Disease Markers - Volume 29, issue 1

Authors: Mailaparambil, Beena | Krueger, Marcus | Heizmann, Ulrike | Schlegel, Katharina | Heinze, Jessica | Heinzmann, Andrea

Article Type: Research Article

Abstract: Bronchopulmonary dysplasia (BPD) is the chronic lung disease of preterm infants and still represents a major burden of prematurity. Several clinical risk factors for the onset of the disease are already known. In addition, some candidate genes have recently been identified. We set out to determine clinical as well as genetic risk factors for the development of BPD in the German population. 155 infants born with a gestational age ⩽ 28 at the tertiary neonatal Centre, Freiburg, were recruited. …Clinical data were recorded from hospital charts. 47 children developed moderate or severe BPD. For genetic analyses, 37 polymorphisms within sixteen genes were genotyped on all children. The strongest epidemiological risk factor for BPD was birth weight, followed by low gestational age. Genetic association was detected with single polymorphisms within Tumour necrosis factor alpha, Toll like receptor 10 and vascular endothelial growth factor. The former two genes showed also association with BPD in haplotype analyses. In conclusion, association of BPD was far more convincingly found with a few clinical factors than with genetic polymorphisms. This underscores the genetic complexity of the disease. Furthermore, the identification of predisposing genetic polymorphisms might be hampered by the complex interaction between clinical and genetic factors. Show more

Keywords: Association, bronchopulmonary dysplasia, genetic, polymorphism

DOI: 10.3233/DMA-2010-0720

Citation: Disease Markers, vol. 29, no. 1, pp. 1-9, 2010

Authors: An, Yanming | Bekesova, Slavka | Edwards, Nathan | Goldman, Radoslav

Article Type: Research Article

Abstract: The incidence of hepatocellular carcinoma (HCC) in the United States is increasing and the increase is projected to continue for several decades. The overall survival of HCC patients is poor and treatments are not effective in part because most of the diagnoses come at a late stage. The development of new markers for detection of HCC would significantly improve patient prognosis. This paper describes identification of candidate markers previously reported in our serologic study of an …Egyptian population by quantitative comparison of matrix assisted laser desorption ionization time of flight (MALDI-TOF) mass spectra. To identify these marker candidates, we performed LC-MS/MS sequencing that identified nine native peptides associated with HCC, including two reported previously. Four truncations of N terminus of complement C3f and a fibrinopeptide increased in control sera; two complement C4α peptides, a zyxin peptide, and a coagulation factor XIII peptide increased in cancer patient sera. We have also identified increased biliverdin diglucuronide in the sera of cancer patients. These peptides could potentially serve as markers of HCC following additional validation studies; however, association of similar peptides with other diseases and cancers dictates a very cautious approach. Show more

Keywords: Hepatocellular carcinoma, mass spectrometry, serum, complement, biliverdin diglucuronide

DOI: 10.3233/DMA-2010-0721

Citation: Disease Markers, vol. 29, no. 1, pp. 11-20, 2010

Authors: Mühlmann, Gilbert | Öfner, Dietmar | Zitt, Matthias | Müller, Hannes M. | Maier, Hans | Moser, Patrizia | Schmid, Kurt W. | Zitt, Marion | Amberger, Albert

Article Type: Research Article

Abstract: 14-3-3 sigma (σ) induces G2 arrest enabling the repair of damaged DNA. The function of 14-3-3 σ is frequently lost in tumor cells, indicating a potential tumor suppressor function. The purpose of this study was to evaluate the prognostic value of 14-3-3 σ expression in human gastric cancer. 14-3-3 σ expression was analyzed by immunohistochemistry in 157 tumor samples of patients, who underwent resection for gastric cancer. Since 14-3-3 σ is involved …in the p53 network, p53 expression was detected in parallel and correlated with 14-3-3 σ. 14-3-3 σ was found to be overexpressed in 75 (47.8%) of 157 cases, the overexpression rate of p53 protein was 27.4%. 14-3-3 σ overexpression was statistically significantly associated with pT-stage (p=0.041) pN-stage (p=0.015) and UICC-stage (p=0.019) and showed a borderline significance with Lauren classification (p=0.057). Univariate survival calculations revealed a coexistent 14-3-3 σ and p53 overexpression as a significant predictor of disease-free survival. Multivariate analysis did not unfold 14-3-3 as an independent prognostic factor for disease-free survival and overall survival. Concomitant 14-3-3 σ and p53 overexpression in tumor cells of patients with gastric cancer identifies a population of patients with relatively unfavorable prognosis. Show more

