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Diagnostic Biomarker (diagnostic + biomarker)
Selected AbstractsDiagnostic biomarker of asbestos-related mesothelioma: Example of translational researchCANCER SCIENCE, Issue 8 2007Hino Okio Mesothelioma is an aggressive tumor arising from the mesothelium, and is usually associated with previous exposure to asbestos. The incubation period of asbestos-related mesothelioma is estimated to be approximately 30,40 years. Once mesothelioma has occurred, there is no effective treatment. So, identification of tumor markers and a method for early diagnosis using such markers are urgently needed. Recently, several enzyme-linked immunosorbent assay systems for Erc/mesothelin have been developed, the reported usefulness of which has been assessed and demonstrated as a diagnostic tool. Asbestos-related mesothelioma should be ascribed as a typical environmental carcinogen. In this review, we will present asbestos-related mesothelioma for the study of problems in environmental carcinogenesis. (Cancer Sci 2007; 98: 1147,1151) [source] Clinical application of measurement of hippocampal atrophy in degenerative dementiasHIPPOCAMPUS, Issue 6 2009Josephine Barnes Abstract Hippocampal atrophy is a characteristic and early feature of Alzheimer's disease. Volumetry of the hippocampus using T1-weighted magnetic resonance imaging (MRI) has been used not only to assess hippocampal involvement in different neurodegenerative diseases as a potential diagnostic biomarker, but also to understand the natural history of diseases, and to track changes in volume over time. Assessing change in structure circumvents issues surrounding interindividual variability and allows assessment of disease progression. Disease-modifying effects of putative therapies are important to assess in clinical trials and are difficult using clinical scales. As a result, there is increasing use of serial MRI in trials to detect potential slowing of atrophy rates as an outcome measure. Automated and yet reliable methods of quantifying such change in the hippocampus would therefore be very valuable. Algorithms capable of measuring such changes automatically have been developed and may be applicable to predict decline to a diagnosis of dementia in the future. This article details the progress in using MRI to understand hippocampal changes in the degenerative dementias and also describes attempts to automate hippocampal segmentation in these diseases. © 2009 Wiley-Liss, Inc. [source] Multiple serological biomarkers for colorectal cancer detectionINTERNATIONAL JOURNAL OF CANCER, Issue 7 2010Chung-Chuan Chan Abstract The aim of this study was to initiate a survey of human autoantibody responses to a panel of select colorectal tumor-associated antigens identified by previous serological analysis of a cDNA expression library and to subsequently identify multiple serological biomarkers for the detection of colorectal cancer. For screening of autoantibodies against colorectal tumor-associated antigens, sera from 94 colorectal cancer patients and 54 normal controls were analyzed by enzyme-linked immunosorbent assay using recombinant rCCCAP, rHDAC5, rP53, rNMDAR and rNY-CO-16 proteins as coating antigens. Seropositivity among colorectal cancer patients to the 5 individual coating antigens varied from 18.1% to 35.1%. Seropositivity to any of the 5 coating antigens was 58.5% and combining this analysis with evaluation of serum carcinoembryonic antigen (,5 ng/ml) significantly increased the seropositivity to 77.6%. Seropositivity of early-stage (Dukes' Stages A and B) colorectal cancer patients to CEA was 21.9%, and seropositivity to any of the 5 colorectal cancer-associated antigens was 53.7%, and the combination of these 2 measurements resulted in a higher diagnostic capacity (65.9%) than either marker alone. In conclusion, these results collectively indicated that combined detection of serum autoantibody profiles against our panel of colorectal tumor-associated antigens and the analysis of carcinoembryonic antigen provides a promising diagnostic biomarker for colorectal cancer, particularly among early-stage patients. [source] Correlates of NT-proBNP concentration in patients with essential hypertension in absence of congestive heart failureJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 1 2010Keizo Toda Abstract Background: N-terminal proBNP (NT-proBNP) is widely used as a diagnostic biomarker and for the risk stratification of patients with heart failure (HF). Its role in the evaluation of patients with essential hypertension (EHT) is less clear. We examined the relationship between NT-proBNP concentrations and various clinical