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Authors: Spisák, Sándor | Galamb, Barnabás | Sipos, Ferenc | Galamb, Orsolya | Wichmann, Barnabás | Solymosi, Norbert | Nemes, Balázs | Molnár, Jeannette | Tulassay, Zsolt | Molnár, Béla
Article Type: Research Article
Abstract: The exact molecular background and the connection between protein and mRNA expression in colorectal cancer (CRC) development and progression are not completely elucidated. Our purposes were the identification of protein markers of colorectal carcinogenesis and progression using protein arrays and validation on tissue microarrays. The connection between antibody and mRNA expression array results was also examined. Using cancerous and adjacent normal samples from 10 patients with early and 6 with advanced CRC, 67 differentially …expressed genes were identified between normal and cancerous samples. A marker set containing 6 proteins (CCNA1, AR, TOP1, TGFB, HSP60, ERK1) was developed which could differentiate normal specimen, early and late stage CRC with high sensitivity and specificity. Dukes D stage samples were analyzed on HGU133plus2.0 microarrays. In these samples, mRNA and protein expression of 143 genes showed strong positive correlations (R^{2} >0.8), while a negative correlation (R^{2} > 0.9) was found in case of 95 genes. Based on our results a correlation could be established between transcriptome and antibody array results, hence the former may be used as a high-capacity screening method before applying antibody arrays containing already planned targets. Antibody microarrays may have a fundamental importance in testing of marker combinations and future application in diagnostics of tumorous diseases. Show more
Keywords: Colorectal cancer, progression marker, antibody microarray, gene expression, transcriptomics, proteomics, bioequivalency
DOI: 10.3233/DMA-2010-0677
Citation: Disease Markers, vol. 28, no. 1, pp. 1-14, 2010
Authors: Veidal, Sanne Skovgård | Bay-Jensen, Anne-Christine | Tougas, Gervais | Karsdal, Morten Asser | Vainer, Ben
Article Type: Research Article
Abstract: Background: Fibrosis is a central histological feature of chronic liver diseases and is characterized by the accumulation and reorganization of the extracellular matrix. The gold standard for assessment of fibrosis is histological evaluation of a percutaneous liver biopsy. Albeit a considerable effort have been invested in finding alternative non-invasive approaches, these have not been sufficiently succesfull to replace biopsy assessment. Aim: To identify the extracellular matrix proteins of interest, that as protein degradation fragments …produced during extracellular matrix metabolism neo-epitopes, may be targeted for novel biochemical marker development in fibrosis. We used the recently proposed BIPED system (Burden of disease, Investigative, Prognostic, Efficacy and Diagnostic) to characterise present serological markers. Methods: Pubmed was search for keywords; Liver fibrosis, neo-epitopes, biomarkers, clinical trail, extra cellular matrix, protease, degradation, fragment. Results and Conclusion: Implementation of BIPED categorization in the development and validation of fibrosis biomarkers to simplify and standardize the use of existing and future biomarkers seems advantageous. In addition, a systematic use of the neo-epitope approach, i.e. the quantification of peptide epitopes generated from enzymatic cleavage of proteins during extracellular remodeling, may prove productive in the quest to find new markers of liver fibrosis. Show more
Keywords: Fibrosis, biomarkers, neo-epitope, liver, diagnostics, BIPED, extracellular matrix, collagen, proteoglycan
DOI: 10.3233/DMA-2010-0678
Citation: Disease Markers, vol. 28, no. 1, pp. 15-28, 2010
Authors: Guzmán-Guzmán, Iris Paola | Muñoz-Valle, José Francisco | Flores-Alfaro, Eugenia | Salgado-Goytia, Lorenzo | Salgado-Bernabé, Aralia Berenice | Parra-Rojas, Isela
Article Type: Research Article
