Disease Markers http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Hypermethylation-Associated Silencing of miR-125a and miR-125b: A Potential Marker in Colorectal Cancer Thu, 26 Nov 2015 12:08:23 +0000 http://www.hindawi.com/journals/dm/2015/345080/ Background. MicroRNAs (miRNAs) have been found to be downregulated in human colorectal cancer (CRC), and some of them may function as tumor suppressor genes (TSGs). Aberrant methylation triggers the inactivation of TSGs during tumorigenesis. Patients and Methods. We investigated the methylation status of miR-125 family in CRC tissues and adjacent nontumor tissues by using bisulfite sequencing PCR (BSP). The expression levels of the two miRNAs were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results. The methylation frequency of miR-125a and miR-125b was higher in CRC tissues. QRT-PCR analysis showed that miR-125a and miR-125b were significantly downregulated in CRC tissues. Moreover, the expression levels of miR-125a and miR-125b were inversely correlated to CpG island methylation in CRC. Conclusions. Our results suggest that DNA hypermethylation may be involved in the inactivation of miR-125a and miR-125b in CRC, and hypermethylation of miR-125 is a potential biomarker for clinical outcome. Hui Chen and Zhiying Xu Copyright © 2015 Hui Chen and Zhiying Xu. All rights reserved. Mean Platelet Volume and Platelet Distribution Width as Markers in the Diagnosis of Acute Gangrenous Appendicitis Wed, 25 Nov 2015 11:37:47 +0000 http://www.hindawi.com/journals/dm/2015/542013/ Introduction. Acute gangrenous appendicitis (AGA) is a common medical condition; however, the grade of appendicitis usually cannot be established preoperatively. We have attempted to identify some indicators, such as the mean platelet volume (MPV) and the platelet distribution width (PDW), to diagnose AGA. Aims. To evaluate whether or not the MPV and PDW are suitable markers to diagnose AGA. Methods. A retrospective study of 160 patients with AGA and 160 healthy patients was undertaken. Disease diagnosis was confirmed based on the pathologic examination of surgical specimens. Patient white blood cell (WBC) count, neutrophil ratio (NR), platelet (PLT) count, MPV, PDW, and hematocrit (HCT) were analyzed. Receiver operating characteristic (ROC) curves were used to evaluate the sensitivity and specificity of these indices in AGA. Results. There were no significant differences between the AGA and control groups in age and gender. Compared to the control group, the WBC count, NR, and PDW were significantly higher (, resp.) and the MPV and HCT were significantly lower (, resp.) in the AGA group. The diagnostic specificities of the WBC count, NR, PLT count, MPV, PDW, and HCT were 86.3%, 92.5%, 58.1%, 81.7%, 83.9%, and 66.3%, respectively. Therefore, the NR had the highest diagnostic specificity for the diagnosis of AGA. Conclusions. This is the first study to assess the MPV and PDW in patients with AGA. Our present study showed that the MPV is reduced and the PDW is increased in patients with AGA; the sensitivity of PDW was superior to the MPV. A decreased MPV value and an increased PDW could serve as two markers to diagnose AGA. The NR had the highest specificity for the diagnosis of AGA. Zhe Fan, Jiyong Pan, Yingyi Zhang, Ziyi Wang, Ming Zhu, Baoshun Yang, Lei Shi, and Huirong Jing Copyright © 2015 Zhe Fan et al. All rights reserved. Association between Estrogen Receptor- Gene XbaI and PvuII Polymorphisms and Periodontitis Susceptibility: A Meta-Analysis Tue, 24 Nov 2015 12:13:56 +0000 http://www.hindawi.com/journals/dm/2015/741972/ Background. Certain studies have previously explored the association between the estrogen receptor-α (ER-α) gene polymorphisms and periodontitis susceptibility, although the current results are controversial. The present study, using meta-analysis, aimed to investigate the nature of the genetic susceptibility of the ER- for developing periodontitis. Methods. A comprehensive literature search of PubMed, Embase, CNKI, and Wanfang databases was conducted up to January 8, 2015. Statistical manipulation was performed using Stata version 13.0 software. Odds ratios (ORs) and corresponding 95% confident intervals (CIs) were calculated to estimate the association in five genetic models. Results. A total of 17 eligible case-control studies from seven identified publications consisting of nine studies for the XbaI polymorphism and eight studies for the PvuII polymorphism were included in the meta-analysis. We found elevated risk of periodontitis in XbaI XX genotype carriers. Moreover, subgroup analyses demonstrated increased risk for chronic periodontitis of XbaI XX genotype carriers, specifically in the Chinese Han female population. No significant association was observed between PvuII polymorphism and periodontitis. Conclusion. Current evidence indicated that the homozygote (XX) genotype of ER- gene XbaI polymorphism, but not PvuII mutation, may increase the risk of chronic periodontitis, specifically in the Chinese Han female population. Hong Weng, Chao Zhang, Yuan-Yuan Hu, Rui-Xia Yuan, Hong-Xia Zuo, Jin-Zhu Yan, and Yu-Ming Niu Copyright © 2015 Hong Weng et al. All rights reserved. Predictive Markers for the Recurrence of Nonmuscle Invasive Bladder Cancer Treated with Intravesical Therapy Mon, 23 Nov 2015 06:03:26 +0000 http://www.hindawi.com/journals/dm/2015/857416/ High recurrence rate is one representative characteristic of bladder cancer. Intravesical therapy after transurethral resection is often performed in patients with nonmuscle invasive bladder cancer (NMIBC) to prevent recurrence. Bacillus Calmette-Guérin (BCG) and several anticancer/antibiotic agents, such as mitomycin C and epirubicin, are commonly used for this therapy. BCG treatment demonstrates strong anticancer effects. However, it is also characterized by a high frequency of adverse events. On the other hand, although intravesical therapies using other anticancer and antibiotic agents are relatively safe, their anticancer effects are lower than those obtained using BCG. Thus, the appropriate selection of agents