Disease Markers http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Urine Cell-Free DNA Integrity Analysis for Early Detection of Prostate Cancer Patients Thu, 27 Aug 2015 14:44:10 +0000 http://www.hindawi.com/journals/dm/2015/574120/ Introduction. The detection of tumor-specific markers in urine has paved the way for new early noninvasive diagnostic approaches for prostate cancer. We evaluated the DNA integrity in urine supernatant to verify its capacity to discriminate between prostate cancer and benign diseases of the urogenital tract. Patients and Methods. A total of 131 individuals were enrolled: 67 prostate cancer patients and 64 patients with benign diseases of the urogenital tract (control group). Prostate-specific antigen (PSA) levels were determined. Urine cell-free (UCF) DNA was isolated and sequences longer than 250 bp corresponding to 3 genes (c-MYC, HER2, and AR) were quantified by Real-Time PCR to assess UCF-DNA integrity. Results. UCF-DNA was quantifiable in all samples, while UCF-DNA integrity was evaluable in all but 16 samples. Receiver operating characteristic analysis showed an area under the curve of 0.5048 for UCF-DNA integrity and 0.8423 for PSA. Sensitivity was 0.58 and 0.95 for UCF-DNA integrity and PSA, respectively. Specificity was 0.44 and 0.69, respectively. Conclusions. UCF-DNA integrity showed lower accuracy than PSA and would not seem to be a reliable marker for early prostate cancer diagnosis. Despite this, we believe that UCF-DNA could represent a source of other biomarkers and could detect gene alterations. Samanta Salvi, Giorgia Gurioli, Filippo Martignano, Flavia Foca, Roberta Gunelli, Giacomo Cicchetti, Ugo De Giorgi, Wainer Zoli, Daniele Calistri, and Valentina Casadio Copyright © 2015 Samanta Salvi et al. All rights reserved. The Prognostic Role of Red Blood Cell Distribution Width in Coronary Artery Disease: A Review of the Pathophysiology Wed, 26 Aug 2015 12:15:13 +0000 http://www.hindawi.com/journals/dm/2015/824624/ Red blood cell distribution width (RDW) is a measure of red blood cell volume variations (anisocytosis) and is reported as part of a standard complete blood count. In recent years, numerous studies have noted the importance of RDW as a predictor of poor clinical outcomes in the settings of various diseases, including coronary artery disease (CAD). In this paper, we discuss the prognostic value of RDW in CAD and describe the pathophysiological connection between RDW and acute coronary syndrome. In our opinion, the negative prognostic effects of elevated RDW levels may be attributed to the adverse effects of independent risk factors such as inflammation, oxidative stress, and vitamin D3 and iron deficiency on bone marrow function (erythropoiesis). Elevated RDW values may reflect the intensity of these phenomena and their unfavorable impacts on bone marrow erythropoiesis. Furthermore, decreased red blood cell deformability among patients with higher RDW values impairs blood flow through the microcirculation, resulting in the diminution of oxygen supply at the tissue level, particularly among patients suffering from myocardial infarction treated with urgent revascularization. Kamil Bujak, Jarosław Wasilewski, Tadeusz Osadnik, Sandra Jonczyk, Aleksandra Kołodziejska, Marek Gierlotka, and Mariusz Gąsior Copyright © 2015 Kamil Bujak et al. All rights reserved. Noncoding Genomics in Gastric Cancer and the Gastric Precancerous Cascade: Pathogenesis and Biomarkers Wed, 26 Aug 2015 11:45:23 +0000 http://www.hindawi.com/journals/dm/2015/503762/ Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related death, whose patterns vary among geographical regions and ethnicities. It is a multifactorial disease, and its development depends on infection by Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV), host genetic factors, and environmental factors. The heterogeneity of the disease has begun to be unraveled by a comprehensive mutational evaluation of primary tumors. The low-abundance of mutations suggests that other mechanisms participate in the evolution of the disease, such as those found through analyses of noncoding genomics. Noncoding genomics includes single nucleotide polymorphisms (SNPs), regulation of gene expression through DNA methylation of promoter sites, miRNAs, other noncoding RNAs in regulatory regions, and other topics. These processes and molecules ultimately control gene expression. Potential biomarkers are appearing from analyses of noncoding genomics. This review focuses on noncoding genomics and potential biomarkers in the context of gastric cancer and the gastric precancerous cascade. Alejandra Sandoval-Bórquez, Kathleen Saavedra, Gonzalo Carrasco-Avino, Benjamin Garcia-Bloj, Jacqueline Fry, Ignacio Wichmann, and Alejandro H. Corvalán Copyright © 2015 Alejandra Sandoval-Bórquez et al. All rights reserved. Site-Specific Secretome Map Evidences VSMC-Related Markers of Coronary Atherosclerosis Grade and Extent in the Hypercholesterolemic Swine Tue, 25 Aug 2015 08:42:00 +0000 http://www.hindawi.com/journals/dm/2015/465242/ A major drawback in coronary atherosclerosis (ATS) research is the difficulty of investigating early phase of plaque growth and related features in the clinical context. In this study, secreted proteins from atherosclerotic coronary arteries in a hypercholesterolemic swine model were characterized by a proteomics approach and their expression was correlated to site-specific ATS stage and extent. A wide coronary artery map of secreted proteins has been obtained in high fat (HF) diet induced ATS swine model and a significantly different expression of many proteins related to vascular smooth muscle cell (VSMC) activation/migration has been identified. Significant associations with ATS stage of HF coronary lesions were found for several VSMC-derived proteins and validated for chitinase 