bluuebunny/crossref_metadata_2025_split huggingface dataset:
Absolute Quantitation of DNA Methylation of 28 Candidate Genes in Prostate Cancer Using Pyrosequencing
Authors: Vasiljeviš Nataڑa , Wu Keqiang , Brentnall Adam R. , Kim Dae Cheol , Thorat Mangesh A. , Kudahetti Sakunthala C. , Mao Xueying , Xue Liyan , Yu Yongwei , Shaw Greg L. , Beltran Luis , Lu Yong-Jie , Berney Daniel M. , Cuzick Jack , Lorincz Attila T. 
Published: June 2013

Aberrant DNA methylation plays a pivotal role in carcinogenesis and its mapping is likely to provide biomarkers for improved diagnostic and risk assessment in prostate cancer (PCa). We quantified and compared absolute methylation levels among 28 candidate genes in 48 PCa and 29 benign prostate hyperplasia (BPH) samples using the pyrosequencing (PSQ) method to identify genes with diagnostic and prognostic potential.RARB, HIN1, BCL2, GSTP1, CCND2, EGFR5, APC, RASSF1A, MDR1, NKX2-5, CDH13, DPYS, PTGS2, EDNRB, MAL, PDLIM4, HLAa, ESR1andTIG1were highly methylated in PCa compared to BPH (p < 0.001), whileSERPINB5, CDH1, TWIST1, DAPK1, THRB, MCAM, SLIT2, CDKN2aandSFNwere not. RARB methylation above 21% completely distinguished PCa from BPH. Separation based on methylation level ofSFN, SLIT2andSERPINB5distinguished low and high Gleason score cancers, e.g.SFNandSERPINB5together correctly classified 81% and 77% of high and low Gleason score cancers respectively. Several genes includingCDH1previously reported as methylation markers in PCa were not confirmed in our study. Increasing age was positively associated with gene methylation (p < 0.0001).Accurate quantitative measurement of gene methylation in PCa appears promising and further validation of genes likeRARB, HIN1, BCL2, APC and GSTP1is warranted for diagnostic potential andSFN, SLIT2andSERPINB5for prognostic potential.
No Association ofPTGDR−441C/TPolymorphism with Asthma in a North Indian Population
Authors: Birbian Niti , Singh Jagtar , Jindal Surinder Kumar , Joshi Amit , Batra Navneet 
Published: June 2013

Background:Asthma is the most prevalent disease in India according to the national survey conducted by NFHS 2 in 1998–399. Prostaglandin D2 (PGD2) is a bronchoconstriction inducing metabolite of arachidonic acid in the mast cells, which is produced on exposure to allergens and acts as a ligand for the Prostaglandin D2 Receptor (PTGDR). Polymorphisms in thePTGDRgene have been suggested to be involved in the mechanism of asthma.Objective:This is the first study conducted in India, investigating the role ofPTGDR−441C/Tpromoter polymorphism in asthma pathogenesis.Methods:A case-control study was performed with a total of 992 subjects, including 410 adult asthmatics and 582 healthy controls from regions of North India. ThePTGDR−441C/Tpolymorphism was genotyped by Tetra-Primer Amplification Refractory Mutation System Polymerase Chain Reaction (Tetra-Primer ARMS PCR).Results:Statistical analysis of the results between asthma cases and controls for thePTGDR−441C/Tpolymorphism showed Chi2(χ2) = 0.29, OR = 0.95, 95% CI (0.70–1.15) andp= 0.599. Neither the genotypic nor the allelic frequencies observed for thePTGDR−441C/Tpolymorphism, were significantly associated with asthma or asthma phenotypes.Conclusions:ThePTGDR−441C/Tpolymorphism is not associated with asthma or its phenotypes in the studied North Indian population.
Epigenetic Aspects of Posttraumatic Stress Disorder
Authors: Schmidt Ulrike , Holsboer Florian , Rein Theo 
Published: June 2013