for intravesical therapy is important to improve treatment outcomes and maintain the quality of life of patients with NMIBC. In this review, we discuss the predictive value of various histological and molecular markers for recurrence after intravesical therapy in patients with NMIBC. Yasuyoshi Miyata and Hideki Sakai Copyright © 2015 Yasuyoshi Miyata and Hideki Sakai. All rights reserved. Increased Avidity of the Sambucus nigra Lectin-Reactive Antibodies to the Thomsen-Friedenreich Antigen as a Potential Biomarker for Gastric Cancer Wed, 18 Nov 2015 09:50:08 +0000 http://www.hindawi.com/journals/dm/2015/761908/ Aim. To determine whether the naturally occurring Thomsen-Friedenreich (TF) antigen-specific antibodies differ in avidity between cancer patients and controls to find a novel biomarker for stomach cancer. Methods. Serum samples were taken from patients with cancer and controls. The level of TF-specific antibodies and their sialylation were determined using ELISA with synthetic TF-polyacrylamide conjugate as antigen and sialic acid-specific Sambucus nigra agglutinin (SNA). The avidity was determined using ammonium thiocyanate as a chaotrope. Results. A significantly higher SNA lectin binding to anti-TF antibodies was found in cancer patients irrespective of disease stage. The avidity of only IgM TF-specific antibodies was significantly higher in cancer patients compared to controls. The SNA-positive anti-TF antibodies of cancer patients showed a significantly higher avidity, . The sensitivity and specificity of this increase for gastric cancer were 73.53% and 73.08%, respectively, with a 73.2% diagnostic accuracy. The higher avidity of SNA-reactive anti-TF antibodies was associated with a benefit in survival of stage 3 cancer patients. Conclusion. The SNA-reactive TF-specific antibodies display a significantly higher avidity in gastric cancer patients compared to controls, which can be used as a potential serologic biomarker for gastric cancer. It appears that IgM is the main target responsible for the above changes. Oleg Kurtenkov and Kersti Klaamas Copyright © 2015 Oleg Kurtenkov and Kersti Klaamas. All rights reserved. Matrix Metalloproteinase-9/Neutrophil Gelatinase-Associated Lipocalin Complex Activity in Human Glioma Samples Predicts Tumor Presence and Clinical Prognosis Wed, 18 Nov 2015 06:46:01 +0000 http://www.hindawi.com/journals/dm/2015/138974/ Matrix metalloproteinase-9/neutrophil gelatinase-associated lipocalin (MMP-9/NGAL) complex activity is elevated in brain tumors and may serve as a molecular marker for brain tumors. However, the relationship between MMP-9/NGAL activity in brain tumors and patient prognosis and treatment response remains unclear. Here, we compared the clinical characteristics of glioma patients with the MMP-9/NGAL activity measured in their respective tumor and urine samples. Using gelatin zymography assays, we found that MMP-9/NGAL activity was significantly increased in tumor tissues (TT) and preoperative urine samples (Preop-1d urine). Activity was reduced by seven days after surgery (Postop-1w urine) and elevated again in cases of tumor recurrence. The MMP-9/NGAL status correlated well with MRI-based tumor assessments. These findings suggest that MMP-9/NGAL activity could be a novel marker to detect gliomas and predict the clinical outcome of patients. Ming-Fa Liu, Yong-Yang Hu, Tao Jin, Ke Xu, Shao-Hong Wang, Guang-Zhou Du, Bing-Li Wu, Li-Yan Li, Li-Yan Xu, En-Min Li, and Hai-Xiong Xu Copyright © 2015 Ming-Fa Liu et al. All rights reserved. Expression of Ribonucleotide Reductase Subunit-2 and Thymidylate Synthase Correlates with Poor Prognosis in Patients with Resected Stages I–III Non-Small Cell Lung Cancer Tue, 17 Nov 2015 12:14:35 +0000 http://www.hindawi.com/journals/dm/2015/302649/ Biomarkers can help to identify patients with early-stages or locally advanced non-small cell lung cancer (NSCLC) who have high risk of relapse and poor prognosis. To correlate the expression of seven biomarkers involved in DNA synthesis and repair and in cell division with clinical outcome, we consecutively collected 82 tumour tissues from radically resected NSCLC patients. The following biomarkers were investigated using IHC and qRT-PCR: excision repair cross-complementation group 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase subunits M1 and M2 (RRM1 and RRM2), subunit p53R2, thymidylate synthase (TS), and class III beta-tubulin (TUBB3). Gene expression levels were also validated in an available NSCLC microarray dataset. Multivariate analysis identified the protein overexpression of RRM2 and TS as independent prognostic factors of shorter overall survival (OS). Kaplan-Meier analysis showed a trend in shorter OS for patients with RRM2, TS, and ERCC1, BRCA1 overexpressed tumours. For all of the biomarkers except TUBB3, the OS trends relative to the gene expression levels were in agreement with those relative to the protein expression levels. The NSCLC microarray dataset showed RRM2 and TS as biomarkers significantly associated with OS. This study suggests that high expression levels of RRM2 and TS might be negative prognostic factors for resected NSCLC patients. Francesco Grossi, Maria Giovanna Dal Bello, Sandra Salvi, Roberto Puzone, Ulrich Pfeffer, Vincenzo Fontana, Angela Alama, Erika Rijavec, Giulia Barletta, Carlo Genova, Claudio Sini, Giovanni Battista Ratto, Mario Taviani, Mauro Truini, and Domenico Franco Merlo Copyright © 2015 Francesco Grossi et al. All rights reserved. Tissue Specific Promoters in Colorectal Cancer Sun, 15 Nov 2015 07:55:08 +0000 http://www.hindawi.com/journals/dm/2015/390161/ Colorectal carcinoma is the third most prevalent cancer in the world. In the most advanced stages, the use of chemotherapy induces a poor response and is usually accompanied by other tissue damage. Significant progress based on suicide gene therapy has demonstrated that it may potentiate the classical cytotoxic effects in colorectal cancer. The inconvenience still rests with the targeting and the specificity efficiency. The main target of gene therapy is to achieve an effective