Abstract: Interleukin-6 (IL-6) is a cytokine involved in inflammatory process, as well as in glucose and lipid metabolism. Several studies of the biological relevance of IL-6 gene polymorphisms have indicated a relationship with cardiovascular disease. The aim of this study was to assess whether the –174 G/C and –572 G/C of IL-6 gene polymorphisms are associated with cardiovascular risk factors in Mexican families. Ninety members of 30 Mexican families, in which an index case (proband) had obesity, …were included in the study. We evaluated the body composition by bioelectrical impedance. Peripheral blood samples were collected to determine biochemical and hematological parameters. High sensitivity C- reactive protein levels were measurement for nephelometric analysis. Screening for both polymorphisms studied was performed by PCR-RFLP. In the parents, both polymorphisms were in Hardy-Weinberg's equilibrium. The genotypes –174 GC/CC were associated with T2D (OR=1.23, IC_{95%} levels of hsCRP (p=0.02), whereas genotype –572 GG was associated with T2D (OR=1.24, IC_{95%} 1.04–1.47) with an inflammatory state determined by the increase in the leukocyte count (OR=1.24, IC_{95%} 1.02–1.51). The genotypes –174 GC/CC and –572 GG may confer susceptibility for the development of subclinical inflammation and type 2 diabetes in Mexican families. Show more
Keywords: Polymorphisms, Interleukin-6, diabetes, inflammation, family study
DOI: 10.3233/DMA-2010-0680
Citation: Disease Markers, vol. 28, no. 1, pp. 29-36, 2010
Authors: Schmid, Maximilian | Grimm, Christoph | Leipold, Heinz | Knöfler, Martin | Haslinger, Peter | Egarter, Christian
Article Type: Research Article
Abstract: Our aim was to investigate whether a genetic variation in the corticotropin-releasing hormone receptor 2 gene might be associated with preterm birth. In this case-control study we evaluated the G/A polymorphism (rs2267717) in intron 2 of the corticotropin-releasing hormone receptor 2 gene in one hundred women with preterm birth and one hundred healthy women with at least one uncomplicated full term pregnancy and no history of preterm birth. No significant correlation was found between the presence …of the investigated polymorphism and preterm birth (p=0.9, odds ratio 0.9 [Confidence interval 0.5–1.7]). A dose dependent association of the investigated polymorphism, in women with preterm birth, with gestational age at delivery (p=0.003) and birth weight was observed (p=0.0001). However, no association between IUGR (n=10) with either one of the investigated genotypes (p=0.3) was found. Stratified analysis within case group {(i.e. PPROM vs. non-PPROM)} revealed no significant difference in genotype distribution (p=0.6). In conclusion, the investigated polymorphism does not increase the risk for preterm birth overall but might modulate the length of pregnancy in a dose dependent fashion in a series of Caucasian women. Show more
Keywords: Corticotropin-releasing hormone receptor 2, polymorphism, preterm birth
DOI: 10.3233/DMA-2010-0681
Citation: Disease Markers, vol. 28, no. 1, pp. 37-42, 2010
Authors: Sambasivan, Venkatasubramanian | Murthy, Kolluri Janaki Rama | Reddy, Ravindra | Vijayalakshimi, Valluri | Hasan, Qurratulain
Article Type: Research Article
Abstract: Objective: Pulmonary tuberculosis (PTB) is a leading cause of morbidity and mortality. Macrophages play an important role in the immunopathogenesis of tuberculosis. Extracellular ATP induces macrophage bactericidal activity through activation of the purinergic P2X7 receptor. This case- control study assesses the association of −762 T/C, 1513A/C and 1729T/A P2X7 polymorphisms in patients with PTB and healthy controls to establish association if any with risk of developing the disease. Materials and methods: The genotyping for …P2X7 was carried out using PCR and RFLP analysis in 256 individuals, which included 156 active PTB patients and 100 age and sex, matched healthy volunteers with no clinical symptoms or family history of PTB as controls. Results: A chi square test showed a significant difference between the PTB patient and controls for −762 C allele; p=0.0051 (OR 1.6972, CI 95% 1.1839 to 2.4332) and1729 T allele was found to be positively associated with the PTB; p < 0.0005 (OR- 2.4623, CI 95% 1.6376 to 3.7022). 1513A/C polymorphism did not show any significant difference between the two groups. Significance: The study revealed a significant association of P2X7-762C allele and P2X7 1729T allele receptor polymorphisms with PTB in Asian Indian population. The use of these alleles as biomarkers for identifying individuals at high risk of developing TB needs to be ascertained. Show more
