Disease Markers - Volume 22, issue 3

Authors: Wu, C.H. | Lin, S.R. | Hsieh, J.S. | Chen, F.M. | Lu, C.Y. | Yu, F.J. | Cheng, T.L. | Huang, T.J. | Huang, S.Y. | Wang, J.Y.

Article Type: Research Article

Abstract: Early detection of disseminated tumor cells in the peripheral blood of patients with early stage gastric cancer could help to improve the outcome after tumor resection. The aim of this study is to evaluate the prognostic significance of tumor-related mRNA for the detection of circulating tumor cells in gastric cancer patients by a reverse-transcriptase polymerase chain reaction (RT-PCR) method. We simultaneously analyzed human telomerase reverse transcriptase (hTERT), cytokeratin-19 (CK-19), cytokeratin-20 (CK-20) and …carcinoembryonic antigen (CEA) mRNA (messenger RNA) expression in the peripheral blood of 42 gastric cancer patients and 30 healthy individuals. Additionally, analyses were carried out for the correlation of these four molecular markers with patients' clinicopathologic features, as well as the occurrence of postoperative recurrence/metastasis. Among 42 gastric cancer patients, the prevalence of mRNA for hTERT, CK-19, CK-20, and CEA was 61.9% (26/42), 69% (29/42), 61.9% (26/42), and 78.6% (33/42), respectively. All 30 healthy individuals were negative for hTERT and CEA mRNA, while two were positive for either CK-19 mRNA or CK-20 mRNA. Positive CEA mRNA was significantly correlated with tumor size p=0.008), vessel invasion (p=0.001), depth of tumor invasion (p=0.007), lymph node metastasis (p< 0.001), and TNM stage (p<0.001). In addition, the multivariate logistic regression demonstrated that CEA mRNA expression was an independent and significant predictor for postoperative recurrence/metastasis (p=0.032). Our findings suggest that CEA mRNA may be a more reliable marker than hTERT, CK-19 and CK-20 for the detection of circulating cancer cells in gastric cancer patients' peripheral blood. Patients with positive CEA mRNA expression in peripheral blood have a significantly higher risk of postoperative recurrence/metastasis. Show more

Keywords: Molecular detection, disseminated tumor cell, gastric cancer, CEA mRNA

Citation: Disease Markers, vol. 22, no. 3, pp. 103-109, 2006

Authors: De Silvestri, A. | Belloni, C. | De Amici, M. | Mazzola, P. | Zorzetto, M. | Martinetti, M. | Salvaneschi, L. | Cuccia, M.

Article Type: Research Article

Abstract: Aim: We investigated on parental history and IgE serum level in 2588 consecutive newborns to individuate babies "at risk" of atopy at birth and we analysed the polymorphisms of class III region to evaluate the association with immunogenetic markers of HLA: C4A, C4B, LTA, RAGE and TNFA genes; we performed TNF and IgE receptor (FCERB1) physiologically related gene polymorphisms. Result: 791 babies/2588 (30.6%) were considered "at risk" for atopy and followed-up: 400 had familial history of atopy (at …least one parent or sibling), 256 had IgE >0.35 kUA/l at birth and during the follow-up and 135 were positive for both conditions. The allele C4B2 was significantly more frequent in the sample of babies at risk (22.1% vs 10%, p< 0.001). Furthermore, the mean value of IgE at birth in babies carrying the allele C4B2 was 2.26 KUA/l versus 0.74 KUA/l in those not carrying this allele (p=0.01). No significant association emerged for RAGE at the centromeric end of class III region and for LTA, TNFA at the telomeric one. TNFRI, TNFRII and FCERB1 gene polymorphisms also seemed not implicated. Conclusion: Our study confirms that HLA class III region seems involved in familial predisposition to atopy, and C4B gene probably acts as a marker of a more restricted subregion. Show more

Citation: Disease Markers, vol. 22, no. 3, pp. 111-117, 2006

Authors: Sánchez-González, V.J. | Ortiz, G.G. | Gallegos-Arreola, P. | Macías-Islas, M.A. | Arias-Merino, E.D. | Loera-Castañeda, V. | Martínez-Cano, E. | Velázquez-Brizuela, I.E. | Rosales-Corral, S.A. | Curiel-Ortega, C.R. | Pacheco-Moisés, F. | García, J.J.

