Disease Markers - Volume 30, issue 6

Authors: Termini, Lara | Filho, Adhemar Longatto | Maciag, Paulo Cesar | Etlinger, Daniela | Alves, Venâncio Avancini Ferreira | Nonogaki, Suely | Soares, Fernando Augusto | Villa, Luisa Lina

Article Type: Research Article

Abstract: Objective: Superoxide dismutase-2 (SOD2) is considered one of the most important antioxidant enzymes that regulate cellular redox state in normal and tumorigenic cells. Overexpression of this enzyme may be involved in carcinogenesis, particularly in lung, gastric, colorectal and breast cancer. Methods: In the present study, we have evaluated SOD2 protein levels by immunohistochemistry (IHC) in 331 cervical histological samples including 31 low-grade cervical intraepithelial neoplasia (LSIL), 51 high-grade cervical intraepithelial neoplasia …(HSIL), 197 squamous cervical carcinomas (SCC) and 52 cervical adenocarcinomas (ADENO). Results: We observed that SOD2 staining increases with cervical disease severity. Intense SOD2 staining was found in 13% of LSIL, 25.5% of HSIL and 40% of SCC. Moreover, 65.4% of ADENO exhibited intense SOD2 staining. Conclusions: Differences in the expression of SOD2 could potentially be used as a biomarker for the characterization of different stages of cervical disease. Show more

Keywords: Human papillomavirus, Tissue Microarray, Biomarker, Cervical Ne oplasia, Superoxide Dismutase-2

DOI: 10.3233/DMA-2011-0784

Citation: Disease Markers, vol. 30, no. 6, pp. 275-281, 2011

Authors: Kokotas, Haris | Grigoriadou, Maria | Korres, George S. | Ferekidou, Elisabeth | Kandiloros, Dimitrios | Korres, Stavros | Petersen, Michael B.

Article Type: Research Article

Abstract: Mitochondrion harbors its own DNA, known as mtDNA, encoding certain essential components of the mitochondrial respiratory chain and protein synthesis apparatus. mtDNA mutations have an impact on cellular ATP production and many of them are undoubtedly a factor that contributes to sensorineural deafness, including both syndromic and non-syndromic forms. Hot spot regions for deafness mutations are the MTRNR1 gene, encoding the 12S rRNA, the MTTS1 gene, encoding the tRNA for Ser^{(UCN)} , and the …MTTL1 gene, encoding the tRNA for Leu^{(UUR)} . We investigated the impact of mtDNA mutations in the Greek hearing impaired population, by testing a cohort of 513 patients suffering from childhood onset prelingual or postlingual, bilateral, sensorineural, syndromic or non-syndromic hearing loss of any degree for six mitochondrial variants previously associated with deafness. Screening involved the MTRNR1 961delT/insC and A1555G mutations, the MTTL1 A3243G mutation, and the MTTS1 A7445G, 7472insC and T7510C mutations. Although two patients were tested positive for the A1555G mutation, we failed to identify any subject carrying the 961delT/insC, A3243G, A7445G, 7472insC, or T7510C mutations. Our findings strongly support our previously raised conclusion that mtDNA mutations are not a major risk factor for sensorineural deafness in the Greek population. Show more

Keywords: 961delT/insC, A1555G, A3243G, A7445G, 7472insC, T7510C, Greece, mitochondrial DNA, mutation, sensorineural deafness

DOI: 10.3233/DMA-2011-0786

Citation: Disease Markers, vol. 30, no. 6, pp. 283-289, 2011

Authors: Suyama, Yoji | Matsuda, Chikashi | Isomura, Minoru | Hamano, Tsuyoshi | Karino, Kenji | Yamasaki, Masayuki | Yamaguchi, Shuhei | Shiwaku, Kuninori | Masuda, Junichi | Nabika, Toru

