’ acceptance and use of new personalized medicine biomarker tests and other nascent tech...

  4. DICOM for quantitative imaging biomarker development: a standards based approach to sharing clinical data and structured PET/CT analysis results in head and neck cancer research

    Science.gov (United States)

    Clunie, David; Ulrich, Ethan; Bauer, Christian; Wahle, Andreas; Brown, Bartley; Onken, Michael; Riesmeier, Jörg; Pieper, Steve; Kikinis, Ron; Buatti, John; Beichel, Reinhard R.

    2016-01-01

    Background. Imaging biomarkers hold tremendous promise for precision medicine clinical applications. Development of such biomarkers relies heavily on image post-processing tools for automated image quantitation. Their deployment in the context of clinical research necessitates interoperability with the clinical systems. Comparison with the established outcomes and evaluation tasks motivate integration of the clinical and imaging data, and the use of standardized approaches to support annotation and sharing of the analysis results and semantics. We developed the methodology and tools to support these tasks in Positron Emission Tomography and Computed Tomography (PET/CT) quantitative imaging (QI) biomarker development applied to head and neck cancer (HNC) treatment response assessment, using the Digital Imaging and Communications in Medicine (DICOM®) international standard and free open-source software. Methods. Quantitative analysis of PET/CT imaging data collected on patients undergoing treatment for HNC was conducted. Processing steps included Standardized Uptake Value (SUV) normalization of the images, segmentation of the tumor using manual and semi-automatic approaches, automatic segmentation of the reference regions, and extraction of the volumetric segmentation-based measurements. Suitable components of the DICOM standard were identified to model the various types of data produced by the analysis. A developer toolkit of conversion routines and an Application Programming Interface (API) were contributed and applied to create a standards-based representation of the data. Results. DICOM Real World Value Mapping, Segmentation and Structured Reporting objects were utilized for standards-compliant representation of the PET/CT QI analysis results and relevant clinical data. A number of correction proposals to the standard were developed. The open-source DICOM toolkit (DCMTK) was improved to simplify the task of DICOM encoding by introducing new API abstractions

  5. DICOM for quantitative imaging biomarker development: a standards based approach to sharing clinical data and structured PET/CT analysis results in head and neck cancer research.

    Science.gov (United States)

    Fedorov, Andriy; Clunie, David; Ulrich, Ethan; Bauer, Christian; Wahle, Andreas; Brown, Bartley; Onken, Michael; Riesmeier, Jörg; Pieper, Steve; Kikinis, Ron; Buatti, John; Beichel, Reinhard R

    2016-01-01

    Background. Imaging biomarkers hold tremendous promise for precision medicine clinical applications. Development of such biomarkers relies heavily on image post-processing tools for automated image quantitation. Their deployment in the context of clinical research necessitates interoperability with the clinical systems. Comparison with the established outcomes and evaluation tasks motivate integration of the clinical and imaging data, and the use of standardized approaches to support annotation and sharing of the analysis results and semantics. We developed the methodology and tools to support these tasks in Positron Emission Tomography and Computed Tomography (PET/CT) quantitative imaging (QI) biomarker development applied to head and neck cancer (HNC) treatment response assessment, using the Digital Imaging and Communications in Medicine (DICOM(®)) international standard and free open-source software. Methods. Quantitative analysis of PET/CT imaging data collected on patients undergoing treatment for HNC was conducted. Processing steps included Standardized Uptake Value (SUV) normalization of the images, segmentation of the tumor using manual and semi-automatic approaches, automatic segmentation of the reference regions, and extraction of the volumetric segmentation-based measurements. Suitable components of the DICOM standard were identified to model the various types of data produced by the analysis. A developer toolkit of conversion routines and an Application Programming Interface (API) were contributed and applied to create a standards-based representation of the data. Results. DICOM Real World Value Mapping, Segmentation and Structured Reporting objects were utilized for standards-compliant representation of the PET/CT QI analysis results and relevant clinical data. A number of correction proposals to the standard were developed. The open-source DICOM toolkit (DCMTK) was improved to simplify the task of DICOM encoding by introducing new API abstractions

  6. An evaluation of logic regression-based biomarker discovery across multiple intergenic regions for predicting host specificity in Escherichia coli.

    Science.gov (United States)

    Zhi, Shuai; Li, Qiaozhi; Yasui, Yutaka; Banting, Graham; Edge, Thomas A; Topp, Edward; McAllister, Tim A; Neumann, Norman F

    2016-10-01

    Several studies have demonstrated that E. coli appears to display some level of host adaptation and specificity. Recent studies in our laboratory support these findings as determined by logic regression modeling of single nucleotide polymorphisms (SNP) in intergenic regions (ITGRs). We sought to determine the degree of host-specific information encoded in various ITGRs across a library of animal E. coli isolates using both whole genome analysis and a targeted ITGR sequencing approach. Our findings demonstrated that ITGRs across the genome encode various degrees of host-specific information. Incorporating multiple ITGRs (i.e., concatenation) into logic regression model building resulted in greater host-specificity and sensitivity outcomes in biomarkers, but the overall level of polymorphism in an ITGR did not correlate with the degree of host-specificity encoded in the ITGR. This suggests that distinct SNPs in ITGRs may be more important in defining host-specificity than overall sequence variation, explaining why traditional unsupervised learning phylogenetic approaches may be less informative in terms of revealing host-specific information encoded in DNA sequence. In silico analysis of 80 candidate ITGRs from publically available E. coli genomes was performed as a tool for discovering highly host-specific ITGRs. In one ITGR (ydeR-yedS) we identified a SNP biomarker that was 98% specific for cattle and for which 92% of all E. coli isolates originating from cattle carried this unique biomarker. In the case of humans, a host-specific biomarker (98% specificity) was identified in the concatenated ITGR sequences of rcsD-ompC, ydeR-yedS, and rclR-ykgE, and for which 78% of E. coli originating from humans carried this biomarker. Interestingly, human-specific biomarkers were dominant in ITGRs regulating antibiotic resistance, whereas in cattle host-specific biomarkers were found in ITGRs involved in stress regulation. These data suggest that evolution towards host

  7. Epigenetic biomarkers in esophageal cancer.

    Science.gov (United States)

    Kaz, Andrew M; Grady, William M

    2014-01-28

    The aberrant DNA methylation of tumor suppressor genes is well documented in esophageal cancer, including adenocarcinoma (EAC) and squamous cell carcinoma (ESCC) as well as in Barrett's esophagus (BE), a pre-malignant condition that is associated with chronic acid reflux. BE is a well-recognized risk factor for the development of EAC, and consequently the standard of care is for individuals with BE to be placed in endoscopic surveillance programs aimed at detecting early histologic changes that associate with an increased risk of developing EAC. Yet because the absolute risk of EAC in individuals with BE is minimal, a clinical need in the management of BE is the identification of additional risk markers that will indicate individuals who are at a significant absolute risk of EAC so that they may be subjected to more intensive surveillance. The best currently available risk marker is the degree of dysplasia in endoscopic biopsies from the esophagus; however, this marker is suboptimal for a variety of reasons. To date, there are no molecular biomarkers that have been translated to widespread clinical practice. The search for biomarkers, including hypermethylated genes, for either the diagnosis of BE, EAC, or ESCC or for risk stratification for the development of EAC in those with BE is currently an area of active research. In this review, we summarize the status of identified candidate epigenetic biomarkers for BE, EAC, and ESCC. Most of these aberrantly methylated genes have been described in the context of early detection or diagnostic markers; others might prove useful for estimating prognosis or predicting response to treatment. Finally, special attention will be paid to some of the challenges that must be overcome in order to develop clinically useful esophageal cancer biomarkers. PMID:22406828

  8. Design Characteristics Influence Performance of Clinical Prediction Rules in Validation: A Meta-Epidemiological Study

    OpenAIRE

    Ban, J-W.; Emparanza, J I; Urreta, I.; Burls, A

    2016-01-01

    BACKGROUND: Many new clinical prediction rules are derived and validated. But the design and reporting quality of clinical prediction research has been less than optimal. We aimed to assess whether design characteristics of validation studies were associated with the overestimation of clinical prediction rules' performance. We also aimed to evaluate whether validation studies clearly reported important methodological characteristics. METHODS: Electronic databases were searched for system...

  9. [Biomarkers in inflammatory bowel diseases].

    Science.gov (United States)

    Roblin, Xavier; Cavaille, Alaric; Clavel, Léa; Paul, Stéphane

    2014-01-01

    Fecal calprotectine is of interest for diagnosis of IBD at the beginning. CRP and fecal calprotectine are predictive of long-term response in patients treated by anti-TNF therapy. Trough levels of anti-TNF are associated to clinical remission and mucosal healing. Detectable antibodies to anti-TNF are associated with lower response to treatment. Interventional studies are waiting before optimization of treatment in function of biomarkers. Trough levels of anti-TNF help to modify our treatment (optimization or de-escalation). PMID:24373717

  10. Rorschach Prediction of Success in Clinical Training: A Second Look

    Science.gov (United States)

    Carlson, Rae

    1969-01-01

    A Rorschach Index based on ego-psychological conceptualization of an optimal personality picture predicted for 155 trainees was compared with predictions from the Miller Analogies Test (MAT) and the Strong Vocational Interest Blank (SVIB). The Index predicted success and failure more effectively. (Author)

  11. Elevated expression of the centromere protein-A(CENP-A)-encoding gene as a prognostic and predictive biomarker in human cancers.

    Science.gov (United States)

    Sun, Xia; Clermont, Pier-Luc; Jiao, Wenlin; Helgason, Cheryl D; Gout, Peter W; Wang, Yuzhuo; Qu, Sifeng

    2016-08-15

    Centromere protein-A (CENP-A), a histone-H3 variant, plays an essential role in cell division by ensuring proper formation and function of centromeres and kinetochores. Elevated CENP-A expression has been associated with cancer development. This study aimed to establish whether elevated CENP-A expression can be used as a prognostic and predictive cancer biomarker. Molecular profiling of CENP-A in human cancers was investigated using genomic, transcriptomic and patient information from databases, including COSMIC, Oncomine, Kaplan-Meier plotter and cBioPortal. A network of CENP-A co-expressed genes was derived from cBioPortal and analyzed using Ingenuity Pathway Analysis (IPA) and Oncomine protocols to explore the function of CENP-A and its predictive potential. Transcriptional and post-transcriptional regulation of CENP-A expression was analyzed in silico. It was found that CENP-A expression was elevated in 20 types of solid cancer compared with normal counterparts. Elevated CENP-A expression highly correlated with cancer progression and poor patient outcome. Genomic analysis indicated that the elevated CENP-A expression was not due to alterations in the sequence or copy number of the CENP-A gene. Furthermore, CENP-A can be regulated by key oncogenic proteins and tumor-suppressive microRNAs. CENP-A co-expression network analysis indicated that CENP-A function is associated with cell cycle progression. Oncomine analysis showed a strong correlation between elevated CENP-A expression and oncolytic response of breast cancer patients to taxane-based chemotherapy. In conclusion, elevated CENP-A expression is coupled to malignant progression of numerous types of cancer. It may be useful as a biomarker of poor patient prognosis and as a predictive biomarker for taxane-based chemotherapy. PMID:27062469

  12. Cancer Pharmacogenomics: Integrating Discoveries in Basic, Clinical and Population Sciences to Advance Predictive Cancer Care

    Science.gov (United States)

    Cancer Pharmacogenomics: Integrating Discoveries in Basic, Clinical and Population Sciences to Advance Predictive Cancer Care, a 2010 workshop sponsored by the Epidemiology and Genomics Research Program.

  13. Blood biomarkers in the early stage of cerebral ischemia.

    Science.gov (United States)

    Maestrini, I; Ducroquet, A; Moulin, S; Leys, D; Cordonnier, C; Bordet, R

    2016-03-01

    In ischemic stroke patients, blood-based biomarkers may be applied for the diagnosis of ischemic origin and subtype, prediction of outcomes and targeted treatment in selected patients. Knowledge of the pathophysiology of cerebral ischemia has led to the evaluation of proteins, neurotransmitters, nucleic acids and lipids as potential biomarkers. The present report focuses on the role of blood-based biomarkers in the early stage of ischemic stroke-within 72h of its onset-as gleaned from studies published in English in such patients. Despite growing interest in their potential role in clinical practice, the application of biomarkers for the management of cerebral ischemia is not currently recommended by guidelines. However, there are some promising clinical biomarkers, as well as the N-methyl-d-aspartate (NMDA) peptide and NMDA-receptor (R) autoantibodies that appear to identify the ischemic nature of stroke, and the glial fibrillary acidic protein (GFAP) that might be able to discriminate between acute ischemic and hemorrhagic strokes. Moreover, genomics and proteomics allow the characterization of differences in gene expression, and protein and metabolite production, in ischemic stroke patients compared with controls and, thus, may help to identify novel markers with sufficient sensitivity and specificity. Additional studies to validate promising biomarkers and to identify novel biomarkers are needed. PMID:26988891

  14. CLINICAL DATABASE ANALYSIS USING DMDT BASED PREDICTIVE MODELLING

    Directory of Open Access Journals (Sweden)

    Srilakshmi Indrasenan

    2013-04-01

    Full Text Available In recent years, predictive data mining techniques play a vital role in the field of medical informatics. These techniques help the medical practitioners in predicting various classes which is useful in prediction treatment. One of such major difficulty is prediction of survival rate in breast cancer patients. Breast cancer is a common disease these days and fighting against it is a tough battle for both the surgeons and the patients. To predict the survivability rate in breast cancer patients which helps the medical practitioner to select the type of treatment a predictive data mining technique called Diversified Multiple Decision Tree (DMDT classification is used. Additionally, to avoid difficulties from the outlier and skewed data, it is also proposed to perform the improvement of training space by outlier filtering and over sampling. As a result, this novel approach gives the survivability rate of the cancer patients based on which the medical practitioners can choose the type of treatment.