Keywords: Tuberculosis, P2X7 Gene polymorphisms, Mycobacterium tuberculosis, Purinergic Receptor
DOI: 10.3233/DMA-2010-0682
Citation: Disease Markers, vol. 28, no. 1, pp. 43-48, 2010
Authors: Amoli, Mahsa M. | Yazdani, Nasrin | Amiri, Parvin | Sayahzadeh, Forogh | Haghpanah, Vahid | Tavangar, Seyed Mohammad | Amirzargar, Ali | Ghaffari, Hamidollah | Nikbin, Behrooz | Larijani, Bagher | Mostaan, Leila V. | Bazzaz, Javad Tavakkoly
Article Type: Research Article
Abstract: Objective: Papillary thyroid carcinoma (PTC) is the most frequent types of thyroid malignancies. Several genes may be involved in susceptibility of thyroid cancer including Human Leukocyte Antigens (HLA). The association of thyroid carcinoma with HLA alleles has been previously studied in other populations and certain HLA alleles were shown to be either predisposing or protective. The aim of this study was to determine the association between HLA-DR and papillary thyroid carcinoma in an Iranian population. …Design: HLA-DR antigen frequencies were determined in patients with papillary thyroid carcinoma (N=70) and non-related healthy controls (N=180) using PCR -SSP. Main Outcome: We found that HLA-DRB1*04 frequency was significantly higher in our patients compared to the controls [P=0.02, OR; 1.9, 95% CI (1.04–3.57)]. Conclusions: Our results revealed HLA-DRB1*04 as predisposing factor in papillary thyroid carcinoma in Iranian population. This confirms the previous findings for associations between HLA-DRB1 and differentiated carcinomas in other populations. Show more
Keywords: Genetics, HLA, Papillary carcinoma
DOI: 10.3233/DMA-2010-0683
Citation: Disease Markers, vol. 28, no. 1, pp. 49-53, 2010
Authors: Hung, Yu-Hung | Wu, Cheng-Chin | Ou, Tsan-Teng | Lin, Chia-Hui | Li, Ruei-Nian | Lin, Yu-Chih | Tsai, Wen-Chan | Liu, Hong-Wen | Yen, Jeng-Hsien
Article Type: Research Article
Abstract: To investigate the role of IκBα promoter polymorphisms in the development of Behçet's disease, eighty-six patients with Behçet's disease and 120 healthy controls were enrolled in this study. The IκBα -881A/G, -826C/T, -550A/T, -519C/T, and -297C/T polymorphisms were measured by the method of polymerase chain reaction/ restriction fragment length polymorphism. This study demonstrated that the genotype frequencies of IκBα -826C/T and -826T/T were significantly higher …in the patients with Behçet's disease than in the controls. Both in the dominant and in the recessive models, the patients with Behçet's disease have higher frequencies of the IκBα -826T containing genotype than the controls. The allele frequency of IκBα -826T was significantly increased in the patients with Behçet's disease. The frequencies of the IκBα -881A -826T -550A -519C -297C and IκBα -881A -826T -550A -519T -297C haplotypes were significantly higher in the patients with Behçet's disease than in the controls. In contrast, the haplotype frequency of IκBα -881A -826C -550A -519C -297C in the patients with Behçet's disease was significantly decreased. This study also revealed that the Behçet's disease patients with IκBα -826T/T have higher prevalence of skin lesions than those without IκBα -826T/T. In summary, the IκBα -826T allele, IκBα -881A -826T -550A -519C -297C and IκBα -881A -826T -550A -519T -297C haplotypes might be associated with susceptibility to Behçet's disease. The IκBα -826T/T genotype was related to the development of skin lesions in the patients with Behçet's disease. Show more
Keywords: IκBα, NFkB inhibitor, polymorphisms, Behçet's disease
DOI: 10.3233/DMA-2010-0684
Citation: Disease Markers, vol. 28, no. 1, pp. 55-62, 2010
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