vehicle to hand over therapeutic genes safely into specific cells. One possibility is the use of tumor-specific promoters overexpressed in cancers. They could induce a specific expression of therapeutic genes in a given tumor, increasing their localized activity. Several promoters have been assayed into direct suicide genes to cancer cells. This review discusses the current status of specific tumor-promoters and their great potential in colorectal carcinoma treatment. A. R. Rama, A. Aguilera, C. Melguizo, O. Caba, and J. Prados Copyright © 2015 A. R. Rama et al. All rights reserved. Association of Cytokeratin and Vimentin Protein in the Genesis of Transitional Cell Carcinoma of Urinary Bladder Patients Thu, 12 Nov 2015 13:09:55 +0000 http://www.hindawi.com/journals/dm/2015/204759/ The aim of study was to examine the localization and distribution of cytokeratin (CK) and vimentin protein and their association with clinical outcome of the TCC patients. Expression pattern of cytokeratin and vimentin was evaluated by immunohistochemistry in TCC cases and inflammatory lesions. Cytoplasmic expression of CK was noticed in 52.17% of TCC cases and its expression was not observed in inflammatory lesions of bladder specimens. Vimentin showed expression in 69.00% cases of TCC. Significant differences were noticed in expression pattern of CK and vimentin in inflammatory lesion and Transitional Cell Carcinoma cases. Vimentin expression increased with the grade of TCC and this difference was statistically significant whereas expression of CK decreased according to the grade of TCC. Furthermore, it was also observed that expression pattern of vimentin was high in ≥55 years as compared to <55 age group patients and these differences were significant in men as compared to women. Expression pattern of CK did not show any significant relation with age and gender. Therefore, it can be concluded that cytokeratin and vimentin will be helpful markers in the early diagnosis of Transitional Cell Carcinoma/bladder carcinoma. Arshad H. Rahmani, Ali Y. Babiker, Wanian M. AlWanian, Shawgi A. Elsiddig, Hassan E. Faragalla, and Salah M. Aly Copyright © 2015 Arshad H. Rahmani et al. All rights reserved. Inhibition of HIF-1α Affects Autophagy Mediated Glycosylation in Oral Squamous Cell Carcinoma Cells Wed, 11 Nov 2015 08:46:05 +0000 http://www.hindawi.com/journals/dm/2015/239479/ Purpose. To validate the function of autophagy with the regulation of hypoxia inhibitor-induced glycosylation in oral squamous cell carcinoma cell. Methods. Human Tca8113 cell line was used to detect autophagy and glycosylation related protein expression by western blotting and immunofluorescence with HIF-1α inhibitor. Short interfering RNA (siRNA) transfection blocked human ATG12 and ATG1. Results. HIF-1α inhibitor PX-478 reduced the amount of LC3-II and LC3-I in Tca8113 cells. PX-478 decreased the expression of O-GlcNAc and OGT and increased OGA expression. The tendency of O-GlcNAc showed a similar pattern to OGT. PX-478 gradually decreased OGT expression in Tca8113 cells. Protein level of O-GlcNAc and OGT increased in ATG12 and ATG1 depletion. The expression of OGT decreased at first and then rose slowly with the treatment of Atg12 and Atg1 siRNA and PX-478 fluctuant. Autophagy affected the stability of OGT when HIF-1α signaling was blocked. Conclusions. Autophagy reduced by hypoxic stress inhibited. HIF-1α inhibitor decreased glycosylation. OGT became unstable in the absence of autophagy when HIF-1α signaling was blocked. Yi-Ning Li, Ji-An Hu, and Hui-Ming Wang Copyright © 2015 Yi-Ning Li et al. All rights reserved. Procalcitonin, MR-Proadrenomedullin, and Cytokines Measurement in Sepsis Diagnosis: Advantages from Test Combination Mon, 09 Nov 2015 09:30:12 +0000 http://www.hindawi.com/journals/dm/2015/951532/ Background. Elevated cytokines levels correlate with sepsis severity and mortality but their role in the diagnosis is controversial, whereas Procalcitonin (PCT) has been largely used. Recently, the mid-regional proadrenomedullin (MR-proADM) has been combined with PCT for diagnosis optimization. In this study the combined measurement of PCT, MR-proADM, and cytokines in patients with sepsis was evaluated. Methods. One hundred and four septic patients and 101 controls were enrolled. Receiver operating characteristic (ROC) analysis and multiple logistic regression were used to evaluate applicant markers for sepsis diagnosis. Markers with best Odds Ratio (OR) were combined, and the posttest probability and a composite score were computed. Results. Based upon ROC curves analysis, PCT, MR-proADM, IL-6, IL-10, TNF-α, and MCP-1 were considered applicant for sepsis diagnosis. Among these PCT, MR-proADM , IL-6, and TNF-α showed the best OR. A better posttest probability was found with the combination of PCT with MR-proADM and PCT with IL-6 or TNF-α compared to the single marker. A composite score of PCT, MR-proADM, and TNF-α showed the best ROC curve in the early diagnosis of sepsis. Conclusion. The combination of PCT with other markers should expedite diagnosis and treatment of sepsis optimizing clinical management. Silvia Angeletti, Giordano Dicuonzo, Marta Fioravanti, Marina De Cesaris, Marta Fogolari, Alessandra Lo Presti, Massimo Ciccozzi, and Lucia De Florio Copyright © 2015 Silvia Angeletti et al. All rights reserved. High Serum Level of β2-Microglobulin in Late Posttransplant Period Predicts Subsequent Decline in Kidney Allograft Function: A Preliminary Study Sun, 08 Nov 2015 14:09:46 +0000 http://www.hindawi.com/journals/dm/2015/562580/ Background. Identification of patients at risk for kidney allograft (KAG) failure beyond the first posttransplant year is an unmet need. We aimed to determine whether serum beta-2-microglobulin (β2MG) in the late posttransplant period could predict a decline in KAG function. Methods. We assessed a value of single measurement of serum β2MG at one to seventeen years after transplantation in predicting the estimated glomerular filtration rate (eGFR) and the decline in eGFR over a period of two years in 79 recipients of KAG. Results. At