Article Type: Research Article

Abstract: Objective: To determine the β-amyloid precursor protein (βAPP) isoforms ratio as a risk factor for Alzheimer's Disease and to assess its relationship with demographic and genetic variables of the disease. Methods: Blood samples from 26 patients fulfilling NINCDS-ADRDA diagnostic criteria for AD and 46 healthy control subjects were collected for Western blotting for βAPP. A ratio of βAPP isoforms, in optical densities, between the upper band (130 Kd) and the lower bands (106–110 …Kd) was obtained. Odds ratios were obtained to determine risk factor of this component. Results: βAPP ratio on AD subjects was lower than that of control subjects: 0.3662 ± 0.1891 vs. 0.6769 ± 0.1021 (mean ± SD, p<0.05). A low βAPP ratio (<0.6) showed an OR of 4.63 (95% CI 1.45–15.33). When onset of disease was taken into account, a βAPP ratio on EOAD subjects of 0.3965 ± 0.1916 was found vs. 0.3445 ± 0.1965 on LOAD subjects (p>0.05). Conclusions: Altered βAPP isoforms is a high risk factor for Alzheimer's disease, although it has no influence on the time of onset of the disease. Show more

Keywords: β-Amyloid precursor protein, Alzheimer's Disease, risk factor

Citation: Disease Markers, vol. 22, no. 3, pp. 119-125, 2006

Authors: Schubert, K. | von Bonnsdorf, H. | Burke, M. | Ahlert, I. | Braun, S. | Berner, R. | Deichmann, K.A. | Heinzmann, A.

Article Type: Research Article

Abstract: Bronchial asthma and juvenile idiopathic arthritis (JIA) are complex genetic diseases. As both represent chronic inflammatory diseases it is likely that they are at least partially influenced by the same genetic variants. One goal in dissecting the genetics of complex diseases is to identify a genetic risk profile. Therefore it is necessary to genotype polymorphisms in many different pathways. Thus we investigated 48 polymorphisms in 24 genes for association with asthma and/or JIA. Genotpying …was performed on 231 asthmatic children, 86 children with JIA and 270 controls. Association analysis was performed by the Armitage's trend test. Furthermore haplotypes were calculated by FAMHAP. We found association of polymorphisms within IL-4, CTLA4 and TNFalpha with asthma and/or JIA. Furthermore, the polymorphisms showed an inverse distribution between children with asthma and JIA. However, we were not able to confirm association of most of the previously described candidate genes. We conclude from our data that it might be very difficult to identify genetic risk profiles for the development of asthma and/or JIA that would be valid across different populations. However, this study adds further evidence that the common genetic background of asthma and JIA is mainly based on polymorphisms in important TH1 and TH2 cytokines. Show more

Keywords: Arthritis, asthma, complex disease, polymorphism

Citation: Disease Markers, vol. 22, no. 3, pp. 127-132, 2006

Authors: Balla, József | Magyar, Mária Tünde | Bereczki, Dániel | Valikovics, Attila | Nagy, Emöke | Barna, Erika | Pál, András | Balla, György | Csiba, László | Blaskó, György

Article Type: Research Article

Abstract: Objective: Soluble CD40 ligand (sCD40L) has been suggested as a key mediator between inflammation and atherosclerosis, and the CD40-CD40L interaction has a role in atherosclerotic lesion progression. We evaluated if platelet released serum sCD40L and sCD40 levels differ between patients with early onset occlusive carotid artery disease and age-matched controls. Methods: sCD40L and sCD40 levels were measured in serum samples of 60 patients with occlusive carotid artery disease and 30 age-matched controls using ELISA. …Degree of stenosis of the internal carotid artery (ICA), and intima-media thickness (IMT) in the common carotid artery were measured by high resolution ultrasound. Values are given as mean ± SD. Results: Mean age was 50.9 ± 3.5 and 50.1 ± 3.5 years in the patient and control groups. IMT was significantly thicker in patients than in controls (0.89 ± 0.14 vs. 0.78 ±0.12 mm, p=0.0003). Serum levels of sCD40L were significantly higher (6.9 ± 5 vs. 4.5 ± 3.0 ng/mL, p=0.038) in patients, whereas sCD40 did not differ significantly between patients and controls (85 ± 56.9 vs. 79.3 ± 18.7 pg/mL, p=0.34). IMT did not correlate with sCD40L or sCD40 levels (R=−0.03, p=0.77; and R=0.109, p=0.308, respectively). Conclusions: sCD40L but not sCD40 levels are significantly higher in patients with occlusive carotid artery disease. Platelet derived sCD40L may be a key mediator among inflammation, thrombosis and atherosclerosis. Show more

Keywords: CD40 ligand, CD40, atherosclerosis, inflammation, intima-media thickness

Citation: Disease Markers, vol. 22, no. 3, pp. 133-140, 2006

Authors: Chen, Han-chun | Cao, Yan-fei | Hu, Wei-xin | Liu, Xin-fa | Liu, Qing-xia | Zhang, Ji | Liu, Jia

