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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Diagnostics".

Deadline for manuscript submissions: closed (15 September 2010)

Special Issue Editor

Guest Editor
Prof. Dr. Robert Bowser

Barrow Neurological Institute & St. Joseph's Hospital and Medical Center, 350 West Thomas Road, Phoenix, AZ 85013, USA
Website | E-Mail
Fax: +1 602 406 6459

Special Issue Information

Dear Colleagues,

The expanding field of biomarkers continues to play important roles in the healthcare industry, basics sciences, and the pharmaceutical industry. Biomarkers are changing the way in which we diagnose and classify disease, as well as providing a means to monitor disease progression or the effects of therapy. In addition, biomarkers are providing new insights into mechanisms of disease and new therapeutic targets. Biomarkers may be any quantitative measure of cellular, biochemical, or genetic alteration that occurs in a physiologic condition. While genomic and proteomic biomarkers have been at the forefront for the past number of years, recent technologic advancements have enabled the development of additional metabolic and peptide based biomarkers to the study of disease states. However it is crucial to demonstrate clinical validation of the biomarker before determining the clinical utility of any biomarker or panel of biomarkers. This special issue on biomarkers for the International Journal of Molecular Sciences will highlight recent advancements in biomarker discovery efforts and their clinical utility.

Prof. Dr. Robert Bowser
Guest Editor

Keywords

  • proteomics
  • genomics
  • metabolomics
  • peptidomics
  • mass spectrometry
  • bioinformatics
  • microarray
  • 2D gel electrophoresis

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Published Papers (19 papers)