3 like protein 1 (CHI3L1) by tissue immunoexpression. A direct correlation was evidenced with intima to media thickness ratio values and ELISA confirmed the higher blood concentrations of CHI3L1 in HF cases. These findings confirmed the pivotal role of VSMCs in coronary plaque development and demonstrated a strong site-specific relation between VSMC-secreted CHI3L1 and lesion grade, suggesting that this protein could be proposed as a useful biomarker for diagnosing and staging of atherosclerotic lesions in coronary artery disease. Silvia Rocchiccioli, Antonella Cecchettini, Nadia Ucciferri, Marianna Terreni, Federica Viglione, Maria Giovanna Trivella, Lorenzo Citti, Oberdan Parodi, and Gualtiero Pelosi Copyright © 2015 Silvia Rocchiccioli et al. All rights reserved. A Genetic Variant in miRNA-219-1 Is Associated with Risk of Esophageal Squamous Cell Carcinoma in Chinese Kazakhs Mon, 24 Aug 2015 14:04:47 +0000 http://www.hindawi.com/journals/dm/2015/541531/ Background. Esophageal cancer (EC), an aggressive digestive tract malignancy, is one of the leading causes of cancer-related deaths worldwide. Besides environmental risk factors, genetic factors might play a key role in the EC carcinogenesis. The aim of the study is to evaluate the association of miR219-1 single-nucleotide polymorphisms (SNPs) with EC. Methods. A total of 248 Kazakh esophageal squamous cell carcinoma (ESCC) cases and 300 frequency-matched control subjects were recruited for this study. Genomic DNA was isolated from the samples. The miR-219-1 rs107822G > A and rs213210T > C genotypes were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Linkage disequilibrium (LD) and haplotype analysis were used to detect the degree of association on miR-219-1 rs107822 and rs213210. Real-time quantitative polymerase chain reaction (qRT-PCR) was performed to detect miR-219-1 expression with miR-219-1 rs107822 polymorphism. Result. The SNP rs107822G > A in the miR-219-1 gene decreased the risk of Kazakh ESCC. Furthermore, two miR-219-1 SNPs, namely, rs107822 and rs213210, may tag each other to decrease the risk of Kazakh ESCC. These findings indicated that functional polymorphisms miR-219-1 rs107822G > A might change individual susceptibility to Kazakh ESCC. Xiaoyue Song, Weiyan You, Jianbo Zhu, Xiaobin Cui, Jianming Hu, Yunzhao Chen, Wei Liu, Lianghai Wang, Shugang Li, Yutao Wei, Lan Yang, and Feng Li Copyright © 2015 Xiaoyue Song et al. All rights reserved. Hiwi Promotes the Proliferation of Colorectal Cancer Cells via Upregulating Global DNA Methylation Tue, 18 Aug 2015 17:26:58 +0000 http://www.hindawi.com/journals/dm/2015/383056/ Hiwi is well known for its role in stem cell renewal, maintaining the resting stage, and downregulating cell cycle of stem cells via RNA silencing. And Hiwi overexpression has been recognized in several types of cancers. In the present study, we examined the Hiwi expression in colorectal cancer (CRC) specimens in both mRNA and protein levels via real-time quantitative PCR, western blot assay, and immunohistochemical staining. Then we explored the role of Hiwi in the cancer cell proliferation and in the DNA methylation in human CRC Caro-2 and HT-29 cell lines. Results demonstrated that both mRNA and protein levels of Hiwi were significantly higher in 38 CRC tissues than in 38 peritumor tissues. Moreover, the Hiwi overexpression with an adenovirus vector significantly promoted the proliferation of Caro-2 and HT-29 cells, associated with significant increase in the global DNA methylation levels. And the chemical inhibition of DNA methylation significantly restrained such proliferation promotion. In summary, we confirmed that Hiwi was overexpressed in CRC tissues and that the forced Hiwi overexpression promoted the proliferation and global DNA methylation of CRC cell lines. Our results imply for the first time that Hiwi promotes the proliferation of CRC cells via promoting global DNA methylation. Lin Yang, Lei Bi, Qingwei Liu, Meng Zhao, Bin Cao, Dong Li, and Jianjun Xiu Copyright © 2015 Lin Yang et al. All rights reserved. Effect of Increased Water Intake on Urinary DNA Adduct Levels and Mutagenicity in Smokers: A Randomized Study Tue, 18 Aug 2015 11:35:58 +0000 http://www.hindawi.com/journals/dm/2015/478150/ The association between fluid intake and bladder cancer risk remains controversial. Very little is known about to which extent the amount of water intake influences the action of excreting toxics upon the urinary system. This proof of concept trial investigates the effect of water intake on mutagenesis in smokers, a high risk population for bladder cancer. Methods. Monocentric randomized controlled trial. Inclusion Criteria. Male subjects aged 2045–45 y/o, smokers, and small drinkers (24-hour urinary volume <1 L and osmolality >700 mOsmol/kg). Outcomes. 4-ABP DNA adducts formation in exfoliated bladder cells in 24-hour urine collection and urinary mutagenicity in 24-hour urine. Test Group. Subjects consumed 1.5 L daily of the study product (EVIAN) on top of their usual water intake for 50 days. Control Group. Subjects continued their usual lifestyle habits. Results. 