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Open AccessReview Cerebrospinal Fluid Biomarkers in Alzheimer’s Disease—From Brain Starch to Bench and Bedside
by , and
Diagnostics 2017, 7(3), 42; doi:10.3390/diagnostics7030042
Received: 6 May 2017 / Revised: 21 June 2017 / Accepted: 6 July 2017 / Published: 13 July 2017
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Abstract
Alzheimer’s disease is the most common cause of dementia. Over the last three decades, research has advanced dramatically and provided a detailed understanding of the molecular events underlying the pathogenesis of Alzheimer’s disease. In parallel, assays for the detection of biomarkers that reflect
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Alzheimer’s disease is the most common cause of dementia. Over the last three decades, research has advanced dramatically and provided a detailed understanding of the molecular events underlying the pathogenesis of Alzheimer’s disease. In parallel, assays for the detection of biomarkers that reflect the typical Alzheimer’s disease-associated pathology have been developed and validated in myriads of clinical studies. Such biomarkers complement clinical diagnosis and improve diagnostic accuracy. The use of biomarkers will become even more important with the advent of disease-modifying therapies. Such therapies will likely be most beneficial when administered early in the disease course. Here, we summarise the development of the core Alzheimer’s disease cerebrospinal fluid biomarkers: amyloid-β and tau. We provide an overview of their role in cellular physiology and Alzheimer’s disease pathology, and embed their development as cerebrospinal fluid biomarkers into the historical context of Alzheimer’s disease research. Finally, we summarise recommendations for their use in clinical practice, and outline perspectives for novel cerebrospinal fluid candidate biomarkers. Full article
(This article belongs to the Special Issue Alzheimer's Disease Imaging Biomarkers)
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Open AccessReview Clinical Applications of Autophagy Proteins in Cancer: From Potential Targets to Biomarkers
by and
Int. J. Mol. Sci. 2017, 18(7), 1496; doi:10.3390/ijms18071496
Received: 3 June 2017 / Revised: 6 July 2017 / Accepted: 7 July 2017 / Published: 11 July 2017
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Abstract
Autophagy, a lysosome-mediated intracellular degradation and recycling pathway, plays multiple context-dependent roles in tumorigenesis and treatment resistance. Encouraging results from various preclinical studies have led to the initiation of numerous clinical trials with the intention of targeting autophagy in various cancers. Accumulating knowledge
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Autophagy, a lysosome-mediated intracellular degradation and recycling pathway, plays multiple context-dependent roles in tumorigenesis and treatment resistance. Encouraging results from various preclinical studies have led to the initiation of numerous clinical trials with the intention of targeting autophagy in various cancers. Accumulating knowledge of the particular mechanisms and players involved in different steps of autophagy regulation led to the ongoing discovery of small molecule inhibitors designed to disrupt this highly orchestrated process. However, the development of validated autophagy-related biomarkers, essential for rational selection of patients entering clinical trials involving autophagy inhibitors, is lagging behind. One possible source of biomarkers for this purpose is the autophagy machinery itself. In this review, we address the recent trends, challenges and advances in the assessment of the biomarker potential of clinically relevant autophagy proteins in human cancers. Full article
(This article belongs to the Special Issue Autophagy at the Intersection of the Immune System and Cancer)
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Open AccessReview Detection of Lipid and Amphiphilic Biomarkers for Disease Diagnostics
by , , , and
Biosensors 2017, 7(3), 25; doi:10.3390/bios7030025
Received: 31 May 2017 / Revised: 27 June 2017 / Accepted: 30 June 2017 / Published: 4 July 2017
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Abstract
Rapid diagnosis is crucial to effectively treating any disease. Biological markers, or biomarkers, have been widely used to diagnose a variety of infectious and non-infectious diseases. The detection of biomarkers in patient samples can also provide valuable information regarding progression and prognosis. Interestingly,
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Rapid diagnosis is crucial to effectively treating any disease. Biological markers, or biomarkers, have been widely used to diagnose a variety of infectious and non-infectious diseases. The detection of biomarkers in patient samples can also provide valuable information regarding progression and prognosis. Interestingly, many such biomarkers are composed of lipids, and are amphiphilic in biochemistry, which leads them to be often sequestered by host carriers. Such sequestration enhances the difficulty of developing sensitive and accurate sensors for these targets. Many of the physiologically relevant molecules involved in pathogenesis and disease are indeed amphiphilic. This chemical property is likely essential for their biological function, but also makes them challenging to detect and quantify in vitro. In order to understand pathogenesis and disease progression while developing effective diagnostics, it is important to account for the biochemistry of lipid and amphiphilic biomarkers when creating novel techniques for the quantitative measurement of these targets. Here, we review techniques and methods used to detect lipid and amphiphilic biomarkers associated with disease, as well as their feasibility for use as diagnostic targets, highlighting the significance of their biochemical properties in the design and execution of laboratory and diagnostic strategies. The biochemistry of biological molecules is clearly relevant to their physiological function, and calling out the need for consideration of this feature in their study, and use as vaccine, diagnostic and therapeutic targets is the overarching motivation for this review. Full article
(This article belongs to the Special Issue Biosensors for the Detection of Biomarkers)
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Open AccessReview Biomarkers and Imaging Findings of Anderson–Fabry Disease—What We Know Now
by , , , , , and
Diseases 2017, 5(2), 15; doi:10.3390/diseases5020015
Received: 4 May 2017 / Revised: 6 June 2017 / Accepted: 7 June 2017 / Published: 11 June 2017
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Abstract
Anderson–Fabry disease (AFD) is an X-linked lysosomal storage disorder, caused by deficiency or absence of the alpha-galactosidase A activity, with a consequent glycosphingolipid accumulation. Biomarkers and imaging findings may be useful for diagnosis, identification of an organ involvement, therapy monitoring and prognosis. The
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Anderson–Fabry disease (AFD) is an X-linked lysosomal storage disorder, caused by deficiency or absence of the alpha-galactosidase A activity, with a consequent glycosphingolipid accumulation. Biomarkers and imaging findings may be useful for diagnosis, identification of an organ involvement, therapy monitoring and prognosis. The aim of this article is to review the current available literature on biomarkers and imaging findings of AFD patients. An extensive bibliographic review from PubMed, Medline and Clinical Key databases was performed by a group of experts from nephrology, neurology, genetics, cardiology and internal medicine, aiming for consensus. Lyso-GB3 is a valuable biomarker to establish the diagnosis. Proteinuria and creatinine are the most valuable to detect renal damage. Troponin I and high-sensitivity assays for cardiac troponin T can identify patients with cardiac lesions, but new techniques of cardiac imaging are essential to detect incipient damage. Specific cerebrovascular imaging findings are present in AFD patients. Techniques as metabolomics and proteomics have been developed in order to find an AFD fingerprint. Lyso-GB3 is important for evaluating the pathogenic mutations and monitoring the response to treatment. Many biomarkers can detect renal, cardiac and cerebrovascular involvement, but none of these have proved to be important to monitoring the response to treatment. Imaging features are preferred in order to find cardiac and cerebrovascular compromise in AFD patients. Full article
(This article belongs to the collection Lysosomal Storage Diseases)
Open AccessReview Undernutrition and Overnutrition Burden for Diseases in Developing Countries: The Role of Oxidative Stress Biomarkers to Assess Disease Risk and Interventional Strategies
by , , , , , , , , , and
Antioxidants 2017, 6(2), 41; doi:10.3390/antiox6020041
Received: 24 April 2017 / Revised: 31 May 2017 / Accepted: 6 June 2017 / Published: 8 June 2017
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Abstract
The increased life expectancy, urbanization, and unhealthy lifestyle characterized by a shift towards a sedentary lifestyle and decreased energy expenditure are considered the main drivers of epidemiological transition. In particular, developing countries are facing a double burden caused by coexisting under- and over-nutrition,
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The increased life expectancy, urbanization, and unhealthy lifestyle characterized by a shift towards a sedentary lifestyle and decreased energy expenditure are considered the main drivers of epidemiological transition. In particular, developing countries are facing a double burden caused by coexisting under- and over-nutrition, which causes a change in the disease profile from infectious diseases to a chronic degenerative pattern. This review discusses the under- and over-nutrition context in Mauritania and India, two countries that are experiencing a nutritional transition, and where we began a collaboration with local medical staff to integrate interventional and diagnostic guidelines. If many studies about diet and its relationship to non-communicable diseases are available for India, very few nutrition and cardiovascular risk studies have been conducted in Mauritania. Presently, with the exponential increase of nutrition-related diseases, targeted approaches are needed to provide balanced diets in parallel with the development of national preventive health systems and screening programs adapted to local needs. In this context, the measurement of oxidative stress biomarkers could be promising as an additive tool to assess cardiovascular (CV) risk in general population, and ameliorating prevention in patients at CV risk or with overt CV disease. Moreover, the possibility of improving the outcome by the direct employment of antioxidant remains plausible. Moreover, studies on the content of antioxidant in different foods may be helpful to develop a balanced diet, and achieve the maximal nutritional and functional properties of cultivars with benefits for human health. Full article
(This article belongs to the Special Issue Dietary Antioxidants and Health Promotion)
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Open AccessArticle Circulating Cell-Free DNA and Circulating Tumor Cells as Prognostic and Predictive Biomarkers in Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Chemotherapy
by , , , , , , , , , , , , and
Int. J. Mol. Sci. 2017, 18(5), 1035; doi:10.3390/ijms18051035
Received: 7 April 2017 / Revised: 4 May 2017 / Accepted: 5 May 2017 / Published: 11 May 2017
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Abstract
Cell-free DNA (cfDNA) and circulating tumor cells (CTCs) are promising prognostic and predictive biomarkers in non-small cell lung cancer (NSCLC). In this study, we examined the prognostic role of cfDNA and CTCs, in separate and joint analyses, in NSCLC patients receiving first line
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Cell-free DNA (cfDNA) and circulating tumor cells (CTCs) are promising prognostic and predictive biomarkers in non-small cell lung cancer (NSCLC). In this study, we examined the prognostic role of cfDNA and CTCs, in separate and joint analyses, in NSCLC patients receiving first line chemotherapy. Seventy-three patients with advanced NSCLC were enrolled in this study. CfDNA and CTC were analyzed at baseline and after two cycles of chemotherapy. Plasma cfDNA quantification was performed by quantitative PCR (qPCR) whereas CTCs were isolated by the ScreenCell Cyto (ScreenCell, Paris, France) device and enumerated according to malignant features. Patients with baseline cfDNA higher than the median value (96.3 hTERT copy number) had a significantly worse overall survival (OS) and double the risk of death (hazard ratio (HR): 2.14; 95% confidence limits (CL) = 1.24–3.68; p-value = 0.006). Conversely, an inverse relationship between CTC median baseline number (6 CTC/3 mL of blood) and OS was observed. In addition, we found that in patients reporting stable disease (SD), the baseline cfDNA and CTCs were able to discriminate patients at high risk of poor survival. cfDNA demonstrated a more reliable biomarker than CTCs in the overall population. In the subgroup of SD patients, both biomarkers identified patients at high risk of poor prognosis who might deserve additional/alternative therapeutic interventions. Full article
(This article belongs to the Special Issue Molecular Classification of Human Cancer: Diagnosis and Treatment 2016)
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Open AccessArticle Protease Expression Levels in Prostate Cancer Tissue Can Explain Prostate Cancer-Associated Seminal Biomarkers—An Explorative Concept Study
by , , , , and
Int. J. Mol. Sci. 2017, 18(5), 976; doi:10.3390/ijms18050976
Received: 24 March 2017 / Revised: 20 April 2017 / Accepted: 29 April 2017 / Published: 4 May 2017
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Abstract
Previously, we described prostate cancer (PCa) detection (83% sensitivity; 67% specificity) in seminal plasma by CE-MS/MS. Moreover, advanced disease was distinguished from organ-confined tumors with 80% sensitivity and 82% specificity. The discovered biomarkers were naturally occurring fragments of larger seminal proteins, predominantly semenogelin
[...] Read more.