  15. The Predictive Role of Inflammatory Biomarkers in Atrial Fibrillation as Seen through Neutrophil-Lymphocyte Ratio Mirror

    OpenAIRE

    Feliciano Chanana Paquissi

    2016-01-01

    Atrial fibrillation (AF) is the most common arrhythmia and is responsible for significant disease burden worldwide. Current evidence has suggested that systemic inflammatory response plays a crucial role in the initiation, maintenance, and progression of AF. So, recent efforts have been directed in search of measurable inflammatory biomarkers as additional tools in severity and prognosis assessment of AF. A simple, and easily obtainable, inflammatory marker is the neutrophil-lymphocyte ratio ...

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

    OpenAIRE

    Elena Nikolayevna Aleksandrova; A A Novikov; Nasonov, E. L.

    2014-01-01

    Significant progress in treating immunoinflammatory rheumatic diseases (RD) is related to the design of a novel family of drugs, genetically engineered (GE) drugs. Molecular and cellular biomarkers (antibodies, indicators of acute inflammation, cytokines, chemokines, growth factors, endothelial activation markers, immunoglobulins, cryoglobulins, T- and B-cell subpopulations, products of bone and cartilage metabolism, genetic and metabolic markers) that allow one to conduct immunological monit...

  17. Galectin-3, a biomarker linking oxidative stress and inflammation with the clinical outcomes of patients with atherothrombosis

    DEFF Research Database (Denmark)

    Madrigal-Matute, Julio; Lindholt, Jes Sandal; Fernandez-Garcia, Carlos Ernesto; Benito-Martin, Alberto; Burillo, Elena; Zalba, Guillermo; Beloqui, Oscar; Llamas-Granda, Patricia; Ortiz, Alberto; Egido, Jesus; Blanco-Colio, Luis Miguel; Martin-Ventura, Jose Luis

    2014-01-01

    .24, 95% confidence interval: 1.06 to 4.73, P<0.05). CONCLUSIONS: Gal-3 extracellular levels could reflect key underlying mechanisms involved in atherosclerosis etiology, development, and plaque rupture, such as inflammation, infiltration of circulating cells and oxidative stress. Moreover, circulating...... a circulating biomarker has been demonstrated in patients with heart failure, but its importance as a biomarker in atherothrombosis is still unknown. METHODS AND RESULTS: Because Gal-3 is involved in monocyte-to-macrophage transition, we used fresh isolated monocytes and the in vitro model of...

  18. Transcriptional analysis of an E2F gene signature as a biomarker of activity of the cyclin-dependent kinase inhibitor PHA-793887 in tumor and skin biopsies from a phase I clinical study.

    Science.gov (United States)

    Locatelli, Giuseppe; Bosotti, Roberta; Ciomei, Marina; Brasca, Maria G; Calogero, Raffaele; Mercurio, Ciro; Fiorentini, Francesco; Bertolotti, Matteo; Scacheri, Emanuela; Scaburri, Angela; Galvani, Arturo; Pesenti, Enrico; De Baere, Thierry; Soria, Jean-Charles; Lazar, Vladimir; Isacchi, Antonella

    2010-05-01

    A transcriptional signature of the pan-cyclin-dependent kinase (Cdk) inhibitor PHA-793887 was evaluated as a potential pharmacodynamic and/or response biomarker in tumor and skin biopsies from patients treated in a phase I clinical study. We first analyzed the expression of a number of known E2F-dependent genes that were predicted to be modulated after Cdk2 and Cdk4 inhibition in xenograft tumor and skin samples of mice treated with the compound. This panel of 58 selected genes was then analyzed in biopsies from seven patients treated with PHA-793887 in a phase I dose escalation clinical trial in solid tumors. Quantitative real-time PCR or microarray analyses were done in paired skin and tumor biopsies obtained at baseline and at cycle 1. Analysis by quantitative real-time PCR of the signature in skin biopsies of patients treated at three different doses showed significant transcriptional downregulation with a dose-response correlation. These data show that PHA-793887 modulates genes involved in cell cycle regulation and proliferation in a clinical setting. The observed changes are consistent with its mechanism of action and correlate with target modulation in skin and with clinical benefit in tumors. PMID:20423997

  19. Predictive value of clinical history compared with urodynamic study in 1,179 women

    Directory of Open Access Journals (Sweden)

    Jorge Milhem Haddad

    2016-02-01

    Full Text Available SUMMARY Objective: to determine the positive predictive value of clinical history in comparison with urodynamic study for the diagnosis of urinary incontinence. Methods: retrospective analysis comparing clinical history and urodynamic evaluation of 1,179 women with urinary incontinence. The urodynamic study was considered the gold standard, whereas the clinical history was the new test to be assessed. This was established after analyzing each method as the gold standard through the difference between their positive predictive values. Results: the positive predictive values of clinical history compared with urodynamic study for diagnosis of stress urinary incontinence, overactive bladder and mixed urinary incontinence were, respectively, 37% (95% CI 31-44, 40% (95% CI 33-47 and 16% (95% CI 14-19. Conclusion: we concluded that the positive predictive value of clinical history was low compared with urodynamic study for urinary incontinence diagnosis. The positive predictive value was low even among women with pure stress urinary incontinence.

  20. 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.

  1. Integrating knowledge-driven and data-driven approaches in the derivation of clinical prediction rules

    OpenAIRE

    Kwiatkowska, Bogumila

    2006-01-01

    Clinical prediction rules play an important role in medical practice. They expedite diagnosis and treatment for the serious cases and limit unnecessary tests for low-probability cases. However, the creation process for prediction rules is costly, lengthy, and involves several steps: initial clinical trials, rule generation and refinement, validation, and evaluation in clinical settings. With the current development of efficient data mining algorithms and growing accessibility to a vast amount...

  2. Islet Oxygen Consumption Rate (OCR) Dose Predicts Insulin Independence in Clinical Islet Autotransplantation

    OpenAIRE

    Papas, Klearchos K.; Bellin, Melena D.; Sutherland, David E.R.; Suszynski, Thomas M.; Kitzmann, Jennifer P; Avgoustiniatos, Efstathios S.; Gruessner, Angelika C.; Mueller, Kathryn R; Beilman, Gregory J.; Balamurugan, Appakalai N.; Loganathan, Gopalakrishnan; Colton, Clark K.; Koulmanda, Maria; Weir, Gordon C; Wilhelm, Josh J.

    2015-01-01

    Background Reliable in vitro islet quality assessment assays that can be performed routinely, prospectively, and are able to predict clinical transplant outcomes are needed. In this paper we present data on the utility of an assay based on cellular oxygen consumption rate (OCR) in predicting clinical islet autotransplant (IAT) insulin independence (II). IAT is an attractive model for evaluating characterization assays regarding their utility in predicting II due to an absence of confoundin...

  3. Islet Oxygen Consumption Rate (OCR) Dose Predicts Insulin Independence in Clinical Islet Autotransplantation

    OpenAIRE

    Papas, Klearchos K; Bellin, Melena D.; Sutherland, David E. R.; Suszynski, Thomas M.; Kitzmann, Jennifer P.; Avgoustiniatos, Efstathios S.; Gruessner, Angelika C.; Mueller, Kathryn R.; Beilman, Gregory J.; Balamurugan, Appakalai N.; Gopalakrishnan Loganathan; Colton, Clark K.; Maria Koulmanda; Weir, Gordon C.; Josh J Wilhelm

    2015-01-01

    Background: Reliable in vitro islet quality assessment assays that can be performed routinely, prospectively, and are able to predict clinical transplant outcomes are needed. In this paper we present data on the utility of an assay based on cellular oxygen consumption rate (OCR) in predicting clinical islet autotransplant (IAT) insulin independence (II). IAT is an attractive model for evaluating characterization assays regarding their utility in predicting II due to an absence of confounding ...

  4. Cell-free DNA in Human Follicular Microenvironment: New Prognostic Biomarker to Predict in vitro Fertilization Outcomes

    OpenAIRE

    Traver, Sabine; Scalici, Elodie; Mullet, Tiffany; Molinari, Nicolas; Vincens, Claire; Anahory, Tal; Hamamah, Samir

    2015-01-01

    Cell-free DNA (cfDNA) fragments, detected in blood and in other biological fluids, are released from apoptotic and/or necrotic cells. CfDNA is currently used as biomarker for the detection of many diseases such as some cancers and gynecological and obstetrics disorders. In this study, we investigated if cfDNA levels in follicular fluid (FF) samples from in vitro fertilization (IVF) patients, could be related to their ovarian reserve status, controlled ovarian stimulation (COS) protocols and I...

  5. Synovial tissue and serum biomarkers of disease activity, therapeutic response and radiographic progression: analysis of a proof-of-concept randomised clinical trial of cytokine blockade.

    LENUS (Irish Health Repository)

    Rooney, Terence

    2012-02-01

    OBJECTIVES: To evaluate synovial tissue and serum biomarkers of disease activity, therapeutic response and radiographic progression during biological therapy for rheumatoid arthritis (RA). METHODS: Patients with active RA entered a randomised study of anakinra 100 mg\\/day, administered as monotherapy or in combination with pegsunercept 800 microg\\/kg twice a week. Arthroscopic synovial tissue biopsies were obtained at baseline and two further time points. Following immunohistochemical staining, selected mediators of RA pathophysiology were quantified using digital image analysis. Selected mediators were also measured in the serum. RESULTS: Twenty-two patients were randomly assigned: 11 received monotherapy and 11 combination therapy. American College of Rheumatology 20, 50 and 70 response rates were 64%, 64% and 46% with combination therapy and 36%, 9% and 0% with monotherapy, respectively. In synovial tissue, T-cell infiltration, vascularity and transforming growth factor beta (TGFbeta) expression demonstrated significant utility as biomarkers of disease activity and therapeutic response. In serum, interleukin 6 (IL-6), matrix metalloproteinase (MMP) 1, MMP-3 and tissue inhibitor of metalloproteinase 1 (TIMP-1) were most useful in this regard. An early decrease in serum levels of TIMP-1 was predictive of the later therapeutic outcome. Pretreatment tissue levels of T-cell infiltration and the growth factors vascular endothelial growth factor\\/TGFbeta, and serum levels of IL-6, IL-8, MMP-1, TIMP-1, soluble tumour necrosis factor receptor types I and II and IL-18 correlated with radiographic progression. CONCLUSIONS: Synovial tissue analysis identified biomarkers of disease activity, therapeutic response and radiographic progression. Biomarker expression in tissue was independent of the levels measured in the serum.

  6. Evaluation of 4β-Hydroxycholesterol as a Clinical Biomarker of CYP3A4 Drug Interactions Using a Bayesian Mechanism–Based Pharmacometric Model

    OpenAIRE

    Leil, T A; Kasichayanula, S; Boulton, D W; LaCreta, F

    2014-01-01

    A Bayesian mechanism–based pharmacokinetic/pharmacodynamic model of cytochrome P450 3A4 (CYP3A4) activity was developed based on a clinical study of the effects of ketoconazole and rifampin on midazolam exposure and plasma 4β-hydroxycholesterol (4βHC) concentrations. Simulations from the model demonstrated that the dynamic range of 4βHC as a biomarker of CYP3A4 induction or inhibition was narrower than that of midazolam; an inhibitor that increases midazolam area under the curve by 20-fold ma...

  7. Pressure Ulcers in Adults: Prediction and Prevention. Clinical Practice Guideline Number 3.

    Science.gov (United States)

    Agency for Health Care Policy and Research (DHHS/PHS), Rockville, MD.

    This package includes a clinical practice guideline, quick reference guide for clinicians, and patient's guide to predicting and preventing pressure ulcers in adults. The clinical practice guideline includes the following: overview of the incidence and prevalence of pressure ulcers; clinical practice guideline (introduction, risk assessment tools…

  8. Comparison of statistical and clinical predictions of functional outcome after ischemic stroke.

    Directory of Open Access Journals (Sweden)

    Douglas D Thompson

    Full Text Available To determine whether the predictions of functional outcome after ischemic stroke made at the bedside using a doctor's clinical experience were more or less accurate than the predictions made by clinical prediction models (CPMs.A prospective cohort study of nine hundred and thirty one ischemic stroke patients recruited consecutively at the outpatient, inpatient and emergency departments of the Western General Hospital, Edinburgh between 2002 and 2005. Doctors made informal predictions of six month functional outcome on the Oxford Handicap Scale (OHS. Patients were followed up at six months with a validated postal questionnaire. For each patient we calculated the absolute predicted risk of death or dependence (OHS≥3 using five previously described CPMs. The specificity of a doctor's informal predictions of OHS≥3 at six months was good 0.96 (95% CI: 0.94 to 0.97 and similar to CPMs (range 0.94 to 0.96; however the sensitivity of both informal clinical predictions 0.44 (95% CI: 0.39 to 0.49 and clinical prediction models (range 0.38 to 0.45 was poor. The prediction of the level of disability after stroke was similar for informal clinical predictions (ordinal c-statistic 0.74 with 95% CI 0.72 to 0.76 and CPMs (range 0.69 to 0.75. No patient or clinician characteristic affected the accuracy of informal predictions, though predictions were more accurate in outpatients.CPMs are at least as good as informal clinical predictions in discriminating between good and bad functional outcome after ischemic stroke. The place of these models in clinical practice has yet to be determined.