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Research

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Open AccessArticle IL8 and Cathepsin B as Melanoma Serum Biomarkers
Int. J. Mol. Sci. 2011, 12(3), 1505-1518; doi:10.3390/ijms12031505
Received: 3 December 2010 / Revised: 15 February 2011 / Accepted: 22 February 2011 / Published: 25 February 2011
Cited by 22 | PDF Full-text (641 KB) | HTML Full-text | XML Full-text
Abstract
Melanoma accounts for only a small portion of skin cancer but it is associated with high mortality. Melanoma serum biomarkers that may aid early diagnosis or guide therapy are needed clinically. However, studies of serum biomarkers have often been hampered by the serum
[...] Read more.
Melanoma accounts for only a small portion of skin cancer but it is associated with high mortality. Melanoma serum biomarkers that may aid early diagnosis or guide therapy are needed clinically. However, studies of serum biomarkers have often been hampered by the serum interference that causes false readouts in immunological tests. Here we show that, after using a special buffer to eliminate the serum interference, IL-8 and cathepsin B levels were significantly elevated in melanoma patients (p < 0.05). More importantly, the combination of IL-8 and cathepsin B were also studied as a prognosis marker for melanoma mortality. Our study provides a novel approach to examine serum biomarkers. Full article
(This article belongs to the Special Issue Biomarkers)
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Open AccessArticle Proteomic Analysis of Whole Human Saliva Detects Enhanced Expression of Interleukin-1 Receptor Antagonist, Thioredoxin and Lipocalin-1 in Cigarette Smokers Compared to Non-Smokers
Int. J. Mol. Sci. 2010, 11(11), 4488-4505; doi:10.3390/ijms11114488
Received: 6 September 2010 / Revised: 25 October 2010 / Accepted: 5 November 2010 / Published: 9 November 2010
Cited by 21 | PDF Full-text (873 KB) | HTML Full-text | XML Full-text
Abstract
A gel-based proteomics approach was used to screen for proteins of differential abundance between the saliva of smokers and those who had never smoked. Subjecting precipitated proteins from whole human saliva of healthy non-smokers to two-dimensional electrophoresis (2-DE) generated typical profiles comprising more
[...] Read more.
A gel-based proteomics approach was used to screen for proteins of differential abundance between the saliva of smokers and those who had never smoked. Subjecting precipitated proteins from whole human saliva of healthy non-smokers to two-dimensional electrophoresis (2-DE) generated typical profiles comprising more than 50 proteins. While 35 of the proteins were previously established by other researchers, an additional 22 proteins were detected in the 2-DE saliva protein profiles generated in the present study. When the 2-DE profiles were compared to those obtained from subjects considered to be heavy cigarette smokers, three saliva proteins, including interleukin-1 receptor antagonist, thioredoxin and lipocalin-1, showed significant enhanced expression. The distribution patterns of lipocalin-1 isoforms were also different between cigarette smokers and on-smokers. The three saliva proteins have good potential to be used as biomarkers for the adverse effects of smoking and the risk for inflammatory and chronic diseases that are associated with it. Full article
(This article belongs to the Special Issue Biomarkers)
Open AccessArticle COMBO-FISH Enables High Precision Localization Microscopy as a Prerequisite for Nanostructure Analysis of Genome Loci
Int. J. Mol. Sci. 2010, 11(10), 4094-4105; doi:10.3390/ijms11104094
Received: 15 September 2010 / Revised: 16 October 2010 / Accepted: 18 October 2010 / Published: 21 October 2010
Cited by 15 | PDF Full-text (592 KB) | HTML Full-text | XML Full-text
Abstract
With the completeness of genome databases, it has become possible to develop a novel FISH (Fluorescence in Situ Hybridization) technique called COMBO-FISH (COMBinatorial Oligo FISH). In contrast to other FISH techniques, COMBO-FISH makes use of a bioinformatics approach for probe set design. By
[...] Read more.
With the completeness of genome databases, it has become possible to develop a novel FISH (Fluorescence in Situ Hybridization) technique called COMBO-FISH (COMBinatorial Oligo FISH). In contrast to other FISH techniques, COMBO-FISH makes use of a bioinformatics approach for probe set design. By means of computer genome database searching, several oligonucleotide stretches of typical lengths of 15–30 nucleotides are selected in such a way that all uniquely colocalize at the given genome target. The probes applied here were Peptide Nucleic Acids (PNAs)—synthetic DNA analogues with a neutral backbone—which were synthesized under high purity conditions. For a probe repetitively highlighted in centromere 9, PNAs labeled with different dyes were tested, among which Alexa 488Ò showed reversible photobleaching (blinking between dark and bright state) a prerequisite for the application of SPDM (Spectral Precision Distance/Position Determination Microscopy) a novel technique of high resolution fluorescence localization microscopy. Although COMBO-FISH labeled cell nuclei under SPDM conditions sometimes revealed fluorescent background, the specific locus was clearly discriminated by the signal intensity and the resulting localization accuracy in the range of 10–20 nm for a detected oligonucleotide stretch. The results indicate that COMBO-FISH probes with blinking dyes are well suited for SPDM, which will open new perspectives on molecular nanostructural analysis of the genome. Full article
(This article belongs to the Special Issue Biomarkers)
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Open AccessArticle Carbonic Anhydrase I Is Recognized by an SOD1 Antibody upon Biotinylation of Human Spinal Cord Extracts