Previously, we described prostate cancer (PCa) detection (83% sensitivity; 67% specificity) in seminal plasma by CE-MS/MS. Moreover, advanced disease was distinguished from organ-confined tumors with 80% sensitivity and 82% specificity. The discovered biomarkers were naturally occurring fragments of larger seminal proteins, predominantly semenogelin 1 and 2, representing endpoints of the ejaculate liquefaction. Here we identified proteases putatively involved in PCa specific protein cleavage, and examined gene expression and tissue protein levels, jointly with cell localization in normal prostate (nP), benign prostate hyperplasia (BPH), seminal vesicles and PCa using qPCR, Western blotting and confocal laser scanning microscopy. We found differential gene expression of chymase (CMA1), matrix metalloproteinases (MMP3, MMP7), and upregulation of MMP14 and tissue inhibitors (TIMP1 and TIMP2) in BPH. In contrast tissue protein levels of MMP14 were downregulated in PCa. MMP3/TIMP1 and MMP7/TIMP1 ratios were decreased in BPH. In seminal vesicles, we found low-level expression of most proteases and, interestingly, we also detected TIMP1 and low levels of TIMP2. We conclude that MMP3 and MMP7 activity is different in PCa compared to BPH due to fine regulation by their inhibitor TIMP1. Our findings support the concept of seminal plasma biomarkers as non-invasive tool for PCa detection and risk stratification. Full article
(This article belongs to the Special Issue Diagnostic, Prognostic and Predictive Biomarkers in Prostate Cancer)
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Open AccessReview Multiplexed Electrochemical Immunosensors for Clinical Biomarkers
by , and
Sensors 2017, 17(5), 965; doi:10.3390/s17050965
Received: 9 March 2017 / Revised: 10 April 2017 / Accepted: 24 April 2017 / Published: 27 April 2017
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Abstract
Management and prognosis of disease requires the accurate determination of specific biomarkers indicative of normal or disease-related biological processes or responses to therapy. Moreover since multiple determinations of biomarkers have demonstrated to provide more accurate information than individual determinations to assist the clinician
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Management and prognosis of disease requires the accurate determination of specific biomarkers indicative of normal or disease-related biological processes or responses to therapy. Moreover since multiple determinations of biomarkers have demonstrated to provide more accurate information than individual determinations to assist the clinician in prognosis and diagnosis, the detection of several clinical biomarkers by using the same analytical device hold enormous potential for early detection and personalized therapy and will simplify the diagnosis providing more information in less time. In this field, electrochemical immunosensors have demonstrated to offer interesting alternatives against conventional strategies due to their simplicity, fast response, low cost, high sensitivity and compatibility with multiplexed determination, microfabrication technology and decentralized determinations, features which made them very attractive for integration in point-of-care (POC) devices. Therefore, in this review, the relevance and current challenges of multiplexed determination of clinical biomarkers are briefly introduced, and an overview of the electrochemical immunosensing platforms developed so far for this purpose is given in order to demonstrate the great potential of these methodologies. After highlighting the main features of the selected examples, the unsolved challenges and future directions in this field are also briefly discussed. Full article
(This article belongs to the Special Issue Electrochemical Immunosensors)
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Open AccessReview Association of Polyphenol Biomarkers with Cardiovascular Disease and Mortality Risk: A Systematic Review and Meta-Analysis of Observational Studies
by , and
Nutrients 2017, 9(4), 415; doi:10.3390/nu9040415
Received: 24 March 2017 / Revised: 12 April 2017 / Accepted: 19 April 2017 / Published: 22 April 2017
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Abstract
Epidemiologic studies have suggested an inverse association between flavonoids and cardiovascular disease (CVD). However, the results might have been influenced by the use of dietary assessment methods, which are error prone. The aim of this paper was to systematically review and analyse the
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Epidemiologic studies have suggested an inverse association between flavonoids and cardiovascular disease (CVD). However, the results might have been influenced by the use of dietary assessment methods, which are error prone. The aim of this paper was to systematically review and analyse the literature for evidence of associations between polyphenol biomarkers and CVD and mortality risk in observational studies. Eligible studies were identified through PubMed, Web of Science, and reference lists. Multivariable adjusted associations were extracted. Data were log-transformed and pooled using the random effects model. In total, eight studies were included, investigating 16 different polyphenol biomarkers in association with CVD and mortality. Blood and urine were used as biospecimens, and enterolactone, a lignan metabolite, was most often investigated. Three meta-analyses were conducted investigating the association between enterolactone, and all-cause and CVD mortality, and non-fatal myocardial infarction. A 30% and 45% reduced all-cause and CVD mortality risk were revealed at higher enterolactone concentrations. Furthermore, inverse associations were observed between polyphenol biomarkers and all-cause mortality, kaempferol, and acute coronary syndrome. There is evidence to suggest that enterolactone is associated with a lower CVD mortality risk. This emphasises the importance of the role of the microbiota in disease prevention. To strengthen the evidence, more studies are warranted. Full article
(This article belongs to the Special Issue Effects of Polyphenol-Rich Foods on Human Health)
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Open AccessReview Electrochemical Genosensing of Circulating Biomarkers
by , and
Sensors 2017, 17(4), 866; doi:10.3390/s17040866
Received: 25 March 2017 / Revised: 11 April 2017 / Accepted: 12 April 2017 / Published: 14 April 2017
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Abstract
Management and prognosis of diseases requires the measurement in non- or minimally invasively collected samples of specific circulating biomarkers, consisting of any measurable or observable factors in patients that indicate normal or disease-related biological processes or responses to therapy. Therefore, on-site, fast and
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Management and prognosis of diseases requires the measurement in non- or minimally invasively collected samples of specific circulating biomarkers, consisting of any measurable or observable factors in patients that indicate normal or disease-related biological processes or responses to therapy. Therefore, on-site, fast and accurate determination of these low abundance circulating biomarkers in scarcely treated body fluids is of great interest for health monitoring and biological applications. In this field, electrochemical DNA sensors (or genosensors) have demonstrated to be interesting alternatives to more complex conventional strategies. Currently, electrochemical genosensors are considered very promising analytical tools for this purpose due to their fast response, low cost, high sensitivity, compatibility with microfabrication technology and simple operation mode which makes them compatible with point-of-care (POC) testing. In this review, the relevance and current challenges of the determination of circulating biomarkers related to relevant diseases (cancer, bacterial and viral infections and neurodegenerative diseases) are briefly discussed. An overview of the electrochemical nucleic acid–based strategies developed in the last five years for this purpose is given to show to both familiar and non-expert readers the great potential of these methodologies for circulating biomarker determination. After highlighting the main features of the reported electrochemical genosensing strategies through the critical discussion of selected examples, a conclusions section points out the still existing challenges and future directions in this field. Full article
(This article belongs to the Special Issue Genosensing)
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Open AccessReview Spondyloarthritis: Matrix Metalloproteinasesas Biomarkers of Pathogenesis and Response to Tumor Necrosis Factor (TNF) Inhibitors
by , , , , and
Int. J. Mol. Sci. 2017, 18(4), 830; doi:10.3390/ijms18040830
Received: 28 February 2017 / Revised: 5 April 2017 / Accepted: 10 April 2017 / Published: 14 April 2017
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Abstract
The term spondyloarthritis (SpA) is used to describe a group of multifactorial chronic inflammatory diseases characterized by a predisposing genetic background and clinical manifestations typically involving the sacroiliac joint. The absence of pathognomonic clinical and/or laboratory findings generally results in a delay in
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The term spondyloarthritis (SpA) is used to describe a group of multifactorial chronic inflammatory diseases characterized by a predisposing genetic background and clinical manifestations typically involving the sacroiliac joint. The absence of pathognomonic clinical and/or laboratory findings generally results in a delay in diagnosis and, consequently, in treatment. In addition, 20–40% of SpA patients are non-responders to tumor necrosis factor (TNF) inhibitor therapies. Given these considerations, it is important to identify biomarkers that can facilitate the diagnosis and assessment of disease activity. As inflammation plays a key role in the pathogenesis of SpA, inflammatory mediators have been investigated as potential biomarkers for diagnosing the disease and predicting response to therapy. Some investigators have focused their attention on the role of matrix metalloproteinases (MMPs), which are known to be markers of synovial inflammation that is generated in the joint in reaction to inflammatory stimuli. Several studies have been carried out to verify if serum MMPs levels could be useful to diagnose SpA, to assess disease severity, and to predict response to TNF inhibitor therapy. The current review focuses on MMPs’ role in SpA pathogenesis, diagnosis and therapeutic implications. Full article
(This article belongs to the Special Issue Metalloproteins 2017)
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Open AccessReview Drug Induced Liver Injury: Can Biomarkers Assist RUCAM in Causality Assessment?