Keywords: Gastric cancer, 14-3-3 sigma, tumorigenesis

DOI: 10.3233/DMA-2010-0722

Citation: Disease Markers, vol. 29, no. 1, pp. 21-29, 2010

Authors: Pandey, Kanti Bhooshan | Mehdi, Mohd Murtaza | Maurya, Pawan Kumar | Rizvi, Syed Ibrahim

Article Type: Research Article

Abstract: Previous studies have indicated that the main molecular characteristic of aging is the progressive accumulation of oxidative damages in cellular macromolecules. Proteins are one of the main molecular targets of age-related oxidative stress, which have been observed during aging process in cellular systems.. Reactive oxygen species (ROS) can lead to oxidation of amino acid side chains, formation of protein-protein cross-linkages, and oxidation of the peptide backbones. In the present study, we report the age-dependent …oxidative alterations in biomarkers of plasma protein oxidation: protein carbonyls (PCO), advanced oxidation protein products (AOPPs) and plasma total thiol groups (T-SH) in the Indian population and also correlate these parameters with total plasma antioxidant potential. We show an age dependent decrease in T-SH levels and increase in PCO and AOPPs level. The alterations in the levels of these parameters correlated significantly with the total antioxidant capacity of the plasma. The levels of oxidized proteins in plasma provide an excellent biomarker of oxidative stress due to the relative long half-life of such oxidized proteins. Show more

Keywords: Human aging, oxidative stress, AOPPs, protein carbonyls, -SH

DOI: 10.3233/DMA-2010-0723

Citation: Disease Markers, vol. 29, no. 1, pp. 31-36, 2010

Authors: Srivastava, Priyanka | Gangwar, Ruchika | Kapoor, Rakesh | Mittal, Rama D.

Article Type: Research Article

Abstract: Matrix metalloproteinases (MMPs) contribute to tumor invasion and microenvironment, hence are associated with bladder cancer risk. We therefore, tested whether polymorphisms in MMP genes modify the risk of bladder cancer (BC) and whether smoke exposure modifies this risk. Genotyping was performed in 200 BC patients and 200 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). MMP1-1607 2G/2G and MMP7-181 GG genotype were associated with increased risk of BC (p < …0.001; OR, 3.04; 95% CI- 1.71–5.39 and p, 0.005; OR, 2.38; 95% CI- 1.30–4.34) respectively. Smokers in BC patients showed significant increased risk for the same SNPs (p, 0.006; OR, 3.20; 95% CI- 1.40–7.31 and p, 0.009; OR, 2.85; 95% CI- 1.30–6.23 respectively). Haplotype analysis too revealed significant association with G/2G of MMP1-519-1607 (p< 0.001; OR, 2.62; 95% CI- 1.68–4.09). The 2G allele carrier (1G/2G + 2G/2G) of MMP1-1607 showed a protective effect and high recurrence free survival in Bacillus Calmette-Guérin (BCG) treated non muscle invasive BC (NMIBC) patients (log rank p, 0.030). Our data suggested that MMP1-1607 2G and MMP7-181 G allele were associated with high risk of BC, which was quite evident amongst smokers too. BCG treated NMIBC patients reflected protective effect for 2G allele carrier (1G/2G + 2G/2G) of MMP1-1607. This study provided new support for the association of MMP1-1607 and MMP7-181 in bladder cancer development, the tumorigenic effect of which was observed to be more enhanced in case of tobacco exposure. Show more

Keywords: Bacillus Calmette-Guérin, bladder cancer, haplotypes, matrix metalloproteinase, polymorphism, recurrence free survival

DOI: 10.3233/DMA-2010-0724

Citation: Disease Markers, vol. 29, no. 1, pp. 37-46, 2010

Authors: Muenst, S. | Hoeller, S. | Willi, N. | Dirnhofer, S. | Tzankov, A.

