Disease Markers http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Expressions of Matrix Metalloproteinases 2, 7, and 9 in Carcinogenesis of Pancreatic Ductal Adenocarcinoma Sun, 26 Jun 2016 09:01:37 +0000 http://www.hindawi.com/journals/dm/2016/9895721/ Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease, usually diagnosed in an advanced stage which gives a slight chance of recovery. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that participate in tissue remodeling and stimulate neovascularization and inflammatory response. The aim of the study was to evaluate the expression of MMP-2, MMP-7, and MMP-9 in normal ducts, tumor pancreatic adenocarcinoma cells, and peritumoral stroma in correlation with clinicohistopathological parameters. The study material was obtained from 29 patients with pancreatic ductal adenocarcinoma. The expressions of MMP-2, MMP-7, and MMP-9 were performed by immunohistochemical technique. Microvessel density (MVD) was visualized by special immunostaining. The expressions of MMP-2, MMP-7, and MMP-9 were mainly observed in tumor cells and peritumoral stroma. MMP-2 expression in cancer cells was correlated with female gender, stronger inflammation, and histopathological type of cancer (, ; , ; , , resp.). The expression of MMP-7 in tumor cells was found to positively correlate with the presence of necrosis and negatively correlate with MVD (, ; , ). We also showed that positive MMP-9 expression in tumor cells was associated with MVD (, ); however, it was not statistically significant. Our results demonstrate that MMP-2, MMP-7, and MMP-9 expressions correlate with various morphological features of the PDAC tumor such as inflammation, necrosis, and formation of the new blood vessels. Katarzyna Jakubowska, Anna Pryczynicz, Joanna Januszewska, Iwona Sidorkiewicz, Andrzej Kemona, Andrzej Niewiński, Łukasz Lewczuk, Bogusław Kędra, and Katarzyna Guzińska-Ustymowicz Copyright © 2016 Katarzyna Jakubowska et al. All rights reserved. Liquid Biopsy of Hepatocellular Carcinoma: Circulating Tumor-Derived Biomarkers Wed, 15 Jun 2016 13:37:59 +0000 http://www.hindawi.com/journals/dm/2016/1427849/ Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide due to latent liver disease, late diagnosis, and nonresponse to systemic treatments. Till now, surgical and/or biopsy specimens are still generally used as a gold standard by the clinicians for clinical decision-making. However, apart from their invasive characteristics, tumor biopsy only mirrors a single spot of the tumor, failing to reflect current cancer dynamics and progression. Therefore, it is imperative to develop new diagnostic strategies with significant effectiveness and reliability to monitor high-risk populations and detect HCC at an early stage. In the past decade, the potent utilities of “liquid biopsy” have attracted intense concern and were developed to evaluate cancer progression in several clinical trials. “Liquid biopsies” represent a series of noninvasive tests that detect cancer byproducts easily accessible in peripheral blood, mainly including circulating tumor cells (CTCs) and cell-free nucleic acids (cfNAs) that are shed into the blood from the tumor sites. In this review, we focus on the recent developments in the field of “liquid biopsy” as well as the diagnostic and prognostic significance of CTCs and cfNAs in HCC patients. Chang-Qing Yin, Chun-Hui Yuan, Zhen Qu, Qing Guan, Hao Chen, and Fu-Bing Wang Copyright © 2016 Chang-Qing Yin et al. All rights reserved. WISP1 Is Increased in Intestinal Mucosa and Contributes to Inflammatory Cascades in Inflammatory Bowel Disease Wed, 15 Jun 2016 12:16:20 +0000 http://www.hindawi.com/journals/dm/2016/3547096/ Inflammatory bowel disease (IBD) is mainly characterized by intestinal tissue damage, which is caused by excessive autoimmune responses poorly controlled by corresponding regulatory mechanisms. WISP1, which belongs to the CCN protein family, is a secreted matricellular protein regulating several inflammatory pathways, such as Wnt/β-catenin pathway, and has been reported in several diseases including cancer. Here we examined the expression, regulatory mechanisms, and functions of WISP1 in IBD. WISP1 mRNA and protein expression was upregulated in colonic biopsies and lamina propria mononuclear cells (LPMC) of IBD patients compared with those of healthy controls. Tumor necrosis factor- (TNF-) α induced WISP1 expression in LPMC from healthy controls. Consistently, WISP1 mRNA expression was downregulated in colonic biopsies from IBD patients who had achieved clinical remission with infliximab (IFX). Furthermore, WISP1 expression was also found to be increased in colons from 2,4,6-trinitrobenzenesulfonic acid- (TNBS-) induced mice compared with those from control mice. Further studies confirmed that administration of rWISP1 could aggravate TNBS-induced colitis in vivo. Therefore, we concluded that WISP1 is increased in IBD and contributes to the proinflammatory cascades in the gut. Qi Zhang, Cuiping Zhang, Xiaoyu Li, Yanan Yu, Kun Liang, Xinzhi Shan, Kun Zhao, Qinghui Niu, and Zibin Tian Copyright © 2016 Qi Zhang et al. All rights reserved. Factors Affecting Morbidity in Solid Organ Injuries Wed, 08 Jun 2016 08:37:24 +0000 http://www.hindawi.com/journals/dm/2016/6954758/ Background and Aim. The aim of this study was to investigate the effects of demographic characteristics, biochemical parameters, amount of blood transfusion, and trauma scores on morbidity in patients with solid organ injury following trauma. Material and Method. One hundred nine patients with solid organ injury due to abdominal trauma during January 2005 and October 2015 were examined retrospectively in the General Surgery Department of Dicle University Medical Faculty. Patients’ age, gender, trauma interval time, vital status (heart rate, arterial tension, and respiratory rate), hematocrit (HCT) value, serum area aminotransferase (ALT) and aspartate aminotransferase (AST) values, presence of free abdominal fluid in USG, trauma mechanism, extra-abdominal system injuries, injured solid organs and their number, degree of injury in abdominal CT, number of blood transfusions, duration of hospital stay, time of operation (for those