65 subjects were randomized. Mean age was 30 y/o and mean cigarettes per day were 20. A slight decrease in adducts formation was observed between baseline and last visit but no statistically significant difference was demonstrated between the groups. Urinary mutagenicity significantly decreased. The study shows that increasing water intake decreases urinary mutagenicity. It is not confirmed by urinary adducts formation. Further research would be necessary. Inmaculada Buendia Jimenez, Pascaline Richardot, Pascaline Picard, Eve M. Lepicard, Michel De Meo, and Glenn Talaska Copyright © 2015 Inmaculada Buendia Jimenez et al. All rights reserved. Prognostic Role of MicroRNA-126 for Survival in Malignant Tumors: A Systematic Review and Meta-Analysis Mon, 17 Aug 2015 14:27:27 +0000 http://www.hindawi.com/journals/dm/2015/739469/ Background. Increasing studies found that miR-126 expression may be associated with the prognosis of cancers. Here, we performed a meta-analysis to assess the prognostic role of miR-126 in different cancers. Methods. Eligible studies were identified by searching in PubMed, Embase, the Cochrane Library, CNKI, and Wan Fang databases up to March 2015. Pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated to investigate the correlation between miR-126 and survival of cancers. Results. Thirty studies including a total of 4497 participants were enrolled in this meta-analysis. The pooled results showed that high level of miR-126 was a predictor for favorable survival of carcinomas, with pooled HR of 0.77 (95% CI 0.64–0.93) for OS, 0.64 (95%CI 0.48–0.85) for DFS, and 0.70 (95% CI 0.50–0.98) for PFS/RFS/DSS. However, high level of circulating miR-126 predicted a significantly worse OS in patients with cancer (HR = 1.65, 95% CI 1.09–2.51). Conclusions. Our results indicated that miR-126 could act as a significant biomarker in the prognosis of various cancers. Jie Bu, Hui Li, Xiao-yang Li, Li-hong Liu, Wei Sun, and Tao Xiao Copyright © 2015 Jie Bu et al. All rights reserved. Blood Contamination in Saliva: Impact on the Measurement of Salivary Oxidative Stress Markers Tue, 11 Aug 2015 13:07:05 +0000 http://www.hindawi.com/journals/dm/2015/479251/ Salivary oxidative stress markers represent a promising tool for monitoring of oral diseases. Saliva can often be contaminated by blood, especially in patients with periodontitis. The aim of our study was to examine the impact of blood contamination on the measurement of salivary oxidative stress markers. Saliva samples were collected from 10 healthy volunteers and were artificially contaminated with blood (final concentration 0.001–10%). Next, saliva was collected from 12 gingivitis and 10 control patients before and after dental hygiene treatment. Markers of oxidative stress were measured in all collected saliva samples. Advanced oxidation protein products (AOPP), advanced glycation end products (AGEs), and antioxidant status were changed in 1% blood-contaminated saliva. Salivary AOPP were increased in control and patients after dental treatment (by 45.7% and 34.1%, ). Salivary AGEs were decreased in patients after microinjury (by 69.3%, ). Salivary antioxidant status markers were decreased in both control and patients after dental treatment ( and ). One % blood contamination biased concentrations of salivary oxidative stress markers. Saliva samples with 1% blood contamination are visibly discolored and can be excluded from analyses without any specific biochemic detection of blood constituents. Salivary markers of oxidative stress were significantly altered in blood-contaminated saliva in control and patients with gingivitis after dental hygiene treatment. Natália Kamodyová, Lenka Baňasová, Katarína Janšáková, Ivana Koborová, Ľubomíra Tóthová, Peter Stanko, and Peter Celec Copyright © 2015 Natália Kamodyová et al. All rights reserved. The Prognostic Value of Pyrosequencing-Detected MGMT Promoter Hypermethylation in Newly Diagnosed Patients with Glioblastoma Tue, 11 Aug 2015 06:14:54 +0000 http://www.hindawi.com/journals/dm/2015/604719/ O6-methylguanine-DNA-methyltransferase (MGMT) has emerged as a relevant predictor of therapeutic response and good prognosis in patients with glioblastoma (GBM). Transcriptionally active MGMT rapidly removes the alkyl adducts, preventing the formation of cross-links and thereby causing resistance to alkylating drugs. Studies with pyrosequencing (PSQ) showed that this technique has a higher reproducibility and sensitivity than other techniques. However, the definition of a prognostically relevant threshold for the percentage of MGMT methylation remains one of the most critical issues in the use of PSQ analysis. The aim of this study was to define the cut-off value correlated with good favourable prognostic outcomes. We retrospectively analyzed 51 patients (33 males, 18 females) with GBM who underwent surgery or biopsy. The Receiver Operating Characteristics analysis showed that the best possible criteria for PSQ-detected percentage of MGMT methylation that predicted progression-free survival (PFS) and overall survival (OS) were 19% and 13%, respectively. Patients with ≤19% of PSQ-detected MGMT had a shorter PFS (HR: 0.24, ); those ones with ≤13% had a shorter OS (HR: 0.33, ). Our study reinforces the importance of MGMT in the management of GBM patients, but future studies with larger sample sizes are warranted to confirm our findings. Veronica Villani, Beatrice Casini, Andrea Pace, Luca Prosperini, Carmine M. Carapella, Antonello Vidiri, Alessandra Fabi, and Mariantonia Carosi Copyright © 2015 Veronica Villani et al. All rights reserved. Chemokine Coreceptor-2 Gene Polymorphisms among HIV-1 Infected Individuals in Kenya Sun, 02 Aug 2015 16:06:34 +0000 http://www.hindawi.com/journals/dm/2015/952067/ Chemokine Coreceptor-2 (CCR2) is an entry coreceptor for HIV-1. A mutation in the coding gene for this coreceptor, CCR2-64I, has been shown to be an important factor for delaying disease progression. In Kenya no studies have been done to determine the status of CCR2 gene polymorphisms among HIV-1 infected individuals. To determine the existence and distribution of CCR2 gene mutations and identify polymorphic groups of the coreceptor gene in the population, a cross-sectional study was conducted to analyze the differences in allelic frequencies of CCR2-64I among HIV-1 seropositive individuals. Blood samples were collected from HIV/AIDS screening centers and analyzed for the presence of CCR2-64I using restriction fragment length polymorphism (RFLP). One hundred and eighteen samples collected from different