  9. Using biomarkers to improve detection of Alzheimer’s disease

    Science.gov (United States)

    Biagioni, Milton C; Galvin, James E

    2011-01-01

    SUMMARY Disease-modifying approaches for Alzheimer’s disease (AD) might be most effective when initiated very early in the course, before the pathologic burden and neuronal and synaptic degeneration make it unlikely that halting disease progression would have a significant impact on patient outcomes. Biomarkers of disease may provide important avenues of research to enhance the diagnosis of individuals with early AD and could assist in the identification of those individuals at risk for developing AD. However, for such biomarkers to become clinically useful, long-term follow-up studies are necessary to evaluate the relevance of cross-sectional biomarker changes to the longitudinal course of the disease. The objective of this article is to review recent progress in AD biomarkers for the early diagnosis, classification, progression and prediction of AD and their usefulness in new treatment trials. PMID:22076127

  10. A multi-centre phase IIa clinical study of predictive testing for preeclampsia

    DEFF Research Database (Denmark)

    Navaratnam, Kate; Alfirevic, Zarko; Baker, Philip N; Gluud, Christian; Grüttner, Berthold; Kublickiene, Karolina; Zeeman, Gerda; Kenny, Louise C

    2013-01-01

    5% of first time pregnancies are complicated by pre-eclampsia, the leading cause of maternal death in Europe. No clinically useful screening test exists; consequentially clinicians are unable to offer targeted surveillance or preventative strategies. IMPROvED Consortium members have pioneered a...... personalised medicine approach to identifying blood-borne biomarkers through recent technological advancements, involving mapping of the blood metabolome and proteome. The key objective is to develop a sensitive, specific, high-throughput and economically viable early pregnancy screening test for pre-eclampsia....

  11. The importance of biomarkers in neonatology.

    Science.gov (United States)

    Mussap, M; Noto, A; Cibecchini, F; Fanos, V

    2013-02-01

    Despite a 35% decline in the mortality rate for infants aged years over the past two decades, every year nearly 40% of all deaths in this age group occur in the neonatal period, defined as the first 28 days of life. New knowledge on molecular and biochemical pathways in neonatal diseases will lead to the discovery of new candidate biomarkers potentially useful in clinical practice. In the era of personalized medicine, biomarkers may play a strategic role in accelerating the decline in neonatal mortality by assessing the risk of developing neonatal diseases, by implementing tailored therapeutic treatment, and by predicting the clinical outcome. However, there is an urgent need to reduce the gap in translating newly acquired knowledge from bench to bedside. Traditional and candidate biomarkers for neonatal sepsis and necrotizing enterocolitis will be discussed in this review, such as C-reactive protein (CRP), procalcitonin (PCT), serum amyloid A (SAA), soluble form of CD14 subtype presepsin (sCD14-ST), lipolysaccharide binding protein (LBP), angiopoietins (Ang)-1 and -2, soluble form of triggering receptor expressed on myeloid cells (sTREM-1), soluble form of urokinase-type plasminogen activator receptor (suPAR), platelet-activating factor (PAF) and calprotectin. New frontiers in managing critically ill newborns may be opened by metabolomics, a diagnostic tool based on the recognition of metabolites contained in biological fluids. Metabolomics represents the passage from a descriptive science to a predictive science, having the potential to translate benchtop research to real clinical benefits. PMID:23164809

  12. Circulating Endothelial-Derived Activated Microparticle: A Useful Biomarker for Predicting One-Year Mortality in Patients with Advanced Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Chin-Chou Wang

    2014-01-01

    Full Text Available Background. This study tested the hypothesis that circulating microparticles (MPs are useful biomarkers for predicting one-year mortality in patients with end-stage non-small cell lung cancer (ES-NSCLC. Methods and Results. One hundred seven patients were prospectively enrolled into the study between April 2011 and February 2012, and each patient received regular follow-up after enrollment. Levels of four MPs in circulation, (1 platelet-derived activated MPs (PDAc-MPs, (2 platelet-derived apoptotic MPs (PDAp-MPs, (3 endothelial-derived activated MPs (EDAc-MPs, and (4 endothelial-derived apoptotic MPs (EDAp-MPs, were measured just after the patient was enrolled into the study using flow cytometry. Patients who survived for more than one year were categorized into group 1 (n=56 (one-year survivors and patients who survived less than one year were categorized into group 2 (n=51 (one-year nonsurvivors. Male gender, incidence of liver metastasis, progression of disease after first-line treatment, poor performance status, and the Charlson comorbidity index were significantly higher in group 2 than in group 1 (all P<0.05. Additionally, as measured by flow cytometry, only the circulating level of EDAc-MPs was found to be significantly higher in group 2 than in group 1 (P=0.006. Multivariate analysis demonstrated that circulating level of EDAc-MPs along with brain metastasis and male gender significantly and independently predictive of one-year mortality (all P<0.035. Conclusion. Circulating EDAc-MPs may be a useful biomarker predictive of one-year morality in ES-NSCLC patients.

  13. Somatic cell count distributions during lactation predict clinical mastitis

    NARCIS (Netherlands)

    Green, M.J.; Green, L.E.; Schukken, Y.H.; Bradley, A.J.; Peeler, E.J.; Barkema, H.W.; Haas, de Y.; Collis, V.J.; Medley, G.F.

    2004-01-01

    This research investigated somatic cell count (SCC) records during lactation, with the purpose of identifying distribution characteristics (mean and measures of variation) that were most closely associated with clinical mastitis. Three separate data sets were used, one containing quarter SCC (n = 14

  14. The Prediction of Academic and Clinical Performance in Medical School

    Science.gov (United States)

    Gough, Harrison G.; Hall, Wallace B.

    1975-01-01

    A study of medical student performance showed the clinical performance factor more or less unpredictable from aptitude and premedical academic achievement indices while the academic performance factor was forecast with acceptable accuracy by equations based on the Medical College Admissions Test and premedical grade point average. (JT)

  15. 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.

  16. Models of Hepatocellular Carcinoma and Biomarker Strategy

    International Nuclear Information System (INIS)

    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

  17. Early sorafenib-related adverse events predict therapy response of TACE plus sorafenib: A multicenter clinical study of 606 HCC patients.

    Science.gov (United States)

    Zhao, Yan; Li, Hailiang; Bai, Wei; Liu, Jueshi; Lv, Weifu; Sahu, Sonia; Guan, Sheng; Qin, Xiao; Wang, Wenhui; Ren, Weixin; Mu, Wei; Guo, Weidong; Gu, Shanzhi; Ma, Yilong; Yin, Zhanxin; Guo, Wengang; Wang, Wenjun; Wang, Yongji; Duran, Rafael; Fan, Daiming; Zhang, Zhuoli; Han, Guohong

    2016-08-15

    The purpose of our study was to test the hypothesis that sorafenib-related dermatologic adverse events (AEs) as an early biomarker can predict the long-term outcomes following the combination therapy of transarterial chemoembolization (TACE) plus sorafenib (TACE-S). The intermediate-stage hepatocellular carcinoma patients who received either TACE-S or TACE-alone treatment were consecutively included into analysis. In the TACE-S group, patients with ≥ grade 2 dermatologic AEs within the first month of sorafenib initiation were defined as responders; whereas those with OS) of the responders was significantly longer than that of nonresponders (28.9 months vs. 16.8 months, respectively; p = 0.004). Multivariate analysis demonstrated that nonresponders were significantly associated with an increased risk of death compared with responders (HR = 1.9; 95% confidence Interval-CI: 1.3-2.7; p = 0.001). The survival analysis showed that the median OS was 27.9 months (95% CI: 25.0-30.8) among responders treated with TACE-S vs.18.3 months (95% CI: 14.5-22.1) among those who received TACE-alone (p = 0.046). The median time to progression was 13.1 months (95% CI: 4.4-21.8) in the TACE-S group, a duration that was significantly longer than that in the TACE-alone group [5 months (95% CI: 6.4-13.3), p = 0.014]. This study demonstrated that sorafenib-related dermatologic AEs are clinical biomarkers to identify responders from all of the patients for TACE-S therapy. Sorafenib-related dermatologic AEs, clinical biomarkers, can predict the efficacy of TACE-S in future randomized controlled trials. PMID:27038145

  18. Role of α-II-spectrin breakdown products in the prediction of the severity and clinical outcome of acute traumatic brain injury

    Science.gov (United States)

    CHEN, SHANGYU; SHI, QIANKUN; ZHENG, SHUYUN; LUO, LIANGSHEN; YUAN, SHOUTAO; WANG, XIANG; CHENG, ZIHAO; ZHANG, WENHAO

    2016-01-01

    αII-spectrin breakdown products are regarded as potential biomarkers for traumatic brain injury (TBI). The aim of the present study was to further evaluate these biomarkers by assessing their clinical utility in predicting the severity of injury and clinical outcome of patients with TBI. Eligible patients with acute TBI (n=17), defined by a Glasgow Coma Scale (GCS) score of ≤8, were enrolled. Ventricular cerebrospinal fluid (CSF) was sampled from each patient at 24, 72 and 120 h following TBI. An immunoblot assay was used to determine the concentrations of SBDPs in the CSF samples. The concentrations of SBDPs combined with the GCS score at 24 h after injury and the Glasgow Outcome Score (GOS) at 30 days after injury were compared and analyzed. The levels of SBDPs in CSF were markedly increased following acute TBI in comparison with those in the control group. In the early period after TBI, the levels of SBDPs were closely associated with GCS score. Comparisons of the SBDP levels with the severity of injury revealed significant differences between patients with the most severe brain injury and patients with severe brain injury in the first 24 h post-injury (Pinjury. The levels of SBDPs differed significantly between patients grouped according to prognosis (Pinjury and clinical outcome of patients.

  19. An update on biomarkers in axial spondyloarthritis.

    Science.gov (United States)

    Prajzlerová, Klára; Grobelná, Kristýna; Pavelka, Karel; Šenolt, Ladislav; Filková, Mária

    2016-06-01

    Axial spondyloarthritis is a chronic inflammatory disease with the onset at a young age, and, if undiagnosed and untreated, it may result in permanent damage and lifelong disability. Rates of early diagnosis have improved, due in particular to the addition of magnetic resonance imaging into the diagnostic armamentaria; however, it is costly, not widely available, and requires experienced readers to interpret the findings. In addition to clinical measures and imaging techniques, biomarkers that will be described in this review may represent useful tools for diagnosis, monitoring disease activity and outcomes as well as therapeutic responses. Currently, HLA-B27 remains the best genetic biomarker for making a diagnosis, while CRP currently appears to be the best circulating measure for assessing disease activity, predicting structural progression and therapeutic response. Interestingly, key molecules in the pathogenesis of the disease and essential therapeutic targets, such as tumour necrosis factor (TNF)α, interleukin (IL)-17 and IL-23, show only limited association with disease characteristics or disease progression. Some genetic biomarkers and particularly anti-CD74 antibodies, may become a promising tool for the early diagnosis of axSpA. Further biomarkers, such as matrix metalloproteinases (MMP)-3, calprotectin (S100A8/9), vascular endothelial growth factor (VEGF), C-terminal telopeptide of type II collagen (CTX-II) or dickkopf-1 (DKK-1), are not sufficient to reflect disease activity, but may predict spinal structural progression. In addition, recent data have shown that monitoring calprotectin might represent a valuable biomarker of therapeutic response. However, all of these results need to be confirmed in large cohort studies prior to use in daily clinical practice. PMID:26851549

  20. Strategies for modern biomarker and drug development in oncology

    OpenAIRE

    Alan D. Smith; Roda, Desam; Yap, Timothy A.

    2014-01-01

    Technological advancements in the molecular characterization of cancers have enabled researchers to identify an increasing number of key molecular drivers of cancer progression. These discoveries have led to multiple novel anticancer therapeutics, and clinical benefit in selected patient populations. Despite this, the identification of clinically relevant predictive biomarkers of response continues to lag behind. In this review, we discuss strategies for the molecular characterization of canc...

  1. Cognitive impairment effects of early life stress in adolescents can be predicted with early biomarkers: Impacts of sex, experience, and cytokines.

    Science.gov (United States)

    Grassi-Oliveira, Rodrigo; Honeycutt, Jennifer A; Holland, Freedom H; Ganguly, Prabarna; Brenhouse, Heather C

    2016-09-01

    Childhood adversity increases vulnerability to psychiatric disorders that emerge in adolescence, in a sex-dependent manner. Early adversity modeled in rodents with maternal separation (MS) affects cognition and medial prefrontal cortex (mPFC) circuitry. Humans and animals exposed to early life adversity also display heightened circulating inflammatory cytokines, however the predictive relationship of these early measures with later behavioral deficits is unknown. Here, male and female rats were exposed to MS or control rearing during the postnatal period (P2-21). Blood samples were taken at distinct developmental time points for analysis of the pro-inflammatory cytokine IL-1β and the anti-inflammatory cytokines IL-4, and IL-10, followed by win-shift cognitive testing and analysis of mPFC parvalbumin (PVB) immunofluorescent interneurons in adolescence. Regression analyses were conducted to explore the relationship between early cytokines and adolescent behavioral measures. We observed sex- and age-dependent effects of MS on circulating cytokines. MS also yielded adolescent decreases in mPFC PVB and cognitive deficits, which were predicted by early cytokine expression in a sex- and experience-dependent manner. Taken together, the present data reveals that circulating cytokines and PVB levels are predictive of adolescent cognitive deficits, and therefore provide compelling evidence for a putative role of early biomarkers in mediating MS-induced behavioral dysfunction. Importantly, predictive relationships often depended on sex and on MS history, suggesting that early life experiences may yield individualistic mechanisms of vulnerability compared to the general population. PMID:27235636

  2. Impact of clinical context on acute kidney injury biomarker performances: differences between neutrophil gelatinase-associated lipocalin and L-type fatty acid-binding protein.