baseline serum β2MG concentration was higher () in patients with allograft dysfunction: 8.67 ± 2.48 µg/mL versus those with satisfactory graft function: 6.67 ± 2.13 µg/mL. Higher β2MG independently predicted the lower eGFR, the drop in eGFR by ≥25% after one and two years, and the value of negative eGFR slope. When combined with proteinuria and acute rejection, serum β2MG had excellent power in predicting certain drop in eGFR after one year (AUC = 0.910). In conjunction with posttransplant time serum β2MG had good accuracy in predicting certain eGFR drop after two years (AUC = 0.821). Conclusions. Elevated serum β2MG in the late posttransplant period is useful in identifying patients at risk for rapid loss of graft function. Andriy V. Trailin, Marina V. Pleten, Tatiana I. Ostapenko, Nadiia F. Iefimenko, and Olexander S. Nikonenko Copyright © 2015 Andriy V. Trailin et al. All rights reserved. Perspective Biological Markers for Autism Spectrum Disorders: Advantages of the Use of Receiver Operating Characteristic Curves in Evaluating Marker Sensitivity and Specificity Sun, 08 Nov 2015 07:49:42 +0000 http://www.hindawi.com/journals/dm/2015/329607/ Autism Spectrum Disorders (ASD) are a heterogeneous group of neurodevelopmental disorders. Recognized causes of ASD include genetic factors, metabolic diseases, toxic and environmental factors, and a combination of these. Available tests fail to recognize genetic abnormalities in about 70% of ASD children, where diagnosis is solely based on behavioral signs and symptoms, which are difficult to evaluate in very young children. Although it is advisable that specific psychotherapeutic and pedagogic interventions are initiated as early as possible, early diagnosis is hampered by the lack of nongenetic specific biological markers. In the past ten years, the scientific literature has reported dozens of neurophysiological and biochemical alterations in ASD children; however no real biomarker has emerged. Such literature is here reviewed in the light of Receiver Operating Characteristic (ROC) analysis, a very valuable statistical tool, which evaluates the sensitivity and the specificity of biomarkers to be used in diagnostic decision making. We also apply ROC analysis to some of our previously published data and discuss the increased diagnostic value of combining more variables in one ROC curve analysis. We also discuss the use of biomarkers as a tool for advancing our understanding of nonsyndromic ASD. Provvidenza M. Abruzzo, Alessandro Ghezzo, Alessandra Bolotta, Carla Ferreri, Renato Minguzzi, Arianna Vignini, Paola Visconti, and Marina Marini Copyright © 2015 Provvidenza M. Abruzzo et al. All rights reserved. Clinicopathological Significance of MicroRNA-20b Expression in Hepatocellular Carcinoma and Regulation of HIF-1α and VEGF Effect on Cell Biological Behaviour Tue, 03 Nov 2015 13:12:33 +0000 http://www.hindawi.com/journals/dm/2015/325176/ miRNA-20b has been shown to be aberrantly expressed in several tumor types. However, the clinical significance of miRNA-20b in the prognosis of patients with hepatocellular carcinoma (HCC) is poorly understood, and the exact role of miRNA-20b in HCC remains unclear. The aim of the present study was to investigate the association of the expression of miR-20b with clinicopathological characteristics and overall survival of HCC patients analyzed by Kaplan-Meier analysis and Cox proportional hazards regression models. Meanwhile, the HIF-1α and VEGF targets of miR-20b have been confirmed. We found not only miR-20b regulation of HIF-1α and VEGF in normal but also regulation of miR-20b in hypoxia. This mechanism would help the tumor cells adapt to the different environments thus promoting the tumor invasion and development. The whole study suggests that miR-20b, HIF-1α, and VEGF serve as a potential therapeutic agent for hepatocellular carcinoma. Tong-min Xue, Li-de Tao, Miao Zhang, Jie Zhang, Xia Liu, Guo-feng Chen, Yi-jia Zhu, and Pei-Jian Zhang Copyright © 2015 Tong-min Xue et al. All rights reserved. Metabolic Serum Profiles for Patients Receiving Allogeneic Stem Cell Transplantation: The Pretransplant Profile Differs for Patients with and without Posttransplant Capillary Leak Syndrome Mon, 02 Nov 2015 12:18:55 +0000 http://www.hindawi.com/journals/dm/2015/943430/ Allogeneic stem cell transplantation is commonly used in the treatment of younger patients with severe hematological diseases, and endothelial cells seem to be important for the development of several posttransplant complications. Capillary leak syndrome is a common early posttransplant complication where endothelial cell dysfunction probably contributes to the pathogenesis. In the present study we investigated whether the pretreatment serum metabolic profile reflects a risk of posttransplant capillary leak syndrome. We investigated the pretransplant serum levels of 766 metabolites for 80 consecutive allotransplant recipients. Patients with later capillary leak syndrome showed increased pretherapy levels of metabolites associated with endothelial dysfunction (homocitrulline, adenosine) altered renal regulation of fluid and/or electrolyte balance (betaine, methoxytyramine, and taurine) and altered vascular function (cytidine, adenosine, and methoxytyramine). Additional bioinformatical analyses showed that capillary leak syndrome was also associated with altered purine/pyrimidine metabolism (i.e., metabolites involved in vascular regulation and endothelial functions), aminoglycosylation (possibly important for endothelial cell functions), and eicosanoid metabolism (also involved in vascular regulation). Our observations are consistent with the hypothesis that the pretransplant metabolic status can be a marker for posttransplant abnormal fluid and/or electrolyte balance. Håkon Reikvam, Ida-Sofie Grønningsæter, Aymen Bushra Ahmed, Kimberley Hatfield, and Øystein Bruserud Copyright © 2015 Håkon Reikvam et al. All rights reserved. Magnetic Resonance Imaging as a Biomarker for Renal Cell Carcinoma Sun, 01 Nov 2015 11:40:02 +0000 http://www.hindawi.com/journals/dm/2015/648495/ As the most common