regions of the country were genotyped for the CCR2-64I mutation. Of these, 4 (3.4%) were homozygous mutants (I/I) and 21 (17.8%) were heterozygous (V/I). Ninety-three subjects (78.8%) were wild type (V/V). With the search for a preventive/therapeutic HIV vaccine elusive, the presence of CCR-2 gene polymorphisms that delay disease progression and prolong the lives of the infected in the Kenyan population may contribute to the growing evidence that host genetic factors are important in predicting susceptibility to HIV-1 infection. Dorcas Wachira, Raphael Lihana, Vincent Okoth, Alex Maiyo, and Samoel Ashimosi Khamadi Copyright © 2015 Dorcas Wachira et al. All rights reserved. The Clinical and Pathological Significance of Nectin-2 and DDX3 Expression in Pancreatic Ductal Adenocarcinomas Thu, 30 Jul 2015 11:46:29 +0000 http://www.hindawi.com/journals/dm/2015/379568/ Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease, but the genetic basis of PDAC is still unclear. In this study, Nectin-2 and DDX3 expression in 106 PDAC, 35 peritumoral tissues, 55 benign pancreatic lesions, and 13 normal pancreatic tissues were measured by immunohistochemical methods. Results showed that the percentage of positive Nectin-2 and DDX3 expression was significantly higher in PDAC tumors than in peritumoral tissues, benign pancreatic tissues, and normal pancreatic tissues (). The percentage of cases with positive Nectin-2 and DDX3 expression was significantly lower in PDAC patients without lymph node metastasis and invasion and having TNM stage I/II disease than in patients with lymph node metastasis, invasion, and TNM stage III/IV disease ( or ). Positive DDX3 expression is associated with poor differentiation of PDAC. Kaplan-Meier survival analysis showed that positive Nectin-2 and DDX3 expression were significantly associated with survival in PDAC patients (). Cox multivariate analysis revealed that positive Nectin-2 and DDX3 expression were independent poor prognosis factors in PDAC patients. In conclusion, positive Nectin-2 and DDX3 expression are associated with the progression and poor prognosis in PDAC patients. Shan Liang, Zhulin Yang, Daiqiang Li, Xiongying Miao, Leping Yang, Qiong Zou, and Yuan Yuan Copyright © 2015 Shan Liang et al. All rights reserved. Corrigendum to “The Analysis of Sialylation, N-Glycan Branching, and Expression of O-Glycans in Seminal Plasma of Infertile Men” Wed, 29 Jul 2015 13:24:11 +0000 http://www.hindawi.com/journals/dm/2015/652781/ Ewa M. Kratz, Anna Kałuża, Mariusz Zimmer, and Mirosława Ferens-Sieczkowska Copyright © 2015 Ewa M. Kratz et al. All rights reserved. Carboxyhemoglobin Formation in Preterm Infants Is Related to the Subsequent Development of Bronchopulmonary Dysplasia Wed, 29 Jul 2015 06:40:01 +0000 http://www.hindawi.com/journals/dm/2015/620921/ Objective. To evaluate the usefulness of carboxyhemoglobin (CO-Hb) levels as a biomarker to predict the development and severity of bronchopulmonary dysplasia (BPD). Methods. Twenty-five infants born at <33 wk of gestational age or with a birth weight of <1,500 g were enrolled. CO-Hb levels were measured between postnatal days 5 and 8, 12 and 15, 19 and 22, and 26 and 29. Urinary levels of 8-hydroxydeoxyguanosine (8-OHdG), advanced oxidation protein products, and Nε-(hexanoyl) lysine were measured between postnatal days 5 and 8 and 26 and 29. Receiver operating characteristic (ROC) analysis was used to compare the biomarkers’ predictive values. Results. Compared with infants in the no-or-mild BPD group, infants with moderate-to-severe BPD exhibited higher CO-Hb levels during the early postnatal period and higher 8-OHdG levels between postnatal days 5 and 8. Using ROC analysis to predict the development of moderate-to-severe BPD, the area under the curve (AUC) for CO-Hb levels between postnatal days 5 and 8 was higher than AUCs for the urinary markers. Conclusions. CO-Hb levels during the early postnatal period may serve as a practical marker for evaluating oxidative stress and the severity of subsequently developing BPD. Shuko Tokuriki, Takashi Okuno, Genrei Ohta, and Yusei Ohshima Copyright © 2015 Shuko Tokuriki et al. All rights reserved. The Effect of PAI-1 4G/5G Polymorphism and Clinical Factors on Coronary Artery Occlusion in Myocardial Infarction Sun, 26 Jul 2015 14:08:10 +0000 http://www.hindawi.com/journals/dm/2015/260101/ Objective. Data on the impact of PAI-1-675 4G/5G genotype for fibrinolysis during myocardial infarction are inconsistent. The aim of our study was to evaluate the association of clinical and genetic (PAI-1-675 4G/5G polymorphism) factors with coronary artery occlusion in patients with myocardial infarction. Materials and Methods. PAI-1-675 4G/5G detection was achieved by using Sanger sequencing in a sample of patients hospitalized for stent implantation due to myocardial infarction. We categorized the patients into two groups: patients with coronary artery occlusion and patients without coronary artery occlusion according to angiographic evaluation. Results. We identified (32.4%) 4G/4G, (49.5%) 4G/5G, and (18.1%) 5G/5G PAI-1 genotype carriers. Univariate and multivariate analysis showed that only the 4G/5G genotype was associated with coronary artery occlusion (OR: 1.656 and 95% CI: 1.009–2.718, ). Conclusions. Our results showed that carriers of PAI-1 4G/5G genotype with myocardial infarction have increased odds of coronary artery occlusion more than 1.6 times in comparison to the carriers of homozygous genotypes. Tajinder Kumar Parpugga, Vacis Tatarunas, Vilius Skipskis, Nora Kupstyte, Diana Zaliaduonyte-Peksiene, and Vaiva Lesauskaite Copyright © 2015 Tajinder Kumar Parpugga et al. All rights reserved. Prognostic Value of FOXM1 in Patients with Malignant Solid Tumor: A Meta-Analysis and System Review Wed, 22 Jul 2015 13:12:20 +0000 http://www.hindawi.com/journals/dm/2015/352478/ Forkhead box M1 (FOXM1), a member of the Fox transcription factors family, was closely related with cell cycle. FOXM1 played an important role in MST and prompted a poor prognosis for MST patients. However, there were also some studies revealing no significant association between the FOXM1 expression and prognosis of patients. Therefore, we conducted meta-analysis to investigate whether the expression of FOXM1 was associated with MST prognosis. We collected 36 relevant studies through PubMed database and obtained research data of 4946 patients. Stata 12.0 was used to express the results as hazard ratio (HR) for time-to-event outcomes with 95% confidence intervals (95% CI). It was shown that overexpression of FOXM1 was relevant to worse survival of MST patients (HR = 1.99, 95% CI = 1.79–2.21, ; %, ). Subgroup analysis suggested that overexpression of FOXM1 in breast cancer (BC), gastric cancer (GC), hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDA), and non-small-cell lung cancer (NSCLC) all predicted a worse survival (), in addition to ovarian cancer (OC) (). In conclusion, our research indicated that overexpression of FOXM1 was to the disadvantage of the prognosis for majority of MST and therefore can be used as an evaluation index of prognosis. Jun Dai, Lili Yang, Jinyu Wang, Ying Xiao, and Qiurong Ruan Copyright © 2015 Jun Dai et al. All rights reserved. Cerebrospinal Fluid Biomarkers in Spinocerebellar Ataxia: A Pilot Study Wed, 22 Jul 2015 11:30:34 +0000 http://www.hindawi.com/journals/dm/2015/413098/ Neurodegenerative diseases, including the spinocerebellar ataxias (SCA), would benefit from the identification of reliable biomarkers that could serve as disease subtype-specific and stage-specific indicators for the development and monitoring of treatments. We analyzed the cerebrospinal fluid (CSF) level of tau, α-synuclein, DJ-1, and glial fibrillary acidic protein (GFAP), proteins previously associated with neurodegenerative processes, in patients with the autosomal dominant SCA1, SCA2, and SCA6, and the sporadic disease multiple system atrophy, cerebellar type (MSA-C), compared with age-matched controls. We estimated disease severity using the Scale for the Assessment and Rating of Ataxia (SARA). Most proteins measured trended higher in disease versus control group yet did not reach statistical significance. We found the levels of tau in both SCA2 and MSA-C patients were significantly higher than control. We found that α-synuclein levels were lower with higher SARA scores in SCA1 and tau levels were higher with greater SARA in MSA-C, although this final correlation did not reach statistical significance after post hoc correction. Additional studies with larger sample sizes are needed to improve the power of these studies and validate the use of CSF biomarkers in SCA and MSA-C. Ashley M. Brouillette, Gülin Öz, and Christopher M. Gomez Copyright © 2015 Ashley M. Brouillette et al. All rights reserved. Clinical Applications of Natriuretic Peptides in Assessment of Valvular Heart Disease Wed, 22 Jul 2015 08:14:36 +0000 http://www.hindawi.com/journals/dm/2015/807861/ Biomarkers such as natriuretic peptides (NPs) have evolving clinical utility beyond the scope of heart failure. The role of NPs in the management of valvular heart disease is a growing area of investigation. NPs have much potential in the assessment of asymptomatic patients with hemodynamically significant valvular lesions who have traditionally been excluded from consideration of surgical intervention. NPs also have a role in the risk stratification of these patients as well as in routine surveillance and monitoring. Together with echocardiographic data and functional status, NPs are being incorporated into the management of valvular heart disease. In this review we examine the evidence for the role of natriuretic peptides in assessment of VHD. Abhishek Sharma, Vaseem Ahmed, Aakash Garg, and Chirag Aggarwal Copyright © 2015 Abhishek Sharma et al. All rights reserved. Serum GRP78 as a Tumor Marker and Its Prognostic Significance in Non-Small Cell Lung Cancers: A Retrospective Study Tue, 21 Jul 2015 06:51:10 +0000 http://www.hindawi.com/journals/dm/2015/814670/ Introduction. Glucose-regulated protein 78 (78 kDa, GRP78), which is also known as immunoglobulin heavy chain binding protein (BIP), is a major chaperone in the endoplasmic reticulum (ER). The expression and clinical significance of GRP78 in the serum of non-small cell lung cancer patients have not yet been clearly described. The aims of the present study were to investigate the expression of GRP78 in the serum of non-small cell lung cancer patients, the relationships with clinicopathological parameters, and the potential implications for survival. Patients and Methods. A total of 163 peripheral blood samples from non-small cell lung cancer patients were prospectively collected at the Department of Thoracic Surgery, Fudan University Shanghai Cancer, China. Clinical characteristics data, including age, gender, stage, overall survival (OS) time, and relapse-free survival (RFS) time, were also collected. Serum GRP78 levels were measured using a commercially available ELISA kit. The associations between GRP78 levels and clinicopathological characteristics and survival were examined using Student’s t-test, Kaplan-Meier, or Cox regression analyses. Results. The mean ± standard error (SE) value of GRP78 was 326.5 ± 49.77 pg/mL. This level was significantly lower compared with the level in late-stage non-small cell lung cancer patients (1227 ± 223.6, ). There were no significant correlations with the clinicopathological parameters. No significant difference was found between high GRP78 expression and low GRP78 expression with regard to RFS . However, the OS of patients with higher GRP78 expression was significantly poorer . Conclusions. GRP78 was expressed in non-small cell lung cancer patients and was highly enriched in late-stage lung cancer. GRP78 may have an important role in the carcinogenesis of non-small cell lung cancer and may be a prognostic marker for non-small cell lung cancer. Xiao Ma, Wei Guo, Su Yang, Xiaoli Zhu, Jiaqing Xiang, and Hecheng Li Copyright © 2015 Xiao Ma et al. All rights reserved. Hemoglobin A1c Level Is Not Related to the Severity of Atherosclerosis in Patients with Acute Coronary Syndrome Thu, 16 Jul 2015 10:31:57 +0000 http://www.hindawi.com/journals/dm/2015/192108/ Background. The relationship between hemoglobin A1c (HbA1c) levels and the extent of coronary artery stenosis in patients with acute coronary syndrome (ACS) remains uncertain. The present study aimed to assess the correlation of HbA1c level with angiographic coronary atherosclerosis. Methods. 