Int. J. Mol. Sci. 2010, 11(10), 4051-4062; doi:10.3390/ijms11104051
Received: 16 September 2010 / Revised: 14 October 2010 / Accepted: 18 October 2010 / Published: 20 October 2010
PDF Full-text (346 KB) | HTML Full-text | XML Full-text
Abstract
We recently reported the presence of a novel 32 kDa protein immunoreactive to a copper, zinc superoxide dismutase (SOD1) antibody within the spinal cord of patients with amyotrophic lateral sclerosis (ALS). This unique protein species was generated by biotinylation of spinal cord tissue
[...] Read more.
We recently reported the presence of a novel 32 kDa protein immunoreactive to a copper, zinc superoxide dismutase (SOD1) antibody within the spinal cord of patients with amyotrophic lateral sclerosis (ALS). This unique protein species was generated by biotinylation of spinal cord tissue extracts to detect conformational changes of SOD1 specific to ALS patients. To further characterize this protein, we enriched the protein by column chromatography and determined its protein identity by mass spectrometry. The protein that gave rise to the 32 kDa species upon biotinylation was identified as carbonic anhydrase I (CA I). Biotinylation of CA I from ALS spinal cord resulted in the generation of a novel epitope recognized by the SOD1 antibody. This epitope could also be generated by biotinylation of extracts from cultured cells expressing human CA I. Peptide competition assays identified the amino acid sequence in carbonic anhydrase I responsible for binding the SOD1 antibody. We conclude that chemical modifications used to identify pathogenic protein conformations can lead to the identification of unanticipated proteins that may participate in disease pathogenesis. Full article
(This article belongs to the Special Issue Biomarkers)
Open AccessArticle Distribution of Endogenous Farnesyl Pyrophosphate and Four Species of Lysophosphatidic Acid in Rodent Brain
Int. J. Mol. Sci. 2010, 11(10), 3965-3976; doi:10.3390/ijms11103965
Received: 24 August 2010 / Revised: 12 October 2010 / Accepted: 13 October 2010 / Published: 15 October 2010
Cited by 9 | PDF Full-text (247 KB) | HTML Full-text | XML Full-text
Abstract
Lysophosphatidic acid (LPA) is the umbrella term for lipid signaling molecules that share structural homology and activate the family of LPA receptors. Farnesyl Pyrophosphate (FPP) is commonly known as an intermediate in the synthesis of steroid hormones; however, its function as a signaling
[...] Read more.
Lysophosphatidic acid (LPA) is the umbrella term for lipid signaling molecules that share structural homology and activate the family of LPA receptors. Farnesyl Pyrophosphate (FPP) is commonly known as an intermediate in the synthesis of steroid hormones; however, its function as a signaling lipid is beginning to be explored. FPP was recently shown to an activator of the G-protein coupled receptor 92 (also known as LPA5) of the calcium channel TRPV3. The LPA receptors (including GPR92) are associated with the signal transduction of noxious stimuli, however, very little is known about the distribution of their signaling ligands (LPAs and FPP) in the brain. Here, using HPLC/MS/MS, we developed extraction and analytical methods for measuring levels of FPP and 4 species of LPA (palmitoyl, stearoyl, oleoyl and arachidonoyl-sn-glycerol-3 phosphate) in rodent brain. Relative distributions of each of the five compounds was significantly different across the brain suggesting divergent functionality for each as signaling molecules based on where and how much of each is being produced. Brainstem, midbrain, and thalamus contained the highest levels measured for each compound, though none in the same ratios while relatively small amounts were produced in cortex and cerebellum. These data provide a framework for investigations into functional relationships of these lipid ligands in specific brain areas, many of which are associated with the perception of pain. Full article
(This article belongs to the Special Issue Biomarkers)
Open AccessArticle Identification of Tetranectin as a Potential Biomarker for Metastatic Oral Cancer
Int. J. Mol. Sci. 2010, 11(9), 3106-3121; doi:10.3390/ijms11093106
Received: 28 July 2010 / Revised: 25 August 2010 / Accepted: 27 August 2010 / Published: 2 September 2010
Cited by 20 | PDF Full-text (464 KB) | HTML Full-text | XML Full-text
Abstract
Lymph node involvement is the most important predictor of survival rates in patients with oral squamous cell carcinoma (OSCC). A biomarker that can indicate lymph node metastasis would be valuable to classify patients with OSCC for optimal treatment. In this study, we have
[...] Read more.
Lymph node involvement is the most important predictor of survival rates in patients with oral squamous cell carcinoma (OSCC). A biomarker that can indicate lymph node metastasis would be valuable to classify patients with OSCC for optimal treatment. In this study, we have performed a serum proteomic analysis of OSCC using 2-D gel electrophoresis and liquid chromatography/tandem mass spectrometry. One of the down-regulated proteins in OSCC was identified as tetranectin, which is a protein encoded by the CLEC3B gene (C-type lectin domain family 3, member B). We further tested the protein level in serum and saliva from patients with lymph-node metastatic and primary OSCC. Tetranectin was found significantly under-expressed in both serum and saliva of metastatic OSCC compared to primary OSCC. Our results suggest that serum or saliva tetranectin may serve as a potential biomarker for metastatic OSCC. Other candidate serum biomarkers for OSCC included superoxide dismutase, ficolin 2, CD-5 antigen-like protein, RalA binding protein 1, plasma retinol-binding protein and transthyretin. Their clinical utility for OSCC detection remains to be further tested in cancer patients. Full article