neoplasm arising from the kidney, renal cell carcinoma (RCC) continues to have a significant impact on global health. Conventional cross-sectional imaging has always served an important role in the staging of RCC. However, with recent advances in imaging techniques and postprocessing analysis, magnetic resonance imaging (MRI) now has the capability to function as a diagnostic, therapeutic, and prognostic biomarker for RCC. For this narrative literature review, a PubMed search was conducted to collect the most relevant and impactful studies from our perspectives as urologic oncologists, radiologists, and computational imaging specialists. We seek to cover advanced MR imaging and image analysis techniques that may improve the management of patients with small renal mass or metastatic renal cell carcinoma. Yan Wu, Young Suk Kwon, Mina Labib, David J. Foran, and Eric A. Singer Copyright © 2015 Yan Wu et al. All rights reserved. DNA Repair Gene Polymorphism and the Risk of Mitral Chordae Tendineae Rupture Wed, 28 Oct 2015 12:02:45 +0000 http://www.hindawi.com/journals/dm/2015/825020/ Polymorphisms in Lys939Gln XPC gene may diminish DNA repair capacity, eventually increasing the risk of carcinogenesis. The aim of the present study was to evaluate the significance of polymorphism Lys939Gln in XPC gene in patients with mitral chordae tendinea rupture (MCTR). Twenty-one patients with MCTR and thirty-seven age and sex matched controls were enrolled in the study. Genotyping of XPC gene Lys939Gln polymorphism was carried out using polymerase chain reaction- (PCR-) restriction fragment length polymorphism (RFLP). The frequencies of the heterozygote genotype (Lys/Gln-AC) and homozygote genotype (Gln/Gln-CC) were significantly different in MCTR as compared to control group, respectively (52.4% versus 43.2%, ; 38.15% versus 16.2%, ). Homozygote variant (Gln/Gln) genotype was significantly associated with increased risk of MCTR (OR = 2.059; 95% CI: 1.097–3.863; ). Heterozygote variant (Lys/Gln) genotype was also highly significantly associated with increased risk of MCTR (OR = 1.489; 95% CI: 1.041–2.129; ). The variant allele C was found to be significantly associated with MCTR (OR = 1.481; 95% CI: 1.101–1.992; ). This study has demonstrated the association of XPC gene Lys939Gln polymorphism with MCTR, which is significantly associated with increased risk of MCTR. Aysel Kalayci Yigin, Mehmet Bulent Vatan, Ramazan Akdemir, Muhammed Necati Murat Aksoy, Mehmet Akif Cakar, Harun Kilic, Unal Erkorkmaz, Keziban Karacan, and Suleyman Kaleli Copyright © 2015 Aysel Kalayci Yigin et al. All rights reserved. High Thyroglobulin Antibody Levels Increase the Risk of Differentiated Thyroid Carcinoma Tue, 27 Oct 2015 14:03:51 +0000 http://www.hindawi.com/journals/dm/2015/648670/ Background. Despite the many studies examining thyroid cancers, the effect of thyroid autoantibodies on differentiated thyroid carcinoma (DTC) remains unclear. Objective. To investigate the association between serologic thyroid autoantibodies (ATAs) and DTC, we retrospectively evaluated data of thyroid nodules obtained from patients who underwent thyroid surgery. Methods. Data of thyroid nodules obtained from 1,638 patients who underwent thyroid surgery were evaluated. Thyroid autoimmunity was assessed by the presence of thyroglobulin (TgAb) or thyroid peroxidase antibodies (TPOAb). Results. Among our study cohort, the prevalence of elevated TgAb (≥40 IU/mL) and TPOAb (≥50 IU/mL) was higher in patients with DTC than those with benign nodules. Patients with DTC and elevated TgAb had a higher prevalence of extrathyroidal invasion. In the multivariate analysis, TgAb ≥ 40 IU/mL was significantly associated with DTC (odds ratio [OR] = 2.10, 95% confidence interval [CI] 1.40–3.15) compared with TgAb < 40 IU/mL group, independent of other confounding factors such as decreased age, single nodule, and elevated TSH level. In conclusion, elevated TgAb was associated with DTC. Conclusions. This study revealed that high levels of TgAb may act as an independent prediction factor for DTC, and suggests that patients with high TgAb concentrations may be predisposed to DTC. Jing Qin, Zhenqian Yu, Haixia Guan, Liangfeng Shi, Yongping Liu, Na Zhao, Zhongyan Shan, Cheng Han, Yushu Li, and Weiping Teng Copyright © 2015 Jing Qin et al. All rights reserved. The Role of Circulating Tight Junction Proteins in Evaluating Blood Brain Barrier Disruption following Intracranial Hemorrhage Mon, 26 Oct 2015 06:23:12 +0000 http://www.hindawi.com/journals/dm/2015/860120/ Brain injury after intracranial hemorrhage (ICH) results in significant morbidity and mortality. Blood brain barrier (BBB) disruption is a hallmark of ICH-induced brain injury; however, data mirroring BBB disruption in human ICH are scarce. The aim of this study was to assess the significance of circulating biomarkers in evaluating BBB disruption after ICH. Twenty-two patients with ICH were recruited in this study. Concentrations of the tight junction proteins (TJs) Claudin-5 (CLDN5), Occludin (OCLN), and zonula occludens 1 (ZO-1) and vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were measured by using enzyme-linked immunosorbent assay in serum and cerebrospinal fluid (CSF) samples obtained from patients with ICH. The white blood cell (WBC) count in blood and CSF, albumin (ALB) levels in the CSF (), and the BBB ratio were significantly higher in the ICH than in controls (). Significantly higher levels of CLDN5, OCLN, ZO-1, MMP-9, and VEGF in CSF were observed in the ICH group; these biomarkers were also positively associated with BBB ratio (). Our data revealed that circulating TJs could be considered the potential biomarkers reflecting the integrity of the BBB in ICH. Xiaoyang Jiao, Ping He, Yazhen Li, Zhicheng Fan, Mengya Si, Qingdong Xie, Xiaolan Chang, and Dongyang Huang Copyright © 2015 Xiaoyang Jiao et al. All rights reserved. NRAMP1 and VDR Gene Polymorphisms in Susceptibility to Tuberculosis in Venezuelan Population Thu, 22 Oct 2015 11:20:30 +0000 http://www.hindawi.com/journals/dm/2015/860628/ Natural resistance-associated