by , , and
Int. J. Mol. Sci. 2017, 18(4), 803; doi:10.3390/ijms18040803
Received: 24 February 2017 / Revised: 31 March 2017 / Accepted: 1 April 2017 / Published: 11 April 2017
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Abstract
Drug induced liver injury (DILI) is a potentially serious adverse reaction in a few susceptible individuals under therapy by various drugs. Health care professionals facing DILI are confronted with a wealth of drug-unrelated liver diseases with high incidence and prevalence rates, which can
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Drug induced liver injury (DILI) is a potentially serious adverse reaction in a few susceptible individuals under therapy by various drugs. Health care professionals facing DILI are confronted with a wealth of drug-unrelated liver diseases with high incidence and prevalence rates, which can confound the DILI diagnosis. Searching for alternative causes is a key element of RUCAM (Roussel Uclaf Causality Assessment Method) to assess rigorously causality in suspected DILI cases. Diagnostic biomarkers as blood tests would be a great help to clinicians, regulators, and pharmaceutical industry would be more comfortable if, in addition to RUCAM, causality of DILI can be confirmed. High specificity and sensitivity are required for any diagnostic biomarker. Although some risk factors are available to evaluate liver safety of drugs in patients, no valid diagnostic or prognostic biomarker exists currently for idiosyncratic DILI when a liver injury occurred. Identifying a biomarker in idiosyncratic DILI requires detailed knowledge of cellular and biochemical disturbances leading to apoptosis or cell necrosis and causing leakage of specific products in blood. As idiosyncratic DILI is typically a human disease and hardly reproducible in animals, pathogenetic events and resulting possible biomarkers remain largely undisclosed. Potential new diagnostic biomarkers should be evaluated in patients with DILI and RUCAM-based established causality. In conclusion, causality assessment in cases of suspected idiosyncratic DILI is still best achieved using RUCAM since specific biomarkers as diagnostic blood tests that could enhance RUCAM results are not yet available. Full article
(This article belongs to the Special Issue Molecular Research on Drug Induced Liver Injury)
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Open AccessReview Theranostic Biomarkers for Schizophrenia
by , , , , and
Int. J. Mol. Sci. 2017, 18(4), 733; doi:10.3390/ijms18040733
Received: 28 February 2017 / Revised: 23 March 2017 / Accepted: 27 March 2017 / Published: 30 March 2017
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Abstract
Schizophrenia is a highly heritable, chronic, severe, disabling neurodevelopmental brain disorder with a heterogeneous genetic and neurobiological background, which is still poorly understood. To allow better diagnostic procedures and therapeutic strategies in schizophrenia patients, use of easy accessible biomarkers is suggested. The most
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Schizophrenia is a highly heritable, chronic, severe, disabling neurodevelopmental brain disorder with a heterogeneous genetic and neurobiological background, which is still poorly understood. To allow better diagnostic procedures and therapeutic strategies in schizophrenia patients, use of easy accessible biomarkers is suggested. The most frequently used biomarkers in schizophrenia are those associated with the neuroimmune and neuroendocrine system, metabolism, different neurotransmitter systems and neurotrophic factors. However, there are still no validated and reliable biomarkers in clinical use for schizophrenia. This review will address potential biomarkers in schizophrenia. It will discuss biomarkers in schizophrenia and propose the use of specific blood-based panels that will include a set of markers associated with immune processes, metabolic disorders, and neuroendocrine/neurotrophin/neurotransmitter alterations. The combination of different markers, or complex multi-marker panels, might help in the discrimination of patients with different underlying pathologies and in the better classification of the more homogenous groups. Therefore, the development of the diagnostic, prognostic and theranostic biomarkers is an urgent and an unmet need in psychiatry, with the aim of improving diagnosis, therapy monitoring, prediction of treatment outcome and focus on the personal medicine approach in order to improve the quality of life in patients with schizophrenia and decrease health costs worldwide. Full article
(This article belongs to the Special Issue Schizophrenia: Pathophysiology, Diagnostics, Therapies, and Prevention)
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Open AccessOpinion A Perspective on Ovarian Cancer Biomarkers: Past, Present and Yet-To-Come
by
Diagnostics 2017, 7(1), 14; doi:10.3390/diagnostics7010014
Received: 7 January 2017 / Revised: 15 February 2017 / Accepted: 23 February 2017 / Published: 8 March 2017
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Abstract
The history of biomarkers and ultrasonography dates back over more than 50 years. The present status of biomarkers used in the context of ovarian cancer is addressed. Attention is given to new interpretations of the etiology of ovarian cancer. Cancer antigen 125 (CA125)
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The history of biomarkers and ultrasonography dates back over more than 50 years. The present status of biomarkers used in the context of ovarian cancer is addressed. Attention is given to new interpretations of the etiology of ovarian cancer. Cancer antigen 125 (CA125) and multivariate index assays (Ova1, Risk of Ovarian Malignancy Algorithm, Overa) are biomarker-driven considerations that are presented. Integration of biomarkers into ovarian cancer diagnostics and screening are presented in conjunction with ultrasound. Consideration is given to the serial application of both biomarkers and ultrasound, as well as morphology-based indices. Attempts are made to foresee how individualized molecular signatures may be able to both provide an alert of the potential for ovarian cancer and to provide molecular treatments tailored to a personalized genetic signature. In the future, an annual pelvic ultrasound and a comprehensive serum biomarker screening/diagnostic panel may replace the much maligned bimanual examination as part of the annual gynecologic examination. Taken together, it is likely that a new medical specialty for screening and early diagnostics will emerge for physicians and epidemiologists, a field of study that is independent of patient gender, organ, or the subspecialties of today. Full article
(This article belongs to the Special Issue Ovarian Cancer Screening)
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Open AccessReview Biomarkers in Pediatric Community-Acquired Pneumonia
by and
Int. J. Mol. Sci. 2017, 18(2), 447; doi:10.3390/ijms18020447
Received: 31 December 2016 / Revised: 7 February 2017 / Accepted: 13 February 2017 / Published: 19 February 2017
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Abstract
Community-acquired pneumonia (CAP) is an infectious disease caused by bacteria, viruses, or a combination of these infectious agents. The severity of the clinical manifestations of CAP varies significantly. Consequently, both the differentiation of viral from bacterial CAP cases and the accurate assessment and
[...] Read more.
Community-acquired pneumonia (CAP) is an infectious disease caused by bacteria, viruses, or a combination of these infectious agents. The severity of the clinical manifestations of CAP varies significantly. Consequently, both the differentiation of viral from bacterial CAP cases and the accurate assessment and prediction of disease severity are critical for effectively managing individuals with CAP. To solve questionable cases, several biomarkers indicating the etiology and severity of CAP have been studied. Unfortunately, only a few studies have examined the roles of these biomarkers in pediatric practice. The main aim of this paper is to detail current knowledge regarding the use of biomarkers to diagnose and treat CAP in children, analyzing the most recently published relevant studies. Despite several attempts, the etiologic diagnosis of pediatric CAP and the estimation of the potential outcome remain unsolved problems in most cases. Among traditional biomarkers, procalcitonin (PCT) appears to be the most effective for both selecting bacterial cases and evaluating the severity. However, a precise cut-off separating bacterial from viral and mild from severe cases has not been defined. The three-host protein assay based on C-reactive protein (CRP), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), plasma interferon-γ protein-10 (IP-10), and micro-array-based whole genome expression arrays might offer more advantages in comparison with former biomarkers. However, further studies are needed before the routine use of those presently in development can be recommended. Full article
(This article belongs to the Special Issue Pneumonia: Pathogenesis, Diagnostics, Therapeutics, and Prevention)
Open AccessReview Detecting Blood-Based Biomarkers in Metastatic Breast Cancer: A Systematic Review of Their Current Status and Clinical Utility
by , , , and
Int. J. Mol. Sci. 2017, 18(2), 363; doi:10.3390/ijms18020363
Received: 20 December 2016 / Revised: 27 January 2017 / Accepted: 3 February 2017 / Published: 9 February 2017
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Abstract
Reviews on circulating biomarkers in breast cancer usually focus on one single biomarker or a selective group of biomarkers. An overview summarizing the discovery and evaluation of all blood-based biomarkers in metastatic breast cancer is lacking. This systematic review aims to identify the
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Reviews on circulating biomarkers in breast cancer usually focus on one single biomarker or a selective group of biomarkers. An overview summarizing the discovery and evaluation of all blood-based biomarkers in metastatic breast cancer is lacking. This systematic review aims to identify the available evidence of known blood-based biomarkers in metastatic breast cancer, regarding their clinical utility and state-of-the-art position in the validation process. The initial search yielded 1078 original studies, of which 420 were assessed for eligibility. A total of 320 studies were included in the final synthesis. A Development, Evaluation and Application Chart (DEAC) of all biomarkers was developed. Most studies focus on identifying new biomarkers and search for relations between these biomarkers and traditional molecular characteristics. Biomarkers are usually investigated in only one study (68.8%). Only 9.8% of all biomarkers was investigated in more than five studies. Circulating tumor cells, gene expression within tumor cells and the concentration of secreted proteins are the most frequently investigated biomarkers in liquid biopsies. However, there is a lack of studies focusing on identifying the clinical utility of these biomarkers, by which the additional value still seems to be limited according to the investigated evidence. Full article
(This article belongs to the Special Issue Precision Medicine—From Bench to Bedside)
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Open AccessReview The Role of Lipid Biomarkers in Major Depression
by , , and
Healthcare 2017, 5(1), 5; doi:10.3390/healthcare5010005
Received: 28 October 2016 / Revised: 20 January 2017 / Accepted: 23 January 2017 / Published: 3 February 2017
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Abstract
In the UK, the lifetime-documented prevalence of major depressive disorder (MDD) is currently 10%. Despite its increasing prevalence and devastating impact on quality of life, the pathophysiological mechanisms underpinning MDD remain to be fully elucidated. Current theories of neurobiological components remain incomplete and
[...] Read more.
In the UK, the lifetime-documented prevalence of major depressive disorder (MDD) is currently 10%. Despite its increasing prevalence and devastating impact on quality of life, the pathophysiological mechanisms underpinning MDD remain to be fully elucidated. Current theories of neurobiological components remain incomplete and protein-centric, rendering pharmacological treatment options suboptimal. In this review, we highlight the pivotal role of lipids in intra- and inter-neuronal functioning, emphasising the potential use of lipids as biomarkers for MDD. The latter has significant implications for improving our understanding of MDD at the cellular and circuit level. There is particular focus on cholesterol (high and low density lipoprotein), omega-3, and omega-6 polyunsaturated fatty acids due to established evidence in the literature of a link between atherosclerotic disease and major depression. We argue that there is significant potential scope for the use of such peripheral biomarkers in the diagnosis, stratification and treatment of MDD. Full article
(This article belongs to the Special Issue Diet Quality)
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Open AccessReview Surface-Enhanced Raman Scattering-Based Immunoassay Technologies for Detection of Disease Biomarkers
by , , , and
Biosensors 2017, 7(1), 7; doi:10.3390/bios7010007
Received: 6 December 2016 / Revised: 2 January 2017 / Accepted: 3 January 2017 / Published: 12 January 2017
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Abstract
Detection of biomarkers is of vital importance in disease detection, management, and monitoring of therapeutic efficacy. Extensive efforts have been devoted to the development of novel diagnostic methods that detect and quantify biomarkers with higher sensitivity and reliability, contributing to better disease diagnosis
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Detection of biomarkers is of vital importance in disease detection, management, and monitoring of therapeutic efficacy. Extensive efforts have been devoted to the development of novel diagnostic methods that detect and quantify biomarkers with higher sensitivity and reliability, contributing to better disease diagnosis and prognosis. When it comes to such devastating diseases as cancer, these novel powerful methods allow for disease staging as well as detection of cancer at very early stages. Over the past decade, there have been some advances in the development of platforms for biomarker detection of diseases. The main focus has recently shifted to the development of simple and reliable diagnostic tests that are inexpensive, accurate, and can follow a patient’s disease progression and therapy response. The individualized approach in biomarker detection has been also emphasized with detection of multiple biomarkers in body fluids such as blood and urine. This review article covers the developments in Surface-Enhanced Raman Scattering (SERS) and related technologies with the primary focus on immunoassays. Limitations and advantages of the SERS-based immunoassay platform are discussed. The article thoroughly describes all components of the SERS immunoassay and highlights the superior capabilities of SERS readout strategy such as high sensitivity and simultaneous detection of a multitude of biomarkers. Finally, it introduces recently developed strategies for in vivo biomarker detection using SERS. Full article
(This article belongs to the Special Issue Raman and IR Spectroscopic Sensing)
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Open AccessReview Biomarkers in Lysosomal Storage Diseases
by , and
Diseases 2016, 4(4), 40; doi:10.3390/diseases4040040
Received: 22 July 2016 / Revised: 4 December 2016 / Accepted: 12 December 2016 / Published: 17 December 2016
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Abstract
A biomarker is generally an analyte that indicates the presence and/or extent of a biological process, which is in itself usually directly linked to the clinical manifestations and outcome of a particular disease. The biomarkers in the field of lysosomal storage diseases (LSDs)