    Science.gov (United States)

    Asada, Toshifumi; Isshiki, Rei; Hayase, Naoki; Sumida, Maki; Inokuchi, Ryota; Noiri, Eisei; Nangaku, Masaomi; Yahagi, Naoki; Doi, Kent

    2016-01-01

    Application of acute kidney injury (AKI) biomarkers with consideration of nonrenal conditions and systemic severity has not been sufficiently determined. Herein, urinary neutrophil gelatinase-associated lipocalin (NGAL), L-type fatty acid-binding protein (L-FABP) and nonrenal disorders, including inflammation, hypoperfusion and liver dysfunction, were evaluated in 249 critically ill patients treated at our intensive care unit. Distinct characteristics of NGAL and L-FABP were revealed using principal component analysis: NGAL showed linear correlations with inflammatory markers (white blood cell count and C-reactive protein), whereas L-FABP showed linear correlations with hypoperfusion and hepatic injury markers (lactate, liver transaminases and bilirubin). We thus developed a new algorithm by combining urinary NGAL and L-FABP with stratification by the Acute Physiology and Chronic Health Evaluation score, presence of sepsis and blood lactate levels to improve their AKI predictive performance, which showed a significantly better area under the receiver operating characteristic curve [AUC-ROC 0.940; 95% confidential interval (CI) 0.793-0.985] than that under NGAL alone (AUC-ROC 0.858, 95% CI 0.741-0.927, P = 0.03) or L-FABP alone (AUC-ROC 0.837, 95% CI 0.697-0.920, P = 0.007) and indicated that nonrenal conditions and systemic severity should be considered for improved AKI prediction by NGAL and L-FABP as biomarkers. PMID:27605390

  3. Emerging Risk Biomarkers in Cardiovascular Diseases and Disorders

    Directory of Open Access Journals (Sweden)

    Ravi Kant Upadhyay

    2015-01-01

    Full Text Available Present review article highlights various cardiovascular risk prediction biomarkers by incorporating both traditional risk factors to be used as diagnostic markers and recent technologically generated diagnostic and therapeutic markers. This paper explains traditional biomarkers such as lipid profile, glucose, and hormone level and physiological biomarkers based on measurement of levels of important biomolecules such as serum ferritin, triglyceride to HDLp (high density lipoproteins ratio, lipophorin-cholesterol ratio, lipid-lipophorin ratio, LDL cholesterol level, HDLp and apolipoprotein levels, lipophorins and LTPs ratio, sphingolipids, Omega-3 Index, and ST2 level. In addition, immunohistochemical, oxidative stress, inflammatory, anatomical, imaging, genetic, and therapeutic biomarkers have been explained in detail with their investigational specifications. Many of these biomarkers, alone or in combination, can play important role in prediction of risks, its types, and status of morbidity. As emerging risks are found to be affiliated with minor and microlevel factors and its diagnosis at an earlier stage could find CVD, hence, there is an urgent need of new more authentic, appropriate, and reliable diagnostic and therapeutic markers to confirm disease well in time to start the clinical aid to the patients. Present review aims to discuss new emerging biomarkers that could facilitate more authentic and fast diagnosis of CVDs, HF (heart failures, and various lipid abnormalities and disorders in the future.

  4. Emerging risk biomarkers in cardiovascular diseases and disorders.

    Science.gov (United States)

    Upadhyay, Ravi Kant

    2015-01-01

    Present review article highlights various cardiovascular risk prediction biomarkers by incorporating both traditional risk factors to be used as diagnostic markers and recent technologically generated diagnostic and therapeutic markers. This paper explains traditional biomarkers such as lipid profile, glucose, and hormone level and physiological biomarkers based on measurement of levels of important biomolecules such as serum ferritin, triglyceride to HDLp (high density lipoproteins) ratio, lipophorin-cholesterol ratio, lipid-lipophorin ratio, LDL cholesterol level, HDLp and apolipoprotein levels, lipophorins and LTPs ratio, sphingolipids, Omega-3 Index, and ST2 level. In addition, immunohistochemical, oxidative stress, inflammatory, anatomical, imaging, genetic, and therapeutic biomarkers have been explained in detail with their investigational specifications. Many of these biomarkers, alone or in combination, can play important role in prediction of risks, its types, and status of morbidity. As emerging risks are found to be affiliated with minor and microlevel factors and its diagnosis at an earlier stage could find CVD, hence, there is an urgent need of new more authentic, appropriate, and reliable diagnostic and therapeutic markers to confirm disease well in time to start the clinical aid to the patients. Present review aims to discuss new emerging biomarkers that could facilitate more authentic and fast diagnosis of CVDs, HF (heart failures), and various lipid abnormalities and disorders in the future. PMID:25949827

  5. Developing Outcomes Assessments as Endpoints for Registrational Clinical Trials of Antibacterial Drugs: 2015 Update From the Biomarkers Consortium of the Foundation for the National Institutes of Health.

    Science.gov (United States)

    Talbot, George H; Powers, John H; Hoffmann, Steven C

    2016-03-01

    One important component in determining the benefits and harms of medical interventions is the use of well-defined and reliable outcome assessments as endpoints in clinical trials. Improving endpoints can better define patient benefits, allowing more accurate assessment of drug efficacy and more informed benefit-vs-risk decisions; another potential plus is facilitating efficient trial design. Since our first report in 2012, 2 Foundation for the National Institutes of Health Biomarkers Consortium Project Teams have continued to develop outcome assessments for potential uses as endpoints in registrational clinical trials of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. In addition, the teams have initiated similar work in the indications of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. This report provides an update on progress to date in these 4 diseases. PMID:26668337

  6. Do clinical prediction models improve concordance of treatment decisions in reproductive medicine?

    NARCIS (Netherlands)

    J.W. van der Steeg; P. Steures; M.J.C. Eijkemans; J.D.F. Habbema; P.M.M. Bossuyt; P.G.A. Hompes; F. van der Veen; B.W.J. Mol

    2006-01-01

    Objective To assess whether the use of clinical prediction models improves concordance between gynaecologists with respect to treatment decisions in reproductive medicine. Design We constructed 16 vignettes of subfertile couples by varying fertility history, postcoital test, sperm motility, follicle

  7. Locus heterogeneity for Waardenburg syndrome is predictive of clinical subtypes

    Energy Technology Data Exchange (ETDEWEB)

    Farrer, L.A.; Hoth, C. [Boston Univ. School of Medicine, MA (United States); Arnos, K.S. [Galludet Univ., Washington, DC (United States); Asher, J.H. Jr.; Friedman, T.B. [Michigan State Univ., East Lansing, MI (United States); Grundfast, K.M.; Lalwani, A.K. [National Institute on Deafness and Other Communication Disorders, Bethesda, MD (United States); Greenberg, J. [Univ. of Cape Town (South Africa); Diehl, S.R. [and others

    1994-10-01

    Waardenburg syndrome (WS) is a dominantly inherited and clinically variable syndrome of deafness, pigmentary changes, and distinctive facial features. Clinically, WS type I (WS1) is differentiated from WS type II (WS2) by the high frequency of dystopia canthorum in the family. In some families, WS is caused by mutations in the PAX3 gene on chromosome 2q. We have typed microsatellite markers within and flanking PAX3 in 41 WS1 kindreds and 26 WS2 kindreds in order to estimate the proportion of families with probable mutations in PAX3 and to study the relationship between phenotypic and genotypic heterogeneity. Evaluation of heterogeneity in location scores obtained by multilocus analysis indicated that WS is linked to PAX3 in 60% of all WS families and in 100% of WS1 families. None of the WS2 families were linked. In those families in which equivocal lod scores (between -2 and +1) were found, PAX3 mutations have been identified in 5 of the 15 WS1 families but in none of the 4 WS2 families. Although preliminary studies do not suggest any association between the phenotype and the molecular pathology in 20 families with known PAX3 mutations and in four patients with chromosomal abnormalities in the vicinity of PAX3, the presence of dystopia in multiple family members is a reliable indicator for identifying families likely to have a defect in PAX3. 59 refs., 3 figs., 5 tabs.

  8. Biomarkers for Response to Neoadjuvant Chemoradiation for Rectal Cancer

    International Nuclear Information System (INIS)

    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.

  9. Outcome prediction in pneumonia induced ALI/ARDS by clinical features and peptide patterns of BALF determined by mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Jochen Frenzel

    Full Text Available BACKGROUND: Peptide patterns of bronchoalveolar lavage fluid (BALF were assumed to reflect the complex pathology of acute lung injury (ALI/acute respiratory distress syndrome (ARDS better than clinical and inflammatory parameters and may be superior for outcome prediction. METHODOLOGY/PRINCIPAL FINDINGS: A training group of patients suffering from ALI/ARDS was compiled from equal numbers of survivors and nonsurvivors. Clinical history, ventilation parameters, Murray's lung injury severity score (Murray's LISS and interleukins in BALF were gathered. In addition, samples of bronchoalveolar lavage fluid were analyzed by means of hydrophobic chromatography and MALDI-ToF mass spectrometry (MALDI-ToF MS. Receiver operating characteristic (ROC analysis for each clinical and cytokine parameter revealed interleukin-6>interleukin-8>diabetes mellitus>Murray's LISS as the best outcome predictors. Outcome predicted on the basis of BALF levels of interleukin-6 resulted in 79.4% accuracy, 82.7% sensitivity and 76.1% specificity (area under the ROC curve, AUC, 0.853. Both clinical parameters and cytokines as well as peptide patterns determined by MALDI-ToF MS were analyzed by classification and regression tree (CART analysis and support vector machine (SVM algorithms. CART analysis including Murray's LISS, interleukin-6 and interleukin-8 in combination was correct in 78.0%. MALDI-ToF MS of BALF peptides did not reveal a single identifiable biomarker for ARDS. However, classification of patients was successfully achieved based on the entire peptide pattern analyzed using SVM. This method resulted in 90% accuracy, 93.3% sensitivity and 86.7% specificity following a 10-fold cross validation (AUC = 0.953. Subsequent validation of the optimized SVM algorithm with a test group of patients with unknown prognosis yielded 87.5% accuracy, 83.3% sensitivity and 90.0% specificity. CONCLUSIONS/SIGNIFICANCE: MALDI-ToF MS peptide patterns of BALF, evaluated by appropriate

  10. An integrative clinical database and diagnostics platform for biomarker identification and analysis in ion mobility spectra of human exhaled air

    DEFF Research Database (Denmark)

    Schneider, Till; Hauschild, Anne-Christin; Baumbach, Jörg Ingo;

    2013-01-01

    Over the last decade the evaluation of odors and vapors in human breath has gained more and more attention, particularly in the diagnostics of pulmonary diseases. Ion mobility spectrometry coupled with multi-capillary columns (MCC/IMS), is a well known technology for detecting volatile organic...... compounds (VOCs) in air. It is a comparatively inexpensive, non-invasive, high-throughput method, which is able to handle the moisture that comes with human exhaled air, and allows for characterizing of VOCs in very low concentrations. To identify discriminating compounds as biomarkers, it is necessary to...

  11. Precision and Negative Predictive Value of Links between ClinicalTrials.gov and PubMed

    OpenAIRE

    Huser, Vojtech; Cimino, James J.

    2012-01-01

    One of the goals of translational science is to shorten the time from discovery to clinical use. Clinical trial registries were established to increase transparency in completed and ongoing clinical trials, and they support linking trials with resulting publications. We set out to investigate precision and negative predictive value (NPV) of links between ClinicalTrials.gov (CT.gov) and PubMed. CT.gov has been established to increase transparency in clinical trials and the link to PubMed is cr...

  12. The predictive value of plasma biomarkers in discharged heart failure patients: role of troponin I/T.

    Science.gov (United States)

    Perna, Eduardo R; Címbaro Canella, Juan P; Coronel, Maria L; Macin, Stella M

    2016-04-01

    Hospitalization for heart failure (HHF) is a frequent manifestation of chronic heart failure (CHF), and represents the moment of greatest impact on costs and on risk for the patient, in particular after discharge. Contributing factors to this disappointingly high postdischarge event rate include the incomplete relief of fluid overload, insufficient patient education, the lack of implementation of evidence-based therapies, poor follow-up and inadequate risk stratification before leaving hospital. Among available tools, different biomarkers have been tested, including cardiac troponin (cTn). The value of cTn to monitoring and to stratifying risk before discharge has been evaluated by mean of three strategies: a single measurement before discharge, monitoring with serial sampling during hospitalization, and comparing admission and predischarge values to establishing the cTn "delta". Acute heart failure syndrome (AHFS) is an active and continuing process, which starts at admission, but its evolution might be unpredictable, and the prevention of ongoing myocardial damage (OMD) might be one of the important targets to improve prognosis. OMD is also a dynamic process and can be detected in CHF and HHF, at different moments and in diverse magnitudes, justifying the cTn monitoring. The favorable effect of drugs on cTn release and its association with better prognosis have increased our expectation for the role of serial determination in HHF patients. PMID:26603616

  13. Sixty-Six Years of Research on the Clinical Versus Actuarial Prediction of Violence

    Science.gov (United States)

    Hilton, N. Zoe; Harris, Grant T.; Rice, Marnie E.

    2006-01-01

    In their meta-analysis of clinical versus statistical prediction models, Aegisdottir et al. (this issue) extended previous findings of statistical-method superiority across such variables as clinicians' experience and familiarity with data. In this reaction, the authors are particularly interested in violence prediction, which yields the greatest…

  14. 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...... literature, there are no specific proteomic biomarkers capable of accurately predicting PTB....