Development of psychiatric diseases such as posttraumatic stress disorder (PTSD) invokes, as with most complex diseases, both genetic and environmental factors. The era of genome-wide high throughput technologies has sparked the initiation of genotype screenings in large cohorts of diseased and control individuals, but had limited success in identification of disease causing genetic variants. It has become evident that these efforts at the genomic level need to be complemented with endeavours in elucidating the proteome, transcriptome and epigenetic profiles. Epigenetics is attractive in particular because there is accumulating evidence that the lasting impact of adverse life events is reflected in certain covalent modifications of the chromatin.In this review, we outline the characteristics of PTSD as a stress-related disease and survey recent developments revealing epigenetic aspects of stress-related disorders in general. There is also increasing direct evidence for gene programming and epigenetic components in PTSD. Finally, we discuss treatment options in the light of recent discoveries of epigenetic mechanisms of psychotropic drugs.
Circulating Endothelial Cells in Patients with Heart Failure and Left Ventricular Dysfunction
Authors: Martínez-Sales Vicenta , Sánchez-Lázaro Ignacio , Vila Virtudes , Almenar Luis , Contreras Teresa , Reganon Edelmiro 
Published: June 2013

Introduction and Aims:Acute and chronic heart failure may manifest different degrees of endothelial damage and angiogenesis. Circulating endothelial cells (CEC) have been identified as marker of vascular damage. The aim of our study was to evaluate the evolution of the CEC at different stages of patients with heart failure. We also investigated a potential correlation between CEC and markers of vascular damage and angiogenesis.Methods:We studied 32 heart failure patients at hospital admission (acute phase) and at revision after 3 months (stable phase) and 32 controls. Circulating markers of endothelial damage (CEC; von Willebrand factor, vWF and soluble E-selectin, sEsel) and angiogenesis (vascular endothelial growth factor, VEGF and thrombospondin-1) were quantified.Results:Levels of CEC, vWF, sEsel and VEGF are significantly higher in heart failure patients than in controls. Levels of CEC (36.9 ± 15.3 vs. 21.5 ± 10.0 cells/ml;p< 0.001), vWF (325 ± 101 vs. 231 ± 82%;p< 0.001) and VEGF (26.3 ± 15.2 vs. 21.9 ± 11.9 ng/ml;p< 0.001) are significantly higher in the acute phase than in the stable phase of heart failure. CEC levels correlate with vWF and VEGF. Results show than 100% of patients in acute phase and 37.5% in stable phase have levels of CEC higher than the 99th percentile of the distribution of controls (16 cells/ml). Therefore, increases in CEC represent a relative risk of 9.5 for heart failure patients suffering from acute phase.Conclusions:CEC, in addition to being elevated in heart failure, correlate with vWF levels, providing further support for CEC as markers of endothelial damage. Levels of CEC are associated with the acute phase of heart failure and could be used as a marker of the worsening in heart failure.
Fucose and Sialic Acid Expressions in Human Seminal Fibronectin andα1-Acid Glycoprotein Associated with Leukocytospermia of Infertile Men
Authors: Kratz Ewa M. , Faundez Ricardo , Kątnik-Prastowska Iwona 
Published: June 2013

Introduction: The aim of this study was to compare fucose and sialic acid residue expression on fibronectin andα1-acid glycoprotein in the seminal plasma of men suspected of infertility and suffering from leukocytospermia.Subjects and methods: Seminal ejaculates were collected from 27 leukocytospermic and 18 healthy, normozoospermic men. The relative degree of fucosylation and sialylation of fibronectin andα1-acid glycoprotein was estimated by ELISA using fucose and sialic acid specific lectins fromAleuria aurantia, Lotus tetragonolobus, andUlex europaeusas well asMaackia amurensisandSambucus nigra, respectively.Results: Leukocytospermic seminal fibronectin, in comparison with fibronectin of normal fertile group, showed lower relative reactivity with AAL, LTA and UEA, and higher reactivity with MAA and SNA, while the AGP of the leukocytospermic group was less reactive with AAL, and the relative reactivity with LTA and MAA was significantly higher. Fibronectin andα1-acid glycoprotein reactivity with UEA and MAA showed high positive correlations.Discussion: Leukocytospermia was associated with the alterations of terminal monosaccharide expression in human seminal fibronectin andα1-acid glycoprotein. The increase of sialyl-Lewisxantigen inα1-acid glycoprotein can be used as a marker of genital tract inflammation manifested by leukocytospermia.
Asymmetric Dimethylarginine (ADMA) Levels Display a Morning Peak in Patients with Acute Myocardial Infarction
Authors: Bergheanu Sandrin C. , van der Laarse Arnoud , van der Bom Johanna G. , van der Hoeven Bas L. , le Cessie Saskia , de Jong Margreet G. , Liem Su-San , Schalij Martin J. , Jukema J. Wouter 
Published: June 2013