undergoing operation), trauma scores (ISS, RTS, Glasgow coma scale, and TRISS), and causes of morbidity and mortality were examined. In posttraumatic follow-up period, intra-abdominal hematoma infection, emboli, catheter infection, and deep vein thrombosis were monitored as factors of morbidity. Results. One hundred nine patients were followed up and treated due to isolated solid organ injury following abdominal trauma. There were 81 males (74.3%) and 28 females (25.7%), and the mean age was (15–78) years. When examining the mechanism of abdominal trauma in patients, the following results were obtained: 58 (53.3%) traffic accidents (22 out-vehicle and 36 in-vehicle), 27 (24.7%) falling from a height, 14 (12.9%) assaults, 5 (4.5%) sharp object injuries, and 5 (4.5%) gunshot injuries. When evaluating 69 liver injuries scaled by CT the following was detected: 14 (20.3%) of grade I, 32 (46.4%) of grade II, 22 (31.8%) of grade III, and 1 (1.5%) of grade IV. In 63 spleen injuries scaled by CT the following was present: grade I in 21 (33.3%), grade II in 27 (42.9%), grade III in 11 (17.5%), and grade IV in 4 (6.3%). The mean length of hospital stay after trauma was 6.46 days in the medically followed patients. This ratio was 8.13 days in 22 patients with morbidity and 5.98 days in 78 patients without morbidity. There was a morbidity in 22 (22%) patients medically followed after trauma. In this study, nonoperative treatment was observed to be performed safely in solid organ injuries after trauma in case of absence of hemodynamic stability and peritoneal irritation. It has been emphasized that injury of both liver and spleen (), high respiratory rate (), trauma scores (GKS, ISS, RTS) (), and elevation of ALT AST values () are stimulants for morbidity that may occur during follow-up. Conclusion. Medical follow-up can be considered in patients with high grade injuries similar to patients with low-grade solid organ injury after trauma. The injury of both liver and spleen, high respiratory rate, high GCS and ISS, low RTS, and elevation of ALT AST values were found to increase morbidity again in the follow-up of these patients. Serdar Baygeldi, Oktay Karakose, Kazım Caglar Özcelik, Hüseyin Pülat, Sedat Damar, Hüseyin Eken, İsmail Zihni, Alpaslan Fedai Çalta, and Bilsel Baç Copyright © 2016 Serdar Baygeldi et al. All rights reserved. Association of lincRNA-p21 Haplotype with Coronary Artery Disease in a Chinese Han Population Thu, 02 Jun 2016 07:04:52 +0000 http://www.hindawi.com/journals/dm/2016/9109743/ lincRNA-p21 plays an important role in the pathogenesis and progression of coronary artery disease (CAD). To date, the biological significance of polymorphisms in lincRNA-p21 on CAD risk remains unknown. Here we aimed to evaluate the influence of lincRNA-p21 polymorphisms on individual susceptibility to CAD. Genotyping of four tagSNPs (rs9380586, rs4713998, rs6930083, and rs6931097) within lincRNA-p21 gene was performed in 615 CAD and 655 controls. The haplotype analysis showed that the haplotype G-A-A-G (rs9380586-rs4713998-rs6930083-rs6931097) was statistically significantly associated with the reduced risk for CAD (OR = 0.78, P = 0.023). Stratified analysis revealed that G-A-A-G haplotype was at a significantly lower risk for myocardial infarction (MI) (OR = 0.68, P = 0.010). We also found that haplotype G-A-A-G had a more pronounced decreased risk for premature CAD or MI subjects (OR = 0.67, P = 0.017 for premature CAD, and OR = 0.65, P = 0.041 for premature MI, resp.). Our data provide the first evidence that the G-A-A-G haplotype of lincRNA-p21 is associated with decreased risk of CAD and MI, particularly among premature CAD/MI in the Chinese Han population. Further studies with more subjects and in diverse ethnic populations are warranted to clarify the general validity of our findings. Sai-sai Tang, Jie Cheng, Meng-yun Cai, Xi-li Yang, Xin-guang Liu, Bi-ying Zheng, and Xing-dong Xiong Copyright © 2016 Sai-sai Tang et al. All rights reserved. Serum Gelatinases Levels in Multiple Sclerosis Patients during 21 Months of Natalizumab Therapy Thu, 02 Jun 2016 06:35:43 +0000 http://www.hindawi.com/journals/dm/2016/8434209/ Background. Natalizumab is a highly effective treatment approved for multiple sclerosis (MS). The opening of the blood-brain barrier mediated by matrix metalloproteinases (MMPs) is considered a crucial step in MS pathogenesis. Our goal was to verify the utility of serum levels of active MMP-2 and MMP-9 as biomarkers in twenty MS patients treated with Natalizumab. Methods. Serum levels of active MMP-2 and MMP-9 and of specific tissue inhibitors TIMP-1 and TIMP-2 were determined before treatment and for 21 months of therapy. Results. Serum levels of active MMP-2 and MMP-9 and of TIMP-1 and TIMP-2 did not differ during the treatment. The ratio between MMP-9 and MMP-2 was increased at the 15th month compared with the 3rd, 6th, and 9th months, greater at the 18th month than at the 3rd and 6th months, and higher at the 21st than at the 3rd and 6th months. Discussion. Our data indicate that an imbalance between active MMP-9 and active MMP-2 can occur in MS patients after 15 months of Natalizumab therapy; however, they do not support the use of serum active MMP-2 and active MMP-9 and TIMP-1 and TIMP-2 levels as biomarkers for monitoring therapeutic response to Natalizumab. Massimiliano Castellazzi, Tiziana Bellini, Alessandro Trentini, Serena Delbue, Francesca Elia, Matteo Gastaldi, Diego Franciotta, Roberto Bergamaschi, Maria Cristina Manfrinato, Carlo Alberto Volta, Enrico Granieri, and Enrico Fainardi Copyright © 2016 Massimiliano Castellazzi et al. All rights reserved. Clinical Significance of Serum Interleukin-31 and Interleukin-33 Levels in Patients of Endometrial Cancer: A Case Control Study Tue, 31 May 2016 06:38:54 +0000 http://www.hindawi.com/journals/dm/2016/9262919/ Aims. Previous evidence has proved that interleukin-31 (IL-31) and interleukin-33 (IL-33) can be potential markers in some cancers’ formulation. We aimed to determine the potential role of IL-31 and IL-33 in prognosis of endometrial cancer patients. Methods. Serum samples were collected from 160 patients with endometrial cancer and 160 healthy controls. The