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A biomarker is generally an analyte that indicates the presence and/or extent of a biological process, which is in itself usually directly linked to the clinical manifestations and outcome of a particular disease. The biomarkers in the field of lysosomal storage diseases (LSDs) have particular relevance where spectacular therapeutic initiatives have been achieved, most notably with the introduction of enzyme replacement therapy (ERT). There are two main types of biomarkers. The first group is comprised of those molecules whose accumulation is directly enhanced as a result of defective lysosomal function. These molecules represent the storage of the principal macro-molecular substrate(s) of a specific enzyme or protein, whose function is deficient in the given disease. In the second group of biomarkers, the relationship between the lysosomal defect and the biomarker is indirect. In this group, the biomarker reflects the effects of the primary lysosomal defect on cell, tissue, or organ functions. There is no “gold standard” among biomarkers used to diagnosis and/or monitor LSDs, but there are a number that exist that can be used to reasonably assess and monitor the state of certain organs or functions. A number of biomarkers have been proposed for the analysis of the most important LSDs. In this review, we will summarize the most promising biomarkers in major LSDs and discuss why these are the most promising candidates for screening systems. Full article
(This article belongs to the collection Lysosomal Storage Diseases)
Open AccessReview Metabolomics and Its Application in the Development of Discovering Biomarkers for Osteoporosis Research
by , , , , , , , , , , , and
Int. J. Mol. Sci. 2016, 17(12), 2018; doi:10.3390/ijms17122018
Received: 6 October 2016 / Revised: 17 November 2016 / Accepted: 28 November 2016 / Published: 2 December 2016
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Abstract
Osteoporosis is a progressive skeletal disorder characterized by low bone mass and increased risk of fracture in later life. The incidence and costs associated with treating osteoporosis cause heavy socio-economic burden. Currently, the diagnosis of osteoporosis mainly depends on bone mineral density and
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Osteoporosis is a progressive skeletal disorder characterized by low bone mass and increased risk of fracture in later life. The incidence and costs associated with treating osteoporosis cause heavy socio-economic burden. Currently, the diagnosis of osteoporosis mainly depends on bone mineral density and bone turnover markers. However, these indexes are not sensitive and accurate enough to reflect the osteoporosis progression. Metabolomics offers the potential for a holistic approach for clinical diagnoses and treatment, as well as understanding of the pathological mechanism of osteoporosis. In this review, we firstly describe the study subjects of osteoporosis and bio-sample preparation procedures for different analytic purposes, followed by illustrating the biomarkers with potentially predictive, diagnosis and pharmaceutical values when applied in osteoporosis research. Then, we summarize the published metabolic pathways related to osteoporosis. Furthermore, we discuss the importance of chronological data and combination of multi-omics in fully understanding osteoporosis. The application of metabolomics in osteoporosis could provide researchers the opportunity to gain new insight into the metabolic profiling and pathophysiological mechanisms. However, there is still much to be done to validate the potential biomarkers responsible for the progression of osteoporosis and there are still many details needed to be further elucidated. Full article
(This article belongs to the Special Issue Translational Molecular Medicine & Molecular Drug Discovery)
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Open AccessReview Advances in Lipidomics for Cancer Biomarkers Discovery
by , , , , , and
Int. J. Mol. Sci. 2016, 17(12), 1992; doi:10.3390/ijms17121992
Received: 29 September 2016 / Revised: 11 November 2016 / Accepted: 22 November 2016 / Published: 28 November 2016
Cited by 5 | Viewed by 850 | PDF Full-text (2034 KB) | HTML Full-text | XML Full-text
Abstract
Lipids play critical functions in cellular survival, proliferation, interaction and death, since they are involved in chemical-energy storage, cellular signaling, cell membranes, and cell–cell interactions. These cellular processes are strongly related to carcinogenesis pathways, particularly to transformation, progression, and metastasis, suggesting the bioactive
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Lipids play critical functions in cellular survival, proliferation, interaction and death, since they are involved in chemical-energy storage, cellular signaling, cell membranes, and cell–cell interactions. These cellular processes are strongly related to carcinogenesis pathways, particularly to transformation, progression, and metastasis, suggesting the bioactive lipids are mediators of a number of oncogenic processes. The current review gives a synopsis of a lipidomic approach in tumor characterization; we provide an overview on potential lipid biomarkers in the oncology field and on the principal lipidomic methodologies applied. The novel lipidomic biomarkers are reviewed in an effort to underline their role in diagnosis, in prognostic characterization and in prediction of therapeutic outcomes. A lipidomic investigation through mass spectrometry highlights new insights on molecular mechanisms underlying cancer disease. This new understanding will promote clinical applications in drug discovery and personalized therapy. Full article
(This article belongs to the Special Issue Metabolomic Technologies in Medicine)
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Open AccessArticle Research on the Relationships between Endogenous Biomarkers and Exogenous Toxic Substances of Acute Toxicity in Radix Aconiti
by , , , , , , and
Molecules 2016, 21(12), 1623; doi:10.3390/molecules21121623
Received: 13 October 2016 / Revised: 13 November 2016 / Accepted: 21 November 2016 / Published: 25 November 2016
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Abstract
Radix Aconiti, a classic traditional Chinese medicine (TCM), has been widely used throughout China for disease treatment due to its various pharmacological activities, such as anti-inflammatory, cardiotonic, and analgesic effects. However, improper use of Radix Aconiti often generated severe acute toxicity. Currently,
[...] Read more.
Radix Aconiti, a classic traditional Chinese medicine (TCM), has been widely used throughout China for disease treatment due to its various pharmacological activities, such as anti-inflammatory, cardiotonic, and analgesic effects. However, improper use of Radix Aconiti often generated severe acute toxicity. Currently, research on the toxic substances of Radix Aconiti is not rare. In our previous study, acute toxic biomarkers of Radix Aconiti have been found. However, few studies were available to find the relationships between these endogenous biomarkers and exogenous toxic substances. Therefore, in this study, toxic substances of Radix Aconiti have been found using UPLC-Q-TOF-MS technology. Then, we used biochemical indicators as a bridge to find the relationships between biomarkers and toxic substances of Radix Aconiti through Pearson correlation analysis and canonical correlation analysis (CCA). Finally, the CCA results showed that LysoPC(22:5) is related to 14-acetyl-talatisamine, mesaconitine, talatisamine and deoxyaconitine in varying degrees; l-acetylcarnitine is negatively correlated with deoxyaconitine and demethyl-14-acetylkaracoline; shikimic acid has a good correlation with karacoline, demethyl-14-acetylkaracoline and deoxyaconitine; and valine is correlated with talatisamine and deoxyaconitine. Research on these relationships provides an innovative way to interpret the toxic mechanism of traditional Chinese medicine, and plays a positive role in the overall study of TCM toxicity. Full article
(This article belongs to the collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)
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Open AccessReview Prostate Cancer Detection and Prognosis: From Prostate Specific Antigen (PSA) to Exosomal Biomarkers
by and
Int. J. Mol. Sci. 2016, 17(11), 1784; doi:10.3390/ijms17111784
Received: 13 September 2016 / Revised: 4 October 2016 / Accepted: 14 October 2016 / Published: 26 October 2016
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Abstract
Prostate specific antigen (PSA) remains the most used biomarker in the management of early prostate cancer (PCa), in spite of the problems related to false positive results and overdiagnosis. New biomarkers have been proposed in recent years with the aim of increasing specificity
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Prostate specific antigen (PSA) remains the most used biomarker in the management of early prostate cancer (PCa), in spite of the problems related to false positive results and overdiagnosis. New biomarkers have been proposed in recent years with the aim of increasing specificity and distinguishing aggressive from non-aggressive PCa. The emerging role of the prostate health index and the 4Kscore is reviewed in this article. Both are blood-based tests related to the aggressiveness of the tumor, which provide the risk of suffering PCa and avoiding negative biopsies. Furthermore, the use of urine has emerged as a non-invasive way to identify new biomarkers in recent years, including the PCA3 and TMPRSS2:ERG fusion gene. Available results about the PCA3 score showed its usefulness to decide the repetition of biopsy in patients with a previous negative result, although its relationship with the aggressiveness of the tumor is controversial. More recently, aberrant microRNA expression in PCa has been reported by different authors. Preliminary results suggest the utility of circulating and urinary microRNAs in the detection and prognosis of PCa. Although several of these new biomarkers have been recommended by different guidelines, large prospective and comparative studies are necessary to establish their value in PCa detection and prognosis. Full article
(This article belongs to the Special Issue Diagnostic, Prognostic and Predictive Biomarkers in Prostate Cancer)
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Open AccessReview Fluid Biomarkers of Traumatic Brain Injury and Intended Context of Use
by , , , and
Diagnostics 2016, 6(4), 37; doi:10.3390/diagnostics6040037
Received: 27 July 2016 / Revised: 27 September 2016 / Accepted: 30 September 2016 / Published: 18 October 2016
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Abstract
Traumatic brain injury (TBI) is one of the leading causes of death and disability around the world. The lack of validated biomarkers for TBI is a major impediment to developing effective therapies and improving clinical practice, as well as stimulating much work in
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Traumatic brain injury (TBI) is one of the leading causes of death and disability around the world. The lack of validated biomarkers for TBI is a major impediment to developing effective therapies and improving clinical practice, as well as stimulating much work in this area. In this review, we focus on different settings of TBI management where blood or cerebrospinal fluid (CSF) biomarkers could be utilized for predicting clinically-relevant consequences and guiding management decisions. Requirements that the biomarker must fulfill differ based on the intended context of use (CoU). Specifically, we focus on fluid biomarkers in order to: (1) identify patients who may require acute neuroimaging (cranial computerized tomography (CT) or magnetic resonance imaging (MRI); (2) select patients at risk for secondary brain injury processes; (3) aid in counseling patients about their symptoms at discharge; (4) identify patients at risk for developing postconcussive syndrome (PCS), posttraumatic epilepsy (PTE) or chronic traumatic encephalopathy (CTE); (5) predict outcomes with respect to poor or good recovery; (6) inform counseling as to return to work (RTW) or to play. Despite significant advances already made from biomarker-based studies of TBI, there is an immediate need for further large-scale studies focused on identifying and innovating sensitive and reliable TBI biomarkers. These studies should be designed with the intended CoU in mind. Full article
(This article belongs to the Special Issue Biomarkers in Blood 2016)
Open AccessArticle Potential Metabolic Biomarkers to Identify Interstitial Lung Abnormalities
by , , , , , , , , , , , , and
Int. J. Mol. Sci. 2016, 17(7), 1148; doi:10.3390/ijms17071148
Received: 23 March 2016 / Revised: 25 May 2016 / Accepted: 15 June 2016 / Published: 16 July 2016
Cited by 1 | Viewed by 641 | PDF Full-text (2518 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Determining sensitive biomarkers in the peripheral blood to identify interstitial lung abnormalities (ILAs) is essential for the simple early diagnosis of ILAs. This study aimed to determine serum metabolic biomarkers of ILAs and the corresponding pathogenesis. Three groups of subjects undergoing health screening,
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Determining sensitive biomarkers in the peripheral blood to identify interstitial lung abnormalities (ILAs) is essential for the simple early diagnosis of ILAs. This study aimed to determine serum metabolic biomarkers of ILAs and the corresponding pathogenesis. Three groups of subjects undergoing health screening, including healthy subjects, subjects with ILAs, and subjects who were healthy initially and with ILAs one year later (Healthy→ILAs), were recruited for this study. The metabolic profiles of all of the subjects’ serum were analyzed by liquid chromatography quadruple time-of-flight mass spectrometry. The metabolic characteristics of the ILAs subjects were discovered, and the corresponding biomarkers were predicted. The metabolomic data from the Healthy→ILAs subjects were collected for further verification. The results indicated that five serum metabolite alterations (up-regulated phosphatidylcholine, phosphatidic acid, betaine aldehyde and phosphatidylethanolamine, as well as down-regulated 1-acylglycerophosphocholine) were sensitive and reliable biomarkers for identifying ILAs. Perturbation of the corresponding biological pathways (RhoA signaling, mTOR/P70S6K signaling and phospholipase C signaling) might be at least partially responsible for the pathogenesis of ILAs. This study may provide a good template for determining the early diagnostic markers of subclinical disease status and for obtaining a better understanding of their pathogenesis. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Open AccessArticle Influence of Gender and SNPs in GPX1 Gene on Biomarkers of Selenium Status in Healthy Brazilians
by , , and
Nutrients 2016, 8(5), 81; doi:10.3390/nu8050081
Received: 2 December 2015 / Revised: 8 January 2016 / Accepted: 18 January 2016 / Published: 5 May 2016
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Abstract
Selenium (Se) status varies worldwide as a result of natural variation of Se content in soils, dietary pattern, and the presence of SNPs. Further, Se status in Brazilians and its relationship between genetic variation and Se biomarkers is unknown. This work investigated the
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Selenium (Se) status varies worldwide as a result of natural variation of Se content in soils, dietary pattern, and the presence of SNPs. Further, Se status in Brazilians and its relationship between genetic variation and Se biomarkers is unknown. This work investigated the association between SNPs in glutathione peroxidase genes and biomarkers of Se status in healthy Brazilians. The study was conducted in 116 healthy adults in São Paulo, Brazil. Plasma and erythrocyte Se were measured by HGFAAS. Erythrocyte GPx (eGPx) activity was measured spectrometrically in a biochemical analyzer. Genotypes were determined by real-time PCR using Taqman® Assays. eGPx activity was higher in females compared with males. Lower erythrocyte Se concentrations were found in heterozygous GC carriers for GPX1 rs8179169. eGPx activity was higher in females with the common genotypes, except for rs8179169. GC carriers for rs8179169 had lower erythrocyte Se in both genders, and only male carriers of the variant alleles of both rs1050450 and rs1800668 had higher eGPx activity. In conclusion, the genotype for SNPs in GPX1 and gender affected biomarkers of Se status in this pilot study with healthy Brazilians. Full article
Open AccessArticle Analysis of Potential Amino Acid Biomarkers in Brain Tissue and the Effect of Galangin on Cerebral Ischemia
by , , , , , , , and
Molecules 2016, 21(4), 438; doi:10.3390/molecules21040438
Received: 15 January 2016 / Revised: 23 March 2016 / Accepted: 28 March 2016 / Published: 6 April 2016
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Abstract
Galangin, a potent scavenger of free radicals, has been used as an herbal medicine for various ailments for centuries in Asia. With complex pathophysiology, ischemic stroke is one of the most frequent causes of death and disability worldwide. We have reported that galangin
[...] Read more.