macrophage protein (Nramp1) and the vitamin D receptor (VDR) are central components of the innate and adaptive immunity against Mycobacterium tuberculosis, and associations between susceptibility to tuberculosis and polymorphisms in the genes NRAMP and VDR have been sought in geographically diverse populations. We investigated associations of NRAMP1 and VDR gene polymorphisms with susceptibility to TB in the Venezuelan population. The results suggest the absence of any association between VDR variants FokI, ApaI, and TaqI and susceptibility to tuberculosis. In contrast, the NRAMP1 3′UTR variants were associated with susceptibility to M. tuberculosis infection, as seen in the comparisons between TST+ and TST− controls, and also with progression to TB disease, as shown in the comparisons between TB patients and TST+ controls. This study confirms the previously described association of the NRAMP1 3′UTR polymorphism with M. tuberculosis infection and disease progression. Mercedes Fernández-Mestre, Ángel Villasmil, Howard Takiff, and Zhenia Fuentes Alcalá Copyright © 2015 Mercedes Fernández-Mestre et al. All rights reserved. Upregulated Expression of SOX4 Is Associated with Tumor Growth and Metastasis in Nasopharyngeal Carcinoma Thu, 22 Oct 2015 08:00:46 +0000 http://www.hindawi.com/journals/dm/2015/658141/ SOX4, which belongs to the sex-determining region Y-related high-mobility group (SRY) box family, plays a critical role in embryonic development, cell fate decision, differentiation, and tumor development. Nasopharyngeal carcinoma (NPC) is one of the most common cancers in China and Southeast Asia. However, the molecular mechanisms of this disease remain unknown. In the present study, we used immunohistochemistry to investigate the correlation between the expression of SOX4 with clinicopathologic variables as well as patients prognosis of NPC. We found overexpression of SOX4 was correlated with clinical stages, lymph node metastasis, and Ki-67 expression in NPC (). Besides, patients who expressed higher levels of SOX4 had poorer survival rate (). Then, in vitro studies, we took serum starvation-refeeding experiment and knocked down the expression of SOX4 with siRNA to demonstrate that SOX4 could promote proliferation of NPC nonkeratinizing cell line CNE2. The regulation of SOX4 on cell migration was determined by the transwell migration assay and wounding healing assay. Besides, we also found SOX4 could promote epithelial-mesenchymal transition (EMT) of CNE2 cells and decrease their cisplatin sensitivity. Our data suggested that SOX4 might play an important role in regulating NPC progression and would provide a potential therapeutic strategy for NPC. Si Shi, Xiaolei Cao, Miao Gu, Bo You, Ying Shan, and Yiwen You Copyright © 2015 Si Shi et al. All rights reserved. Effects of Antitumor Necrosis Factor Therapy on Osteoprotegerin, Neopterin, and sRANKL Concentrations in Patients with Rheumatoid Arthritis Wed, 21 Oct 2015 13:23:05 +0000 http://www.hindawi.com/journals/dm/2015/276969/ Background. Rheumatoid arthritis is a systemic autoimmune disease characterized by joint erosions, progressive focal bone loss, and chronic inflammation. Methods. 20 female patients with moderate-to-severe rheumatoid arthritis were treated with anti-TNF-antibody adalimumab in addition to concomitant antirheumatic therapies. Patients were assessed for overall disease activity using the DAS28 score, and neopterin, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) concentrations as well as osteoprotegerin (OPG) and soluble receptor activator of NF-κB ligand (sRANKL) concentrations were determined before therapy and at week 12. Neopterin as well as OPG and sRANKL were determined by commercial ELISAs. Results. Before anti-TNF therapy patients presented with high disease activity and elevated concentrations of circulating inflammatory markers. OPG concentrations correlated with neopterin (, ), but not with DAS28. OPG concentrations and disease activity scores declined during anti-TNF-treatment (both ). Patients who achieved remission () or showed a good response according to EULAR criteria () presented with initially higher baseline OPG levels, which subsequently decreased significantly during treatment ( for remission, for good response). Conclusions. Adalimumab therapy was effective in modifying disease activity and reducing proinflammatory and bone remodelling cascades. Katharina Kurz, Manfred Herold, Elisabeth Russe, Werner Klotz, Guenter Weiss, and Dietmar Fuchs Copyright © 2015 Katharina Kurz et al. All rights reserved. Clinicopathologic and Prognostic Value of Serum Carbohydrate Antigen 19-9 in Gastric Cancer: A Meta-Analysis Wed, 21 Oct 2015 08:45:22 +0000 http://www.hindawi.com/journals/dm/2015/549843/ Background. The clinical value of carbohydrate antigen (CA) 19-9 in gastric cancer is controversial. We evaluated the clinicopathologic and prognostic value of CA 19-9 in gastric cancer. Methods. A literature search was conducted in PubMed and Embase databases. Odds ratios (ORs), risk ratios (RR), hazard ratios (HRs), and 95% confidence intervals (CIs) were used as effect measures. Results. Thirty-eight studies were included. Results showed that there were significant differences in the incidence of high CA 19-9 levels between stages III/IV and I/II groups (OR = 3.36; 95% CI = 2.34–4.84), the pT3/T4 and pT1/T2 groups (OR = 2.40; 95% CI = 1.60–3.59), the lymph node-positive and node-negative groups (OR = 2.91; 95% CI = 2.21–3.84), the metastasis-positive and metastasis-negative groups (OR = 2.76; 95% CI = 1.12–6.82), and vessel invasion-positive and invasion-negative groups (OR = 1.66; 95% CI = 1.11–2.48). Moreover, CA 19-9 was significantly associated with poor overall survival (HR = 1.83; 95% CI = 1.56–2.15), disease-free survival (HR = 1.85; 95% CI = 1.16–2.95), and disease-specific survival (HR = 1.33; 95% CI = 1.10–1.60) in gastric cancer. Conclusions. Our meta-analysis showed that CA 19-9 indicates clinicopathologic characteristics of gastric cancer and is associated with a poor prognosis. Yong-xi Song, Xuan-zhang Huang, Peng Gao, Jing-xu