(This article belongs to the Special Issue Biomarkers)
Open AccessArticle Decreased Erythrocyte CCS Content is a Biomarker of Copper Overload in Rats
Int. J. Mol. Sci. 2010, 11(7), 2624-2635; doi:10.3390/ijms11072624
Received: 26 May 2010 / Revised: 25 June 2010 / Accepted: 30 June 2010 / Published: 2 July 2010
Cited by 3 | PDF Full-text (81 KB) | HTML Full-text | XML Full-text
Abstract
Copper (Cu)is an essential trace metal that is toxic in excess. It is therefore important to be able to accurately assess Cu deficiency or overload. Cu chaperone for Cu/Zn superoxide dismutase (CCS) protein expression is elevated in tissues of Cu-deficient animals. Increased CCS
[...] Read more.
Copper (Cu)is an essential trace metal that is toxic in excess. It is therefore important to be able to accurately assess Cu deficiency or overload. Cu chaperone for Cu/Zn superoxide dismutase (CCS) protein expression is elevated in tissues of Cu-deficient animals. Increased CCS content in erythrocytes is particularly sensitive to decreased Cu status. Given the lack of a non-invasive, sensitive and specific biomarker for the assessment of Cu excess, we investigated whether CCS expression in erythrocytes reflects Cu overload. Rats were fed diets containing normal or high levels of Cu for 13 weeks. Diets contained 6.3 ± 0.6 (Cu-N), 985 ± 14 (Cu-1000) or 1944 ± 19 (Cu-2000) mg Cu/kg diet. Rats showed a variable response to the high Cu diets. Some rats showed severe Cu toxicity, while other rats showed no visible signs of toxicity and grew normally. Also, some rats had high levels of Cu in liver, whereas others had liver Cu concentrations within the normal range. Erythrocyte CCS protein expression was 30% lower in Cu-2000 rats compared to Cu-N rats (P < 0.05). Notably, only rats that accumulated high levels of Cu in liver had lower erythrocyte CCS (47% reduction, P < 0.05) compared to rats fed normal levels of Cu. Together, these data indicate that decreased erythrocyte CCS content is associated with Cu overload in rats and should be evaluated further as a potential biomarker for assessing Cu excess in humans. Full article
(This article belongs to the Special Issue Biomarkers)
Open AccessArticle Serum Concentrations of TNF α and Its Soluble Receptors in Patients with Adrenal Tumors Treated by Surgery
Int. J. Mol. Sci. 2010, 11(6), 2281-2290; doi:10.3390/ijms11062281
Received: 29 April 2010 / Accepted: 21 May 2010 / Published: 26 May 2010
Cited by 2 | PDF Full-text (278 KB) | HTML Full-text | XML Full-text
Abstract
The peripheral blood levels of TNF α and its soluble receptors were studied in 39 patients with malignant and benign adrenal tumors treated by adrenalectomy. The concentrations of TNF α were significantly elevated in patients with malignant tumors of the adrenal cortex and
[...] Read more.
The peripheral blood levels of TNF α and its soluble receptors were studied in 39 patients with malignant and benign adrenal tumors treated by adrenalectomy. The concentrations of TNF α were significantly elevated in patients with malignant tumors of the adrenal cortex and in patients with Conn's syndrome compared to control. In patients with non-functioning adenomas and pheochromocytomas, TNF α levels were similar to those detected in the control. In subjects with myelolipomas, the serum concentration of TNF α was lower compared to the control. After adrenalectomy, the levels of TNF α were decreased in patients with malignant tumors and in patients with Conn's syndrome, non-functioniong adenomas and pheochromocytomas compared to the concentration before surgery. The serum concentrations of soluble receptors of TNF α did not differ among different patient groups and compared to the control. After adrenalectomy, the blood concentrations of TNF α R1 and TNF α R2 were decreased in patients with Conn's syndrome. However, to confirm practicality of the evaluation of TNF α and its soluble receptors in differential diagnosis in patients with adrenal tumors, a larger study group is needed. Full article
(This article belongs to the Special Issue Biomarkers)
Open AccessArticle Differential Proteomics Identification of HSP90 as Potential Serum Biomarker in Hepatocellular Carcinoma by Two-dimensional Electrophoresis and Mass Spectrometry
Int. J. Mol. Sci. 2010, 11(4), 1423-1433; doi:10.3390/ijms11041423
Received: 11 January 2010 / Revised: 14 March 2010 / Accepted: 17 March 2010 / Published: 31 March 2010
Cited by 27 | PDF Full-text (201 KB) | HTML Full-text | XML Full-text
Abstract
The aim of the current study is to identify the potential biomarkers involved in Hepatocellular carcinoma (HCC) carcinogenesis. A comparative proteomics approach was utilized to identify the differentially expressed proteins in the serum of 10 HCC patients and 10 controls. A total of
[...] Read more.
The aim of the current study is to identify the potential biomarkers involved in Hepatocellular carcinoma (HCC) carcinogenesis. A comparative proteomics approach was utilized to identify the differentially expressed proteins in the serum of 10 HCC patients and 10 controls. A total of 12 significantly altered proteins were identified by mass spectrometry. Of the 12 proteins identified, HSP90 was one of the most significantly altered proteins and its over-expression in the serum of 20 HCC patients was confirmed using ELISA analysis. The observations suggest that HSP90 might be a potential biomarker for early diagnosis, prognosis, and monitoring in the therapy of HCC. This work demonstrates that a comprehensive strategy of proteomic identification combined with further validation should be adopted in the field of cancer biomarker discovery. Full article
(This article belongs to the Special Issue Biomarkers)