Galangin, a potent scavenger of free radicals, has been used as an herbal medicine for various ailments for centuries in Asia. With complex pathophysiology, ischemic stroke is one of the most frequent causes of death and disability worldwide. We have reported that galangin provides direct protection against ischemic injury as a potential neuroprotective agent and has potential therapeutic effects on the changes of serum amino acids in ischemic stroke; however, the mechanism of the changes of amino acids in the ischemic brain tissue has not yet been clarified. In this paper, we explored brain tissue amino acid biomarkers in the acute phase of cerebral ischemia and the effect of galangin on those potential biomarkers. Finally, we identified that glutamic acid, alanine and aspartic acid showed significant changes (p < 0.05 or p < 0.01) in galangin-treated groups compared with vehicle-treated rats and the four enzymes associated with these three AAs’ metabolic pathways; GLUD1, SLC16A10, SLC1A1 and GPT were identified by multiplex interactions with the three amino acids. By metabolite-protein network analysis and molecular docking, six of 28 proteins were identified and might become potential galangin biomarkers for acute ischemic stroke. The data in our study provides thoughts for exploring the mechanism of disease, discovering new targets for drug candidates and elucidating the related regulatory signal network. Full article
(This article belongs to the collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)
Open AccessReview Epigenetic Regulation of Epidermal Stem Cell Biomarkers and Their Role in Wound Healing
by , , and
Int. J. Mol. Sci. 2016, 17(1), 16; doi:10.3390/ijms17010016
Received: 7 November 2015 / Revised: 11 December 2015 / Accepted: 16 December 2015 / Published: 24 December 2015
Cited by 2 | Viewed by 1356 | PDF Full-text (681 KB) | HTML Full-text | XML Full-text
Abstract
As an actively renewable tissue, changes in skin architecture are subjected to the regulation of stem cells that maintain the population of cells responsible for the formation of epidermal layers. Stems cells retain their self-renewal property and express biomarkers that are unique to
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As an actively renewable tissue, changes in skin architecture are subjected to the regulation of stem cells that maintain the population of cells responsible for the formation of epidermal layers. Stems cells retain their self-renewal property and express biomarkers that are unique to this population. However, differential regulation of the biomarkers can initiate the pathway of terminal cell differentiation. Although, pockets of non-clarity in stem cell maintenance and differentiation in skin still exist, the influence of epigenetics in epidermal stem cell functions and differentiation in skin homeostasis and wound healing is clearly evident. The focus of this review is to discuss the epigenetic regulation of confirmed and probable epidermal stem cell biomarkers in epidermal stratification of normal skin and in diseased states. The role of epigenetics in wound healing, especially in diseased states of diabetes and cancer, will also be conveyed. Full article
(This article belongs to the Section Biochemistry and Molecular Biology)
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Open AccessReview Serum Biomarkers of (Anti)Oxidant Status for Epidemiological Studies
by and
Int. J. Mol. Sci. 2015, 16(11), 27378-27390; doi:10.3390/ijms161126032
Received: 19 September 2015 / Revised: 30 October 2015 / Accepted: 2 November 2015 / Published: 16 November 2015
Cited by 3 | Viewed by 1409 | PDF Full-text (1718 KB) | HTML Full-text | XML Full-text
Abstract
In this review, we disclose a selection of serum/plasma biomarkers of (anti)oxidant status related to nutrition, which can be used for measurements in large-scale epidemiological studies. From personal experience, we have come to the following proposal of a set of biomarkers for nutritional
[...] Read more.
In this review, we disclose a selection of serum/plasma biomarkers of (anti)oxidant status related to nutrition, which can be used for measurements in large-scale epidemiological studies. From personal experience, we have come to the following proposal of a set of biomarkers for nutritional intake, (anti)oxidant status, and redox status. We have selected the individual antioxidant vitamins E and A, and the carotenoids which can be measured in large series by HPLC. In addition, vitamin C was selected, which can be measured by an auto-analyzer or HPLC. As a biomarker for oxidative stress, the ROM assay (reactive oxygen metabolites) was selected; for the redox status, the total thiol assay; and for the total antioxidant status the BAP assay (biological antioxidant potential). All of these biomarkers can be measured in large quantities by an auto-analyzer. Critical points in biomarker validation with respect to blood sampling, storage conditions, and measurements are discussed. With the selected biomarkers, a good set is presented for use in the risk assessment between nutrition and (chronic) diseases in large-scale epidemiological studies. Examples of the successful application of these biomarkers in large international studies are presented. Full article
(This article belongs to the Special Issue Antioxidant 2.0——Redox Modulation by Food and Drugs)
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Open AccessReview Early Pregnancy Biomarkers in Pre-Eclampsia: A Systematic Review and Meta-Analysis
by , , , , , , , and
Int. J. Mol. Sci. 2015, 16(9), 23035-23056; doi:10.3390/ijms160923035
Received: 31 July 2015 / Revised: 30 August 2015 / Accepted: 13 September 2015 / Published: 23 September 2015
Cited by 12 | Viewed by 1873 | PDF Full-text (2530 KB) | HTML Full-text | XML Full-text
Abstract
Pre-eclampsia (PE) complicates 2%–8% of all pregnancies and is an important cause of perinatal morbidity and mortality worldwide. In order to reduce these complications and to develop possible treatment modalities, it is important to identify women at risk of developing PE. The use
[...] Read more.
Pre-eclampsia (PE) complicates 2%–8% of all pregnancies and is an important cause of perinatal morbidity and mortality worldwide. In order to reduce these complications and to develop possible treatment modalities, it is important to identify women at risk of developing PE. The use of biomarkers in early pregnancy would allow appropriate stratification into high and low risk pregnancies for the purpose of defining surveillance in pregnancy and to administer interventions. We used formal methods for a systematic review and meta-analyses to assess the accuracy of all biomarkers that have been evaluated so far during the first and early second trimester of pregnancy to predict PE. We found low predictive values using individual biomarkers which included a disintegrin and metalloprotease 12 (ADAM-12), inhibin-A, pregnancy associated plasma protein A (PAPP-A), placental growth factor (PlGF) and placental protein 13 (PP-13). The pooled sensitivity of all single biomarkers was 0.40 (95% CI 0.39–0.41) at a false positive rate of 10%. The area under the Summary of Receiver Operating Characteristics Curve (SROC) was 0.786 (SE 0.02). When a combination model was used, the predictive value improved to an area under the SROC of 0.893 (SE 0.03). In conclusion, although there are multiple potential biomarkers for PE their efficacy has been inconsistent and comparisons are difficult because of heterogeneity between different studies. Therefore, there is an urgent need for high quality, large-scale multicentre research in biomarkers for PE so that the best predictive marker(s) can be identified in order to improve the management of women destined to develop PE. Full article
(This article belongs to the Special Issue Prediction, Diagnostics and Prevention of Pregnancy Complications)
Open AccessReview Biomarkers of Renal Disease and Progression in Patients with Diabetes
by , , and
J. Clin. Med. 2015, 4(5), 1010-1024; doi:10.3390/jcm4051010
Received: 22 March 2015 / Revised: 24 April 2015 / Accepted: 6 May 2015 / Published: 19 May 2015
Cited by 7 | Viewed by 1386 | PDF Full-text (180 KB) | HTML Full-text | XML Full-text
Abstract
Diabetes prevalence is increasing worldwide, mainly due to the increase in type 2 diabetes. Diabetic nephropathy occurs in up to 40% of people with type 1 or type 2 diabetes. It is important to identify patients at risk of diabetic nephropathy and those
[...] Read more.
Diabetes prevalence is increasing worldwide, mainly due to the increase in type 2 diabetes. Diabetic nephropathy occurs in up to 40% of people with type 1 or type 2 diabetes. It is important to identify patients at risk of diabetic nephropathy and those who will progress to end stage renal disease. In clinical practice, most commonly used markers of renal disease and progression are serum creatinine, estimated glomerular filtration rate and proteinuria or albuminuria. Unfortunately, they are all insensitive. This review summarizes the evidence regarding the prognostic value and benefits of targeting some novel risk markers for development of diabetic nephropathy and its progression. It is focused mainly on tubular biomarkers (neutrophil-gelatinase associated lipocalin, kidney injury molecule 1, liver-fatty acid-binding protein, N-acetyl-beta-d-glucosaminidase), markers of inflammation (pro-inflammatory cytokines, tumour necrosis factor-α and tumour necrosis factor-α receptors, adhesion molecules, chemokines) and markers of oxidative stress. Despite the promise of some of these new biomarkers, further large, multicenter prospective studies are still needed before they can be used in everyday clinical practice. Full article
(This article belongs to the Special Issue Diabetic Nephropathy)
Open AccessArticle Improved Blood Biomarkers but No Cognitive Effects from 16 Weeks of Multivitamin Supplementation in Healthy Older Adults
by , and
Nutrients 2015, 7(5), 3796-3812; doi:10.3390/nu7053796
Received: 30 March 2015 / Revised: 11 May 2015 / Accepted: 13 May 2015 / Published: 19 May 2015
Cited by 3 | Viewed by 1625 | PDF Full-text (676 KB) | HTML Full-text | XML Full-text
Abstract
Supplementation with vitamins, minerals and phytonutrients may be beneficial for cognition, especially in older adults. The aim of this study was to assess the effects of multivitamin supplementation in older adults on cognitive function and associated blood biomarkers. In a randomised, double blind,
[...] Read more.