ELISA kits (Raybio® Systems) specific for human IL-31 and human IL-33 were used. Serum levels of tumor markers (CEA, CA-125, and CA19-9) were measured by chemiluminescence immunoassay. A two-side P value < 0.05 was indicated to be significant. Results. Serum levels of IL-31 and IL-33 in patients were significantly elevated compared to those of healthy controls. The interleukin levels were also related to clinical characteristics, including tumor stages, depth of invasion, and existence of node metastases and distant metastases. The sensitivity and specificity of IL-31 and IL-33 were higher than the counterparts of tumor markers, both separately and in combination of IL-31, IL-33, and the clinical markers. Conclusions. This report is the first one mentioning the possible association between serum IL-31 and IL-33 and endometrial cancer. With their sensitivity and specificity, the interleukins may be useful biomarkers for endometrial cancer’s prognosis. Xi Zeng, Zhu Zhang, Qian-Qian Gao, Yan-Yun Wang, Xiu-Zhang Yu, Bin Zhou, and Ming-Rong Xi Copyright © 2016 Xi Zeng et al. All rights reserved. Discovery of Novel Biomarkers for Alzheimer’s Disease from Blood Sun, 29 May 2016 12:59:54 +0000 http://www.hindawi.com/journals/dm/2016/4250480/ Blood-based biomarkers for Alzheimer’s disease would be very valuable because blood is a more accessible biofluid and is suitable for repeated sampling. However, currently there are no robust and reliable blood-based biomarkers for practical diagnosis. In this study we used a knowledge-based protein feature pool and two novel support vector machine embedded feature selection methods to find panels consisting of two and three biomarkers. We validated these biomarker sets using another serum cohort and an RNA profile cohort from the brain. Our panels included the proteins ECH1, NHLRC2, HOXB7, FN1, ERBB2, and SLC6A13 and demonstrated promising sensitivity (>87%), specificity (>91%), and accuracy (>89%). Jintao Long, Genhua Pan, Emmanuel Ifeachor, Robert Belshaw, and Xinzhong Li Copyright © 2016 Jintao Long et al. All rights reserved. Uroplakin II Expression in Breast Carcinomas Showing Apocrine Differentiation: Putting Some Emphasis on Invasive Pleomorphic Lobular Carcinoma as a Potential Mimic of Urothelial Carcinoma at Metastatic Sites Thu, 26 May 2016 12:56:52 +0000 http://www.hindawi.com/journals/dm/2016/2940496/ Uroplakin II antibody is exclusively specific for urothelial carcinoma. Nonurothelial carcinoma has not been reported to be immunoreactive for uroplakin II. In the present study, we hypothesized that breast carcinoma showing apocrine differentiation, such as invasive pleomorphic lobular carcinoma (IPLC) and apocrine carcinoma (AC), stains positive for uroplakin II. We identified 6 cases of IPLC between 2000 and 2014 by searching a computerized pathological database. We randomly selected 10 cases of each classic invasive lobular carcinoma (cILC) and AC and five cases of apocrine metaplasia (AM) that coexisted in a surgically resected breast carcinoma specimen. Immunohistochemistry was performed for uroplakin II, GATA3, CK7, CK20, and other representative markers positive for urothelial carcinoma. All cases of IPLC, AC, and AM, except those of cILC, showed immunoreactivity for uroplakin II. Poorly differentiated urothelial carcinoma sometimes shows similar morphology to IPLC with the following immunophenotype: CK7+, CK20−, GATA3+, and uroplakin II+. In the present study, this immunophenotype was observed in all the cases of IPLC and AC. Therefore, when studying metastatic, poorly differentiated carcinoma showing the aforementioned immunophenotype, we should consider the possibility of it being IPLC in addition to metastatic urothelial carcinoma. Shogo Tajima and Kenji Koda Copyright © 2016 Shogo Tajima and Kenji Koda. All rights reserved. Pulmonary Embolism in Pneumonia: Still a Diagnostic Challenge? Results of a Case-Control Study in 100 Patients Wed, 25 May 2016 06:29:57 +0000 http://www.hindawi.com/journals/dm/2016/8682506/ This study evaluated the diagnostic value of D-dimer, CRP, and leucocytes count to detect an underlying pulmonary embolism (PE) in patients with pneumonia. A predictive model of an underlying PE, based on laboratory markers and clinical symptoms, was our ultimate objective. Overall 100 patients underwent a computed tomography angiography (CTA) of the lung: 54 with coexistence of PE and pneumonia (cases) and 46 with pneumonia without PE (controls). Cases and controls were matched 1 : 1. Symptoms and paraclinical findings were registered on admission. Receiver operating characteristic (ROC) curves, search for an optimal threshold, and conditional logistic regression analysis were conducted. D-dimer has a moderate ability to detect PE in pneumonia. Sensitivity of D-dimer was estimated at 97.78% and specificity at 11.11%. No optimal cut-point has acceptable diagnostic ability. After excluding patients with sepsis, sensitivity was reduced to 96.97%, whereas specificity increased to 16.13%. Consolidation in chest X-ray and positive D-dimer predict better an underlying PE as D-dimer itself. Thus, discriminatory power of the prediction model (AUC of 0.740) is not much greater than D-dimer (AUC of 0.703). No threshold that could increase the diagnostic value of D-dimer or a prediction model which is significantly better than D-dimer itself was identified. Maria Paparoupa, Loukia Spineli, Theodor Framke, Huy Ho, Frank Schuppert, and Adrian Gillissen Copyright © 2016 Maria Paparoupa et al. All rights reserved. Circulating Omentin-1 Levels Are Decreased in Dilated Cardiomyopathy Patients with Overt Heart Failure Tue, 24 May 2016 08:41:02 +0000 http://www.hindawi.com/journals/dm/2016/6762825/ Background. Recent evidence demonstrated that the circulating levels of omentin-1 are related to the presence of ischemic heart disease and heart failure. However, omentin-1 plasma levels in patients with nonischemic dilated cardiomyopathy (DCM), which is the most common etiology of heart failure, have yet to be investigated. Methods. Plasma levels of omentin-1 and adiponectin were measured in 100 patients with DCM and 45 healthy controls. Results. Plasma omentin-1 levels significantly decreased