  15. Biomarkers for drug development in early psychosis: Current issues and promising directions.

    Science.gov (United States)

    Goff, Donald C; Romero, Klaus; Paul, Jeffrey; Mercedes Perez-Rodriguez, M; Crandall, David; Potkin, Steven G

    2016-06-01

    A major goal of current research in schizophrenia is to understand the biology underlying onset and early progression and to develop interventions that modify these processes. Biomarkers can play a critical role in identifying disease state, factors contributing to underlying progression, as well as predicting and monitoring response to treatment. Once biomarker-based therapeutics are established, biomarkers can guide treatment selection. It is increasingly clear that a wide range of potential biomarkers should be examined in schizophrenia, given the large number of genetic and environmental factors that have been identified as risk factors. New models for analysis of biomarkers are needed that represent the central nervous system as a highly complex, dynamic, and interactive system. Many tools are available with which to study relevant brain chemistry, but most are indirect measures and represent only a small fraction of the potential etiologic factors contributing to the molecular, structural and functional components of schizophrenia. This review represents the work of the International Society for CNS Clinical Trials and Methodology (ISCTM) Biomarkers Working Group. It discusses advantages and disadvantages of different categories of biomarkers and provides a summary of evidence that biomarkers representing inflammation, oxidative stress, endocannabinoids, glucocorticoid, and biogenic amines systems are dysregulated and potentially interactive in early phase schizophrenia. As has been recently demonstrated in several neurodevelopmental and neurodegenerative disorders, a multi-modal, longitudinal strategy involving a diverse array of biomarkers and new approaches to statistical modeling are needed to improve early interventions based on the fuller understanding. PMID:27005595

  16. Biomarker- versus drug-driven tumor growth inhibition models: an equivalence analysis.

    Science.gov (United States)

    Sardu, Maria Luisa; Poggesi, Italo; De Nicolao, Giuseppe

    2015-12-01

    The mathematical modeling of tumor xenograft experiments following the dosing of antitumor drugs has received much attention in the last decade. Biomarker data can further provide useful insights on the pathological processes and be used for translational purposes in the early clinical development. Therefore, it is of particular interest the development of integrated pharmacokinetic-pharmacodynamic (PK-PD) models encompassing drug, biomarker and tumor-size data. This paper investigates the reciprocal consistency of three types of models: drug-to-tumor, such as established drug-driven tumor growth inhibition (TGI) models, drug-to-biomarker, e.g. indirect response models, and biomarker-to-tumor, e.g. the more recent biomarker-driven TGI models. In particular, this paper derives a mathematical relationship that guarantees the steady-state equivalence of the cascade of drug-to-biomarker and biomarker-to-tumor models with a drug-to-tumor TGI model. Using the Simeoni TGI model as a reference, conditions for steady-state equivalence are worked out and used to derive a new biomarker-driven model. Simulated and real data are used to show that in realistic cases the steady-state equivalence extends also to transient responses. The possibility of predicting the drug-to-tumor potency of a new candidate drug based only on biomarker response is discussed. PMID:26209955

  17. Clinical parameters predictive of malignancy of thyroid follicular neoplasms

    International Nuclear Information System (INIS)

    Needle aspiration biopsy is commonly employed in the evaluation of thyroid nodules. Unfortunately, the cytologic finding of a 'follicular neoplasm' does not distinguish between a thyroid adenoma and a follicular cancer. The purpose of this study was to identify clinical parameters that characterize patients with an increased risk of having a thyroid follicular cancer who preoperatively have a 'follicular neoplasm' identified by needle aspiration biopsy. A total of 395 patients initially treated at Vancouver General Hospital and the British Columbia Cancer Agency between the years of 1965 and 1985 were identified and their data were entered into a computer database. Patients with thyroid adenomas were compared to patients with follicular cancer using the chi-square test and Student's t-test. Statistically significant parameters that distinguished patients at risk of having a thyroid cancer (p less than 0.05) included age greater than 50 years, nodule size greater than 3 cm, and a history of neck irradiation. Sex, family history of goiter or neoplasm, alcohol and tobacco use, and use of exogenous estrogen were not significant parameters. Patients can be identified preoperatively to be at an increased risk of having a follicular cancer and accordingly appropriate surgical resection can be planned

  18. Use of clinical movement screening tests to predict injury in sport

    OpenAIRE

    Chimera, Nicole J; Warren, Meghan

    2016-01-01

    Clinical movement screening tests are gaining popularity as a means to determine injury risk and to implement training programs to prevent sport injury. While these screens are being used readily in the clinical field, it is only recently that some of these have started to gain attention from a research perspective. This limits applicability and poses questions to the validity, and in some cases the reliability, of the clinical movement tests as they relate to injury prediction, intervention,...

  19. Systematic Evaluation of the Prognostic Impact and Intratumour Heterogeneity of Clear Cell Renal Cell Carcinoma Biomarkers

    DEFF Research Database (Denmark)

    Gulati, Sakshi; Martinez, Pierre; Joshi, Tejal; Birkbak, Nicolai Juul; Santos, Claudio R.; Rowan, Andrew J.; Pickering, Lisa; Gore, Martin; Larkin, James; Szallasi, Zoltan Imre; Bates, Paul A.; Swanton, Charles; Gerlinger, Marco

    2014-01-01

    BackgroundCandidate biomarkers have been identified for clear cell renal cell carcinoma (ccRCC) patients, but most have not been validated. ObjectiveTo validate published ccRCC prognostic biomarkers in an independent patient cohort and to assess intratumour heterogeneity (ITH) of the most promising...... the ability of published biomarkers to predict the survival of patients with clear cell kidney cancer in an independent patient cohort. Only one molecular test adds prognostic information to routine clinical assessments. This marker showed good and poor prognosis results within most individual cancers...

  20. Regular consumption of vitamin D-fortified yogurt drink (Doogh improved endothelial biomarkers in subjects with type 2 diabetes: a randomized double-blind clinical trial

    Directory of Open Access Journals (Sweden)

    Shab-Bidar Sakineh

    2011-11-01

    Full Text Available Abstract Background Endothelial dysfunction has been proposed as the underlying cause of diabetic angiopathy that eventually leads to cardiovascular disease, the major cause of death in diabetes. We recently demonstrated the ameliorating effect of regular vitamin D intake on the glycemic status of patients with type 2 diabetes (T2D. In this study, the effects of improvement of vitamin D status on glycemic status, lipid profile and endothelial biomarkers in T2D subjects were investigated. Methods Subjects with T2D were randomly allocated to one of the two groups to receive either plain yogurt drink (PYD; containing 170 mg calcium and no vitamin D/250 mL, n1 = 50 or vitamin D3-fortified yogurt drink (FYD; containing 170 mg calcium and 500 IU/250 mL, n2 = 50 twice a day for 12 weeks. Anthropometric measures, glycemic status, lipid profile, body fat mass (FM and endothelial biomarkers including serum endothelin-1, E-selectin and matrix metalloproteinase (MMP-9 were evaluated at the beginning and after the 12-week intervention period. Results The intervention resulted in a significant improvement in fasting glucose, the Quantitative Insulin Check Index (QUICKI, glycated hemoglobin (HbA1c, triacylglycerols, high-density lipoprotein cholesterol (HDL-C, endothelin-1, E-selectin and MMP-9 in FYD compared to PYD (P P = 0.028; -3.8 ± 7.3 versus 0.95 ± 8.3, P = 0.003 and -2.3 ± 3.7 versus 0.44 ± 7.1 ng/mL, respectively, P P = 0.009 and P = 0.005, respectively but disappeared for E-selectin (P = 0.092. On the contrary, after controlling for serum 25(OHD, the differences disappeared for endothelin-1(P = 0.066 and MMP-9 (P = 0.277 but still remained significant for E-selectin (P = 0.011. Conclusions Ameliorated vitamin D status was accompanied by improved glycemic status, lipid profile and endothelial biomarkers in T2D subjects. Our findings suggest both direct and indirect ameliorating effects of vitamin D on the endothelial biomarkers. Trial registration

  1. Prognosis after Acute Myocardial Infarction as Predicted by C-reactive Protein and Clinical Variables

    Directory of Open Access Journals (Sweden)

    Angelo Modica MD, PhD

    2013-02-01

    Full Text Available Background:Raised concentrations of C-reactive protein (CRP have been reported to be strongly related to an adverse long term prognosis in patients with acute myocardial infarction (AMI. However, adjustments for clinical variables as well as interaction between variables have been incomplete. The aims of this study were to examine the predictive value of baseline concentrations of CRP for mortality after adjustment for important clinical variables and to compare the clinical usefulness of CRP with easily available clinical variables in the prediction of long term survival.Methods:Five hundred and thirty-one patients with AMI were included. A blood sample for CRP was obtained on admission. All patients were followed for a minimum of two years and death of any cause was recorded as the study end point.Results:In logistic regression analysis, the interaction term Age by Killip class > 1, the variable glomerular filtration rate as well as the interaction term Age by Atrial fibrillation were retained. The resulting model correctly predicted death or not in 81% of the patients. CRP did not contribute to the final model.Conclusions:CRP does not independently predict long-term mortality after an AMI after adjustments for clinical variables and interaction. CRP has no value beyond clinical variables in predicting death after AMI.

  2. Evidence that the blood biomarker SNTF predicts brain imaging changes and persistent cognitive dysfunction in mild TBI patients

    Directory of Open Access Journals (Sweden)

    Robert eSiman

    2013-11-01

    Full Text Available Although mild traumatic brain injury (mTBI, or concussion, is not typically associated with abnormalities on computed tomography (CT, it nevertheless causes persistent cognitive dysfunction for many patients. Consequently, new prognostic methods for mTBI are needed to identify at-risk cases, especially at an early and potentially treatable stage. Here, we quantified plasma levels of the neurodegeneration biomarker calpain-cleaved alphaII-spectrin N-terminal fragment (SNTF from 38 participants with CT-negative mTBI, orthopedic injury (OI and normal uninjured controls (age range 12-30 years, and compared them with findings from diffusion tensor magnetic resonance imaging (DTI and long-term cognitive assessment. SNTF levels were at least twice the lower limit of detection in 7 of 17 mTBI cases and in 3 of 13 OI cases, but in none of the uninjured controls. An elevation in plasma SNTF corresponded with significant differences in fractional anisotropy and the apparent diffusion coefficient in the corpus callosum and uncinate fasciculus measured by DTI. Furthermore, increased plasma SNTF on the day of injury correlated significantly with cognitive impairment that persisted for at least 3 months, both across all study participants and also among the mTBI cases by themselves. The elevation in plasma SNTF in the subset of OI cases, accompanied by corresponding white matter and cognitive abnormalities, raises the possibility of identifying undiagnosed cases of mTBI. These data suggest that the blood level of SNTF on the day of a CT-negative mTBI may identify a subset of patients at risk of white matter damage and persistent disability. SNTF could have prognostic and diagnostic utilities in the assessment and treatment of mTBI.

  3. Personalized medicine using DNA biomarkers: a review

    OpenAIRE

    Ziegler, Andreas; Koch, Armin; Krockenberger, Katja; Großhennig, Anika

    2012-01-01

    Biomarkers are of increasing importance for personalized medicine, with applications including diagnosis, prognosis, and selection of targeted therapies. Their use is extremely diverse, ranging from pharmacodynamics to treatment monitoring. Following a concise review of terminology, we provide examples and current applications of three broad categories of biomarkers—DNA biomarkers, DNA tumor biomarkers, and other general biomarkers. We outline clinical trial phases for identifying and validat...

  4. Computer-aided assessment of hepatic contour abnormalities as an imaging biomarker for the prediction of hepatocellular carcinoma development in patients with chronic hepatitis C

    Energy Technology Data Exchange (ETDEWEB)

    Goshima, Satoshi [Department of Radiology, Gifu University Hospital, 1-1 Yanagido, 501-1194 Gifu (Japan); Kanematsu, Masayuki, E-mail: masa_gif@yahoo.co.jp [Department of Radiology, Gifu University Hospital, 1-1 Yanagido, 501-1194 Gifu (Japan); Kondo, Hiroshi; Watanabe, Haruo; Noda, Yoshifumi [Department of Radiology, Gifu University Hospital, 1-1 Yanagido, 501-1194 Gifu (Japan); Fujita, Hiroshi [Department of Intelligent Image Information Division of Regeneration and Advanced Medical Sciences, Graduate School of Medicine, Gifu University, Gifu (Japan); Bae, Kyongtae T. [Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, PA (United States)

    2015-05-15

    Highlights: • Hepatic contour was quantified and converted to hepatic fibrosis index (HFI). • HFI was a significant risk factor for HCC with an odds ratio of 26.4. • HFI may be an important imaging biomarker for managing cirrhotic patients. - Abstract: Purpose: To evaluate whether a hepatic fibrosis index (HFI), quantified on the basis of hepatic contour abnormality, is a risk factor for the development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. Materials and methods: Our institutional review board approved this retrospective study and written informed consent was waved. During a 14-month period, consecutive 98 patients with chronic hepatitis C who had no medical history of HCC treatment (56 men and 42 women; mean age, 70.7 years; range, 48–91 years) were included in this study. Gadoxetic acid-enhanced hepatocyte specific phase was used to detect and analyze hepatic contour abnormality. Hepatic contour abnormality was quantified and converted to HFI using in-house proto-type software. We compared HFI between patients with (n = 54) and without HCC (n = 44). Serum levels of albumin, total bilirubin, aspartate transferase, alanine transferase, percent prothrombin time, platelet count, alpha-fetoprotein, protein induced by vitamin K absence-II, and HFI were tested as possible risk factors for the development of HCC by determining the odds ratio with logistic regression analysis. Results: HFIs were significantly higher in patients with HCC (0.58 ± 0.86) than those without (0.36 ± 0.11) (P < 0.001). Logistic analysis revealed that only HFI was a significant risk factor for HCC development with an odds ratio (95% confidence interval) of 26.4 (9.0–77.8) using a cutoff value of 0.395. Conclusion: The hepatic fibrosis index, generated using a computer-aided assessment of hepatic contour abnormality, may be a useful imaging biomarker for the prediction of HCC development in patients with chronic hepatitis C.