Article Type: Research Article

Abstract: Oxidative stress is an important risk factor for cardiovascular diseases. Although a variety of genetic factors are assumed to contribute to the regulation of oxidative stress, evidence in human populations is insufficient. In this study, we therefore evaluated the effects of six functional single-nucleotide polymorphisms (SNPs) on the oxidative stress under a cross-sectional study design. Participants of the health examination in two neighboring counties were recruited in a mountainous region of Shimane …prefeture, Japan (n=1092). As a marker for the oxidative stress, the urinary 8-isoprostane (IsoP) was measured by ELISA. The six SNPs were genotyped using the Taqman method. None of the SNPs showed a significant effect on the IsoP level. However, the Generalized Multiple Dimensionality Reduction (GMDR) method identified that the combination of the two SNPs, MTHFR C677T and eNOS T-786C, showed a significant effect on the IsoP level in this population. The linear regression analysis confirmed that the high risk genotype identified in the GMDR was an independent factor influencing the IsoP even after adjustment of confounding factors. This result suggested that GMDR analysis might be useful to identify concealed effects of combined SNPs. Show more

Keywords: Oxidative stress, generalized multiple dimensionality reduction, SNPs, 8-isoprostane

DOI: 10.3233/DMA-2011-0787

Citation: Disease Markers, vol. 30, no. 6, pp. 291-298, 2011

Authors: Gursoy, Ulvi Kahraman | Könönen, Eija | Pussinen, Pirkko J. | Tervahartiala, Taina | Hyvärinen, Kati | Suominen, Anna L. | Uitto, Veli-Jukka | Paju, Susanna | Sorsa, Timo

Article Type: Research Article

Abstract: In the present study, we propose a novel diagnostic approach, using 3 different salivary markers, representing periodontal pathogen burden, inflammation, and tissue degradation, for detecting periodontitis. The salivary concentrations of Porphyromonas gingivalis, interleukin-1β, and matrix metalloproteinase-8, available from salivary specimens of 165 subjects (84 subjects with advanced periodontitis and 81 controls), were calculated together to obtain a cumulative risk score (CRS). In the calculation of CRS, the concentrations of each marker were divided into tertiles, and …cumulative sub-score per each subject were calculated by the multiplication of the tertile values. Three CRS groups, indicating the lowest, medium, or highest risk, were formed with the cumulative sub-scores. Logistic regression analysis and ROC curves were performed to study the association of CRS with periodontitis. The results indicate that CRS, calculated from the 3 salivary biomarkers, is associated with advanced periodontitis more strongly than any of the markers individually. CRS offers a novel, non-invasive model for advanced periodontitis risk categorization that is especially useful in large population surveys where a periodontal examination is not feasible. Show more

Keywords: IL-1β, MMP-8, Porphyromonas gingivalis, risk score, saliva

DOI: 10.3233/DMA-2011-0788

Citation: Disease Markers, vol. 30, no. 6, pp. 299-305, 2011

Authors: Jirun, Peng | Zhang, Guoxin | Kim, Hyun Kee | Ha, Seon-Ah | Zhongtian, Jin | Shishi, Qiao | Zhuqingqing, Cui | Lei, Gong | Yoo, Jinah | Kim, Sanghee | Park, Yong Gyu | Wang, Jing | Yang, Yang | Xu, Zekuan | Huang, Zuhu | Lee, Yun Kyung | Song, Eun Young | Kim, Jin Woo

Article Type: Research Article

Abstract: Serum alpha fetoprotein (AFP) is the most widely used tumor marker in detecting patients with hepatocellular carcinoma (HCC). However, it has been indicated that HCCR-1 (human cervical cancer oncogene 1) might be supplementary to AFP in the detection. We conducted a prospective study in 120 normal and 524 liver disease patients to evaluate the significance of simultaneous measurement of 2 tumor markers (AFP and HCCR-1) in the diagnosis of HCC through the cohort study in Korea …and China. We also performed immunohistochemical studies using 25 normal subjects (N), 32 liver cirrhosis (LC) and 116 HCC tissues. The sensitivities of AFP (20 ng/mL) and HCCR-1 (10 ng/mL) in HCC were 55.8% (164/294) and 44.2% (130/294), respectively. When AFP was combined with HCCR-1, sensitivities increased to 4.2% (N), 12.7% (chronic hepatitis; CH), 50.0% (LC), and 77.2% (HCC), respectively. Although there was no significant difference in the diagnostic rate for HCC between AFP and HCCR-1, many cases for AFP-negative HCC were positive for HCCR-1 and vice versa. Moreover, the combined use of AFP and HCCR-1 improved the diagnostic rate to 70.8% in small HCC (< 2 cm) and 81.6% in large HCC (⩾ 2 cm), respectively. AFP and HCCR-1 are independent markers. Our result suggests that the HCCR-1 could be an useful biomarker for HCC while the diagnostic rate could be significantly improved in the combined use of HCCR-1 and AFP. Show more