292 consecutive ACS patients were enrolled and stratified into three groups according to HbA1c levels (group 1: <6.0%, ; group 2: 6.0–6.4%, ; group 3: ≥6.5%, ). The severity of coronary arteriosclerosis was assessed by Gensini score. The relationship between HbA1c and Gensini score was analyzed by multiple variables analysis. Results. HbA1c level was not associated with the severity of CAD assessed by Gensini score in patients with ACS, even after the adjustment for other risk factors. However, NT-proBNP, ApoA1 and LVEF levels were independent predictors for CAD severity. Moreover, HbA1c level was not associated with the risk of high Gensini score (>40) by logistic regression analysis. Diabetes mellitus (DM) and LVEF levels were two independent risk factors for high Gensini score. Conclusions. HbA1c level is not a significant and independent marker for the severity of angiography in ACS patients, even in high-risk patients. Xinhong Wang, Zhenhua Han, Guanghua Hao, Yongqin Li, Xin Dong, and Congxia Wang Copyright © 2015 Xinhong Wang et al. All rights reserved. Characteristics of Three-Dimensional Power Doppler in Gestational Trophoblastic Disease Thu, 16 Jul 2015 10:01:43 +0000 http://www.hindawi.com/journals/dm/2015/917687/ Purpose. In the present study, the three-dimensional power Doppler was used as a quantitative method to evaluate its reliability in detecting and assessing of gestational trophoblastic disease (GTD). Methods. 52 GTD patients who received diagnosis and treatment at the first affiliated hospitals of Xi’an Jiaotong University in China between 2011 and 2013 were evaluated using Voluson E8 (GE Medical System). Demographic information, pathological characteristics, clinical history, sonographic images, and related indices (resistance index, vascularization index, and flow and vascularization index) were evaluated. Result. Three-dimension power Doppler indicated that there were significant differences in the resistance index, vascularization index, flow index, and vascularization-flow index between the healthy individuals and each subgroup of patients (). Further, in combining invasive hydatidiform mole and choriocarcinoma groups, there was a significant difference between hydatidiform mole and the combined malignant group (). And the abnormal sonographic and power Doppler findings in GTD were resolved when chemotherapy was done successfully. Conclusion. Combined with the clinical features, sonography and three-dimension power Doppler imaging were helpful in diagnosing GTD as a noninvasive method, distinguishing the invasive nature of disease, detecting the recurrence of the disease, and assessing the effectiveness of the chemotherapy. Wei Wang, Xueye Tian, Ting Zhang, Yanyan Wang, Zhen Han, and Ruifang An Copyright © 2015 Wei Wang et al. All rights reserved. Electrocardiographic Predictors of Cardiovascular Mortality Thu, 16 Jul 2015 07:39:17 +0000 http://www.hindawi.com/journals/dm/2015/727401/ Cardiovascular diseases are the main causes of mortality. Sudden cardiac death may also appear in athletes, due to underlying congenital or inherited cardiac abnormalities. The electrocardiogram is used in clinical practice and clinical trials, as a valid, reliable, accessible, inexpensive method. The aim of the present paper was to review electrocardiographic (ECG) signs associated with cardiovascular mortality and the mechanisms underlying those associations, providing a brief description of the main studies in this area, and consider their implication for clinical practice in the general population and athletes. The main ECG parameters associated with cardiovascular mortality in the present paper are the P wave (duration, interatrial block, and deep terminal negativity of the P wave in V1), prolonged QT and Tpeak-Tend intervals, QRS duration and fragmentation, bundle branch block, ST segment depression and elevation, T waves (inverted, T wave axes), spatial angles between QRS and T vectors, premature ventricular contractions, and ECG hypertrophy criteria. Ioana Mozos and Alexandru Caraba Copyright © 2015 Ioana Mozos and Alexandru Caraba. All rights reserved. Association of DNA Repair Gene APE1 Asp148Glu Polymorphism with Breast Cancer Risk Thu, 16 Jul 2015 07:04:24 +0000 http://www.hindawi.com/journals/dm/2015/869512/ Objective. The aim of this study was to investigate the role of APE1 Asp148Glu polymorphism in breast cancer progression in Saudi population. Methods. We examined the genetic variations (rs1130409) in the DNA base excision repair gene APE1 at codon 148 (Asp148Glu) and its association with breast cancer risk using genotypic assays and in silico structural as well as functional predictions. In silico structural analysis was performed with Asp148Glu allele and compared with the predicted native protein structure. The wild and mutant 3D structures of APE1 were compared and analyzed using solvent accessibility models for protein stability confirmation. Results. Genotypic analysis of APE1 (rs1130409) showed