Sun, Xiao-wan Chen, Yu-chong Yang, Cong Zhang, Hong-peng Liu, Hong-chi Wang, and Zhen-ning Wang Copyright © 2015 Yong-xi Song et al. All rights reserved. The Role of Vitamin D in Diabetes and Cardiovascular Disease: An Updated Review of the Literature Tue, 20 Oct 2015 12:56:17 +0000 http://www.hindawi.com/journals/dm/2015/580474/ The dietary reference values for Vitamin D were set primarily considering its role in bone health, but with the discovery of Vitamin D receptors throughout body tissues, new links with other health conditions are now studied, such as for diabetes and cardiovascular diseases (CVD). This paper shall analyze and examine all new research studies carried out, especially in 2013–2015 regarding diabetes mellitus (DM) and cardiovascular diseases (CVD). Vast research has been carried out to establish strong relationship between Vitamin D serum levels, supplementation, diabetes, and CVD. However, the results from researches identified in this paper are disputable. Benefits of Vitamin D adequate levels were recognized from gestational period until later in disease development such as diabetes and/or CVD, but since not all studies are in agreement further investigation is suggested. Researches conducting large randomized controlled trials, exploring range of supplement doses, with variable baseline serum Vitamin D levels, and inclusion of array of associated parameters, are still required to conduct large-scale analysis and draw conclusion as a risk factor. Until then it is possible to conclude that maintenance of serum Vitamin D levels holds advantageous aspects in diabetic and cardiovascular conditions, and people should strive to attain them. Dimitrios Papandreou and Zujaja-Tul-Noor Hamid Copyright © 2015 Dimitrios Papandreou and Zujaja-Tul-Noor Hamid. All rights reserved. Prognostic Role of MicroRNA-200c-141 Cluster in Various Human Solid Malignant Neoplasms Sun, 18 Oct 2015 07:00:18 +0000 http://www.hindawi.com/journals/dm/2015/935626/ The miR-200 family has emerged recently as a noticeable marker for predicting cancer prognosis and tumor progression. We aimed to review the evidence of miR-200c-141 genomic cluster as prognostic biomarkers in cancers. The results suggested that high level of miR-200c had no significant impact on OS (HR = 1.14 [0.77–1.69], ) and DFS/PFS (HR = 0.72 [0.45–1.14], ). Stratified analyses revealed that high miR-200c expression was significantly related to poor OS in serum/plasma (HR = 2.12 [1.62–2.77], ) but not in tissues (HR = 0.89 [0.58–1.37], ). High miR-200c expression was significantly associated with favorable DFS/PFS in tissues (HR = 0.56 [0.43–0.73], ) but worse DFS/PFS in serum/plasma (HR = 1.90 [1.08–3.36], ). For miR-141, we found that high miR-141 expression predicted no significant impact on OS (HR = 1.18 [0.74–1.88], ) but poor DFS/PFS (HR = 1.11 [1.04–1.20], ). Similarly, subgroup analyses showed that high miR-141 expression predicted poor OS in serum/plasma (HR = 4.34 [2.30–8.21], ) but not in tissues (HR = 1.00 [0.92–1.09], ). High miR-141 expression was significantly associated with worse DFS/PFS in tissues (HR = 1.12 [1.04–1.20], ) but not in serum/plasma (HR = 0.90 [0.44–1.83], ). Our findings indicated that, compared to their tissue counterparts, the expression level of miR-200c and miR-141 in peripheral blood may be more effective for monitoring cancer prognosis. High miR-141 expression was better at predicting tumor progression than survival for malignant tumors. Xiao-yang Li, Hui Li, Jie Bu, Liang Xiong, Hong-bin Guo, Li-hong Liu, and Tao Xiao Copyright © 2015 Xiao-yang Li et al. All rights reserved. Complement Split Products in Amniotic Fluid in Pregnancies Subsequently Developing Early-Onset Preeclampsia Sun, 18 Oct 2015 06:17:46 +0000 http://www.hindawi.com/journals/dm/2015/263109/ Objective. To determine the second-trimester amniotic fluid concentrations of complement split products in pregnancies subsequently affected by early-onset preeclampsia. Study Design. Cohort of 731 women with singleton pregnancies undergoing second-trimester genetic amniocentesis followed up to delivery and analyzed as a nested case-control study. Cases of preeclampsia developing before 34 weeks’ gestation () were compared with 47 uncomplicated term controls. Amniotic fluid collected at amniocentesis was tested for complement split products Bb, C4a, C3a, and C5a. Results. Women who developed early-onset preeclampsia as compared with the term pregnant controls had significantly higher () median amniotic fluid C3a levels (318.7 ng/mL versus 254.5 ng/mL). Median amniotic fluid Bb levels were also significantly higher () in preeclamptic women than in normal pregnant women (1127 ng/mL versus 749 ng/mL). Median levels of C4a and C5a were not significantly different between the groups. Conclusion. Our data suggest that complement activation in early pregnancy is associated with early-onset preeclampsia. We believe this to be the first prospective study to link complement activation in amniotic fluid in early pregnancy and later development of preeclampsia. Our findings provide evidence that immune dysregulation may precede the clinical manifestations of preeclampsia and that the alternative complement pathway is principally involved. Manu Banadakoppa, Alex C. Vidaeff, Uma Yallampalli, Susan M. Ramin, Michael A. Belfort, and Chandra Yallampalli Copyright © 2015 Manu Banadakoppa et al. All rights reserved. Allelic Imbalance of mRNA Associated with α2-HS Glycoprotein (Fetuin-A) Polymorphism Thu, 15 Oct 2015 11:53:55 +0000 http://www.hindawi.com/journals/dm/2015/865053/ Alpha 2-HS glycoprotein (AHSG), also designated as fetuin-A, exhibits polymorphism in population genetics consisting of two major alleles of 1 and 2. The serum level in the 1 homozygote is significantly higher than that of the 2 homozygote. This study examined the molecular mechanism for the cis-regulatory expression. To quantitate allele-specific mRNA in intra-assays of the heterozygote, RT-PCR method employing primers that were incorporated to the two closely located SNPs was developed. The respective magnitudes