Disease Markers - Volume 28, issue 2

Authors: Zhu, Zhen-Long | Zhao, Zeng-Ren | Zhang, Yu | Yang, Yan-Hong | Wang, Zheng-Min | Cui, Dong-Sheng | Wang, Ming-Wei | Kleeff, Jörg | Kayed, Hany | Yan, Bao-Yong | Sun, Xiao-Feng

Article Type: Research Article

Abstract: Objective: FXYD-3, also known as Mat-8, is a member of the FXYD protein family. It was reported that this protein can associate with and modify the transport properties of Na, K-ATPase, and may play an important role in a variety of physiological and pathological states. This protein is up-regulated in certain types of cancers (such as breast, prostate and pancreatic cancer), but down-regulated in other types of cancers (such as colon and kidney cancer). No study …has been performed in gastric cancer; therefore, the aim of this project was to investigate FXYD-3 expression and its clinicopathological significance in gastric adenocarcinoma. Patients and methods: FXYD-3 protein was examined by immunohistochemistry in normal gastric mucous (n= 29) and gastric adenocarcinoma (n=51), obtained from surgical resection of gastric cancer patients. Results: FXYD-3 protein was present in the cytoplasm of normal gastric epithelial cells or gastric cancer cells. The rate of FXYD-3 strong expression was significantly higher in cancer (51% of 51) than in normal mucosa (10% of 29, X^{2} =13.210, p < 0.0001). FXYD-3 expressed strongly in ulcerative/infiltrating types of cancers compared to polypoid/fungating ones (X^{2} =5.765, p=0.016). However, FXYD-3 expression was not correlated with patient's gender, age, tumor size, lymph node status and histological grade (p > 0.05). Conclosion: Up-regulated expression of FXYD-3 protein may be involved in tumourgenesis and invasion of gastric adenocarcinoma. Show more

Keywords: FXYD-3, gastric cancer, immunohistochemistry

DOI: 10.3233/DMA-2010-0669

Citation: Disease Markers, vol. 28, no. 2, pp. 63-69, 2010

Authors: Ihnen, M. | Köhler, N. | Kersten, J.F. | Milde-Langosch, K. | Beck, K. | Höller, S. | Müller, V. | Witzel, I. | Jänicke, F. | Kilic, E.

Article Type: Research Article

Abstract: Introduction: Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166) gained increasing attention regarding tumorprogression and metastatic spread in breast cancer. The aim of this study was to examine ALCAM expression levels in primary breast cancer and distant metastases of the same patient within 29 autopsy cases to better understand the underlying mechanisms of metastases and the role of adhesion molecules in this process. Material and Methods: Paraffin-embedded tissue of the primary and distant metastases (N=84) …were collected and ALCAM immunohistochemistry was performed. Results: The primary tumor and all metastases showed a statistically normally distributed ALCAM expression. ALCAM expression level average differs between immunoreactive score (IRS) (mean) 4.16 (lung)-5.00 (adrenal gland). Of the metastatic ALCAM expression levels we obtained an intra-class correlation (ICC) of 80.9%, indicating a strong cluster effect of measurements in the same patient. ALCAM expression scores in metastatic sites and in the primary analyzed by hierarchical regression analysis showed that ALCAM expression in the primary is prognostic for ALCAM expression in all different sites of metastases (slope=0.773, p < 0.001, r^{2} = 0.504). Conclusion: ALCAM expression in the primary is positively correlated to ALCAM expression in metastases within one single patient. This could show a tumorbiological context of ALCAM for the development of metastases in breast cancer. Show more

Keywords: Adhesion molecules, ALCAM, breast cancer, distant metastasis, metastasis development

DOI: 10.3233/DMA-2010-0685

Citation: Disease Markers, vol. 28, no. 2, pp. 71-78, 2010

Authors: Wang, Gang | Kwan, Bonnie Ching-Ha | Lai, Fernand Mac-Moune | Chow, Kai-Ming | Kam-Tao Li, Philip | Szeto, Cheuk-Chun