Review

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Open AccessReview Cell Surface Markers in Colorectal Cancer Prognosis
Int. J. Mol. Sci. 2011, 12(1), 78-113; doi:10.3390/ijms12010078
Received: 30 November 2010 / Revised: 16 December 2010 / Accepted: 20 December 2010 / Published: 28 December 2010
Cited by 26 | PDF Full-text (443 KB) | HTML Full-text | XML Full-text
Abstract
The classification of colorectal cancers (CRC) is currently based largely on histologically determined tumour characteristics, such as differentiation status and tumour stage, i.e., depth of tumour invasion, involvement of regional lymph nodes and the occurrence of metastatic spread to other organs. These
[...] Read more.
The classification of colorectal cancers (CRC) is currently based largely on histologically determined tumour characteristics, such as differentiation status and tumour stage, i.e., depth of tumour invasion, involvement of regional lymph nodes and the occurrence of metastatic spread to other organs. These are the conventional prognostic factors for patient survival and often determine the requirement for adjuvant therapy after surgical resection of the primary tumour. However, patients with the same CRC stage can have very different disease-related outcomes. For some, surgical removal of early-stage tumours leads to full recovery, while for others, disease recurrence and metastasis may occur regardless of adjuvant therapy. It is therefore important to understand the molecular processes that lead to disease progression and metastasis and to find more reliable prognostic markers and novel targets for therapy. This review focuses on cell surface proteins that correlate with tumour progression, metastasis and patient outcome, and discusses some of the challenges in finding prognostic protein markers in CRC. Full article
(This article belongs to the Special Issue Biomarkers)
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Open AccessReview Biomarkers in Rare Disorders: The Experience with Spinal Muscular Atrophy
Int. J. Mol. Sci. 2011, 12(1), 24-38; doi:10.3390/ijms12010024
Received: 10 November 2010 / Revised: 6 December 2010 / Accepted: 16 December 2010 / Published: 23 December 2010
Cited by 6 | PDF Full-text (187 KB) | HTML Full-text | XML Full-text
Abstract
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by homozygous mutations of the SMN1 gene. Based on clinical severity, three forms of SMA are recognized (type I–III). All patients have at least one (usually 2–4) copies of a highly homologous
[...] Read more.
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by homozygous mutations of the SMN1 gene. Based on clinical severity, three forms of SMA are recognized (type I–III). All patients have at least one (usually 2–4) copies of a highly homologous gene (SMN2) which produces insufficient levels of functional SMN protein, due to alternative splicing of exon7. Recently, evidence has been provided that SMN2 expression can be enhanced by different strategies. The availability of potential candidates to treat SMA has raised a number of issues, including the availability of data on the natural history of the disease, the reliability and sensitivity of outcome measures, the duration of the studies, and the number and clinical homogeneity of participating patients. Equally critical is the availability of reliable biomarkers. So far, different tools have been proposed as biomarkers in SMA, classifiable into two groups: instrumental (the Compound Motor Action Potential, the Motor Unit Number Estimation, and the Dual-energy X-ray absorptiometry) and molecular (SMN gene products dosage, either transcripts or protein). However, none of the biomarkers available so far can be considered the gold standard. Preclinical studies on SMA animal models and double-blind, placebo-controlled studies are crucial to evaluate the appropriateness of biomarkers, on the basis of correlations with clinical outcome. Full article
(This article belongs to the Special Issue Biomarkers)
Open AccessReview Protein Microarrays and Biomarkers of Infectious Disease
Int. J. Mol. Sci. 2010, 11(12), 5165-5183; doi:10.3390/ijms11125165
Received: 19 November 2010 / Revised: 11 December 2010 / Accepted: 15 December 2010 / Published: 16 December 2010
Cited by 13 | PDF Full-text (277 KB) | HTML Full-text | XML Full-text
Abstract
Protein microarrays are powerful tools that are widely used in systems biology research. For infectious diseases, proteome microarrays assembled from proteins of pathogens will play an increasingly important role in discovery of diagnostic markers, vaccines, and therapeutics. Distinct formats of protein microarrays have
[...] Read more.