statistically significant association of Asp148Glu with elevated susceptibility to breast cancer. The in silico analysis results indicated that the nsSNP Asp148Glu may cause changes in the protein structure and is associated with breast cancer risk. Conclusion. Taken together, this is the first report that established that Asp148Glu variant has structural and functional effect on the APE1 and may play an important role in breast cancer progression in Saudi population. Fatima AlMutairi, Akbar Ali Khan Pathan, Mohammed Alanazi, Manal Shalaby, Huda A. Alabdulkarim, Abdullah Alamri, Abdulrahman Al Naeem, Moammad Elrobh, Jilani P. Shaik, Wajahatullah Khan, Zahid Khan, and Narasimha Reddy Parine Copyright © 2015 Fatima AlMutairi et al. All rights reserved. Toll-Like Receptor 9 Inactivation Alleviated Atherosclerotic Progression and Inhibited Macrophage Polarized to M1 Phenotype in ApoE−/− Mice Wed, 15 Jul 2015 12:43:37 +0000 http://www.hindawi.com/journals/dm/2015/909572/ Objective. Toll-like receptor 9 (TLR9) is involved in many inflammatory diseases, but its role in atherosclerosis remains controversial. This study aimed to investigate the role of TLR9 in atherosclerosis development and macrophage polarization. Methods. ApoE−/− mice were treated with vehicle or IRS869 for 12 weeks. Plaque vulnerability was assessed with immunohistochemical analysis, picro-sirius red, and oil red O staining. The expressions of M1- and M2-associated markers in plaques were detected by RT-PCR and immunofluorescence. The aorta TLR9 and its downstream molecules including myeloid differentiation protein 88 (MyD88), phosphorylated nuclear factor-kappa B (p-NF-κB), and interferon regulatory factor 7 (IRF7) were determined by western blot analysis. The frequency of M1 and M2 subtype in RAW264.7 cells treated with IRS869 and/or ODN1826 was evaluated with flow cytometry. Results. In ApoE−/− mice, functional inactivation of TLR9 pathway resulted in attenuated atherosclerosis development, as manifested by reduced plaque burden and by decreased plaque vulnerability. Mechanistically, TLR9 inhibition prevented the activation of MyD88/NF-κB pathway and shifted the balance of M1/M2 toward M2 macrophages that were involved. Conclusions. Our data indicated that TLR9 inactivation ameliorated atherosclerosis via skewing macrophage plasticity to M2 phenotype in ApoE-deficient mice. These findings may provide a promising therapeutic strategy for atherosclerosis. Chunmei Ma, Qiufang Ouyang, Ziyang Huang, Xiaoqing Chen, Ye Lin, Weiping Hu, and Ling Lin Copyright © 2015 Chunmei Ma et al. All rights reserved. The Difference between Growth Factor Expression after Single and Multiple Fractures: Preliminary Results in Human Fracture Healing Mon, 13 Jul 2015 07:55:55 +0000 http://www.hindawi.com/journals/dm/2015/203136/ Objectives. Circulating levels of VEGF-A (Vascular Endothelia Growth Factor-A), TGF-β1 (Transforming Growth Factor-beta 1), and M-CSF (Macrophage-Colony Stimulating Factor) were found to be predictors of bone healing and therefore prognostic criteria of delayed bone healing or nonunion. The aim of this study was to evaluate a potential rise of these markers in patients with multiple fractures of long bones compared to patients with single fractured long bone. Methods. 92 patients were included in the study and finally after excluding all female patients 45 male patients were left for final analysis and divided into the single or multiple fracture group. TGF-β1, M-CSF, and VEGF-A serum levels were analysed over a time period of two weeks. Results. MCSF serum concentrations were higher in the group with multiple fractures as also TGF-β1 serum concentrations were at one and two weeks after trauma. No statistically significant difference was observed in the VEGF-A serum concentrations of both groups at either measurement point. Conclusion. We did observe a correlation between the quantity of the M-CSF and TGF-β1 expressions in serum and the number of fractured bones; surprisingly there was no statistically significant difference in the serum levels between patients with single and multiple fractures of long bones. Harald Binder, Stefan Eipeldauer, Markus Gregori, Leonard Höchtl-Lee, Anita Thomas, Thomas M. Tiefenboeck, Stefan Hajdu, and Kambiz Sarahrudi Copyright © 2015 Harald Binder et al. All rights reserved. Hemostatic Parameters according to Renal Function and Time after Transplantation in Brazilian Renal Transplanted Patients Wed, 01 Jul 2015 11:52:07 +0000 http://www.hindawi.com/journals/dm/2015/472750/ Kidney transplantation is the key for patients with end-stage renal disease, improving quality of life and longer survival. However, kidney transplant triggers an intense inflammatory response and alters the hemostatic system, but the pathophysiological mechanisms of these changes are not completely understood. The aim of this cross-sectional cohort study was to investigate hemostatic biomarkers in Brazilian renal transplanted patients according to renal function and time after transplantation. A total of 159 renal transplanted patients were enrolled and D-Dimer (D-Di), Thrombomodulin (TM), von Willebrand Factor (VWF), and ADAMTS13 plasma levels were assessed by ELISA. An increase of D-Di was observed in patients with higher levels of creatinine. ADAMTS13 levels were associated with creatinine plasma levels and D-Di levels with Glomerular Filtration Rate. These results suggested that D-Di and ADAMTS13 can be promising markers to estimate renal function. ADAMTS13 should be investigated throughout the posttransplant time to clarify the participation of this enzyme in glomerular filtration and acceptance or rejection of the graft in Brazilian transplanted patients. Ana Paula Lucas Mota, Patrícia Nessralla Alpoim, Roberta Carvalho de Figueiredo, Ana Cristina Simões e Silva, Karina Braga Gomes, and Luci