characteristics in hypertensive patients without HF. Methods: This study included 186 consecutive patients with EHT and no history of HF, ischemic heart disease, or atrial fibrillation. Single and multiple variable regression analyses were performed in search of clinical correlates of NT-proBNP concentrations. Results: In patients with EHT, median serum concentration of NT-proBNP was 73,pg/ml, and interquartile range (IQR) was 40,128,pg/ml. NT-proBNP was significantly higher (P<0.001) in women (87,pg/ml; IQR 55,137,pg/ml) than in men (52,pg/ml; IQR 24,115,pg/ml). Age (r=0.371, P<0.001), precordial QRS voltage (r=0.223, P<0.001), hemoglobin (Hgb) concentration, (r=,0.208, P=0.023) and estimated glomerular filtration rate (r=,0.139, P=0.044) were correlated with log-transformed NT-proBNP by multiple variable analysis. In men, age (r=0.453, P<0.001) and QRS voltage (r=0.283, P=0.004), and in women age (r=0.299, P=0.006), QRS voltage (r=0.212, P=0.019), Hgb (r=,0.182, P=0.049), and estimated glomerular filtration rate (r=,0.272, P=0.009) were correlated with serum concentrations of NT-proBNP. Conclusions: Age, gender, Hgb, left ventricular hypertrophy and renal function were correlated with NT-proBNP in patients with EHT. J. Clin. Lab. Anal. 24:12,16, 2010. © 2010 Wiley-Liss, Inc. [source] Preoperative plasma osteopontin level as a biomarker complementary to carbohydrate antigen 125 in predicting ovarian cancerJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 3 2006Mitsuhiro Nakae Abstract Aim:, New biomarkers other than carbohydrate antigen (CA) 125 are needed for the detection of ovarian cancer. Osteopontin (OPN) is one of the candidates identified by high-throughput complementary DNA microarray techniques. We evaluated the preoperative plasma OPN level as a diagnostic biomarker for ovarian cancer in comparison with CA125. Methods:, Preoperative plasma OPN and CA125 levels were measured and compared in 32 patients with ovarian cancer, 34 patients with benign ovarian tumor, 30 patients with other gynecologic cancers and 31 healthy women. Preoperative plasma OPN levels were also assessed according to tumor stage, the volume of ascites and histological types. The sensitivity and specificity for predicting ovarian cancer was compared between OPN and CA125. Results:, Preoperative plasma OPN levels were significantly higher in patients with ovarian cancer than in those with benign ovarian tumor, in other gynecologic patients or in healthy women. Stage IV ovarian cancer patients and ovarian cancer patients with ascites had higher plasma OPN levels than those without ascites and in a lower stage. There was no relation between OPN and the histological type. The sensitivity of preoperative plasma OPN in detecting ovarian cancer was 81.3% and almost reached that of CA125. The specificity was moderate. Sensitivity increased to 93.8% with the combination of CA125, compared to 84.4% with CA125 alone. Conclusion:, Preoperative OPN is a useful biomarker for predicting ovarian cancer. It is especially useful when used complementary to CA125. Larger studies of patients with ovarian cancer showing a low CA125 level or in early stages of ovarian cancer are needed. [source] Differentially expressed proteins in gastrointestinal stromal tumors with KIT and PDGFRA mutationsPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 4 2006Hyun Ju Kang Abstract Most gastrointestinal stromal tumors (GIST) have activating mutations in either KIT or PDGFRA. However, a small subset of GIST lacks either mutation. To investigate the molecular characteristics of GIST according to mutation type, protein expression profiles in 12 GIST (2 cases with PDGFRA mutations, 8 cases with KIT mutations and 2 cases lacking either mutation) were analyzed using 2-DE and MALDI-TOF-MS. Comparative analysis of the respective spot patterns using 2-DE showed that 15 proteins were differently expressed according to the mutation status. Expression levels of septin and heat shock protein (HSP) 27 were increased in GIST with KIT mutations and annexin V was overexpressed in GIST lacking either mutation. Among the 15 proteins, overexpression of 5 proteins [annexin V, high mobility group protein 1 (HMGB1), C13orf2, glutamate dehydrogenase 1 and fibrinogen beta chain] and decreased expression of RoXaN correlated with a higher tumor grade. These findings suggest that differential protein expression can be used as a diagnostic biomarker. Moreover, it may play a role in the development and progression of GIST according to activating mutation type, as these proteins have been shown to be involved in tumor metastasis, apoptosis and immune response. [source] Progressive Supranuclear Palsy: Pathology and GeneticsBRAIN PATHOLOGY, Issue 1 2007Dennis W. Dickson Progressive supranuclear palsy (PSP) is an atypical Parkinsonian disorder associated with progressive axial rigidity, vertical gaze palsy, dysarthria and dysphagia. Neuropathologically, the subthalamic nucleus and brainstem, especially the midbrain tectum and the superior cerebellar peduncle, show atrophy. The substantia nigra shows loss of pigment corresponding to nigrostriatal dopaminergic degeneration. Microscopic findings include neuronal loss, gliosis and neurofibrillary tangles in basal ganglia, diencephalon and brainstem. Characteristic tau pathology is also found in glia. The major genetic risk factor for sporadic PSP is a common variant in the gene encoding microtubule-associated protein tau (MAPT) and recent studies have suggested that this may result in the altered expression of specific tau protein isoforms. Imaging studies suggest that there may be sensitive and specific means to differentiate PSP from other parkinsonian disorders, but identification of a diagnostic biomarker is still elusive. [source] Stanniocalcin 2 overexpression in castration-resistant prostate cancer and aggressive prostate cancerCANCER SCIENCE, Issue 5 2009Kenji Tamura Prostate cancer is usually androgen-dependent and responds well to androgen ablation therapy based on castration. However, at a certain stage some prostate cancers eventually acquire a castration-resistant phenotype where they progress aggressively and show very poor response to any anticancer therapies. To characterize the molecular features of these clinical castration-resistant prostate cancers, we previously analyzed gene expression profiles by genome-wide cDNA microarrays combined with microdissection and found dozens of trans -activated genes in clinical castration-resistant prostate cancers. Among them, we report the identification of a new biomarker, stanniocalcin 2, as an overexpressed gene in castration-resistant prostate cancer cells. Real-time polymerase chain reaction and immunohistochemical analysis confirmed overexpression of stanniocalcin 2, a 302-amino-acid glycoprotein hormone, specifically in castration-resistant prostate cancer cells and aggressive castration-naïve prostate cancers with high Gleason scores (8,10). The gene was not expressed in normal prostate, nor in most indolent castration-naïve prostate cancers. Knockdown of stanniocalcin 2 expression by short interfering RNA in a prostate cancer cell line resulted in drastic attenuation of prostate cancer cell growth. Concordantly, stanniocalcin 2 overexpression in a prostate cancer cell line promoted prostate cancer cell growth, indicating its oncogenic property. These findings suggest that stanniocalcin 2 could be involved in aggressive phenotyping of prostate cancers, including castration-resistant prostate cancers, and that it should be a potential molecular target for development of new therapeutics and a diagnostic biomarker for aggressive prostate cancers. (Cancer Sci 2009; 100: 914,919) [source] MicroRNAs: Master Regulators of Ethanol Abuse and Toxicity?ALCOHOLISM, Issue 4 2010Rajesh C. Miranda Ethanol exerts complex effects on human physiology and health. Ethanol is not only addictive, but it is also a fetal teratogen, an adult neurotoxin, and an etiologic agent in hepatic and cardiovascular disease, inflammation, bone loss, and fracture susceptibility. A large number of genes and signaling mechanisms have been implicated in ethanol's deleterious effects leading to the suggestion that ethanol is a "dirty drug." An important question is, are there cellular "master-switches" that can explain these pleiotropic effects of ethanol? MicroRNAs (miRNAs) have been recently identified as master regulators of the cellular transcriptome and proteome. miRNAs play an increasingly appreciated and crucial role in shaping the differentiation and function of tissues and organs in both health and disease. This critical review discusses new evidence showing that ethanol-sensitive miRNAs are indeed regulatory master-switches. More specifically, miRNAs control the development of tolerance, a crucial component of ethanol addiction. Other drugs of abuse also target some ethanol-sensitive miRNAs suggesting that common biochemical mechanisms underlie addiction. This review also discusses evidence that miRNAs mediate several ethanol pathologies, including disruption of neural stem cell proliferation and differentiation in the exposed fetus, gut leakiness that contributes to endotoxemia and alcoholic liver disease, and possibly also hepatocellular carcinomas and other gastrointestinal cancers. Finally, this review provides a perspective on emerging