in DCM patients compared with the control group, whereas adiponectin levels significantly increased in DCM patients compared with the control group. Plasma omentin-1 levels were negatively correlated with adiponectin (, ), C-reactive protein (CRP) (, ), and N-terminal pro-brain natriuretic peptide (NT-proBNP) (, ) levels as well as left ventricular end-diastolic diameter (LVEDD) (, ) but were positively correlated with left ventricular ejection fraction (LVEF) (, ). Plasma adiponectin levels were positively correlated with CRP (, ) and NT-proBNP (, ) levels but were negatively correlated with fasting glucose (, ) and LVEF (, ) levels. Furthermore, omentin-1 (OR 0.983, 95% CI 0.970 to 0.996; ) levels were independently associated with the presence of DCM before NT-proBNP was added. Conclusions. Omentin-1 is a novel biomarker of DCM. Ying Huang, Yingzhong Lin, Shumin Zhang, Zhijian Wang, Jianwei Zhang, Chao Chang, Ling Liu, Qingwei Ji, and Xiaofei Liu Copyright © 2016 Ying Huang et al. All rights reserved. Immunohistochemical Expression of VEGF and Podoplanin in Uterine Cervical Squamous Intraepithelial Lesions Tue, 24 May 2016 05:51:16 +0000 http://www.hindawi.com/journals/dm/2016/8293196/ VEGF and podoplanin (PDPN) have been identified as angiogenesis and/or lymphangiogenesis regulators and might be essential to restrict tumor growth, progression, and metastasis. In the present study, we evaluate the association between the expression of these markers and CIN grade. Immunohistochemistry was performed in 234 uterine cervical samples using conventional histologic sections or TMA with the monoclonal antibodies to VEGF (C-1 clone) and podoplanin (D2-40 clone). Positive-staining rates of VEGF in 191 CIN specimens were significantly associated with histological grade (). Negative and/or focal immunostaining for PDPN were more frequent in CIN 3 (). We found that patients with CIN 3 more frequently had strong and more diffuse staining for VEGF and diminished staining for PDPN (). Strong and more diffuse VEGF immunoexpressions in CIN 2 and CIN 3 were detected when compared to CIN 1. Negative and/or focal PDPN immunoexpression appear to be more frequent in CIN 3. Moderate to strong VEGF expression may be a tendency among patients with high-grade lesions and diminished PDPN expression. Patrícia Napoli Belfort-Mattos, Gustavo Rubino de Azevedo Focchi, Julisa Chamorro Lascasas Ribalta, Tatiana Megale De Lima, Carmen Regina Nogueira Carvalho, Fernanda Kesselring Tso, and Neila Maria De Góis Speck Copyright © 2016 Patrícia Napoli Belfort-Mattos et al. All rights reserved. Plasma miR-10a: A Potential Biomarker for Coronary Artery Disease Sun, 22 May 2016 11:11:00 +0000 http://www.hindawi.com/journals/dm/2016/3841927/ Aims. MicroRNAs (miRNAs) are involved in the pathogenesis of coronary artery disease (CAD). The objective of this study is to determine plasma levels of miR-10a in CAD and analyze its association with the severity of CAD. Materials and Methods. Plasma miR-10a levels in 60 CAD patients including stable angina pectoris (SAP) (), unstable angina pectoris (UAP) or non-ST elevation myocardial infarction (MI) (NSTEMI) (), or ST elevation MI (STEMI) () and 20 non-CAD subjects were assessed by real-time polymerase chain reaction (qRT-PCR), and associations of miR-10a levels with risk factors of CAD and its severity were analyzed. Results. The qRT-PCR results showed that plasma miR-10a levels were decreased in CAD patients, and CAD with high SYNTAX scores or STEMI was significantly associated with lower miR-10a levels. Conclusions. Lower plasma miR-10a levels were negatively associated with the presence as well as severity of CAD, and plasma miR-10a can act as a potential biomarker for estimating the presence and severity of CAD. Liyun Luo, Bairong Chen, Songbiao Li, Xiaoliang Wei, Tianmin Liu, Yin Huang, and Xiufang Lin Copyright © 2016 Liyun Luo et al. All rights reserved. Comparative Study of Circulating MMP-7, CCL18, KL-6, SP-A, and SP-D as Disease Markers of Idiopathic Pulmonary Fibrosis Tue, 17 May 2016 14:22:14 +0000 http://www.hindawi.com/journals/dm/2016/4759040/ Background. Recent reports indicate that matrix metalloproteinase-7 (MMP-7) and CC-chemokine ligand 18 (CCL18) are potential disease markers of idiopathic pulmonary fibrosis (IPF). The objective of this study was to perform direct comparisons of these two biomarkers with three well-investigated serum markers of IPF, Krebs von den Lungen-6 (KL-6), surfactant protein-A (SP-A), and SP-D. Methods. The serum levels of MMP-7, CCL18, KL-6, SP-A, and SP-D were evaluated in 65 patients with IPF, 31 patients with bacterial pneumonia, and 101 healthy controls. The prognostic performance of these five biomarkers was evaluated in patients with IPF. Results. The serum levels of MMP-7, KL-6, and SP-D in patients with IPF were significantly elevated compared to those in patients with bacterial pneumonia and in the healthy controls. Multivariate survival analysis showed that serum MMP-7 and KL-6 levels were independent predictors in IPF patients. Moreover, elevated levels of both KL-6 and MMP-7 were associated with poorer survival rates in IPF patients, and the combination of both markers provided the best risk discrimination using the C statistic. Conclusions. The present results indicated that MMP-7 and KL-6 were promising prognostic markers of IPF, and the combination of the two markers might improve survival prediction in patients with IPF. Kosuke Hamai, Hiroshi Iwamoto, Nobuhisa Ishikawa, Yasushi Horimasu, Takeshi Masuda, Shintaro Miyamoto, Taku Nakashima, Shinichiro Ohshimo, Kazunori Fujitaka, Hironobu Hamada, Noboru Hattori, and Nobuoki Kohno Copyright © 2016 Kosuke Hamai et al. All rights reserved. Evaluation of Adipokines, Inflammatory Markers, and Sex Hormones in Simple and Complex Breast Cysts’ Fluid Thu, 12 May 2016 17:23:50 +0000 http://www.hindawi.com/journals/dm/2016/5174929/ Objective. The aim of the study was to analyze the association between levels of adipokines in the breast cyst fluid and in the circulation in relation to the type of cysts. Material and Measurements. A cross-sectional study involved 86 women with breast cysts (42 with simple cysts and 44 with complex