  5. Computer-aided assessment of hepatic contour abnormalities as an imaging biomarker for the prediction of hepatocellular carcinoma development in patients with chronic hepatitis C

    International Nuclear Information System (INIS)

    Highlights: • Hepatic contour was quantified and converted to hepatic fibrosis index (HFI). • HFI was a significant risk factor for HCC with an odds ratio of 26.4. • HFI may be an important imaging biomarker for managing cirrhotic patients. - Abstract: Purpose: To evaluate whether a hepatic fibrosis index (HFI), quantified on the basis of hepatic contour abnormality, is a risk factor for the development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. Materials and methods: Our institutional review board approved this retrospective study and written informed consent was waved. During a 14-month period, consecutive 98 patients with chronic hepatitis C who had no medical history of HCC treatment (56 men and 42 women; mean age, 70.7 years; range, 48–91 years) were included in this study. Gadoxetic acid-enhanced hepatocyte specific phase was used to detect and analyze hepatic contour abnormality. Hepatic contour abnormality was quantified and converted to HFI using in-house proto-type software. We compared HFI between patients with (n = 54) and without HCC (n = 44). Serum levels of albumin, total bilirubin, aspartate transferase, alanine transferase, percent prothrombin time, platelet count, alpha-fetoprotein, protein induced by vitamin K absence-II, and HFI were tested as possible risk factors for the development of HCC by determining the odds ratio with logistic regression analysis. Results: HFIs were significantly higher in patients with HCC (0.58 ± 0.86) than those without (0.36 ± 0.11) (P < 0.001). Logistic analysis revealed that only HFI was a significant risk factor for HCC development with an odds ratio (95% confidence interval) of 26.4 (9.0–77.8) using a cutoff value of 0.395. Conclusion: The hepatic fibrosis index, generated using a computer-aided assessment of hepatic contour abnormality, may be a useful imaging biomarker for the prediction of HCC development in patients with chronic hepatitis C

  6. Biomarkers in mood disorders research: developing new and improved therapeutics

    Directory of Open Access Journals (Sweden)

    MARK J. NICIU

    2014-01-01

    Full Text Available Background Recently, surrogate neurobiological biomarkers that correlate with target engagement and therapeutic response have been developed and tested in early phase studies of mood disorders. Objective The identification of biomarkers could help develop personalized psychiatric treatments that may impact public health. Methods These biomarkers, which are associated with clinical response post-treatment, can be directly validated using multimodal approaches including genetic tools, proteomics/metabolomics, peripheral measures, neuroimaging, biostatistical predictors, and clinical predictors. Results To date, early phase biomarker studies have sought to identify measures that can serve as “biosignatures”, or biological patterns of clinical response. These studies have also sought to identify clinical predictors and surrogate outcomes associated with pathophysiological domains consistently described in the National Institute of Mental Health’s (NIMH new Research Domain Criteria (RDoC. Using the N-methyl-D-aspartate (NMDA antagonist ketamine as an example, we identified changes in several domains (clinical, cognitive, and neurophysiological that predicted ketamine’s rapid and sustained antidepressant effects in individuals with treatment-resistant major depressive disorder (MDD or bipolar depression. Discussion These approaches may ultimately provide clues into the neurobiology of psychiatric disorders and may have enormous impact Backon the development of novel therapeutics.

  7. Identification of Biomarkers for Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2014-12-01

    Full Text Available BACKGROUND: Prostate cancer (PCa was the second most common type of cancer and the fifth leading cause of cancer-related death in men. The great challenge for physicians is being able to accurately predict PCa prognosis and treatment response in order to reduce PCa-speciic mortality while avoiding overtreatment by identifying of when to intervene, and in which patients. CONTENT: Currently, PCa prognosis and treatment decision of PCa involved digital rectal examination, Prostate-Speciic Antigens (PSA, and subsequent biopsies for histopathological staging, known as Gleason score. However, each procedure has its shortcomings. Efforts to find a better clinically meaningful and non-invasive biomarkers still developed involving proteins, circulating tumor cells, nucleic acids, and the ‘omics' approaches. SUMMARY: Biomarkers for PCa will most likely be an assay employing multiple biomarkers in combination using protein and gene microarrays, containing markers that are differentially expressed in PCa. KEYWORDS: prostate cancer, PSA, biomarkers, nomograms, miRNA, proteomic, genomic, metabolomic.

  8. Clinical and MRI models predicting amyloid deposition in progressive aphasia and apraxia of speech.

    Science.gov (United States)

    Whitwell, Jennifer L; Weigand, Stephen D; Duffy, Joseph R; Strand, Edythe A; Machulda, Mary M; Senjem, Matthew L; Gunter, Jeffrey L; Lowe, Val J; Jack, Clifford R; Josephs, Keith A

    2016-01-01

    Beta-amyloid (Aβ) deposition can be observed in primary progressive aphasia (PPA) and progressive apraxia of speech (PAOS). While it is typically associated with logopenic PPA, there are exceptions that make predicting Aβ status challenging based on clinical diagnosis alone. We aimed to determine whether MRI regional volumes or clinical data could help predict Aβ deposition. One hundred and thirty-nine PPA (n = 97; 15 agrammatic, 53 logopenic, 13 semantic and 16 unclassified) and PAOS (n = 42) subjects were prospectively recruited into a cross-sectional study and underwent speech/language assessments, 3.0 T MRI and C11-Pittsburgh Compound B PET. The presence of Aβ was determined using a 1.5 SUVR cut-point. Atlas-based parcellation was used to calculate gray matter volumes of 42 regions-of-interest across the brain. Penalized binary logistic regression was utilized to determine what combination of MRI regions, and what combination of speech and language tests, best predicts Aβ (+) status. The optimal MRI model and optimal clinical model both performed comparably in their ability to accurately classify subjects according to Aβ status. MRI accurately classified 81% of subjects using 14 regions. Small left superior temporal and inferior parietal volumes and large left Broca's area volumes were particularly predictive of Aβ (+) status. Clinical scores accurately classified 83% of subjects using 12 tests. Phonological errors and repetition deficits, and absence of agrammatism and motor speech deficits were particularly predictive of Aβ (+) status. In comparison, clinical diagnosis was able to accurately classify 89% of subjects. However, the MRI model performed well in predicting Aβ deposition in unclassified PPA. Clinical diagnosis provides optimum prediction of Aβ status at the group level, although regional MRI measurements and speech and language testing also performed well and could have advantages in predicting Aβ status in unclassified PPA subjects

  9. Clinical proteomics identifies urinary CD14 as a potential biomarker for diagnosis of stable coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Min-Yi Lee

    Full Text Available Inflammation plays a key role in coronary artery disease (CAD and other manifestations of atherosclerosis. Recently, urinary proteins were found to be useful markers for reflecting inflammation status of different organs. To identify potential biomarker for diagnosis of CAD, we performed one-dimensional SDS-gel electrophoresis followed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS. Among the proteins differentially expressed in urine samples, monocyte antigen CD14 was found to be consistently expressed in higher amounts in the CAD patients as compared to normal controls. Using enzyme-linked immunosorbent assays to analyze the concentrations of CD14 in urine and serum, we confirmed that urinary CD14 levels were significantly higher in patients (n = 73 with multi-vessel and single vessel CAD than in normal control (n = 35 (P < 0.001. Logistic regression analysis further showed that urinary CD14 concentration level is associated with severity or number of diseased vessels and SYNTAX score after adjustment for potential confounders. Concomitantly, the proportion of CD14+ monocytes was significantly increased in CAD patients (59.7 ± 3.6% as compared with healthy controls (14.9 ± 2.1% (P < 0.001, implicating that a high level of urinary CD14 may be potentially involved in mechanism(s leading to CAD pathogenesis. By performing shotgun proteomics, we further revealed that CD14-associated inflammatory response networks may play an essential role in CAD. In conclusion, the current study has demonstrated that release of CD14 in urine coupled with more CD14+ monocytes in CAD patients is significantly correlated with severity of CAD, pointing to the potential application of urinary CD14 as a novel noninvasive biomarker for large-scale diagnostic screening of susceptible CAD patients.

  10. A Method for Biomarker Directed Survival Prediction in Advanced Non-Small-Cell Lung Cancer Patients Treated with Carboplatin-Based Therapy

    Directory of Open Access Journals (Sweden)

    Wei Chen

    2013-09-01

    Full Text Available Platinum-based chemotherapy is a primary treatment of choice for advanced non-small-cell lung cancer (NSCLC. Analytical methods to specifically evaluate biomarkers predictive of therapeutic efficacy have not been developed. Two randomized phase III trials of carboplatin-based chemotherapy in advanced NSCLC were used for learning and validating the predictive value of ERCC1 in situ protein levels, as measured by accurate quantitative analysis (AQUA. A novel Bayesian method was applied to identify the outcome-based threshold in the learning trial only. Overall survival (OS was assessed by Kaplan-Meier analysis with log rank testing to determine statistical significance in the validating trial. For patients treated with gemcitabine and carboplatin, the median OS was 9.5 months (95% CI 6.7 to 11.8 for the high ERCC1 group compared to 15.6 months (95% CI 11.6 to 24.8 for the low ERCC1 group in the validation trial (log rank p-value = 0.007. The hazard ratio for low ERCC1 was 0.598 (95% CI, 0.394 to 0.908; p = 0.016 relative to high ERCC1 adjusted for age, sex, and histology. Conclusions: Patients with advanced NSCLC could be stratified into high and low ERCC1 expression groups. Patients with low levels benefited from platinum-based chemotherapy, whereas those with high levels did not.

  11. Genomic Copy Number Variations in the Genomes of Leukocytes Predict Prostate Cancer Clinical Outcomes.

    Directory of Open Access Journals (Sweden)

    Yan P Yu

    Full Text Available Accurate prediction of prostate cancer clinical courses remains elusive. In this study, we performed whole genome copy number analysis on leukocytes of 273 prostate cancer patients using Affymetrix SNP6.0 chip. Copy number variations (CNV were found across all chromosomes of the human genome. An average of 152 CNV fragments per genome was identified in the leukocytes from prostate cancer patients. The size distributions of CNV in the genome of leukocytes were highly correlative with prostate cancer aggressiveness. A prostate cancer outcome prediction model was developed based on large size ratio of CNV from the leukocyte genomes. This prediction model generated an average prediction rate of 75.2%, with sensitivity of 77.3% and specificity of 69.0% for prostate cancer recurrence. When combined with Nomogram and the status of fusion transcripts, the average prediction rate was improved to 82.5% with sensitivity of 84.8% and specificity of 78.2%. In addition, the leukocyte prediction model was 62.6% accurate in predicting short prostate specific antigen doubling time. When combined with Gleason's grade, Nomogram and the status of fusion transcripts, the prediction model generated a correct prediction rate of 77.5% with 73.7% sensitivity and 80.1% specificity. To our knowledge, this is the first study showing that CNVs in leukocyte genomes are predictive of clinical outcomes of a human malignancy.

  12. Epigenetic Biomarkers of Preterm Birth and Its Risk Factors.

    Science.gov (United States)

    Knight, Anna K; Smith, Alicia K

    2016-01-01

    A biomarker is a biological measure predictive of a normal or pathogenic process or response. Biomarkers are often useful for making clinical decisions and determining treatment course. One area where such biomarkers would be particularly useful is in identifying women at risk for preterm delivery and related pregnancy complications. Neonates born preterm have significant morbidity and mortality, both in the perinatal period and throughout the life course, and identifying women at risk of delivering preterm may allow for targeted interventions to prevent or delay preterm birth (PTB). In addition to identifying those at increased risk for preterm birth, biomarkers may be able to distinguish neonates at particular risk for future complications due to modifiable environmental factors, such as maternal smoking or alcohol use during pregnancy. Currently, there are no such biomarkers available, though candidate gene and epigenome-wide association studies have identified DNA methylation differences associated with PTB, its risk factors and its long-term outcomes. Further biomarker development is crucial to reducing the health burden associated with adverse intrauterine conditions and preterm birth, and the results of recent DNA methylation studies may advance that goal. PMID:27089367

  13. 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.

  14. A review of molecular biomarkers for bladder cancer

    Directory of Open Access Journals (Sweden)

    Miakhil I

    2013-01-01

    Full Text Available Background: Numerous molecular markers for bladder cancer have been identified and investigated with various laboratory techniques. Molecular markers are isolated from tissue, serum and urine. They fall into proteomic, genetic and epigenetic categories. Some of molecular markers show promising results in terms of facilitating early diagnosis and guiding treatment. Molecular markers or the so- called biomarkers can provide additional information alongside staging, grading and lymphovascular invasion, for better prognostication.Aim:This studyprovides an up-to-date review of the frequently studied and most important biomarkers that have shown consistent relevance in relation to bladder cancer. Methods: The key words were searched on the PubMed, Google scholar and NHS library search engines. Results: More than twenty biomarkers as per our methodology were identified but only half of them have shown consistence relevance in bladder cancer. Conclusion: It is envisaged that a combination of a few biomarkers, which are investigated frequently and have shown clinical relevance, could possibly provide useful information in predicting recurrence and provide useful prognostic information. So far none of the biomarkers for bladder cancer are adopted in the UK standard practice. Despite that the Food and Drug Administration (FDA had approved some of these biomarkers, none of the urology associations incorporated them in to their guidelines as yet. However, it won’t be long before a final consensus is reached to integrate molecular staging in to the current TNM staging system.

  15. Predictive indices of empirical clinical diagnosis of malaria among under-five febrile children attending paediatric outpatient clinic

    Directory of Open Access Journals (Sweden)

    Hassan A Elechi

    2015-01-01

    Full Text Available Background: Malaria has remained an important public health problem in Nigeria with children under 5 years of age bearing the greatest burden. Accurate and prompt diagnosis of malaria is an important element in the fight against the scourge. Due to the several limitations of microscopy, diagnosis of malaria has continued to be made based on clinical ground against several World Health Organization (WHO recommendations. Thus, we aim to assess the performance of empirical clinical diagnosis among febrile children under 5 years of age in a busy pediatric outpatient clinic. Materials and Methods: The study was a cross-sectional study. Children aged <5 years with fever or 72 h history of fever were recruited. Children on antimalarial prophylaxis or on treatment for malaria were excluded. Relevant information was obtained from the caregiver and clinical note of the child using interviewer administered questionnaire. Two thick and two thin films were made, stained, and read for each recruited child. Data was analysed using SPSS version 16. Results: Of the 433 children studied, 98 (22.6% were empirically diagnosed as having malaria and antimalarial drug prescribed. Twenty-three (23.5% of these children were confirmed by microscopy to have malaria parasitemia, while 75 (76.5% were negative for malaria parasitemia. Empirical clinical diagnosis show poor predictive indices with sensitivity of 19.2%, specificity of 76.0%, positive predictive value of 23.5% and negative predictive value of 71%. Conclusion and Recommendations: Empirical clinical diagnosis of malaria among the under-five children with symptoms suggestive of acute malaria is highly not reliable and hence the need to strengthen parasitological diagnosis.

  16. 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.