Supplementation with vitamins, minerals and phytonutrients may be beneficial for cognition, especially in older adults. The aim of this study was to assess the effects of multivitamin supplementation in older adults on cognitive function and associated blood biomarkers. In a randomised, double blind, placebo-controlled trial, healthy women (n = 68) and men (n = 48) aged 55–65 years were supplemented daily for 16 weeks with women’s and men’s formula multivitamin supplements. Assessments at baseline and post-supplementation included computerised cognitive tasks and blood biomarkers relevant to cognitive aging. No cognitive improvements were observed after supplementation with either formula; however, several significant improvements were observed in blood biomarkers including increased levels of vitamins B6 and B12 in women and men; reduced C-reactive protein in women; reduced homocysteine and marginally reduced oxidative stress in men; as well as improvements to the lipid profile in men. In healthy older people, multivitamin supplementation improved a number of blood biomarkers that are relevant to cognition, but these biomarker changes were not accompanied by improved cognitive function. Full article
(This article belongs to the Special Issue Nutrition in Cognitive Function)
Open AccessReview A Review of the Pathophysiology and Potential Biomarkers for Peripheral Artery Disease
by , and
Int. J. Mol. Sci. 2015, 16(5), 11294-11322; doi:10.3390/ijms160511294
Received: 16 February 2015 / Revised: 29 March 2015 / Accepted: 8 April 2015 / Published: 18 May 2015
Cited by 14 | Viewed by 1735 | PDF Full-text (981 KB) | HTML Full-text | XML Full-text
Abstract
Peripheral artery disease (PAD) is due to the blockage of the arteries supplying blood to the lower limbs usually secondary to atherosclerosis. The most severe clinical manifestation of PAD is critical limb ischemia (CLI), which is associated with a risk of limb loss
[...] Read more.
Peripheral artery disease (PAD) is due to the blockage of the arteries supplying blood to the lower limbs usually secondary to atherosclerosis. The most severe clinical manifestation of PAD is critical limb ischemia (CLI), which is associated with a risk of limb loss and mortality due to cardiovascular events. Currently CLI is mainly treated by surgical or endovascular revascularization, with few other treatments in routine clinical practice. There are a number of problems with current PAD management strategies, such as the difficulty in selecting the appropriate treatments for individual patients. Many patients undergo repeated attempts at revascularization surgery, but ultimately require an amputation. There is great interest in developing new methods to identify patients who are unlikely to benefit from revascularization and to improve management of patients unsuitable for surgery. Circulating biomarkers that predict the progression of PAD and the response to therapies could assist in the management of patients. This review provides an overview of the pathophysiology of PAD and examines the association between circulating biomarkers and PAD presence, severity and prognosis. While some currently identified circulating markers show promise, further larger studies focused on the clinical value of the biomarkers over existing risk predictors are needed. Full article
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)
Open AccessCommunication New Developments in Biomarkers for Atopic Dermatitis
by , , , and
J. Clin. Med. 2015, 4(3), 479-487; doi:10.3390/jcm4030479
Received: 23 December 2014 / Revised: 9 February 2015 / Accepted: 24 February 2015 / Published: 16 March 2015
Cited by 6 | Viewed by 1506 | PDF Full-text (50 KB) | HTML Full-text | XML Full-text
Abstract
The application of biomarkers in medicine is evolving. Biomarkers do not only give us a better understanding of pathogenesis, but also increase treatment efficacy and safety, further enabling more precise clinical care. This paper focuses on the current use of biomarkers in atopic
[...] Read more.
The application of biomarkers in medicine is evolving. Biomarkers do not only give us a better understanding of pathogenesis, but also increase treatment efficacy and safety, further enabling more precise clinical care. This paper focuses on the current use of biomarkers in atopic dermatitis, new developments and future perspectives. Biomarkers can be used for many different purposes, including the objective determination of disease severity, confirmation of clinical diagnosis, and to predict response to treatment. In atopic dermatitis, many biomarkers have been investigated as a marker for disease severity. Currently serum thymus and activation-regulated chemokine (TARC) is the superior biomarker for assessing disease severity. However, we have recently shown that the use of a panel of serum biomarkers is more suitable for assessing disease severity than an individual biomarker. In this overview, we will discuss alternative sources for biomarkers, such as saliva and capillary blood, which can increase the user friendliness of biomarkers in atopic dermatitis (AD). Both methods offer simple, non-invasive and cost effective alternatives to venous blood. This provides great translational and clinical potential. Biomarkers will play an increasingly important role in AD research and personalized medicine. The use of biomarkers will enhance the efficacy of AD treatment by facilitating the individualization of therapy targeting the patients’ specific biological signature and also by providing tools for predicting and monitoring of therapeutic response. Full article
(This article belongs to the Special Issue Epidemiology and Treatment of Atopic Eczema)
Open AccessReview Emerging Biomarkers in Heart Failure and Cardiac Cachexia
by , , , and
Int. J. Mol. Sci. 2014, 15(12), 23878-23896; doi:10.3390/ijms151223878
Received: 8 November 2014 / Revised: 11 December 2014 / Accepted: 11 December 2014 / Published: 22 December 2014
Cited by 9 | Viewed by 1797 | PDF Full-text (748 KB) | HTML Full-text | XML Full-text
Abstract
Biomarkers are objective tools with an important role for diagnosis, prognosis and therapy optimization in patients with heart failure (HF). To date, natriuretic peptides are closest to optimal biomarker standards for clinical implications in HF. Therefore, the efforts to identify and test new
[...] Read more.
Biomarkers are objective tools with an important role for diagnosis, prognosis and therapy optimization in patients with heart failure (HF). To date, natriuretic peptides are closest to optimal biomarker standards for clinical implications in HF. Therefore, the efforts to identify and test new biomarkers in HF are reasonable and justified. Along the natural history of HF, cardiac cachexia may develop, and once at this stage, patient performance and prognosis is particularly poor. For these reasons, numerous biomarkers reflecting hormonal, inflammatory and oxidative stress pathways have been investigated, but only a few convey relevant information. The complex pathophysiology of HF appears far too complex to be embraced by a single biomarker; thus, a combined approach appears reasonable. With these considerations, we have reviewed the recent developments in the field to highlight key candidates with diagnostic, prognostic and therapy optimization properties, either alone or in combination. Full article
(This article belongs to the Special Issue Emerging Classes of Biomarkers for Molecular Diagnostics)
Open AccessReview MicroRNA Signatures as Biomarkers and Therapeutic Target for CNS Embryonal Tumors: The Pros and the Cons
by , , and
Int. J. Mol. Sci. 2014, 15(11), 21554-21586; doi:10.3390/ijms151121554
Received: 19 September 2014 / Revised: 7 November 2014 / Accepted: 8 November 2014 / Published: 24 November 2014
Cited by 11 | Viewed by 1602 | PDF Full-text (1422 KB) | HTML Full-text | XML Full-text
Abstract
Embryonal tumors of the central nervous system represent a heterogeneous group of childhood cancers with an unknown pathogenesis; diagnosis, on the basis of histological appearance alone, is controversial and patients’ response to therapy is difficult to predict. They encompass medulloblastoma, atypical teratoid/rhabdoid tumors
[...] Read more.
Embryonal tumors of the central nervous system represent a heterogeneous group of childhood cancers with an unknown pathogenesis; diagnosis, on the basis of histological appearance alone, is controversial and patients’ response to therapy is difficult to predict. They encompass medulloblastoma, atypical teratoid/rhabdoid tumors and a group of primitive neuroectodermal tumors. All are aggressive tumors with the tendency to disseminate throughout the central nervous system. The large amount of genomic and molecular data generated over the last 5–10 years encourages optimism that new molecular targets will soon improve outcomes. Recent neurobiological studies have uncovered the key role of microRNAs (miRNAs) in embryonal tumors biology and their potential use as biomarkers is increasingly being recognized and investigated. However the successful use of microRNAs as reliable biomarkers for the detection and management of pediatric brain tumors represents a substantial challenge. This review debates the importance of miRNAs in the biology of central nervous systemembryonal tumors focusing on medulloblastoma and atypical teratoid/rhabdoid tumors and highlights the advantages as well as the limitations of their prospective application as biomarkers and candidates for molecular therapeutic targets. Full article
(This article belongs to the collection Regulation by Non-Coding RNAs)
Open AccessArticle Circulating Biomarkers in Advanced Colorectal Cancer Patients Randomly Assigned to Three Bevacizumab-Based Regimens
by , , , , , , , , , , and
Cancers 2014, 6(3), 1753-1768; doi:10.3390/cancers6031753
Received: 21 February 2014 / Revised: 8 August 2014 / Accepted: 11 August 2014 / Published: 29 August 2014
Cited by 6 | Viewed by 1570 | PDF Full-text (1169 KB) | HTML Full-text | XML Full-text
Abstract
The need to identify biomarkers for bevacizumab-based treatment in advanced colorectal cancer is imperative. The aim of this study was to investigate the prognostic role of circulating VEGF, PDGF, SDF-1, osteopontin and CEA in patients randomly assigned to three bevacizumab-based regimens. Plasma samples
[...] Read more.
The need to identify biomarkers for bevacizumab-based treatment in advanced colorectal cancer is imperative. The aim of this study was to investigate the prognostic role of circulating VEGF, PDGF, SDF-1, osteopontin and CEA in patients randomly assigned to three bevacizumab-based regimens. Plasma samples from 50 patients treated at a single Institution were analysed using the multiplex assay BioPlex™ 2200 (Bio-Rad Laboratories, Inc, Berkeley, CA, USA) at baseline, before first three cycles and subsequently every three cycles until disease progression. Prognostic analyses of baseline values were performed using multivariable Cox models, including disease extension >10 cm or ≤10 cm (measured as the sum of the diameters for all target lesions) as adjustment factor. The association between progression-free and overall survival and biomarkers modulation during treatment was studied using multivariable Cox models, which included summary statistics synthesizing during-treatment modulation together with disease extension. The biomarkers significantly associated with disease extension were baseline CEA (p = 0.012) and SDF-1 (p = 0.030). High values of VEGF and SDF-1 tended to be associated with worse prognosis, especially in terms of overall survival. The negative prognostic trend was more marked for baseline CEA as compared to other biomarkers; increasing values during treatment was significantly related to worse prognosis independently of disease extension (p = 0.007 and 0.016 for progression-free and overall survival, respectively). VEGF is related to bevacizumab pharmacodynamics and is associated to other angiogenic cytokines; some of the proposed biomarkers such as SDF-1 and CEA should be further validated for prognosis assessment and monitoring of bevacizumab-based treatment of advanced colorectal cancer. Full article
(This article belongs to the Special Issue Cancer Drug Resistance)
Open AccessReview Established and Emerging Biomarkers in Cutaneous Malignant Melanoma
by , and
Healthcare 2014, 2(1), 60-73; doi:10.3390/healthcare2010060
Received: 27 September 2013 / Revised: 4 December 2013 / Accepted: 7 January 2014 / Published: 14 January 2014
Viewed by 1537 | PDF Full-text (108 KB) | HTML Full-text | XML Full-text
Abstract
In an era of personalized medicine, disease specific biomarkers play an increasing role in the stratification of high-risk patient groups. Cutaneous malignant melanoma is the most deadly form of skin cancer with an ever-increasing global incidence, especially in patients under 35-years of age.