cysts). Plasma and breast cyst fluid leptin, adiponectin, visfatin/NAMPT, resistin, TNF-α, and IL-6 levels, in addition to serum levels of estradiol, progesterone and prolactin, and anthropometric parameters and body composition (by bioimpedance method), were measured. Results. The levels of leptin, adiponectin, and resistin were significantly lower in breast cyst fluid than in plasma regardless of the cyst type. Contrarily, the levels of visfatin/NAMPT and TNF-α were significantly increased, and IL-6 levels were similar in the breast cyst fluid and plasma in both study groups. There was no correlation between corresponding levels of leptin, adiponectin, resistin, visfatin/NAMPT, TNF-α, and IL-6 in breast cyst fluid and plasma. Conclusions. Higher levels of visfatin/NAMPT and TNF-α in the fluid from simple and complex breast cysts than in plasma suggest that their local production is related to inflammation. Paweł Madej, Grzegorz Franik, Piotr Kurpas, Aleksander Owczarek, Jerzy Chudek, and Magdalena Olszanecka-Glinianowicz Copyright © 2016 Paweł Madej et al. All rights reserved. Influence of βS-Globin Haplotypes and Hydroxyurea on Arginase I Levels in Sickle Cell Disease Wed, 04 May 2016 10:59:47 +0000 http://www.hindawi.com/journals/dm/2016/9172726/ Introduction. Sickle cell disease (SCD) is characterized by hemoglobin S homozygosity, leading to hemolysis and vasoocclusion. The hemolysis releases arginase I, an enzyme that decreases the bioavailability of nitric oxide, worsening the symptoms. The different SCD haplotypes are related to clinical symptoms and varied hemoglobin F (HbF) concentration. The aim of this study was to evaluate the impact of the βS gene haplotypes and HbF concentration on arginase I levels in SCD patients. Methods. Fifty SCD adult patients were enrolled in the study and 20 blood donors composed the control group. Arginase I was measured by ELISA. The βS haplotypes were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Statistical analyses were performed with GraphPad Prism program and the significance level was . Results. Significant increase was observed in the arginase I levels in SCD patients compared to the control group (). The comparison between the levels of arginase I in three haplotypes groups showed a difference between the Bantu/Bantu Bantu/Benin groups; Bantu/Bantu Benin/Benin, independent of HU dosage. An inverse correlation with the arginase I levels and HbF concentration was observed. Conclusion. The results support the hypothesis that arginase I is associated with HbF concentration, also measured indirectly by the association with haplotypes. J. A. Moreira, R. P. G. Machado, M. R. Laurentino, Romelia Pinheiro Gonçalves Lemes, M. C. Barbosa, T. E. Santos, I. C. J. Bandeira, and A. M. C. Martins Copyright © 2016 J. A. Moreira et al. All rights reserved. The Relationship between Betatrophin Levels in Blood and T2DM: A Systematic Review and Meta-Analysis Tue, 03 May 2016 12:40:01 +0000 http://www.hindawi.com/journals/dm/2016/9391837/ Background. In order to clarify previous ambiguous research conclusions, a meta-analysis was made to investigate the relationship between betatrophin levels in blood and type 2 diabetes mellitus (T2DM). Methods. We have searched all the English and Chinese references regarding the relationship between betatrophin and diabetes in database both manually and online. Strict criteria have been established to include and exclude articles, with Mean and Standard Deviation as statistics to evaluate strength of association. We have chosen either fixed- or random effect model according to heterogeneity inspection results and used Begg’s test and Egger’s test to analyze publication bias. Results. A total of 11 studies were included in this meta-analysis. Meta-analysis indicated a significant association between betatrophin and T2DM (Mean: 329.46; 95% confidence interval: 182.51 to 476.42, ). However, in the subgroup analysis, there was no significant statistic between betatrophin concentration and T2DM within Caucasian population (Mean: 98.40; 95% confidence interval: −1585.08 to 1781.88, ). Conclusions. Such relationship may suggest preference for association between betatrophin and T2DM in different population. Song Yue, Jingyang Wu, Jiahua Zhang, Lei Liu, and Lei Chen Copyright © 2016 Song Yue et al. All rights reserved. CYC1 Predicts Poor Prognosis in Patients with Breast Cancer Thu, 28 Apr 2016 08:50:20 +0000 http://www.hindawi.com/journals/dm/2016/3528064/ Cytochrome c-1 (CYC1) is an important subunit of mitochondrial complex III. However, its role in tumor progression is unclear. We found that CYC1 was upregulated in breast tumor tissues, especially in tissues with lymph node metastasis. And higher expression of CYC1 correlates with poor prognosis in breast cancer patients using online databases and tools. Then we confirmed that CYC1 contributed to metastasis and proliferation in two highly metastatic human breast cancer cell lines. Digging into the biological function of CYC1, we found the activity of mitochondrial complex III decreased due to silencing CYC1. Then the ratio of AMP to ATP increased and AMPK was activated. Analyzing units of other mitochondrial complexes, we did not find knockdown of CYC1 expression reduced expression of any other unit of OXPHOS. We concluded that CYC1 promoted tumor metastasis via suppressing activation of AMPK and contributed to tumor growth via facilitating production of ATP. Our results indicated that CYC1 plays crucial roles in breast cancer progression and might be a predictive factor assisting future patient diagnosis. Yingyan Han, Shujuan Sun, Meisong Zhao, Zeyu Zhang, Song Gong, Peipei Gao, Jia Liu, Jianfeng Zhou, Ding Ma, Qinglei Gao, and Peng Wu Copyright © 2016 Yingyan Han et al. All rights reserved. TP53 Mutations and Survival in Osteosarcoma Patients: A Meta-Analysis of Published Data Wed, 27 Apr 2016 11:26:12 +0000 http://www.hindawi.com/journals/dm/2016/4639575/ Several research groups have examined the association between TP53 mutations and prognosis in human osteosarcoma. However, the results were controversial. The purpose of this study was to evaluate the prognostic value of TP53 mutations in osteosarcoma patients. A