High Asymmetric Dimethylarginine (ADMA) levels are associated with increased platelet activity, elevated blood pressure, vasoconstriction and impaired vascular relaxation. We hypothesized that the myocardial infarction morning peak of occurrence is closely related to a morning peak of ADMA levels. We performed a cross-sectional study among patients with documented myocardial infarction who had been enrolled in the prospective MISSION! Intervention Study. In total, serum ADMA levels were measured in their acute setting of myocardial infarction in 120 patients. The frequency of myocardial infarction onset of symptoms and emergency coronary catheterization and the ADMA levels displayed a similar daily pattern with a morning peak between 06:00–11:59 h. The absolute ADMA levels peak was between 06:00–07:59 h with a median (interquartile range) peak value of 1.01 (0.84–1.21) μmol/L for then= 9 patients vs. 0.75 (0.61–0.89) μmol/L for the remaining 111 patients admitted throughout the rest of the 24-hour interval (p= 0.003 for between groups comparison). The amplitude (95% confidence interval) of the circadian variation of ADMA levels was 0.08 μmol/L (0.004–0.16) withp= 0.042 for statistic model significance.In conclusion, ADMA levels display a 24-hour variation with a significant morning peak in patients with acute myocardial infarction. These findings may relate ADMA levels to the acute onset of thrombotic cardiovascular events.
Assessment of Sialic Acid Diversity in Cancer- and Non-Cancer Related CA125 Antigen Using Sialic Acid-Binding Ig-Like Lectins (Siglecs)
Authors: Mitic N. , Milutinovic B. , Jankovic M. 
Published: June 2013

This study was aimed at obtaining insight into the diversity of sialic acids in cancer- and non-cancer-related CA125 antigen, tumour marker of serous ovarian cancer. Starting from available data suggesting the possible relevance of sialic acids for discriminating CA125 antigens of different origin, we have employed a new experimental approach based on the use of human sialic acid-binding Ig-like lectins, Siglecs, as tools for the investigation of sialylation.Siglec−2, belonging to the group of evolutionarily conserved Siglecs, and Siglec−3, −6, −7, −9 and −10, which are CD33-like Siglecs, were probed in solid-phase binding assays with cancer-related CA125 antigens from pleural fluid of patients with ovarian carcinoma (pfCA125), the OVCAR-3 ovarian carcinoma cell line (clCA125) and a non-cancer-related CA125 antigen, i.e. pregnancy-associated pCA125 antigen.All Siglecs used showed detectable binding to pCA125 antigen. Siglec−3, Siglec−7 and Siglec−2 exhibited moderately stronger binding to pCA125 antigen than the others. In contrast to this, Siglec−2 and Siglec−3 preferentially recognized pfCA125 with greater total binding than for pCA125, whereas Siglec−9 and Siglec−10 were highly selective for clCA125.Siglecs promise to be powerful tools for discriminating CA125 of different origin and could propagate further research on other molecular markers of biomedical and diagnostic importance.
Human Neutrophil Peptides 1–3 as Gastric Cancer Tissue Markers Measured by MALDI-Imaging Mass Spectrometry: Implications for Infiltrated Neutrophils as a Tumor Target
Authors: Cheng Chun-Chia , Chang Jungshan , Chen Ling-Yun , Ho Ai-Sheng , Huang Ker-Jer , Lee Shui-Cheng , Mai Fu-Der , Chang Chun-Chao 
Published: June 2013