Article Type: Research Article

Abstract: Aims: Programmed death-1 (PD-1) is expressed by germinal center-associated helper T-cells and acts as a negative regulator of the immune system. PD-1 is encountered on tumor cells of angioimmunoblastic T-cell lymphoma and is a postulated diagnostic marker in chronic lymphocytic leukemia (CLL/SLL). Recent data suggest prognostic importance of PD-1 in follicular lymphoma (FL). We assessed the diagnostic potential and the prognostic importance of PD-1 in B-cell lymphomas. Methods: Distribution of PD-1+ lymphocytes in B-cell …lymphomas was studied on 403 cases. Correlation with known biologic and clinical key data was performed. Prognostic cut-off scores were determined by receiver operating curve analysis. Results: PD-1+ tumor-infiltrating lymphocytes were numerous in extranodal marginal zone lymphomas and FL. Their amount decreased from FL grade 1 to grade 3 and to FL with transformation to diffuse large B-cell lymphoma. An increased amount of PD-1 tumor-infiltrating lymphocytes above the prognostic cut-off score (> 2.8%) was a positive prognostic factor of disease-specific survival (DSS) in FL-patients. Five percent of the studied 66 CLL/SLL cases showed unequivocal PD-1 positivity of neoplastic cells. Conclusions: Increased number of PD-1+ tumor-infiltrating lymphocytes is associated with significantly improved DSS in FL and may be useful to predict its heterogeneous clinical behavior. PD-1 has probably limited diagnostic value for primary histopathological CLL/SLL diagnostics. Show more

DOI: 10.3233/DMA-2010-0725

Citation: Disease Markers, vol. 29, no. 1, pp. 47-53, 2010

Authors: Dalamaga, Maria | Karmaniolas, Konstantinos | Lekka, Antigoni | Antonakos, George | Thrasyvoulides, Apollon | Papadavid, Evangelia | Spanos, Nikolaos | Dionyssiou-Asteriou, Amalia

Article Type: Research Article

Abstract: Background: Altered thrombocyte morphology and function have been reported in patients with diabetes mellitus (DM) type 2. The aim of the present study was to determine the associations between platelet morphology markers and hemoglobin A1C (HbA_{1c} ), fasting glucose (FG), hypertension and coronary heart disease (CHD) in patients with myelodysplastic syndromes (MDS) and DM, in patients with DM and in controls. Methods: This cross-sectional study included 30 cases with primary MDS with normal …platelet count and non-insulin dependent diabetes, 30 non-insulin dependent diabetic patients and 30 non-diabetic, non-MDS controls matched on age and gender. Results: After adjusting for body mass index, platelet number, CHD and hypertension, HbA_{1c} and FG were significant predictors of mean platelet volume (MPV) and platelet distribution width (PDW) in diabetic patients. There was no correlation between platelet parameters and HbA_{1c} or FG in diabetic MDS patients. In controls, FG and hypertension predicted significant differences in platelet morphology. Platelet count correlated with platelet morphology in diabetic MDS and control groups, but not in diabetics. Conclusions: MPV and PDW are associated with glycemic indices in diabetic patients but not in diabetic MDS patients with normal platelet counts. Non-diabetic controls also exhibit FG related changes in platelet morphology. This suggests other factors inherent to bone marrow dysplasia, platelet turnover and biochemistry, or vascular environment affect platelet morphology in diabetic MDS patients even with normal platelet count. Platelet morphology in this population may be an early marker for myelodysplasia. These findings also support platelet morphology change as a marker for elevated macrovascular disease risk. Show more

Keywords: Myelodysplastic syndrome, diabetes, glycohemoglobin, glucose, mean platelet volume

DOI: 10.3233/DMA-2010-0726

Citation: Disease Markers, vol. 29, no. 1, pp. 55-61, 2010