  17. Neuroimmune biomarkers in schizophrenia.

    Science.gov (United States)

    Tomasik, Jakub; Rahmoune, Hassan; Guest, Paul C; Bahn, Sabine

    2016-09-01

    Schizophrenia is a heterogeneous psychiatric disorder with a broad spectrum of clinical and biological manifestations. Due to the lack of objective tests, the accurate diagnosis and selection of effective treatments for schizophrenia remains challenging. Numerous technologies have been employed in search of schizophrenia biomarkers. These studies have suggested that neuroinflammatory processes may play a role in schizophrenia pathogenesis, at least in a subgroup of patients. The evidence indicates alterations in both pro- and anti-inflammatory molecules in the central nervous system, which have also been found in peripheral tissues and may correlate with schizophrenia symptoms. In line with these findings, certain immunomodulatory interventions have shown beneficial effects on psychotic symptoms in schizophrenia patients, in particular those with distinct immune signatures. In this review, we evaluate these findings and their potential for more targeted drug interventions and the development of companion diagnostics. Although currently no validated markers exist for schizophrenia patient stratification or the prediction of treatment efficacy, we propose that utilisation of inflammatory markers for diagnostic and theranostic purposes may lead to novel therapeutic approaches and deliver more effective care for schizophrenia patients. PMID:25124519

  18. Biomarkers for Success: Using Neuroimaging to Predict Relapse and Develop Brain Stimulation Treatments for Cocaine-Dependent Individuals.

    Science.gov (United States)

    Hanlon, C A; Dowdle, L T; Jones, J L

    2016-01-01

    Cocaine dependence is one of the most difficult substance use disorders to treat. While the powerful effects of cocaine use on behavior were documented in the 19th century, it was not until the late 20th century that we realized cocaine use was affecting brain tissue and function. Following a brief introduction (Section 1), this chapter will summarize our current knowledge regarding alterations in neural circuit function typically observed in chronic cocaine users (Section 2) and highlight an emerging body of literature which suggests that pretreatment limbic circuit activity may be a reliable predictor of clinical outcomes among individuals seeking treatment for cocaine (Section 3). Finally, as the field of addiction research strives to translate this neuroimaging data into something clinically meaningful, we will highlight several new brain stimulation approaches which utilize functional brain imaging data to design noninvasive brain stimulation interventions for individuals seeking treatment for substance dependence disorders (Section 4). PMID:27503451

  19. A nomogram to predict Gleason sum upgrading of clinically diagnosed localized prostate cancer among Chinese patients

    Institute of Scientific and Technical Information of China (English)

    Jin-You Wang; Yao Zhu; Chao-Fu Wang; Shi-Lin Zhang; Bo Dai; Ding-Wei Ye

    2014-01-01

    Although several models have been developed to predict the probability of Gleason sum upgrading between biopsy and radical prostatectomy specimens, most of these models are restricted to prostate-specific antigen screening-detected prostate cancer. This study aimed to build a nomogram for the prediction of Gleason sum upgrading in clinical y diagnosed prostate cancer. The study cohort comprised 269 Chinese prostate cancer patients who underwent prostate biopsy with a minimum of 10 cores and were subsequently treated with radical prostatectomy. Of al included patients, 220 (81.8%) were referred with clinical symptoms. The prostate-specific antigen level, primary and secondary biopsy Gleason scores, and clinical T category were used in a multivariate logistic regression model to predict the probability of Gleason sum upgrading. The developed nomogram was validated internally. Gleason sum upgrading was observed in 90 (33.5%) patients. Our nomogram showed a bootstrap-corrected concordance index of 0.789 and good calibration using 4 readily available variables. The nomogram also demonstrated satisfactory statistical performance for predicting significant upgrading. External validation of the nomogram published by Chun et al. in our cohort showed a marked discordance between the observed and predicted probabilities of Gleason sum upgrading. In summary, a new nomogram to predict Gleason sum upgrading in clinically diagnosed prostate cancer was developed, and it demonstrated good statistical performance upon internal validation.

  20. A nomogram to predict Gleason sum upgrading of clinically diagnosed localized prostate cancer among Chinese patients

    Directory of Open Access Journals (Sweden)

    Jin-You Wang

    2014-05-01

    Full Text Available Although several models have been developed to predict the probability of Gleason sum upgrading between biopsy and radical prostatectomy specimens, most of these models are restricted to prostate-specific antigen screening-detected prostate cancer. This study aimed to build a nomogram for the prediction of Gleason sum upgrading in clinically diagnosed prostate cancer. The study cohort comprised 269 Chinese prostate cancer patients who underwent prostate biopsy with a minimum of 10 cores and were subsequently treated with radical prostatectomy. Of all included patients, 220 (81.8% were referred with clinical symptoms. The prostate-specific antigen level, primary and secondary biopsy Gleason scores, and clinical T category were used in a multivariate logistic regression model to predict the probability of Gleason sum upgrading. The developed nomogram was validated internally. Gleason sum upgrading was observed in 90 (33.5% patients. Our nomogram showed a bootstrap-corrected concordance index of 0.789 and good calibration using 4 readily available variables. The nomogram also demonstrated satisfactory statistical performance for predicting significant upgrading. External validation of the nomogram published by Chun et al. in our cohort showed a marked discordance between the observed and predicted probabilities of Gleason sum upgrading. In summary, a new nomogram to predict Gleason sum upgrading in clinically diagnosed prostate cancer was developed, and it demonstrated good statistical performance upon internal validation.

  1. Assessment of T Regulatory Cells and Expanded Profiling of Autoantibodies May Offer Novel Biomarkers for the Clinical Management of Systemic Sclerosis and Undifferentiated Connective Tissue Disease

    Directory of Open Access Journals (Sweden)

    Paola Cordiali-Fei

    2013-01-01

    Full Text Available In order to identify disease biomarkers for the clinical and therapeutic management of autoimmune diseases such as systemic sclerosis (SSc and undifferentiated connective tissue disease (UCTD, we have explored the setting of peripheral T regulatory (T reg cells and assessed an expanded profile of autoantibodies in patients with SSc, including either limited (lcSSc or diffuse (dcSSc disease, and in patients presenting with clinical signs and symptoms of UCTD. A large panel of serum antibodies directed towards nuclear, nucleolar, and cytoplasmic antigens, including well-recognized molecules as well as less frequently tested antigens, was assessed in order to determine whether different antibody profiles might be associated with distinct clinical settings. Beside the well-recognized association between lcSSc and anti-centromeric or dcSSC and anti-topoisomerase-I antibodies, we found a significative association between dcSSc and anti-SRP or anti-PL-7/12 antibodies. In addition, two distinct groups emerged on the basis of anti-RNP or anti-PM-Scl 75/100 antibody production among UCTD patients. The levels of T reg cells were significantly lower in patients with SSc as compared to patients with UCTD or to healthy controls; in patients with lcSSc, T reg cells were inversely correlated to disease duration, suggesting that their levels may represent a marker of disease progression.

  2. Use of clinical movement screening tests to predict injury in sport.

    Science.gov (United States)

    Chimera, Nicole J; Warren, Meghan

    2016-04-18

    Clinical movement screening tests are gaining popularity as a means to determine injury risk and to implement training programs to prevent sport injury. While these screens are being used readily in the clinical field, it is only recently that some of these have started to gain attention from a research perspective. This limits applicability and poses questions to the validity, and in some cases the reliability, of the clinical movement tests as they relate to injury prediction, intervention, and prevention. This editorial will review the following clinical movement screening tests: Functional Movement Screen™, Star Excursion Balance Test, Y Balance Test, Drop Jump Screening Test, Landing Error Scoring System, and the Tuck Jump Analysis in regards to test administration, reliability, validity, factors that affect test performance, intervention programs, and usefulness for injury prediction. It is important to review the aforementioned factors for each of these clinical screening tests as this may help clinicians interpret the current body of literature. While each of these screening tests were developed by clinicians based on what appears to be clinical practice, this paper brings to light that this is a need for collaboration between clinicians and researchers to ensure validity of clinically meaningful tests so that they are used appropriately in future clinical practice. Further, this editorial may help to identify where the research is lacking and, thus, drive future research questions in regards to applicability and appropriateness of clinical movement screening tools. PMID:27114928

  3. Development of a label-free LC-MS/MS strategy to approach the identification of candidate protein biomarkers of disease recurrence in prostate cancer patients in a clinical trial of combined hormone and radiation therapy.

    LENUS (Irish Health Repository)

    Morrissey, Brian

    2013-06-01

    Combined hormone and radiation therapy (CHRT) is one of the principle curative regimes for localised prostate cancer (PCa). Following treatment, many patients subsequently experience disease recurrence however; current diagnostics tests fail to predict the onset of disease recurrence. Biomarkers that address this issue would be of significant advantage.

  4. Biomarkers: A Challenging Conundrum in Cardiovascular Disease.

    Science.gov (United States)

    Libby, Peter; King, Kevin

    2015-12-01

    The use of biomarkers has proven utility in cardiovascular medicine and holds great promise for future advances, but their application requires considerable rigor in thinking and methodology. Numerous confounding factors can cloud the clinical and investigative uses of biomarkers. Yet, the thoughtful and critical use of biomarkers can doubtless aid discovery of new pathogenic pathways, identify novel therapeutic targets, and provide a bridge between the laboratory and the clinic. Biomarkers can provide diagnostic and prognostic tools to the practitioner. The careful application of biomarkers can also help design and guide clinical trials required to establish the efficacy of novel interventions to improve patient outcomes. Point of care testing, technological advances, such as microfluidic and wearable devices, and the power of omics approaches all promise to elevate the potential contributions of biomarkers to discovery science, translation, clinical trials, and the practice of cardiovascular medicine. PMID:26543097

  5. DNA damage induction and/or repair as mammalian cell biomarker for the prediction of cellular radiation response

    Science.gov (United States)

    Baumstark-Khan, C.

    DNA damage and its repair processes are key factors in cancer induction and also in the treatment of malignancies. Cancer prevention during extended space missions becomes a topic of great importance for space radiobiology. The knowledge of individual responsiveness would allow the protection strategy to be tailored optimally in each case. Radiobiological analysis of cultured cells derived from tissue explants from individuals has shown that measurement of the surviving fraction after 2 Gy (SF2) may be used to predict the individual responsiveness. However, clonogenic assays are timeconsuming, thus alternative assays for the determination of radiore-sponse are being sought. For that reason CHO cell strains having different repair capacities were used for examining whether DNA strand break repair is a suitable experimental design to allow predictive statements. Cellular survival (CFA assay) and DNA strand breaks (total DNA strand breaks: FADU technique; DSBs: non-denaturing elution) were determined in parallel immediately after irradiation as well as after a 24 hour recovery period according to dose. There were no correlations between the dose-response curves of the initial level of DNA strand breaks and parameters that describe clonogenic survival curves (SF2). A good correlation exists between intrinsic cellular radioresistance and the extent of residual DNA strand breaks.

  6. Accuracy of clinical prediction rules in peptic ulcer perforation: an observational study

    DEFF Research Database (Denmark)

    Buck, David Levarett; Vester-Andersen, Morten; Møller, Morten Hylander

    2012-01-01

    Abstract Objective. The aim of the present study was to compare the ability of four clinical prediction rules to predict adverse outcome in perforated peptic ulcer (PPU): the Boey score, the American Society of Anesthesiologists (ASA) score, the Acute Physiology and Chronic Health Evaluation...... breastfeeding women, non-surgically treated patients, patients with malignant ulcers, and patients with perforation of other organs were excluded. Primary outcome measure: 30-day mortality rate. Statistical analysis: the ability of four clinical prediction rules to distinguish survivors from non...... patients had at least one co-existing disease. The 30-day mortality proportion was 17% (20/117). The AUCs: the Boey score, 0.63; the sepsis score, 0.69; the ASA score, 0.73; and the APACHE II score, 0.76. Overall, the PPVs of all four prediction rules were low and the NPVs high. Conclusions. The Boey score...

  7. Biomarkers in Transplantation-Proteomics and Metabolomics.

    Science.gov (United States)

    Christians, Uwe; Klawitter, Jelena; Klawitter, Jost

    2016-04-01

    Modern multianalyte "omics" technologies allow for the identification of molecular signatures that confer significantly more information than measurement of a single parameter as typically used in current medical diagnostics. Proteomics and metabolomics bioanalytical assays capture a large set of proteins and metabolites in body fluids, cells, or tissues and, complementing genomics, assess the phenome. Proteomics and metabolomics contribute to the development of novel predictive clinical biomarkers in transplantation in 2 ways: they can be used to generate a diagnostic fingerprint or they can be used to discover individual proteins and metabolites of diagnostic potential. Much fewer metabolomics than proteomics biomarker studies in transplant patients have been reported, and, in contrast to proteomics discovery studies, new lead metabolite markers have yet to emerge. Most clinical proteomics studies have been discovery studies. Several of these studies have assessed diagnostic sensitivity and specificity. Nevertheless, none of these newly discovered protein biomarkers have yet been implemented in clinical decision making in transplantation. The currently most advanced markers discovered in proteomics studies in transplant patients are the chemokines CXCL-9 and CXCL-10, which have successfully been validated in larger multicenter trials in kidney transplant patients. These chemokines can be measured using standard immunoassay platforms, which should facilitate clinical implementation. Based on the published evidence, it is reasonable to expect that these chemokine markers can help guiding and individualizing immunosuppressive regimens, may be able to predict acute and chronic T-cell-mediated and antibody-mediated rejection, and may be useful tools for risk stratification of kidney transplant patients. PMID:26418702

  8. GliomaPredict: a clinically useful tool for assigning glioma patients to specific molecular subtypes

    Directory of Open Access Journals (Sweden)

    Fine Howard A

    2010-07-01

    Full Text Available Abstract Background Advances in generating genome-wide gene expression data have accelerated the development of molecular-based tumor classification systems. Tools that allow the translation of such molecular classification schemas from research into clinical applications are still missing in the emerging era of personalized medicine. Results We developed GliomaPredict as a computational tool that allows the fast and reliable classification of glioma patients into one of six previously published stratified subtypes based on sets of extensively validated classifiers derived from hundreds of glioma transcriptomic profiles. Our tool utilizes a principle component analysis (PCA-based approach to generate a visual representation of the analyses, quantifies the confidence of the underlying subtype assessment and presents results as a printable PDF file. GliomaPredict tool is implemented as a plugin application for the widely-used GenePattern framework. Conclusions GliomaPredict provides a user-friendly, clinically applicable novel platform for instantly assigning gene expression-based subtype in patients with gliomas thereby aiding in clinical trial design and therapeutic decision-making. Implemented as a user-friendly diagnostic tool, we expect that in time GliomaPredict, and tools like it, will become routinely used in translational/clinical research and in the clinical care of patients with gliomas.