[...] Read more.
In an era of personalized medicine, disease specific biomarkers play an increasing role in the stratification of high-risk patient groups. Cutaneous malignant melanoma is the most deadly form of skin cancer with an ever-increasing global incidence, especially in patients under 35-years of age. Despite the excellent prognosis for patients diagnosed with early stage disease, metastatic disease still carries significant overall mortality. Biomarkers aim not only to identify high-risk patients, but also to provide potential therapeutic targets for differing patient subgroups. Furthermore, accessibility to tissue samples from a range of disease stages in malignant melanoma, unlike most other solid tissue tumours, provides the unique opportunity to explore the biology of tumour progression that may be relevant in the biology of cancer as a whole. Over the past decade, there have been major advances in targeted therapies, providing new avenues and hope to patients with this devastating disease. This review will focus on most up to date histological, serological and molecular biomarkers in malignant melanoma. Full article
(This article belongs to the Special Issue Melanoma and Neoplasms of Skin)
Open AccessArticle Evaluation of Individual and Combined Applications of Serum Biomarkers for Diagnosis of Hepatocellular Carcinoma: A Meta-Analysis
by , , and
Int. J. Mol. Sci. 2013, 14(12), 23559-23580; doi:10.3390/ijms141223559
Received: 10 September 2013 / Revised: 31 October 2013 / Accepted: 7 November 2013 / Published: 2 December 2013
Cited by 30 | Viewed by 2397 | PDF Full-text (490 KB) | HTML Full-text | XML Full-text
Abstract
The clinical value of Serum alpha-fetoprotein (AFP) to detect early hepatocellular carcinoma (HCC) has been questioned due to its low sensitivity and specificity found in recent years. Other than AFP, several new serum biomarkers including the circulating AFP isoform AFP-L3, des-gamma-carboxy prothrombin (DCP)
[...] Read more.
The clinical value of Serum alpha-fetoprotein (AFP) to detect early hepatocellular carcinoma (HCC) has been questioned due to its low sensitivity and specificity found in recent years. Other than AFP, several new serum biomarkers including the circulating AFP isoform AFP-L3, des-gamma-carboxy prothrombin (DCP) and Golgi protein-73 (GP73) have been identified as useful HCC markers. In this investigation, we review the current knowledge about these HCC-related biomarkers, and sum up the results of our meta-analysis on studies that have addressed the utility of these biomarkers in early detection and prognostic prediction of HCC. A systematic search in PubMed, Web of Science, and the Cochrane Library was performed for articles published in English from 1999 to 2012, focusing on serum biomarkers for HCC detection. Data on sensitivity and specificity of tests were extracted from 40 articles that met the inclusion criteria, and the summary receiver operating characteristic curve (sROC) was obtained. A meta-analysis was carried out in which the area under the curve (AUC) for each biomarker or biomarker combinations (AFP, DCP, GP73, AFP-L3, AFP + DCP, AFP + AFP-L3, and AFP + GP73) was used to compare the diagnostic accuracy of different biomarker tests. The AUC of AFP, DCP, GP73, AFP-L3, AFP + DCP, AFP + AFP-L3, and AFP + GP73 are 0.835, 0.797, 0.914, 0.710, 0.874, 0.748, and 0.932 respectively. A combination of AFP + GP73 is superior to AFP in detecting HCC and differentiating HCC patients from non-HCC patients, and may prove to be a useful marker in the diagnosis and screening of HCC. In addition, the AUC of GP73, AFP + DCP and AFP + GP73 are better than that of AFP. The clinical value of GP73, AFP + DCP, or AFP + GP73 as serological markers for HCC diagnosis needs to be addressed further in future studies. Full article
(This article belongs to the Special Issue Advances in Cancer Diagnosis)
Open AccessReview High-Throughput Proteomic Approaches to the Elucidation of Potential Biomarkers of Chronic Allograft Injury (CAI)
by , , , , and
Proteomes 2013, 1(2), 159-179; doi:10.3390/proteomes1020159
Received: 19 July 2013 / Revised: 6 September 2013 / Accepted: 9 September 2013 / Published: 23 September 2013
Cited by 1 | Viewed by 1719 | PDF Full-text (944 KB) | HTML Full-text | XML Full-text
Abstract
This review focuses on the role of OMICs technologies, concentrating in particular on proteomics, in biomarker discovery in chronic allograft injury (CAI). CAI is the second most prevalent cause of allograft dysfunction and loss in the first decade post-transplantation, after death with functioning
[...] Read more.
This review focuses on the role of OMICs technologies, concentrating in particular on proteomics, in biomarker discovery in chronic allograft injury (CAI). CAI is the second most prevalent cause of allograft dysfunction and loss in the first decade post-transplantation, after death with functioning graft (DWFG). The term CAI, sometimes referred to as chronic allograft nephropathy (CAN), describes the deterioration of renal allograft function and structure as a result of immunological processes (chronic antibody-mediated rejection), and other non-immunological factors such as calcineurin inhibitor (CNI) induced nephrotoxicity, hypertension and infection. Current methods for assessing allograft function are costly, insensitive and invasive; traditional kidney function measurements such as serum creatinine and glomerular filtration rate (GFR) display poor predictive abilities, while the current “gold-standard” involving histological diagnosis with a renal biopsy presents its own inherent risks to the overall health of the allograft. As early as two years post-transplantation, protocol biopsies have shown more than 50% of allograft recipients have mild CAN; ten years post-transplantation more than 50% of the allograft recipients have progressed to severe CAN which is associated with diminishing graft function. Thus, there is a growing medical requirement for minimally invasive biomarkers capable of identifying the early stages of the disease which would allow for timely intervention. Proteomics involves the study of the expression, localization, function and interaction of the proteome. Proteomic technologies may be powerful tools used to identify novel biomarkers which would predict CAI in susceptible individuals. In this paper we will review the use of proteomics in the elucidation of novel predictive biomarkers of CAI in clinical, animal and in vitro studies. Full article
(This article belongs to the Special Issue Insights and Trends into Proteome Science)
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Open AccessReview Emerging Biomarkers in Glioblastoma
by , and
Cancers 2013, 5(3), 1103-1119; doi:10.3390/cancers5031103
Received: 29 June 2013 / Revised: 14 August 2013 / Accepted: 19 August 2013 / Published: 22 August 2013
Cited by 25 | Viewed by 2979 | PDF Full-text (400 KB) | HTML Full-text | XML Full-text
Abstract
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.
[...] Read more.
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. Full article
(This article belongs to the Special Issue Glioblastoma)
Open AccessReview MicroRNAs as Biomarkers in Cancer
by , and
Diagnostics 2013, 3(1), 84-104; doi:10.3390/diagnostics3010084
Received: 15 November 2012 / Revised: 28 December 2012 / Accepted: 14 January 2013 / Published: 16 January 2013
Cited by 3 | Viewed by 3540 | PDF Full-text (715 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRNAs) are small non-coding RNA molecules, which in recent years have emerged to have enormous potential as biomarkers. Recently, there have been significant developments in understanding miRNA biogenesis, their regulatory mechanisms and role in disease process, and their potential as effective therapies.
[...] Read more.
MicroRNAs (miRNAs) are small non-coding RNA molecules, which in recent years have emerged to have enormous potential as biomarkers. Recently, there have been significant developments in understanding miRNA biogenesis, their regulatory mechanisms and role in disease process, and their potential as effective therapies. The identification of miRNAs as biomarkers provides possibilities for development of less or non-invasive and more specific methods for monitoring tumor growth and progression. This review summarizes the recent developments in methods to detect and quantitate miRNAs in body fluids and their applications as biomarkers in cancers. The prospect of miRNAs as potential diagnostic and prognostic biomarkers with clinical applications is significant as more evidence points to their central role in cancer pathobiology. Full article
(This article belongs to the Special Issue Molecular Biomarkers for Cancer Targeted Therapeutics)
Open AccessReview Biomarkers in Tumor Angiogenesis and Anti-Angiogenic Therapy
by , , , , and
Int. J. Mol. Sci. 2011, 12(10), 7077-7099; doi:10.3390/ijms12107077
Received: 15 August 2011 / Accepted: 9 October 2011 / Published: 21 October 2011
Cited by 38 | Viewed by 3763 | PDF Full-text (261 KB) | HTML Full-text | XML Full-text
Abstract
Tumor angiogenesis has been identified to play a critical role in tumor growth and tumor progression, and is regulated by a balance of angiogenic and anti-angiogenic cytokines. Among them VEGF (vascular endothelial growth factor) and its signaling through its receptors are of crucial
[...] Read more.
Tumor angiogenesis has been identified to play a critical role in tumor growth and tumor progression, and is regulated by a balance of angiogenic and anti-angiogenic cytokines. Among them VEGF (vascular endothelial growth factor) and its signaling through its receptors are of crucial relevance. Inhibition of VEGF signaling by monoclonal antibodies or small molecules (kinase inhibitors) has already been successfully established for the treatment of different cancer entities and multiple new drugs are being tested in clinical trials. However not all patients are likely to respond to these therapies, but to date there are no reliable biomarkers available to predict therapy response. Many studies integrated biomarker programs in their study protocols, thus several potential biomarkers have been identified which are currently under clinical investigation in prospective randomized studies. This review intends to give an overview of the described potential biomarkers as well as different imaging techniques such as ultrasound and magnetic resonance imaging that can indicate benefit, resistance and toxicity to anti-angiogenic therapies. Full article
(This article belongs to the Special Issue Biomarkers 2011)
Open AccessReview Prognostic Value of Colorectal Cancer Biomarkers
by , , and
Cancers 2011, 3(2), 2080-2105; doi:10.3390/cancers3022080
Received: 18 February 2011 / Revised: 21 March 2011 / Accepted: 23 March 2011 / Published: 19 April 2011
Viewed by 3664 | PDF Full-text (280 KB) | HTML Full-text | XML Full-text
Abstract
Despite the large amount of data in cancer biology and many studies into the likely survival of colorectal cancer (CRC) patients, knowledge regarding the issue of CRC prognostic biomarkers remains poor. The Tumor-Node-Metastasis (TNM) staging system continues to be the most powerful and
[...] Read more.
Despite the large amount of data in cancer biology and many studies into the likely survival of colorectal cancer (CRC) patients, knowledge regarding the issue of CRC prognostic biomarkers remains poor. The Tumor-Node-Metastasis (TNM) staging system continues to be the most powerful and reliable predictor of the clinical outcome of CRC patients. The exponential increase of knowledge in the field of molecular genetics has lead to the identification of specific alterations involved in the malignant progression. Many of these genetic alterations were proposed as biomarkers which could be used in clinical practice to estimate CRC prognosis. Recently there has been an explosive increase in the number of putative biomarkers able to predict the response to specific adjuvant treatment. In this review we explore and summarize data concerning prognostic and predictive biomarkers and we attempt to shed light on recent research that could lead to the emergence of new biomarkers in CRC. Full article
(This article belongs to the Special Issue Prognostic and Predictive Factors in Colorectal Cancer)
Open AccessReview Isoprostanes-Biomarkers of Lipid Peroxidation: Their Utility in Evaluating Oxidative Stress and Analysis
by , , and
Int. J. Mol. Sci. 2010, 11(11), 4631-4659; doi:10.3390/ijms11114631
Received: 29 September 2010 / Revised: 29 October 2010 / Accepted: 16 November 2010 / Published: 17 November 2010
Cited by 39 | Viewed by 4644 | PDF Full-text (569 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Isoprostanes (IsoPs) are key biomarkers for investigating the role of free radical generation in the pathogenesis of humandisorders. To solve IsoPs-related problems with regard to isoprostanes, analytical tools are required. This paper reviews the problems and trends in this field focusing on
[...] Read more.