meta-analysis was conducted with all eligible studies which quantitatively evaluated the relationship between TP53 mutations and clinical outcome of osteosarcoma patients. Eight studies with a total of 210 patients with osteosarcoma were included in this meta-analysis. The risk ratio (RR) with a 95% confidence interval (95% CI) was calculated to assess the effect of TP53 mutations on 2-year overall survival. The quantitative synthesis of 8 published studies showed that TP53 mutations were associated with 2-year overall survival in osteosarcoma patients. These data suggested that TP53 mutations had an unfavorable impact on 2-year overall survival when compared to the counterparts with wild type (WT) TP53 (RR: 1.79; 95% CI: 1.12 to 2.84; ; %). There was no between-study heterogeneity. TP53 mutations are an effective prognostic marker for survival of patients with osteosarcoma. However, further large-scale prospective trials should be performed to clarify the prognostic value of TP53 mutations on 3- or 5-year survival in osteosarcoma patients. Zhe Chen, Jiayi Guo, Kun Zhang, and Yanxing Guo Copyright © 2016 Zhe Chen et al. All rights reserved. Detection of Autoantibodies to Vascular Endothelial Growth Factor Receptor-3 in Bile Duct Ligated Rats and Correlations with a Panel of Traditional Markers of Liver Diseases Sun, 24 Apr 2016 15:38:34 +0000 http://www.hindawi.com/journals/dm/2016/6597970/ There is a need for new noninvasive biomarkers (NIBMs) able to assess cholestasis and fibrosis in chronic cholestatic liver diseases (CCLDs). Tumorigenesis can arise from CCLDs. Therefore, autoantibodies to tumor-associated antigens (TAA) may be early produced in response to abnormal self-antigen expression caused by cholestatic injury. Vascular endothelial growth factor receptor-3 (VEGFR-3) has TAA potential since it is involved in cholangiocytes and lymphatic vessels proliferations during CCLDs. This study aims to detect autoantibodies directed at VEGFR-3 during bile duct ligation- (BDL-) induced cholestatic injury in rat sera and investigate whether they could be associated with traditional markers of liver damage, cholestasis, and fibrosis. An ELISA was performed to detect anti-VEGFR-3 autoantibodies in sera of rats with different degree of liver injury and results were correlated with aminotransferases, total bilirubin, and the relative fibrotic area. Mean absorbances of anti-VEGFR-3 autoantibodies were significantly increased from week one to week five after BDL. The highest correlation was observed with total bilirubin ( = 0.8450, ). In conclusion, anti-VEGFR-3 autoantibodies are early produced during BDL-induced cholestatic injury, and they are closely related to cholestasis, suggesting the potential of anti-VEGFR-3 autoantibodies as NIBMs of cholestasis in CCLDs and justifying the need for further investigations in patients with CCLD. Florent Duval, Delia Elva Cruz-Vega, Ivonne González-Gamboa, María Teresa González-Garza, Fernando Ponz, Flora Sánchez, Gabriela Alarcón-Galván, and Jorge E. Moreno-Cuevas Copyright © 2016 Florent Duval et al. All rights reserved. IL-4 Gene Polymorphism May Contribute to an Increased Risk of Atopic Dermatitis in Children Sun, 24 Apr 2016 12:23:35 +0000 http://www.hindawi.com/journals/dm/2016/1021942/ This study aimed to elucidate the associations between interleukin-4 (IL-4) single nucleotide polymorphisms (SNPs), 590C/T and 589C/T, serum IL-4 levels, and atopic dermatitis (AD) in children. Methods. A total of 82 children with AD were randomly selected as the case group and divided into mild group (15 cases), moderate group (46 cases), and severe group (21 cases). Additionally, 100 healthy children were selected as the control group. Genotype frequencies of IL-4 SNPs were detected by PCR-RFLP. Serum IL-4 levels were measured by ELISA. Results. Significant differences were shown in genotype distributions and allele frequencies of 589C/T and allele frequencies of 590C/T (all ). Serum IL-4 levels in the mild, moderate, and severe groups were significantly higher than those in the control group; significant differences were found among these three groups with increased severity of AD. Serum IL-4 levels of heterozygote and mutant homozygote carriers in the mild, moderate, and severe groups were higher than wild homozygote carriers in those three groups and the control group (all ). Conclusion. 590T and 589T alleles of IL-4 gene may be associated with high levels of serum IL-4, which may increase the risk of AD in children. Hong Shang, Xiu-Li Cao, Yu-Jie Wan, Jin Meng, and Lu-Hong Guo Copyright © 2016 Hong Shang et al. All rights reserved. Prognostic and Clinicopathological Significance of Downregulated p16 Expression in Patients with Bladder Cancer: A Systematic Review and Meta-Analysis Wed, 20 Apr 2016 12:58:25 +0000 http://www.hindawi.com/journals/dm/2016/5259602/ p16, encoded by the CDKN2A gene, is a tumor suppressor that has been widely studied in cancer research. However, the relationship of p16 with prognostic and clinicopathological parameters in patients with bladder cancer remains unclear. Data inclusion criteria were articles reporting on the relationship between p16 expression and the prognosis or clinicopathology in patients with bladder cancer. Meta-analyses were performed with Stata software. Hazard ratios (HRs) or odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated to evaluate the relative risks. The source of heterogeneity was analyzed by subgroup analysis. A total of 37 studies with 2246 cases were included and analyzed. The results identified an important link between downregulated p16 expression and poor prognosis in patients with bladder cancer in terms of recurrence-free survival (RFS), overall survival (OS), progression-free survival (PFS), and some clinicopathological parameters including clinical staging, pathological degree, and lymph node metastasis. Subgroup analysis also showed that low p16 expression could function as a warning sign for RFS and PFS in patients with early-stage (Ta–T1) bladder cancer. In conclusion, p16 might play an essential role in the deterioration of bladder cancer and could serve as a biomarker for the prediction for patients’ progression and