of 1 to 2 in the liver tissues and hepatic culture cells of PLC/PRF/5 were determined quantitatively as 2.5-fold and 6.2-fold. The mRNA expressional difference of two major alleles was observed, which is consistent with that in the serum level. The culture cells carried heterozygous genotypes in rs4917 and rs4918, but homozygous one in rs2248690. It was unlikely that the imbalance was derived from the SNP located in the promotor site. Furthermore, to investigate the effect of mRNA degradation, RNA synthesis in the cell culture was inhibited potently by the addition of actinomycin-D. No marked change was apparent between the two alleles. The results indicated that the cis-regulatory expressional difference is expected to occur at the level of transcription or splicing of mRNA. Yoshihiko Inaoka, Motoki Osawa, Nahoko Mukasa, Keiko Miyashita, Fumiko Satoh, and Yu Kakimoto Copyright © 2015 Yoshihiko Inaoka et al. All rights reserved. Antibodies against C1q Are a Valuable Serological Marker for Identification of Systemic Lupus Erythematosus Patients with Active Lupus Nephritis Tue, 13 Oct 2015 16:52:56 +0000 http://www.hindawi.com/journals/dm/2015/450351/ Objective. An early diagnosis of lupus nephritis (LN) has an important clinical implication in guiding treatments of systemic lupus erythematosus (SLE) in clinical settings. In this study, the diagnostic values of circulating autoantibodies to C1q alone or in combination with other markers for accessing active SLE and LN were evaluated. Methods. The diagnostic value of anti-C1q autoantibodies for identification of patients with active SLE disease and LN was evaluated by analyzing the level of anti-C1q antibodies in sera from 95 SLE patients, 40 non-SLE patients, and 34 healthy cohorts. Results. The prevalence of anti-C1q antibodies was significantly higher in patients with SLE (50/95, 52.6%), active SLE (40/51, 78.4%), and LN (30/35, 85.7%) in comparison with non-SLE patient controls, patients with inactive SLE, and non-LN, respectively. A combination of anti-C1q with anti-dsDNA and/or levels of complements C3 and C4 exhibited an increased specificity but a decreased sensitivity for identification of patients with active SLE and LN diseases relative to each of these markers alone. Conclusion. Anti-C1q antibodies were strongly associated with disease activity and LN in SLE patients, suggesting that it may be a reliable serological marker for identification of SLE patients with active LN and active SLE disease. Shuhong Chi, Yunxia Yu, Juan Shi, Yurong Zhang, Jijuan Yang, Lijuan Yang, and Xiaoming Liu Copyright © 2015 Shuhong Chi et al. All rights reserved. CD73 Predicts Favorable Prognosis in Patients with Nonmuscle-Invasive Urothelial Bladder Cancer Mon, 12 Oct 2015 13:55:16 +0000 http://www.hindawi.com/journals/dm/2015/785461/ Aims. CD73 is a membrane associated 5′-ectonucleotidase that has been proposed as prognostic biomarker in various solid tumors. The aim of this study is to evaluate CD73 expression in a cohort of patients with primary bladder cancer in regard to its association with clinicopathological features and disease course. Methods. Tissue samples from 174 patients with a primary urothelial carcinoma were immunohistochemically assessed on a tissue microarray. Associations between CD73 expression and retrospectively obtained clinicopathological data were evaluated by contingency analysis. Survival analysis was performed to investigate the predictive value of CD73 within the subgroup of pTa and pT1 tumors in regard to progression-free survival (PFS). Results. High CD73 expression was found in 46 (26.4%) patients and was significantly associated with lower stage, lower grade, less adjacent carcinoma in situ and with lower Ki-67 proliferation index. High CD73 immunoreactivity in the subgroup of pTa and pT1 tumors was significantly associated with longer PFS (HR: 0.228; ) in univariable Cox regression analysis. Conclusion. High CD73 immunoreactivity was associated with favorable clinicopathological features. Furthermore, it predicts better outcome in the subgroup of pTa and pT1 tumors and may thus serve as additional tool for the selection of patients with favorable prognosis. Marian S. Wettstein, Lorenz Buser, Thomas Hermanns, Filip Roudnicky, Daniel Eberli, Philipp Baumeister, Tullio Sulser, Peter Wild, and Cédric Poyet Copyright © 2015 Marian S. Wettstein et al. All rights reserved. Gamma-Glutamyltransferase: A Predictive Biomarker of Cellular Antioxidant Inadequacy and Disease Risk Mon, 12 Oct 2015 08:09:56 +0000 http://www.hindawi.com/journals/dm/2015/818570/ Gamma-glutamyltransferase (GGT) is a well-established serum marker for alcohol-related liver disease. However, GGT’s predictive utility applies well beyond liver disease: elevated GGT is linked to increased risk to a multitude of diseases and conditions, including cardiovascular disease, diabetes, metabolic syndrome (MetS), and all-cause mortality. The literature from multiple population groups worldwide consistently shows strong predictive power for GGT, even across different gender and ethnic categories. Here, we examine the relationship of GGT to other serum markers such as serum ferritin (SF) levels, and we suggest a link to exposure to environmental and endogenous toxins, resulting in oxidative and nitrosative stress. We observe a general upward trend in population levels of GGT over time, particularly in the US and Korea. Since the late 1970s, both GGT and incident MetS and its related disorders have risen in virtual lockstep. GGT is an early predictive marker for atherosclerosis, heart failure, arterial stiffness and plaque, gestational diabetes, and various liver diseases, including viral hepatitis, other infectious diseases, and several life-threatening cancers. We review literature both from the medical sciences and from life insurance industries demonstrating that serum GGT is a superior marker for future disease risk, when compared against multiple other known mortality risk factors. Gerald Koenig and Stephanie Seneff Copyright © 2015 Gerald Koenig and Stephanie Seneff. All rights reserved.