Objective: Human neutrophil peptides (HNPs) -1, -2 and -3 are significantly upregulated and were reported as biomarkers in gastric cancer (GC). However, the tissue location and function of HNPs 1-3 are still unclear in GC, and the spatial distribution of the triad needs to be disclosed. The aims of this study were to investigate the distribution and relationships among HNPs-1, -2 and -3, and assess whether infiltrated neutrophils accumulate in gastric tumor.Methods: In this study, paired samples (n=33) of the GC tissues and adjacent normal tissues from the same patients were obtained from surgery. Expression of HNPs 1-3 were detected by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The distributions of the HNPs 1-3 in GC tissues were investigated. After verification of HNPs-1 by immunohistochemistry, infiltrated neutrophils were also detected. Then, an in vitro assay was used to observe the binding capacity and measure the cytotoxic effect of HNPs-1 against AGS cells.Results: Comparing to neighboring normal tissue, expressional level of HNPs 1-3 were significantly higher and their distributions overlapped in cancerous tissues of GC patients with high abundance in the lamina propria, whereas HNPs-1 was identified as the highest major peak. Moreover, HNPs-1, -2 and -3 correlated with each other. Besides, we also observed that increased infiltrated neutrophils accumulating in GC tissues, indicating that a strong positive correlation between HNPs 1-3 and infiltrated neutrophils. In addition, the further investigated demonstrated that the major peptide, HNPs-1, was statistically increased with the advance of tumor development from the early to advanced stage of GC (p < 0.05). Moreover, we also noticed that HNPs-1 with a great binding capacity to GC AGS cells in vitro can inhibit tumor cell growth.Conclusions: Our results suggest that neutrophil secreted peptides, HNPs 1-3, increased in the GC tissues and could be used as potential biomarkers detected using MALDI-TOF MS, implying that elevated neutrophils may be used as a tumor target for tumor treatment. The binding capacity of HNPs-1 with GC cells implies that tracking molecules conjugated with HNPs-1 could be applied as a specific probe for GC diagnoses.
Polymorphisms of Glutathione S-Transferase Mu 1 (GSTM1), Theta 1 (GSTT1), and Pi 1 (GSTP1) Genes and Epithelial Ovarian Cancer Risk
Authors: Oliveira Cristiane , Lourenço Gustavo Jacob , Sagarra Regina Aparecida Martinho , Derchain Sophie Françoise Mauricette , Segalla José Getulio , Lima Carmen Silvia Passos 
Published: June 2013

Background: Exposure of ovarian cells to estrogen, which is detoxified by glutathione S-transferases (GSTs), has been associated with epithelial ovarian cancer (EOC) development.Objectives: We tested in this study whether theGSTM1,GSTT1andGSTP1Ile105Val polymorphisms alter the risk of EOC.Materials and methods: Genomic DNA from 132 EOC patients and 132 controls was analyzed by polymerase chain reaction and restriction fragment length polymorphism methods. The differences between groups were analyzed byχ2or Fisher’s exact test.Results: The frequencies ofGSTP1Ile/Ile (57.6% versus 45.5%,P= 0.03),GSTM1null plusGSTP1Ile/Ile (43.5% versus 25.8%;P= 0.03) andGSTM1null plusGSTT1null plusGSTP1Ile/Ile (30.3% versus 7.7%;P= 0.007) genotypes were higher in patients than in controls. Individuals with the respective genotypes had a 1.80 (95% CI: 1.06–3.06), 2.38 (95% CI: 1.08–5.24) and 11.28 (95%CI: 1.95–65.30)-fold increased risks of EOC than those with the remaining genotypes.Conclusions: Our data present preliminary evidence thatGSTM1,GSTT1andGSTP1polymorphisms, particularly in combination, constitute important inherited EOC determinants in individuals from Southeastern Brazil.
Relation between MicroRNA Expression in Peritoneal Dialysis Effluent and Peritoneal Transport Characteristics
Authors: Chen Jin , Kam-Tao Philip , Kwan Bonnie Ching-Ha , Chow Kai-Ming , Lai Ka-Bik , Luk Cathy Choi-Wan , Szeto Cheuk-Chun 
Published: June 2013