prognosis. Xiaoning Gan, Xiaomiao Lin, Rongquan He, Xinggu Lin, Hanlin Wang, Liyan Yan, Hong Zhou, Hui Qin, and Gang Chen Copyright © 2016 Xiaoning Gan et al. All rights reserved. Association of Common Variants in MMPs with Periodontitis Risk Tue, 19 Apr 2016 07:14:22 +0000 http://www.hindawi.com/journals/dm/2016/1545974/ Background. Matrix metalloproteinases (MMPs) are considered to play an important role during tissue remodeling and extracellular matrix degradation. And functional polymorphisms in MMPs genes have been reported to be associated with the increased risk of periodontitis. Recently, many studies have investigated the association between MMPs polymorphisms and periodontitis risk. However, the results remain inconclusive. In order to quantify the influence of MMPs polymorphisms on the susceptibility to periodontitis, we performed a meta-analysis and systematic review. Results. Overall, this comprehensive meta-analysis included a total of 17 related studies, including 2399 cases and 2002 healthy control subjects. Our results revealed that although studies of the association between MMP-8 −799 C/T variant and the susceptibility to periodontitis have not yielded consistent results, MMP-1 (−1607 1G/2G, −519 A/G, and −422 A/T), MMP-2 (−1575 G/A, −1306 C/T, −790 T/G, and −735 C/T), MMP-3 (−1171 5A/6A), MMP-8 (−381 A/G and +17 C/G), MMP-9 (−1562 C/T and +279 R/Q), and MMP-12 (−357 Asn/Ser), as well as MMP-13 (−77 A/G, 11A/12A) SNPs are not related to periodontitis risk. Conclusions. No association of these common MMPs variants with the susceptibility to periodontitis was found; however, further larger-scale and multiethnic genetic studies on this topic are expected to be conducted to validate our results. Wenyang Li, Ying Zhu, Pradeep Singh, Deepal Haresh Ajmera, Jinlin Song, and Ping Ji Copyright © 2016 Wenyang Li et al. All rights reserved. The Diagnostic Value of the Pleural Fluid C-Reactive Protein in Parapneumonic Effusions Mon, 18 Apr 2016 13:04:07 +0000 http://www.hindawi.com/journals/dm/2016/7539780/ Purpose. The aim of this study was to evaluate the sensitivity of pleural C-reactive protein (CRP) biomarker levels in identifying parapneumonic effusions. Methods. A single-center, retrospective review of 244 patients diagnosed with pleural effusions was initiated among patients at the Rabin Medical Center, Petah Tikva, Israel, between January 2011 and December 2013. The patients were categorized into 4 groups according to their type of pleural effusion as follows: heart failure, malignant, post-lung transplantation, and parapneumonic effusion. Results. The pleural CRP levels significantly differentiated the four groups () with the following means: parapneumonic effusion,  mg/dL; lung transplant,  mg/dL; malignancy,  mg/dL; and heart failure,  mg/dL. The pleural fluid CRP cut-off value for differentiating among parapneumonic effusions and the other 3 groups was 1.38 mg/dL. The sensitivity, specificity, positive predictive value, and negative predictive value were 84.2%, 71.5%, 37%, and 95%, respectively. A backward logistic regression model selected CRP as the single predictor of parapneumonic effusion (OR = 1.59, 95% CI = 1.37–1.89). Conclusions. Pleural fluid CRP levels can be used to distinguish between parapneumonic effusions and other types of exudative effusions. CRP levels < 0.64 mg/dL are likely to indicate a pleural effusion from congestive heart failure, whereas levels ≥ 1.38 mg/dL are suggestive of an infectious etiology. Shimon Izhakian, Walter G. Wasser, Benjamin D. Fox, Baruch Vainshelboim, and Mordechai R. Kramer Copyright © 2016 Shimon Izhakian et al. All rights reserved. Postnatal Changes in Humerus Cortical Bone Thickness Reflect the Development of Metabolic Bone Disease in Preterm Infants Mon, 18 Apr 2016 13:03:57 +0000 http://www.hindawi.com/journals/dm/2016/2176594/ Objective. To use cortical bone thickness (CBT) of the humerus to identify risk factors for the development of metabolic bone disease in preterm infants. Methods. Twenty-seven infants born at <32 weeks of gestational age, with a birth weight of <1,500 g, were enrolled. Humeral CBT was measured from chest radiographs at birth and at 27-28, 31-32, and 36–44 weeks of postmenstrual age (PMA). The risk factors for the development of osteomalacia were statistically analyzed. Results. The humeral CBT at 36–44 weeks of PMA was positively correlated with gestational age and birth weight and negatively correlated with the duration of mechanical ventilation. CBT increased with PMA, except in six very early preterm infants in whom it decreased. Based on logistic regression analysis, gestational age and duration of mechanical ventilation were identified as risk factors for cortical bone thinning. Conclusions. Humeral CBT may serve as a radiologic marker of metabolic bone disease at 36–44 weeks of PMA in preterm infants. Cortical bones of extremely preterm infants are fragile, even when age is corrected for term, and require extreme care to lower the risk of fractures. Shuko Tokuriki, Aiko Igarashi, Takashi Okuno, Genrei Ohta, Takuya Kosaka, and Yusei Ohshima Copyright © 2016 Shuko Tokuriki et al. All rights reserved. MUC1 Immunohistochemical Expression as a Prognostic Factor in Gastric Cancer: Meta-Analysis Sun, 17 Apr 2016 13:39:07 +0000 http://www.hindawi.com/journals/dm/2016/9421571/ MUC1, a member of the mucin family, is expressed in tumors of various human organs and may function as an antiadhesion molecule that inhibits cell-to-cell adhesion, inducing tumor metastasis, and served as a potential biomarker of tumor progression in early gastric cancer. However, its prognostic significance in gastric cancer is still in dispute. We performed a meta-analysis to evaluate the relationship between MUC1 expression and prognosis of gastric cancer. A total of ten eligible studies with 834 cases and 548 controls were included. MUC1 positive cases were highly positive in intestinal-type carcinomas (OR = 1.76, 95% CI: 1.27–2.44, fixed-effect), higher rate of vascular invasion (OR = 1.64, 95% CI: 1.13–2.39, fixed-effect), and lymph node metastasis (OR = 2.10, 95% CI: 1.20–3.67, random-effect), as well as lower 5-year survival rate (HR = 0.27, 95% CI: 