Protein microarrays are powerful tools that are widely used in systems biology research. For infectious diseases, proteome microarrays assembled from proteins of pathogens will play an increasingly important role in discovery of diagnostic markers, vaccines, and therapeutics. Distinct formats of protein microarrays have been developed for different applications, including abundance-based and function-based methods. Depending on the application, design issues should be considered, such as the need for multiplexing and label or label free detection methods. New developments, challenges, and future demands in infectious disease research will impact the application of protein microarrays for discovery and validation of biomarkers. Full article
(This article belongs to the Special Issue Biomarkers)
Open AccessReview Matrix-Assisted Laser Desorption/Ionization Imaging Mass Spectrometry
Int. J. Mol. Sci. 2010, 11(12), 5040-5055; doi:10.3390/ijms11125040
Received: 10 November 2010 / Revised: 25 November 2010 / Accepted: 27 November 2010 / Published: 7 December 2010
Cited by 29 | PDF Full-text (372 KB) | HTML Full-text | XML Full-text
Abstract
Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a powerful tool that enables the simultaneous detection and identification of biomolecules in analytes. MALDI-imaging mass spectrometry (MALDI-IMS) is a two-dimensional MALDI-mass spectrometric technique used to visualize the spatial distribution of biomolecules without extraction, purification, separation,
[...] Read more.
Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a powerful tool that enables the simultaneous detection and identification of biomolecules in analytes. MALDI-imaging mass spectrometry (MALDI-IMS) is a two-dimensional MALDI-mass spectrometric technique used to visualize the spatial distribution of biomolecules without extraction, purification, separation, or labeling of biological samples. MALDI-IMS has revealed the characteristic distribution of several biomolecules, including proteins, peptides, amino acids, lipids, carbohydrates, and nucleotides, in various tissues. The versatility of MALDI-IMS has opened a new frontier in several fields such as medicine, agriculture, biology, pharmacology, and pathology. MALDI-IMS has a great potential for discovery of unknown biomarkers. In this review, we describe the methodology and applications of MALDI-IMS for biological samples. Full article
(This article belongs to the Special Issue Biomarkers)
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Open AccessReview Colorimetric Immunoassay for Detection of Tumor Markers
Int. J. Mol. Sci. 2010, 11(12), 5077-5094; doi:10.3390/ijms11125077
Received: 7 November 2010 / Revised: 24 November 2010 / Accepted: 25 November 2010 / Published: 7 December 2010
Cited by 17 | PDF Full-text (317 KB) | HTML Full-text | XML Full-text
Abstract
Tumor markers are substances, usually proteins, produced by the body in response to cancer growth, or by the cancer tissue itself. They can be detected in blood, urine, or tissue samples, and the discovery and detection of tumor markers may provide earlier diagnosis
[...] Read more.
Tumor markers are substances, usually proteins, produced by the body in response to cancer growth, or by the cancer tissue itself. They can be detected in blood, urine, or tissue samples, and the discovery and detection of tumor markers may provide earlier diagnosis of cancer and improved therapeutic intervention. Colorimetric immunoassays for tumor marker detection have attracted considerable attention, due to their simplicity and high efficiency. The traditionally used colorimetric immunoassays for the detection of tumor markers are based on enzyme-linked immunosorbent assays, and the great achievement of nanotechnology has further opened opportunities for the development of such kind of immunoassays. This paper will summarize recent advances in the field of colorimetric immunoassays for detecting tumor markers, which is aimed to provide an overview in this field, as well as experimental guidance for the learner. Full article
(This article belongs to the Special Issue Biomarkers)
Open AccessReview Biomarker Analysis of Stored Blood Products: Emphasis on Pre-Analytical Issues
Int. J. Mol. Sci. 2010, 11(11), 4601-4617; doi:10.3390/ijms11114601
Received: 18 October 2010 / Revised: 10 November 2010 / Accepted: 14 November 2010 / Published: 17 November 2010
Cited by 18 | PDF Full-text (217 KB) | HTML Full-text | XML Full-text
Abstract
Millions of blood products are transfused every year; many lives are thus directly concerned by transfusion. The three main labile blood products used in transfusion are erythrocyte concentrates, platelet concentrates and fresh frozen plasma. Each of these products has to be stored according
[...] Read more.