Background:The role of microRNAs (miRNAs) in peritoneal transport is uncertain.Methods:We studied 82 new peritoneal dialysis (PD) patients, 22 prevalent patients without ultrafiltration problem, and 6 patients with documented ultrafiltration problem. Peritoneal transport was determined by standard peritoneal equilibration test (PET). RNA was extracted from the PD effluent after PET, and intra-peritoneal expression of miRNA targets were quantified.Results:There were significant difference in the PDE expressions of miR-15a and miR-21. There were modest inverse correlations between ultrafiltration volume and PDE expression of miR-17 (r= −0.198,p= 0.041) and miR-377 (r= −0.201,p= 0.041). There was an inverse correlations between dialysate-to-plasma creatinine concentration at 4 hours and PDE expression of miR-192 (r= −0.199,p= 0.040); while mass transfer area coefficient of creatinine correlated with PDE expression of miR-192 (r= −0.191,p= 0.049) and miR-377 (r= 0.201,p= 0.041). Amongst 7 randomly selected patients who had repeat PET after one year, there was a significant correlation between baseline PDE expression of miR-377 and change in ultrafiltration volume (r= −0.852,p= 0.015).Conclusion:The miRNA expression in PDE, including miR-15a, miR-17, miR-21, miR-30, miR-192, and miR-377, correlated with peritoneal transport characteristics. Our result suggests that miRNA may play a role in the regulation of peritoneal membrane function.
Micro-RNA Expression in the Urinary Sediment of Patients with Chronic Kidney Diseases
Authors: Szeto Cheuk-Chun , Ching-Ha Kwan Bonnie , Ka-Bik Lai , Mac-Moune Lai Fernand , Cheung-Lung Choi Paul , Gang Wang , Kai-Ming Chow , Kam-Tao Li Philip 
Published: June 2013

Background: Evidence indicates that microRNAs (miRNA) play a role in the pathogenesis of chronic kidney diseases (CKD). We explored the possibility of using urinary miRNA as non-invasive biomarkers for CKD.Methods: We quantified miRNA expression in urinary sediment of 56 CKD patients who underwent kidney biopsy. Patients were followed for 16.2 ± 15.5 months.Results: Patients with diabetic glomerulosclerosis had lower urinary miR-15 expression, while those with IgA nephropathy had higher urinary miR-17 expression, than other diagnosis groups. Baseline proteinuria had significant inverse correlation with urinary expression of miR-15, miR-192, and miR-216a; baseline renal function correlated with urinary expression of miR-15, miR-17, miR-192, and miR-217. The rate of renal function decline correlated with urinary expression of miR-21 (r= 0.301,p= 0.026) and miR-216a (r= 0.515, p < 0.0001). Patients with a high urinary expression of miR-21 and miR-216a had better dialysis-free survival than those with low expression (log rank test,p= 0.005 andp= 0.003, respectively).Conclusions: Urinary miR-21 and miR-216a expression correlated with the rate of renal function decline and risk of progression to dialysis-dependent renal failure. Our results suggest that urinary miRNA profiling has the potential of further development as biomarkers of CKD.
PINCH Expression and Its Clinicopathological Significance in Gastric Adenocarcinoma
Authors: Zhu Zhen-Long , Yan Bao-Yong , Zhang Yu , Yang Yan-Hong , Wang Zheng-Min , Zhang Hong-Zhen , Wang Ming-Wei , Zhang Xiang-Hong , Sun Xiao-Feng 
Published: June 2013