0.11–0.66, random-effect). However, the presence of MUC1 was not associated with gender, tumor size, histologic differentiation, and clinical stage. In summary, MUC1 is a prognostic factor in gastric cancer, which acts as a marker of poor outcome in patients with gastric cancer. Further clinical studies are needed to confirm the role of MUC1 in clinical practice. Xiao-Tong Wang, Fan-Biao Kong, Wei Mai, Lei Li, and Li-Ming Pang Copyright © 2016 Xiao-Tong Wang et al. All rights reserved. Long Noncoding RNAs as Novel Biomarkers Have a Promising Future in Cancer Diagnostics Sun, 10 Apr 2016 15:16:00 +0000 http://www.hindawi.com/journals/dm/2016/9085195/ Cancers have a high mortality rate due to lack of suitable specific early diagnosis tumor biomarkers. Emerging evidence is accumulating that lncRNAs (long noncoding RNAs) are involved in tumorigenesis, tumor cells proliferation, invasion, migration, apoptosis, and angiogenesis. Furthermore, extracellular lncRNAs can circulate in body fluids; they can be detected and strongly resist RNases. Many researchers have found that lncRNAs could be good candidates for tumor biomarkers and possessed high specificity, high sensitivity, and noninvasive characteristics. In this review, we summarize the detection methods and possible sources of circulating lncRNAs and outline the biological functions and expression level of the most significant lncRNAs in tissues, cell lines, and body fluids (whole blood, plasma, urine, gastric juice, and saliva) of different kinds of tumors. We evaluate the diagnostic performance of lncRNAs as tumor biomarkers. However, the biological functions and the mechanisms of circulating lncRNAs secretion have not been fully understood. The uniform normalization protocol of sample collection, lncRNAs extraction, endogenous control selection, quality assessment, and quantitative data analysis has not been established. Therefore, we put forward some recommendations that might be investigated in the future if we want to adopt lncRNAs in clinical practice. Ting Shi, Ge Gao, and Yingli Cao Copyright © 2016 Ting Shi et al. All rights reserved. Detection of OSR2, VAV3, and PPFIA3 Methylation in the Serum of Patients with Gastric Cancer Thu, 07 Apr 2016 11:10:36 +0000 http://www.hindawi.com/journals/dm/2016/5780538/ Aim. This study was to evaluate the diagnostic value of OSR2, VAV3, and PPFIA3 hypermethylation in gastric cancer (GC) patients. Patients and Methods. By using methylation-specific polymerase chain reaction (MSP), we detected the methylation status in tissue and serum samples from 48 gastric cancer (GC) patients and 25 normal individuals. Results. We found that OSR2, VAV3, and PPFIA3 were methylated in 70.8% (34/48), 54.2% (26/48), and 60.4% (29/48) of GC tissue, respectively. On the contrary, those genes were barely methylated in their paired paracancerous histological normal tissues (PCHNTs) (all values < 0.01). We next analyzed the methylated OSR2, VAV3, and PPFIA3 in serum DNA. Compared with 25 normal individuals, those three genes were significantly hypermethylated in GC patients serum samples (all values < 0.01). Regarding their diagnostic value in serum samples, the combined sensitivity of at least one positive among the three markers in serum was 83.3%, with a specificity of 88%. Conclusion. Our test suggested that methylation of OSR2, VAV3, and PPFIA3 genes in serum sample may offer a good alternative in a simple, promising, and noninvasive detection of GC. Wen-han Li, Zhang-jian Zhou, Tian-he Huang, Kun Guo, Wei Chen, Ying Wang, Hao Zhang, Yong-chun Song, and Dong-min Chang Copyright © 2016 Wen-han Li et al. All rights reserved. Salivary Markers for Periodontal and General Diseases Wed, 06 Apr 2016 08:05:16 +0000 http://www.hindawi.com/journals/dm/2016/9179632/ The determination of biomarkers in saliva is becoming an important part of laboratory diagnostics and the prediction of not only periodontal, but also other tissue and organ diseases. Biomarkers in saliva (e.g., enzymes, protein markers, or oxidative stress markers) can be used for activity determination and for periodontal disease prognosis. Saliva also contains many markers which can predict the risk of certain diseases (e.g., diabetes mellitus, cardiovascular, oncology, endocrinology, and psychiatric diseases). The study of salivary components proteomics clearly shows the relationship of periodontal diseases and diseases of distant systems, organs, or tissues. Stepan Podzimek, Lucie Vondrackova, Jana Duskova, Tatjana Janatova, and Zdenek Broukal Copyright © 2016 Stepan Podzimek et al. All rights reserved. Two tagSNPs rs352493 and rs3760908 within SIRT6 Gene Are Associated with the Severity of Coronary Artery Disease in a Chinese Han Population Mon, 28 Mar 2016 10:29:42 +0000 http://www.hindawi.com/journals/dm/2016/1628041/ SIRT6 has been demonstrated to exert protective effects on endothelial cells and is closely associated with lipid metabolism, glucose metabolism, and obesity, indicating an important role in the pathogenesis and progression of coronary artery disease (CAD). Nonetheless, the biological significance of SIRT6 variants on CAD is far to be elucidated. Here we aimed to investigate the influence of SIRT6 polymorphisms on individual susceptibility and severity of CAD. Multivariate logistic regression analysis exhibited no significant association between these five polymorphisms and CAD risk in the genotype and allele frequencies. However, we found that the rs352493 polymorphism in SIRT6 exhibited a significant effect on the severity of CAD; C allele (χ2 = 7.793, adjusted ) and the combined CC/CT genotypes (χ2 = 5.609, adjusted ) presented the greater CAD severity. In addition, A allele (χ2 = 5.208, adjusted ) and AA (χ2 = 4.842, adjusted ) of rs3760908 were also associated with greater CAD severity in Chinese subjects. Our data provided the first evidence that SIRT6 tagSNPs rs352493 and rs3760908 play significant roles in the severity of CAD in Chinese Han subjects, which might be useful predictors of the severity of CAD. Sai-sai Tang, Shun Xu, Jie Cheng, Meng-yun Cai, Lin Chen, Li-li Liang, Xi-li Yang, Can Chen, Xin-guang Liu, and Xing-dong Xiong Copyright © 2016 Sai-sai Tang et al. All rights reserved.