  9. Early seizures in patients with acute stroke: Frequency, predictive factors, and effect on clinical outcome

    OpenAIRE

    Andrea Alberti; Maurizio Paciaroni; Valeria Caso; Michele Venti; Francesco Palmerini; Giancarlo Agnelli

    2008-01-01

    Andrea Alberti, Maurizio Paciaroni, Valeria Caso, Michele Venti, Francesco Palmerini, Giancarlo AgnelliStroke Unit and Division of Internal and Cardiovascular Medicine, University of Perugia, Perugia, ItalyBackground: Early seizure (ES) may complicate the clinical course of patients with acute stroke. The aim of this study was to assess the rate of and the predictive factors for ES as well the effects of ES on the clinical outcome at hospital discharge in patients with first-ever stroke.Patie...

  10. Pulmonary embolism in intensive care unit: Predictive factors, clinical manifestations and outcome

    OpenAIRE

    Bahloul Mabrouk; Chaari Anis; Kallel Hatem; Abid Leila; Hamida Chokri Ben; Dammak Hassen; Rekik Noureddine; Mnif Jameleddine; Chelly Hedi; Bouaziz Mounir

    2010-01-01

    Objective : To determine predictive factors, clinical and demographics characteristics of patients with pulmonary embolism (PE) in ICU, and to identify factors associated with poor outcome in the hospital and in the ICU. Methods : During a four-year prospective study, a medical committee of six ICU physicians prospectively examined all available data for each patient in order to classify patients according to the level of clinical suspicion of pulmonary thromboembolism. During the study...

  11. Clinical Nomogram for Predicting Survival of Esophageal Cancer Patients after Esophagectomy

    OpenAIRE

    Jinlin Cao; Ping Yuan; Luming Wang; Yiqing Wang; Honghai Ma; Xiaoshuai Yuan; Wang Lv; Jian Hu

    2016-01-01

    The aim of this study was to construct an effective clinical nomogram for predicting the survival of esophageal cancer patients after esophagectomy. We identified esophageal cancer patients (n = 4,281) who underwent esophagectomy between 1988 and 2007 from the Surveillance, Epidemiology, and End Results (SEER) 18 registries database. Clinically significant parameters for survival were used to construct a nomogram based on Cox regression analyses. The model was validated using bootstrap resamp...

  12. Endometrial histology and predictable clinical factors for endometrial disease in women with polycystic ovary syndrome

    OpenAIRE

    Park, Joon Cheol; Lim, Su Yeon; Jang, Tae Kyu; Bae, Jin Gon; Kim, Jong In; Rhee, Jeong Ho

    2011-01-01

    Objective This study was aimed to investigate endometrial histology and to find predictable clinical factors for endometrial disease (hyperplasia or cancer) in women with polycystic ovary syndrome (PCOS). Methods We investigated the endometrial histology and analyzed the relationship between endometrial histology and clinical parameters, such as LH, FSH, estradiol, testosterone, fasting and 2 hours postprandial glucose and insulin, insulin resistance, body mass index, endometrial thickness, m...

  13. Nomograms for the Prediction of Pathologic Stage of Clinically Localized Prostate Cancer in Korean Men

    OpenAIRE

    Song, Cheryn; Kang, Taejin; Ro, Jae Y.; Lee, Moo-Song; Kim, Choung-Soo; Ahn, Hanjong

    2005-01-01

    We analyzed the prostate cancer data of 317 Korean men with clinically localized prostate cancer who underwent radical prostatectomy at Asan Medical Center between June 1990 and November 2003 to construct nomograms predicting the pathologic stage of these tumors, and compared the outcome with preexisting nomograms. Multinomial log-linear regression was performed for the simultaneous prediction of organ-confined disease (OCD), extracapsular extension (ECE), seminal vesicle invasion (SVI) and l...

  14. A nomogram to predict Gleason sum upgrading of clinically diagnosed localized prostate cancer among Chinese patients

    OpenAIRE

    Jin-You Wang; Yao Zhu; Chao-Fu Wang; Shi-Lin Zhang; Bo Dai; Ding-Wei Ye

    2014-01-01

    Although several models have been developed to predict the probability of Gleason sum upgrading between biopsy and radical prostatectomy specimens, most of these models are restricted to prostate-specific antigen screening-detected prostate cancer. This study aimed to build a nomogram for the prediction of Gleason sum upgrading in clinically diagnosed prostate cancer. The study cohort comprised 269 Chinese prostate cancer patients who underwent prostate biopsy with a minimum of 10 cores and w...

  15. Biomarkers and Pharmacogenetics in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Xunhai Xu

    2011-07-01

    Full Text Available Appropriate identification and validation of biomarkers as well as pharmacogenetics are important in formulating patient-oriented, individualized chemotherapy or biological therapy in cancer patients. These markers can be especially valuable in pancreatic cancer, where high mortality and complex disease biology are frequently encountered. Recently, several advances have been made to further our knowledge in this specific area of pancreatic cancer. In the 2011 American Society of Clinical Oncology (ASCO Annual Meeting, researchers have presented several interesting results in biomarkers development: the identifications of 9 single nucleotide polymorphisms (SNPs that is associated with positive efficacy of gemcitabine (Abstract #4022; the introduction of circulating tumor cells as a prognostic markers in pancreatic adenocarcinoma (Abstract #e14657; the re-affirmation of plasma cytidine deaminase (CDA as a positive predictive markers for gemcitabine efficacy, as well as the postulations that CDA*3 as a potential genotype marker to predict gemcitabine responses (Abstract #e14645; and finally the retrospective tumor tissues analysis in the Arbeitsgemeinschaft Internistische Onkologie (AIO trial in an attempt for epidermal growth factor receptor (EGFR pathway biomarker identifications (Abstract #4047

  16. Testing of the preliminary OMERACT validation criteria for a biomarker to be regarded as reflecting structural damage endpoints in rheumatoid arthritis clinical trials: the example of C-reactive protein

    DEFF Research Database (Denmark)

    Keeling, Stephanie O; Landewe, Robert; van der Heijde, Desiree;

    2007-01-01

    OBJECTIVE: A list of 14 criteria for guiding the validation of a soluble biomarker as reflecting structural damage endpoints in rheumatoid arthritis (RA) clinical trials was drafted by an international working group after a Delphi consensus exercise. C-reactive protein (CRP), a soluble biomarker...... individual criteria in the draft set. METHODS: A systematic literature review was conducted to elicit evidence in support of each specific criterion composing the 14-criteria draft set. A summary of the key literature findings per criterion was presented to both the working group and to participants in a...

  17. Chromosomal aberrations in lymphocytes predict human cancer independently of exposure to carcinogens. European Study Group on Cytogenetic Biomarkers and Health

    DEFF Research Database (Denmark)

    Bonassi, S; Hagmar, L; Strömberg, U; Montagud, A H; Tinnerberg, H; Forni, A; Heikkilä, P; Wanders, S; Wilhardt, P; Hansteen, I L; Knudsen, Lisbeth E.; Norppa, H

    2000-01-01

    played by exposure to carcinogens is still uncertain because of the requisite information concerning occupation and lifestyle was lacking. We evaluated in the present study whether CAs predicted cancer because they were the result of past exposure to carcinogens or because they were an intermediate end...... point in the pathway leading to disease. A nested case-control study was performed on 93 incident cancer cases and 62 deceased cancer cases coming from two prospective cohort studies performed in Nordic countries (Denmark, Finland, Norway, and Sweden) and Italy. For each case, four controls matched by...... compared to those with a low level in the Nordic cohort (odds ratio, 2.35; 95% confidence interval, 1.31-4.23) and in the Italian cohort (odds ratio, 2.66; 95% confidence interval, 1.26-5.62). These estimates were not affected by the inclusion of occupational exposure level and smoking habit in the...

  18. Perfusion CT in acute stroke: prediction of vessel recanalization and clinical outcome in intravenous thrombolytic therapy

    International Nuclear Information System (INIS)

    This study evaluated perfusion computed tomography (PCT) for the prediction of vessel recanalization and clinical outcome in patients undergoing intravenous thrombolysis. Thirty-nine patients with acute ischemic stroke of the middle cerebral artery territory underwent intravenous thrombolysis within 3 h of symptom onset. They all had non-enhanced CT (NECT), PCT, and CT angiography (CTA) before treatment. The Alberta Stroke Program Early Computed Tomography (ASPECT) score was applied to NECT and PCT maps to assess the extent of ischemia. CTA was assessed for the site of vessel occlusion. The National Institute of Health Stroke Scale (NIHSS) score was used for initial clinical assessment. Three-month clinical outcome was assessed using the modified Rankin scale. Vessel recanalization was determined by follow-up ultrasound. Of the PCT maps, a cerebral blood volume (CBV) ASPECT score of >6 versus ≤6 was the best predictor for clinical outcome (odds ratio, 31.43; 95% confidence interval, 3.41-289.58; P < 0.002), and was superior to NIHSS, NECT and CTA. No significant differences in ASPECT scores were found for the prediction of vessel recanalization. ASPECT score applied to PCT maps in acute stroke patients predicts the clinical outcome of intravenous thrombolysis and is superior to both early NECT and clinical parameters. (orig.)

  19. Biomarkers in psoriatic arthritis: a systematic literature review.

    Science.gov (United States)

    Generali, Elena; Scirè, Carlo A; Favalli, Ennio G; Selmi, Carlo

    2016-06-01

    Psoriatic arthritis (PsA) is characterized by chronic inflammation of peripheral joints and axial skeleton, associated with a strong genetic background. Clinics include enthesitis or dactylitis and extra-articular involvement as uveitis or inflammatory bowel disease, while treatment options range from nonsteroidal anti-inflammatory drugs (NSAIDs) to biologics, targeting TNF α or Th17. No serum autoantibody is associated with PsA, while other biomarkers have been proposed for early diagnosis or to predict treatment response. To better discuss this area of growing interest we performed a systematic review of the literature on biomarkers in PsA. Our research retrieved 408 papers, and 38 were included in the analysis. Based on the available literature, we draw some recommendations for the use of biomarkers in the management of patients with PsA. PMID:26821681

  20. Identification of a Predictive Biomarker for the Beneficial Effect of Keishibukuryogan, a Kampo (Japanese Traditional Medicine, on Patients with Climacteric Syndrome

    Directory of Open Access Journals (Sweden)

    Takao Namiki

    2014-01-01

    Full Text Available Keishibukuryogan (KBG; Guizhi-Fuling-Wan in Chinese is one of the Kampo (Japanese traditional medicines used to treat patients with climacteric syndrome. KBG can be used by patients who cannot undergo hormone replacement therapy due to a history of breast cancer. We evaluated whether cytosine-adenine (CA repeat polymorphism of the estrogen receptor β gene can be a predictor of the beneficial effect of KBG on climacteric syndrome. We also investigated the relationship between CA repeat polymorphism, the patients’ profiles, and the therapeutic effect. We found that CA was an SS, SL, or LL genotype according to the number of repeats. We studied 39 consecutive patients with climacteric disorders who took KBG for 12 weeks. The diagnosis of climacteric disorders was made on the basis of the Kupperman index. KBG significantly improved the patients’ climacteric symptoms (i.e., vasomotor symptoms in the patients with the LL genotype and melancholia in the patients with the SL genotype. No relationship between the patients’ profiles and CA repeat polymorphism was recognized. CA repeat polymorphism could thus be a potential biomarker to predict the efficacy of KBG in climacteric syndrome, and its use will help to reduce the cost of treating this syndrome by focusing the administration of KBG on those most likely to benefit from it.

  1. A Multi-Center Prospective Derivation and Validation of a Clinical Prediction Tool for Severe Clostridium difficile Infection.

    LENUS (Irish Health Repository)

    Na, Xi

    2015-04-23

    Prediction of severe clinical outcomes in Clostridium difficile infection (CDI) is important to inform management decisions for optimum patient care. Currently, treatment recommendations for CDI vary based on disease severity but validated methods to predict severe disease are lacking. The aim of the study was to derive and validate a clinical prediction tool for severe outcomes in CDI.

  2. Clinical values of multiple Epstein-Barr virus (EBV serological biomarkers detected by xMAP technology

    Directory of Open Access Journals (Sweden)

    Chen Li-Zhen

    2009-08-01

    Full Text Available Abstract Background Serological examination of Epstein-Barr virus (EBV antibodies has been performed for screening nasopharyngeal carcinoma (NPC and other EBV-associated diseases. Methods By using xMAP technology, we examined immunoglobulin (Ig A antibodies against Epstein-Barr virus (EBV VCA-gp125, p18 and IgA/IgG against EA-D, EBNA1 and gp78 in populations with distinct diseases, or with different genetic or geographic background. Sera from Cantonese NPC patients (n = 547 and healthy controls (n = 542, 90 members of high-risk NPC families and 52 non-endemic healthy individuals were tested. Thirty-five of NPC patients were recruited to observe the kinetics of EBV antibody levels during and after treatment. Patients with other EBV-associated diseases were collected, including 16 with infectious mononucleosis, 28 with nasal NK/T cell lymphoma and 14 with Hodgkin's disease. Results Both the sensitivity and specificity of each marker for NPC diagnosis ranged 61–84%, but if combined, they could reach to 84.5% and 92.4%, respectively. Almost half of NPC patients displayed de