Objective: Particularly interesting new cysteine-histidine rich protein (PINCH) is an important component of the local adhesion complexes and upregulated in several types of malignancies, and involved in the incidence and development of tumours. PINCH expression is also independently correlated with poorer survival in patients with colorectal cancer. However, there is no study of PINCH in gastric cancer, therefore, the aim of this project was to investigate PINCH expression and its clinicopathological significance in gastric adenocarcinoma.Patients and methods: PINCH expression was immunohistochemically examined in normal gastric mucous (n= 30) and gastric adenocarcinoma (n= 73), from gastric cancer patients.Results: PINCH expression in the associated-stroma of gastric cancers was heterogeneous, and its positive rate (75%) was higher than that of normal gastric mucosa (43%,X2= 9.711,p= 0.002). The stronger staining was observed at the invasive edge of tumour when compared to the inner area of tumour. The rate of positive PINCH (88%) in the cases with lymph node metastasis was higher than that (52%) in the cases without metastasis (X2= 11.151,p= 0.001). PINCH expression was not correlated with patients’ gender, age, tumour size, differentiation and invasion depth (p> 0.05).Comclusion: PINCH protein might play an important role in the tumourigenesis and metastasis of gastric adenocarcinoma.
Predictive Role of Cytokine Gene Polymorphisms for the Development of Femoral Head Osteonecrosis
Authors: Samara S. , Kollia P. , Dailiana Z. , Chassanidis C. , Papatheodorou L. , Koromila T. , Malizos K.N. 
Published: June 2013

Introduction: Osteonecrosis (ON) is a multifactorial disease that leads to hip destruction. Lately, much focus has been at femoral head preservation with nonsurgical methods. In this study we examined the polymorphisms of IL-1α, IL-1R, IL-1RA, IL-4Rα, IL-1β, IL-12,γIFN, TGF-β, TNF-a, IL-2, IL-4, IL-6 and IL-10 genes for evaluation of their contribution in ON.Material and methods: DNA was extracted from 112 ON patients and 438 healthy donors. Analysis of the polymorphisms was completed using the PCR-SSP method. Statistical analysis was performed using theχ2test to compare the genotype and allelic frequency distribution.Results: The CT and GA genotypes of the IL-1α(-889) and TNF-a (-238) genes were found higher in the patients (51.8% and 10.8%, respectively) compared to the healthy donors (39.7% and 2.1%, respectively). In TGF-βcodon 25, the G to C polymorphism in the homozygous state was found in 1.8% of the patients and the C allele frequency was 8.9%, whereas the G allele frequency was 91.1%. Also, at the IL-10 (-1082) gene the GG genotype was 16.2% in the controls whereas in the patients was 7.2%.Conclusions: Based on the above, we showed that certain genotypes of the IL-1α, TGF-β, IL-10 and TNF-a genes could be related in the pathogenesis of a complicated disease, such as osteonecrosis. The presence of one of the above mentioned polymorphisms or the simultaneous carriage of more than one may further increase the risk for osteonecrosis, especially in those at high risk, such as patients receiving corticosteroids.
TMEM25Is a Candidate Biomarker Methylated and Down-Regulated in Colorectal Cancer
Authors: Hrašovec Sonja , Hauptman Nina , Glavač Damjan , Jelenc Franc , Ravnik-Glavač Metka 
Published: June 2013

The identification of novel genes involved in colorectal cancerogenesis is of high clinical relevance for early diagnosis, applying new therapeutic strategies and monitoring disease recurrence, in order to reduce disease incidence and mortality. Gene silencing through CpG island hypermethylation is a major epigenetic mechanism involved in cancer development. In our study, we aimed to identify and validate novel genes with a tumour specific DNA methylation profile in colorectal cancer. We performed a whole-genome methylation scan and identified several possible candidate genes that are hypermethylated in tumour in comparison to healthy colon mucosa. Using methylation-specific high-resolution melting analysis in a set consisting of 133 colorectal cancer samples, we were able to confirm an altered CpG site inTMEM25in 69.2% (92/133) tumours analysed. Furthermore, the expression ofTMEM25was found to be significantly lower in tumour tissue. An inverse correlation between hypermethylation ofTMEM25andTMEM25down-regulated expression was observed.Our results suggest that epigenetic down-regulation ofTMEM25is cancer-related; we thus suggest thatTMEM25hypermethylation might play a significant role in altering expression of this gene in colorectal cancer.