Isoprostanes (IsoPs) are key biomarkers for investigating the role of free radical generation in the pathogenesis of human disorders. To solve IsoPs-related problems with regard to isoprostanes, analytical tools are required. This paper reviews the problems and trends in this field focusing on the methodology for assaying biomarkers in exhaled breath condensate (EBC) samples. A large amount of work has been done in the qualitative and quantitative analysis of IsoPs, but a standardized method has yet to emerge. The methodologies described differ, either in the sample preparation steps or in the detection techniques, or both. Requiring a number of chromatographic steps, the relevant extraction and purification procedures are often critical and time-consuming, and they lead to a substantial loss of target compounds. Recent data show that EBC is a promising non‑invasive tool for the evaluation of different diseases. Two main analytical approaches have been adopted for IsoPs measurement: immunological methods and mass spectrometry. The methodologies for the extraction, purification and analysis of IsoPs in EBC samples are presented.Isoprostanes (IsoPs) are key biomarkers for investigating the role of free radical generation in the pathogenesis of human disorders. To solve IsoPs-related problems with regard to isoprostanes, analytical tools are required. This paper reviews the problems and trends in this field focusing on the methodology for assaying biomarkers in exhaled breath condensate (EBC) samples. A large amount of work has been done in the qualitative and quantitative analysis of IsoPs, but a standardized method has yet to emerge. The methodologies described differ, either in the sample preparation steps or in the detection techniques, or both. Requiring a number of chromatographic steps, the relevant extraction and purification procedures are often critical and time-consuming, and they lead to a substantial loss of target compounds. Recent data show that EBC is a promising non‑invasive tool for the evaluation of different diseases. Two main analytical approaches have been adopted for IsoPs measurement: immunological methods and mass spectrometry. The methodologies for the extraction, purification and analysis of IsoPs in EBC samples are presented. Full article
(This article belongs to the Special Issue Biomarkers)
Open AccessReview Biomarkers for Colorectal Cancer
by , , and
Int. J. Mol. Sci. 2010, 11(9), 3209-3225; doi:10.3390/ijms11093209
Received: 18 August 2010 / Revised: 2 September 2010 / Accepted: 3 September 2010 / Published: 13 September 2010
Cited by 50 | Viewed by 5684 | PDF Full-text (165 KB) | HTML Full-text | XML Full-text
Abstract
Colorectal cancer (CRC) is the third most common epithelial malignancy in the world. Since CRC develops slowly from removable precancerous lesions, detection of the lesion at an early stage by regular health examinations can reduce the incidence and mortality of this malignancy. Colonoscopy
[...] Read more.
Colorectal cancer (CRC) is the third most common epithelial malignancy in the world. Since CRC develops slowly from removable precancerous lesions, detection of the lesion at an early stage by regular health examinations can reduce the incidence and mortality of this malignancy. Colonoscopy significantly improves the detection rate of CRC, but the examination is expensive and inconvenient. Therefore, we need novel biomarkers that are non-invasive to enable us to detect CRC quite early. A number of validation studies have been conducted to evaluate genetic, epigenetic or protein markers for identification in the stool and/or serum. Currently, the fecal occult blood test is the most widely used method of screening for CRC. However, advances in genomics and proteomics will lead to the discovery of novel non-invasive biomarkers. Full article
(This article belongs to the Special Issue Biomarkers)
Open AccessReview Biomarkers for Basal-like Breast Cancer
by and
Cancers 2010, 2(2), 1040-1065; doi:10.3390/cancers2021040
Received: 19 March 2010 / Revised: 11 May 2010 / Accepted: 19 May 2010 / Published: 28 May 2010
Cited by 18 | Viewed by 5106 | PDF Full-text (484 KB) | HTML Full-text | XML Full-text
Abstract
Initially recognized through microarray-based gene expression profiling, basal-like breast cancer, for which we lack effective targeted therapies, is an aggressive form of carcinoma with a predilection for younger women. With some success, immunohistochemical studies have attempted to reproduce the expression profile classification of
[...] Read more.
Initially recognized through microarray-based gene expression profiling, basal-like breast cancer, for which we lack effective targeted therapies, is an aggressive form of carcinoma with a predilection for younger women. With some success, immunohistochemical studies have attempted to reproduce the expression profile classification of breast cancer through identification of subtype-specific biomarkers. This review aims to present an in depth summary and analysis of the current status of basal-like breast cancer biomarker research. While a number of biomarkers show promise for future clinical application, the next logical step is a comprehensive investigation of all biomarkers against a gene expression profile gold standard for breast cancer subtype assignment. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
Open AccessReview The Evolution of Biomarkers in Thyroid Cancer—From Mass Screening to a Personalized Biosignature
by , and
Cancers 2010, 2(2), 885-912; doi:10.3390/cancers2020885
Received: 26 March 2010 / Revised: 10 May 2010 / Accepted: 19 May 2010 / Published: 20 May 2010
Cited by 14 | Viewed by 7047 | PDF Full-text (255 KB) | HTML Full-text | XML Full-text
Abstract
Thyroid cancer is the most common malignancy of the endocrine system. The diagnosis of thyroid nodules, made by neck examination and ultrasonography, is a common event occurring in over 50% of the patient population over the age of 50. Yet, only 5% of
[...] Read more.
Thyroid cancer is the most common malignancy of the endocrine system. The diagnosis of thyroid nodules, made by neck examination and ultrasonography, is a common event occurring in over 50% of the patient population over the age of 50. Yet, only 5% of these patients will be diagnosed with cancer. Fine needle aspiration biopsy is the gold standard for diagnosing thyroid nodules. However, 10–15% of these biopsies are inconclusive, ultimately requiring a diagnostic thyroid lobectomy. Consequently, research in thyroid biomarkers has become an area of active interest. In the 40 years since calcitonin was first described as the biomarker for medullary thyroid cancer, new biomarkers in thyroid cancer have been discovered. Advances in genomic and proteomic technologies have defined many of these novel thyroid biomarkers. The purpose of this article is to provide a comprehensive literature review of how these biomarkers have evolved from simple screening tests into a complex array of multiple markers to help predict the malignant potential and genetic signature of thyroid neoplasms. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
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Open AccessReview Breath Analysis Using Laser Spectroscopic Techniques: Breath Biomarkers, Spectral Fingerprints, and Detection Limits
by and
Sensors 2009, 9(10), 8230-8262; doi:10.3390/s91008230
Received: 1 September 2009 / Revised: 9 October 2009 / Accepted: 10 October 2009 / Published: 19 October 2009
Cited by 201 | Viewed by 14483 | PDF Full-text (1532 KB) | HTML Full-text | XML Full-text
Abstract
Breath analysis, a promising new field of medicine and medical instrumentation, potentially offers noninvasive, real-time, and point-of-care (POC) disease diagnostics and metabolic status monitoring. Numerous breath biomarkers have been detected and quantified so far by using the GC-MS technique. Recent advances in laser
[...] Read more.
Breath analysis, a promising new field of medicine and medical instrumentation, potentially offers noninvasive, real-time, and point-of-care (POC) disease diagnostics and metabolic status monitoring. Numerous breath biomarkers have been detected and quantified so far by using the GC-MS technique. Recent advances in laser spectroscopic techniques and laser sources have driven breath analysis to new heights, moving from laboratory research to commercial reality. Laser spectroscopic detection techniques not only have high-sensitivity and high-selectivity, as equivalently offered by the MS-based techniques, but also have the advantageous features of near real-time response, low instrument costs, and POC function. Of the approximately 35 established breath biomarkers, such as acetone, ammonia, carbon dioxide, ethane, methane, and nitric oxide, 14 species in exhaled human breath have been analyzed by high-sensitivity laser spectroscopic techniques, namely, tunable diode laser absorption spectroscopy (TDLAS), cavity ringdown spectroscopy (CRDS), integrated cavity output spectroscopy (ICOS), cavity enhanced absorption spectroscopy (CEAS), cavity leak-out spectroscopy (CALOS), photoacoustic spectroscopy (PAS), quartz-enhanced photoacoustic spectroscopy (QEPAS), and optical frequency comb cavity-enhanced absorption spectroscopy (OFC-CEAS). Spectral fingerprints of the measured biomarkers span from the UV to the mid-IR spectral regions and the detection limits achieved by the laser techniques range from parts per million to parts per billion levels. Sensors using the laser spectroscopic techniques for a few breath biomarkers, e.g., carbon dioxide, nitric oxide, etc. are commercially available. This review presents an update on the latest developments in laser-based breath analysis. Full article
(This article belongs to the Special Issue Gas Sensors 2009)
Open AccessReview Biomarkers of Induced Active and Passive Smoking Damage
by and
Int. J. Environ. Res. Public Health 2009, 6(3), 874-888; doi:10.3390/ijerph6030874
Received: 23 December 2008 / Accepted: 20 February 2009 / Published: 26 February 2009
Cited by 30 | Viewed by 5271 | PDF Full-text (293 KB) | HTML Full-text | XML Full-text
Abstract
In addition to thewell-known link between smoking and lung cancer, large epidemiological studies have shown a relationship between smoking and cancers of the nose, oral cavity, oropharynx, larynx, esophagus, pancreas, bladder, kidney, stomach, liver, colon and cervix, as well as myeloid leukemia. Epidemiological
[...] Read more.
In addition to thewell-known link between smoking and lung cancer, large epidemiological studies have shown a relationship between smoking and cancers of the nose, oral cavity, oropharynx, larynx, esophagus, pancreas, bladder, kidney, stomach, liver, colon and cervix, as well as myeloid leukemia. Epidemiological evidence has reported a direct link between exposure of non-smokers to environmental tobacco smoke and disease, most notably, lung cancer. Much evidence demonstrates that carcinogenic-DNA adducts are useful markers of tobacco smoke exposure, providing an integrated measurement of carcinogen intake, metabolic activation, and delivery to the DNA in target tissues. Monitoring accessible surrogate tissues, such as white blood cells or bronchoalveolar lavage (BAL) cells, also provides a means of investigating passive and active tobacco exposure in healthy individuals and cancer patients. Levels of DNA adducts measured in many tissues of smokers are significantly higher than in non-smokers. While some studies have demonstrated an association between carcinogenic DNA adducts and cancer in current smokers, no association has been observed in ex or never smokers. The role of genetic susceptibility in the development of smoking related-cancer is essential. In order to establish whether smoking-related DNA adducts are biomarkers of tobacco smoke exposure and/or its carcinogenic activity we summarized all data that associated tobacco smoke exposure and smoking-related DNA adducts both in controls and/or in cancer cases and studies where the effect of genetic polymorphisms involved in the activation and deactivation of carcinogens were also evaluated. In the future we hope we will be able to screen for lung cancer susceptibility by using specific biomarkers and that subjects of compared groups can be stratified for multiple potential modulators of biomarkers, taking into account various confounding factors. Full article
(This article belongs to the Special Issue Tobacco Smoking and Public Health)
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