Maria SantAna Dusse Copyright © 2015 Ana Paula Lucas Mota et al. All rights reserved. Radiosynthesis, In Vivo Biological Evaluation, and Imaging of Brain Lesions with [123I]-CLINME, a New SPECT Tracer for the Translocator Protein Thu, 25 Jun 2015 11:10:42 +0000 http://www.hindawi.com/journals/dm/2015/729698/ The high affinity translocator protein (TSPO) ligand 6-chloro-2-(4′-iodophenyl)-3-(N,N-methylethyl)imidazo[1,2-a]pyridine-3-acetamide (CLINME) was radiolabelled with iodine-123 and assessed for its sensitivity for the TSPO in rodents. Moreover neuroinflammatory changes on a unilateral excitotoxic lesion rat model were detected using SPECT imaging. [123I]-CLINME was prepared in 70–80% radiochemical yield. The uptake of [123I]-CLINME was evaluated in rats by biodistribution, competition, and metabolite studies. The unilateral excitotoxic lesion was performed by injection of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid unilaterally into the striatum. The striatum lesion was confirmed and correlated with TSPO expression in astrocytes and activated microglia by immunohistochemistry and autoradiography. In vivo studies with [123I]-CLINME indicated a biodistribution pattern consistent with TPSO distribution and the competition studies with PK11195 and Ro 5-4864 showed that [123I]-CLINME is selective for this site. The metabolite study showed that the extractable radioactivity was unchanged [123I]-CLINME in organs which expresses TSPO. SPECT/CT imaging on the unilateral excitotoxic lesion indicated that the mean ratio uptake in striatum (lesion : nonlesion) was 2.2. Moreover, TSPO changes observed by SPECT imaging were confirmed by immunofluorescence, immunochemistry, and autoradiography. These results indicated that [123I]-CLINME is a promising candidate for the quantification and visualization of TPSO expression in activated astroglia using SPECT. F. Mattner, M. Quinlivan, I. Greguric, T. Pham, X. Liu, T. Jackson, P. Berghofer, C. J. R. Fookes, B. Dikic, M.-C. Gregoire, F. Dolle, and A. Katsifis Copyright © 2015 F. Mattner et al. All rights reserved. Aldehyde Dehydrogenase Polymorphisms and Blood Pressure Elevation in the Japanese: A Cross-Sectional and a Longitudinal Study over 20 Years in the Shimane CoHRE Study Mon, 22 Jun 2015 11:19:35 +0000 http://www.hindawi.com/journals/dm/2015/825435/ Purpose. Effects of a genetic polymorphism in the aldehyde dehydrogenase-2 (ALDH2) on blood pressure (BP) were investigated in a cross-sectional and a longitudinal study over 20 years on Japanese rural residents. Methods. Health examinations were held through 2006 to 2012, and 3,202 participates were recruited for this study. Among these participants, 560 individuals had medical records that were obtained in a health examination 20 years ago. Genomic DNA of participants was extracted from blood and the genotype of a polymorphism in ALDH2 was determined by the TaqMan method. Multivariate regression analyses were performed to examine association between BP and the genetic polymorphism in the ALDH2 gene. Results. Systolic and diastolic BP were higher in the ALDH21/1 than the others (ALDH21/2 or ALDH22/2). Genetic variation of the ALDH2 gene apparently influenced drinking behavior as the number of the drinkers was significantly reduced in the ALDH22/2 after 20 years of the observation period. This polymorphism, however, did not confer a risk for BP increase in the longitudinal observation. Conclusion. The present cross-sectional study confirmed a genetic effect of the ALDH2 gene on BP. In contrast, no significant effects on BP were identified in a longitudinal study, which may require a careful consideration. Minoru Isomura, Tao Wang, Masayuki Yamasaki, Md. Zahid Hasan, Kuninori Shiwaku, and Toru Nabika Copyright © 2015 Minoru Isomura et al. All rights reserved. The Impact of Gene Polymorphisms on the Success of Anticholinergic Treatment in Children with Overactive Bladder Wed, 17 Jun 2015 11:55:50 +0000 http://www.hindawi.com/journals/dm/2015/732686/ Aim. To determine the impact of gene polymorphisms on detrusor contraction-relaxation harmony in children with lower urinary tract symptoms (LUTS). Materials and Methods. Toilet trained children older than 5 years of age with LUTS and normal neurological examination underwent videourodynamic study. The control group was composed of age matched children with no voiding complaints. The study group who filled out the voiding dysfunction symptom score before and after the treatment received standard oxybutynin treatment and was reevaluated 1 year after treatment. Genomic DNA was isolated from all patients and subjected to PCR for amplification. Genotyping of ARGHEF10, ROCK2, ADRB3, and CYP3A4 was carried out with Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) method. Results. 34 (45%) and 42 (55%) patients were enrolled in the study and control group, respectively. ARGEF10 GG, ADRB3 TC, and CYP3A4 AG genotype patients displayed insignificant difference between pre- and posttreatment voiding dysfunction symptom score and bladder volumes. Conclusions. The polymorphism of genes in the cholinergic pathway did not significantly differ clinical parameters. On the other hand, polymorphic patients in the adrenergic pathway seemed to suffer from clinical disappointment. For this reason, we think that the neglected adrenergic pathway could be a new therapeutic target for the treatment of anticholinergic resistant LUTS in children. Serhat Gurocak, Ece Konac, Iyimser Ure, Cem Senol, Ilke Hacer Onen, Sinan Sozen, and Adnan Menevse Copyright © 2015 Serhat Gurocak et al. All rights reserved. Retracted: System Accuracy Evaluation of the GlucoRx Nexus Voice TD-4280 Blood Glucose Monitoring System Wed, 17 Jun 2015 08:59:13 +0000 http://www.hindawi.com/journals/dm/2015/496928/ Disease Markers Copyright © 2015 Disease Markers. All rights reserved.