Keywords: HCC, biomarker, AFP, HCCR-1

DOI: 10.3233/DMA-2011-0789

Citation: Disease Markers, vol. 30, no. 6, pp. 307-315, 2011

Authors: Ansari, Nadeem A. | Moinuddin, | Ali, Rashid

Article Type: Research Article

Abstract: Nonenzymatic glycosylation or glycation of macromolecules, especially proteins leading to their oxidation, play an important role in diseases. Glycation of proteins primarily results in the formation of an early stage and stable Amadori-lysine product which undergo further irreversible chemical reactions to form advanced glycation endproducts (AGEs). This review focuses these products in lysine rich proteins such as collagen and human serum albumin for their role in aging and age-related diseases. Antigenic characteristics …of glycated lysine residues in proteins together with the presence of serum autoantibodies to the glycated lysine products and lysine-rich proteins in diabetes and arthritis patients indicates that these modified lysine residues may be a novel biomarker for protein glycation in aging and age-related diseases. Show more

Keywords: Lysine, Glycation, Amadori products, AGEs, autoantibodies, diabetes, biomarker

DOI: 10.3233/DMA-2011-0791

Citation: Disease Markers, vol. 30, no. 6, pp. 317-324, 2011

Authors: Chen, Mei-Lin | Chai, Chee-Yin | Yeh, Kun-Tu | Wang, Shen-Nien | Tsai, Chia-Jung | Yeh, Yao-Tsung | Yang, Sheau-Fang

Article Type: Research Article

Abstract: C-Src activity is regulated by tyrosine phosphorylation at two distinct sites, Tyr416 and Tyr527, with opposite effects. However, the clinical roles of these sites in human cancers are not well defined. This study aims to determine whether the alterations and crosstalk of these two sites may contribute to hepatocellular carcinoma (HCC). Specimens from 85 patients who had undergone curative hepatectomy were collected for this study. The patterns of p-Tyr416-Src and p-Tyr527-Src, as well as the non-phosphorylated …status for each site, were determined using immunohistochemistry and statistically correlated with clinicopathological characteristics and overall survival rate. The active state of c-Src, p-Tyr416-c-Src, was positively correlated with tumour grade (P=0.062) but inversely correlated with vascular invasion (P=0.071). Its non-phosphorylated status, non-p-Tyr416-c-Src, was positively correlated with tumour stage and grade (P= 0.041 and 0.020). The inactive state of c-Src, p-Tyr527-c-Src, was decreased in male patients but increased HCV-infected patients (P=0.044 and 0.033). The Kaplan-Meier survival curve further showed that increased p-Tyr416-c-Src and decreased non-p-Tyr527-c-Src expression were associated with a poor patient survival rate (P=0.004 and 0.025). Interestingly, the expression of non-p-Tyr416-c-Src was positively correlated with that of p-Tyr527-c-Src in the HCC lesions (P=0.040). In addition, the patients with concomitantly low p-Tyr416-c-Src and non-p-Tyr527-c-Src expression had a prolonged overall survival rate (P=0.030). A multivariable COX regression model showed that p-Tyr416-c-Src expression was an effective predictor for patient survival in HCC [OR =3.78, 95% CI =1.46–9.76; P=0.006]. Our results suggest that the active state of c-Src, p-Tyr416-c-Src, may serve as an independent prognostic marker of patient survival in HCC. Relative levels of other phosphorylated or non-phosphorylated c-Src kinases may also present different statuses during HCC development and require further investigation. Show more

Keywords: Hepatocellular carcinoma, c-Src, phosphorylation status

DOI: 10.3233/DMA-2011-0792

Citation: Disease Markers, vol. 30, no. 6, pp. 325-333, 2011