Millions of blood products are transfused every year; many lives are thus directly concerned by transfusion. The three main labile blood products used in transfusion are erythrocyte concentrates, platelet concentrates and fresh frozen plasma. Each of these products has to be stored according to its particular components. However, during storage, modifications or degradation of those components may occur, and are known as storage lesions. Thus, biomarker discovery of in vivo blood aging as well as in vitro labile blood products storage lesions is of high interest for the transfusion medicine community. Pre-analytical issues are of major importance in analyzing the various blood products during storage conditions as well as according to various protocols that are currently used in blood banks for their preparations. This paper will review key elements that have to be taken into account in the context of proteomic-based biomarker discovery applied to blood banking. Full article
(This article belongs to the Special Issue Biomarkers)
Open AccessReview Isoprostanes-Biomarkers of Lipid Peroxidation: Their Utility in Evaluating Oxidative Stress and Analysis
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 35 | 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 α-Synuclein and DJ-1 as Potential Biological Fluid Biomarkers for Parkinson’s Disease
Int. J. Mol. Sci. 2010, 11(11), 4257-4266; doi:10.3390/ijms11114257
Received: 14 September 2010 / Revised: 20 October 2010 / Accepted: 28 October 2010 / Published: 29 October 2010
Cited by 10 | PDF Full-text (145 KB) | HTML Full-text | XML Full-text
Abstract
Parkinson’s disease (PD) is the most common form of movement disorder and affects approximately 4% of the population aged over 80 years old. Currently, PD cannot be prevented or cured, and no single diagnostic biomarkers are available. Notably, recent studies suggest that two
[...] Read more.
Parkinson’s disease (PD) is the most common form of movement disorder and affects approximately 4% of the population aged over 80 years old. Currently, PD cannot be prevented or cured, and no single diagnostic biomarkers are available. Notably, recent studies suggest that two familial PD-linked molecules, α-synuclein and DJ-1, are present in cerebrospinal fluid (CSF) and that their levels may be altered during the progression of PD. In this regard, sensitive and accurate methods for evaluation of α-synuclein and DJ-1 levels in the CSF and blood have been developed, and the results suggest that the levels of both molecules are significantly decreased in the CSF in patients with PD compared with age-matched controls. Furthermore, specific detection and quantification of neurotoxic oligometric forms of α-synuclein in the blood using enzyme-linked immunosorbent assays might be expected as potential peripheral biomarkers for PD, although further validation is required. Currently, neither α-synuclein nor DJ-1 is satisfactory as a single biomarker for PD, but combinatory evaluation of these biological fluid molecules with other biomarkers and imaging techniques may provide reliable information for diagnosis of PD. Full article
(This article belongs to the Special Issue Biomarkers)
Open AccessReview Proteomic Serum Biomarkers and Their Potential Application in Cancer Screening Programs
Int. J. Mol. Sci. 2010, 11(11), 4175-4193; doi:10.3390/ijms11114175
Received: 15 September 2010 / Revised: 16 October 2010 / Accepted: 18 October 2010 / Published: 26 October 2010
Cited by 24 | PDF Full-text (132 KB) | HTML Full-text | XML Full-text
Abstract
Early diagnosis of cancer is of pivotal importance to reduce disease-related mortality. There is great need for non-invasive screening methods, yet current screening protocols have limited sensitivity and specificity. The use of serum biomarkers to discriminate cancer patients from healthy persons might be
[...] Read more.
Early diagnosis of cancer is of pivotal importance to reduce disease-related mortality. There is great need for non-invasive screening methods, yet current screening protocols have limited sensitivity and specificity. The use of serum biomarkers to discriminate cancer patients from healthy persons might be a tool to improve screening programs. Mass spectrometry based proteomics is widely applied as a technology for mapping and identifying peptides and proteins in body fluids. One commonly used approach in proteomics is peptide and protein profiling. Here, we present an overview of profiling methods that have the potential for implementation in a clinical setting and in national screening programs. Full article
(This article belongs to the Special Issue Biomarkers)
Open AccessReview Biomarkers for Colorectal Cancer
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
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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
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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)

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