Article Type: Research Article

Abstract: Background: Micro-RNAs (miRNAs) regulate one-third of all protein-coding genes and are fundamental in the pathophysiology of a wide range of diseases. We studied the expression of several miRNA species (miR-200 family, miR-205 and miR-192) in the urinary sediment of patients with IgA nephropathy (IgAN). Methods: We studied 43 patients with biopsy-proven IgAN. Urinary expression of miRNAs was determined and compared to that from 13 healthy controls. Results: The levels of urinary miR-200a, miR-200b …and miR-429, but not miR-200c, miR-141, miR-205, or miR-192, were down-regulated in patients with IgAN. Proteinuria significantly correlated with urinary expression of miR-200a (r= −0.483, P < 0.001), miR-200b (r= −0.448, P=0.001) and miR-429 (r=−0.466, P=0.001). Baseline renal function significantly correlated with urinary expression of miR-200b (r= 0.512, P < 0.001) and miR-429 (r=0.425, P=0.005). Urinary gene expression of ZEB2 inversely correlated with miR-200b (r=−0.321, P=0.017); and vimentin expression inversely correlated with that of miR-200a (r=−0.360, P=0.007), miR-200b (r=−0.416, $P =$ 0.002) and miR-429 (r=−0.375, P=0.005). After 33.4 ± 12.6 months, the rate of renal function decline significantly correlated with urinary expression of miR-200b (r=0.316, P=0.034). Conclusions: Urinary expression of miR-200a, miR-200b and miR-429 were down-regulated in patients with IgAN, and the degree of reduction correlated with disease severity and rate of progression. The results suggested that these miRNA species might play important roles in the pathophysiology of IgAN. Further studies are needed to clarify the role of urinary miRNA repression as a non-invasive marker of IgAN. Show more

Keywords: Glomerulonephritis, biomarker, proteinuria

DOI: 10.3233/DMA-2010-0687

Citation: Disease Markers, vol. 28, no. 2, pp. 79-86, 2010

Authors: Singh, Madhu | Khanna, Vinay K. | Shukla, Rakesh | Parmar, Devendra

Article Type: Research Article

Abstract: The present case-control study was carried out to investigate the association of polymorphism in cytochrome P450 2D6 (CYP2D6) and N-acteyltransferase-2 (NAT2}, that are involved in the metabolism and detoxification of chemicals causing Parkinson disease (PD) like symptoms, with PD. Our data demonstrated increased frequency of CYP2D6*2 (1749G/C and 2938C/T), CYP2D6*4 (1934G/A) and CYP2D6*10A (188C/T) polymorphisms in PD cases when compared to the controls. Statistical analysis revealed the significant association of CYP2D6*4 (1934G/A) …and CYP2D6*10A (188C/T) polymorphism with PD. Likewise, increased frequency of NAT2*7 polymorphism that leads to the slow acetylator phenotype was observed in PD patients with more than fivefold increased risk (OR: 5.55; 95% CI: 0.56–54). No change was observed in the frequency of NAT*5 or NAT*6 alleles in the cases. Further, cases carrying combination of heterozygous genotypes of CYP2D6*4 or CYP2D6*10A(188C > T) and NAT2*5 were found to be at significantly higher risk for PD demonstrating the importance of gene-gene interactions in determining susceptibility to PD. Show more

Keywords: Cytochrome P450 2D6, N-acetyltransferase-2, poor metabolizers, parkinson disease, risk

DOI: 10.3233/DMA-2010-0688

Citation: Disease Markers, vol. 28, no. 2, pp. 87-93, 2010

Authors: Erciyas, Kamile | Pehlivan, Sacide | Sever, Tugce | Orbak, Recep

Article Type: Research Article

Abstract: Myeloperoxidase (MPO) is a lysosomal enzyme found in the azurophilic granules of polymorphonuclear leukocytes. It is involved in the defense against periodontal bacteria, and is also able to mediate inflammatory tissue destruction in aggressive and chronic periodontitis. The aim of this study was to explore the association between MPO-463G/A gene polymorphism and aggressive periodontitis (AgP) and chronic periodontitis (CP). The study included 147 subjects. Probing depth (PD), clinical attachment loss (CAL), plaque index …(PI), and gingival index (GI) were recorded as the clinical parameters. Genomic DNA was obtained from the peripheral blood of 32 subjects with AgP, 25 with CP, and 90 reference controls. We genotyped the MPO-463G/A polymorphism using the PCR-RFLP method. All data were analyzed using SPSS version 13.0 for windows. There were no significant differences between the CP patients and controls regarding MPO-463A/G gene polymorphism either in terms of allele frequency or genotype frequency of MPO-463A/G. However, either in terms of allele frequency or genotype frequency of MPO-463A/G, there were significant differences between the AgP patients and the controls. In conclusion, our data suggest that MPO-463G/A may be associated with increased risk of aggressive periodontitis in Turkish patients. Show more

Keywords: Periodontal disease, myeloperoxidase, gene polymorphism, DNA, PCR-RFLP

DOI: 10.3233/DMA-2010-0689

Citation: Disease Markers, vol. 28, no. 2, pp. 95-99, 2010

Authors: Surdacki, Andrzej | Marewicz, Ewa | Rakowski, Tomasz | Szumańska, Monika | Szastak, Grzegorz | Pryjma, Juliusz | Dubiel, Jacek S.