investigations into potential roles of miRNAs as mediators of ethanol's effects on inflammation and fracture healing, as well as the potential for miRNAs as diagnostic biomarkers and as targets for therapeutic interventions for alcohol-related disorders. [source] Oncoproteomics of hepatocellular carcinoma: from cancer markers' discovery to functional pathwaysLIVER INTERNATIONAL, Issue 8 2007Stella Sun Abstract Hepatocellular carcinoma (HCC) is a heterogeneous cancer with no promising treatment and remains one of the most prevailing and lethal malignancies in the world. Researchers in many biological areas now routinely identify and characterize protein markers by a mass spectrometry-based proteomic approach, a method that has been commonly used to discover diagnostic biomarkers for cancer detection. The proteomic research platforms span from the classical two-dimensional polyacrylamide gel electrophoresis (2-DE) to the latest Protein Chip or array technology, which are often integrated with the MALDI (matrix-assisted laser-desorption ionization), SELDI (surface-enhanced laser desorption/ionization) or tandem mass spectrometry (MS/MS). New advances on quantitative proteomic analysis (e.g. SILAC, ICAT, and ITRAQ) and multidimensional protein identification technology (MudPIT) have greatly enhanced the capability of proteomic methods to study the expressions, modifications and functions of protein markers. The present article reviews the latest proteomic development and discovery of biomarkers in HCC that may provide insights into the underlying mechanisms of hepatocarcinogenesis and the readiness of biomarkers for clinical uses. [source] Review: The role of microRNAs in kidney diseaseNEPHROLOGY, Issue 6 2010JORDAN YZ LI ABSTRACT MicroRNAs (miRNAs) are short non-coding RNAs that modulate physiological and pathological processes by inhibiting target gene expression via blockade of protein translation or by inducing mRNA degradation. These miRNAs potentially regulate the expression of thousands of proteins. As a result, miRNAs have emerged rapidly as a major new area of biomedical research with relevance to kidney disease. MiRNA expression has been shown to differ between the kidney and other organs as well as between different kidney regions. Furthermore, miRNAs have been found to be functionally important in models of podocyte development, diabetic nephropathy and polycystic kidney disease. Of particular interest, podocyte-specific deletion of Dicer, a key enzyme in the biogenesis of miRNA, results in proteinuria and severe renal impairment in mice. One miRNA (miR-192) can also act as an effector of transforming growth factor-, activity in the high-glucose environment of diabetic nephropathy. Differential expression of miRNAs has been reported in kidney allograft rejection. It is anticipated that future studies involving miRNAs will generate new insights into the complex pathophysiology underlying various kidney diseases, generate diagnostic biomarkers and might be of value as therapeutic targets for progressive kidney diseases. The purpose of this review is to highlight key miRNA developments in kidney diseases and how this might influence the diagnosis and management of patients with kidney disease in the future. [source] Proteomic analysis of sera of asymptomatic, early-stage patients with Wilson's diseasePROTEOMICS - CLINICAL APPLICATIONS, Issue 10 2009Jung-Young Park Abstract Wilson's disease (WD) is characterized by excessive accumulation of intracellular copper in liver and extrahepatic tissues, leading to significant oxidative stress and tissue damage. To date, several diagnostic biomarkers for WD such as serum ceruloplasmin, serum or urine copper levels and copper content in liver have been identified. However, these biomarkers may not be convincing for the diagnosis in some WD patients. To identify additional novel diagnostic biomarkers, we compared the serum protein profiles of asymptomatic childhood WD patients (n=20), without neurologic manifestation or liver cirrhosis, with normal controls (n=13). Fourteen spots, five up-regulated and nine down-regulated (>2-fold), were differentially expressed in WD patients in comparison to normal control on 2-DE. Among them, three spots were down-regulated in both male and female WD. MS/MS analysis revealed that the three spots were complement component C3, complement factor B and alpha-2 macroglobulin. By comparative proteome analysis, complement component C3, complement factor B and alpha-2 macroglobulin, which are related to oxidative stress and inflammation, turned out to be good candidates for novel diagnostic biomarkers for early stages of WD. [source] | |||||||||||||