Article Type: Research Article

Abstract: Aim: To assess endothelial progenitor cells (EPC) counts, a novel prognostic marker, in relation to classical adverse outcome predictors – N-terminal pro{–}B-type natriuretic peptide (NT-proBNP), impaired left ventricular (LV) relaxation and exercise-induced ischemia – in stable coronary artery disease (CAD) with preserved LV systolic function. Methods: We studied 30 non-diabetic men with one-vessel CAD, LV ejection fraction ⩾ 60% and normal LV diastolic function (n=16) or impaired LV relaxation (by …ultrasound including tissue Doppler) (n=14), and 14 non-CAD controls matched for risk profile and medication. CD34+/kinase-insert domain receptor (KDR)+ cells (CD34+/KDR+ cells), a leukocytes subpopulation enriched for EPC, were enumerated by flow cytometry. Results: CAD patients with abnormal LV relaxation exhibited significantly elevated NT-proBNP and decreased CD34+/KDR+ cells vs. CAD with regular diastolic function and non-CAD controls. An inverse NT-proBNP–CD34+/KDR+ cells relationship was precipitated by the clustering of high resting NT-proBNP and low CD34+/KDR+ cells in the subjects with a lower Duke treadmill score. Conclusions: Propensity to symptomatic exertional ischemia may underlie the coincidence of moderately elevated NT-proBNP and EPC deficiency in stable angina. Additionally, chronic subclinical ischemia can also be involved in these associations. These might result from BNP overexpression in the ischemic myocardium and a hypothetical exhaustion of the bone marrow capacity to mobilize EPC at multiple ischemic episodes, thus contributing to NT-proBNP prognostic effect irrespective of hemodynamic factors. Show more

Keywords: B-type natriuretic peptide, endothelial progenitor cells, coronary artery disease, left ventricular diastolic dysfunction, myocardial ischemia

DOI: 10.3233/DMA-2010-0690

Citation: Disease Markers, vol. 28, no. 2, pp. 101-114, 2010

Authors: Barisione, Chiara | Garibaldi, Silvano | Ghigliotti, Giorgio | Fabbi, Patrizia | Altieri, Paola | Casale, Maria Carla | Spallarossa, Paolo | Bertero, Giovanni | Balbi, Manrico | Corsiglia, Luca | Brunelli, Claudio

Article Type: Research Article

Abstract: Our aim was to define the distribution of monocyte subsets in a cohort of congestive heart failure (CHF) patients, to verify whether increased severity of CHF is linked to the expansion of specific monocyte subsets, and finally to investigate the relationship between monocyte subset relative frequencies, laboratory parameters of inflammation, and monocyte ACE expression. Thirty consecutive CHF patients and 26 healthy control subjects were evaluated for peripheral blood monocyte expression of CD14, CD16 and …CD143 (ACE) by flow-cytometry, and for endothelial-derived soluble CD146 levels by ELISA. CD14^{++} CD16^{+} frequency was significantly higher in CHF patients than in Controls (%, median value and IQ) (12.3, 8.7–14.8 vs 5.9, 4.7–6.9, p< 0.05, CHF vs Controls), and it increased depending on how high NYHA class was, on worsening LV ejection fraction and on circulating pro-BNP values. Furthermore, it was associated with increasing creatinine and with decreasing GFR and albumin levels. Monocyte CD143 expression was significantly elevated in CHF patients as compared to Controls, and positively associated with CD14^{++} CD16^{+} levels. Frequencies of CD14^{+} CD16^{+} monocytes were significantly lower in CHF patients as compared to Controls, and negatively correlated with levels of soluble CD146 (r=−0.529; p 0.048). In conclusion, monocytic CD14^{++} CD16^{+} frequency and CD143 levels are increased and reflect disease status and progressive cardiac deterioration in CHF patients. The CD14^{+} CD16^{+} subset is depleted in CHF and is linked to endothelial damage in this group of patients. Although the question of whether differences in monocyte CD14CD16 expansion are causal or whether they represent a marker of HF progression which is potentially relevant for risk prediction remains unanswered, we believe that our data represent an important tool for exploring the role of selective inflammatory pathways in CHF progression. Show more

Keywords: Angiotensin, congestive heart failure, monocytes, peptidyl-dipeptidase A, antigens, CD14, receptors, IgG, kidney failure, chronic

DOI: 10.3233/DMA-2010-0691

Citation: Disease Markers, vol. 28, no. 2, pp. 115-124, 2010