Article Type: Research Article

Abstract: A case-control study was conducted for analyzing the genetic polymorphisms of phase II metabolic enzymes in 97 patients with lung cancer and 197 healthy subjects from Han ethnic group of Hunan Province located in Central South China. The results showed that the frequencies of glutathione S-transferase (GST) M1-null (GSTM1-) or GSTT1-null (GSTT1-) genotype alone, or combined form of both in lung cancer patients were significantly higher than those of the controls. Genotypes of combining GSTP1 mutant/GSTM1(-) …or GSTP1 mutant/GSTT1(-) led to high risk of lung cancer. Individuals carrying any two or all three of GSTM1(-), GSTT1(-) and GSTP1 mutant genotypes have a distinctly increased risk of lung cancer when compared to those with GSTM1 present (GSTM1+: GSTM1+/+ or GSTM1+/−), GSTT1 present (GSTT1+: GSTT1+/+ or GSTT1+/−) and GSTP1 wild genotypes. Furthermore, individuals possessing combined genotypes of N-acetyltransferase 2 (NAT2) rapid acetylator, GSTP1 mutant and both GSTT1(-) and GSTM1(-) have a remarkably higher lung cancer risk than those carrying combined NAT2 slow acetylator genotype, GSTP1 wild genotype and both GSTT1(+) and GSTM1(+) genotypes. All these findings suggest that the genetic polymorphisms of phase II metabolic enzymes affect the susceptibility of lung cancer in the Han ethnic group of Central South China. Show more

Keywords: Genetic polymorphism, GST, NAT2, lung cancer, susceptibility

Citation: Disease Markers, vol. 22, no. 3, pp. 141-152, 2006

Authors: Cho, William C.S. | Yip, Tai-Tung | Chung, Wai-Shing | Leung, Albert W.N. | Cheng, Christopher H.K. | Yue, Kevin K.M.

Article Type: Research Article

Abstract: Diabetes mellitus (DM) is an alarming threat to health of mankind, yet its pathogenesis is unclear. The purpose of this study was to find potential biomarkers to serve as indicators for the pathogenesis of DM in a time course manner. Based on our previous findings that oxidative stress occurred at week 8, aorta lysate and sera of 102 streptozotocin (STZ)-induced diabetic and 85 control male Sprague-Dawley rats were obtained at the 4th, 8th and 12th week …after STZ injection. The protein profiles were studied employing surface-enhanced laser desorption/ionization time-of-flight mass spectrometry technology in attomole sensitivity range. In the aorta, a multiple biomarker panel was discovered at the 4th week. At the 8th week, 4 biomarkers were found, while at the 12th week, 3 biomarkers were identified. In the sera, a triplet of 3 peaks and 2 biomarkers were all discovered to have 100% classification accuracy rate to differentiate the DM and control groups at all time intervals. Besides, 2 biomarkers were also found to have high classification value at week 12. Comparing the aorta and sera from DM and non-DM rats, a bundle of potential biomarkers with significant changes in peak intensities and high classification values were found. Two of the serum biomarkers matched with islet amyloid polypeptide and resistin in the SWISS-PROT knowledgebase. Validation has been conducted using immunoassay kits. These potential biomarkers may provide valuable insight on the pathogenesis of DM and macrovascular complications. Show more

Keywords: Diabetes mellitus, protein profiling, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, macrovascular complications

Citation: Disease Markers, vol. 22, no. 3, pp. 153-166, 2006

Authors: Nasti, Sabina | Spallarossa, Paolo | Altieri, Paola | Garibaldi, Silvano | Fabbi, Patrizia | Polito, Luisa | Bacino, Luca | Brunelli, Michele | Brunelli, Claudio | Barsotti, Antonio | Ghigliotti, Giorgio

Article Type: Research Article

Abstract: Background: specific polymorphisms of genes regulating intracellular redox balance and oxidative stress are related to atherogenesis. Some studies have identified a relationship between progression of atherosclerosis and C242T mutation in CYBA gene coding for p22^{phox} , a subunit of the NADH/NADPH oxidase system. Design: we investigated whether the C242T nucleotide transition is associated with the presence of coronary artery disease (CAD) in a population of 494 Caucasian Italians undergoing coronary angiography to diagnose …the cause of chest pain. Results: the frequency of the T mutant allele that we found in 276 patients with angiographically documented CAD was significantly higher compared to what we observed in 218 subjects with normal coronary arteries (Controls) (respectively: 0.400 and 0.332, p<0.01). The prevalence of the T allele was even stronger when we compared: 1) early onset (age <55) vs late onset (age >65) single-vessel CAD patients (respectively: 0.75 and 0.48, p<0.05), and 2) the subgroup of CAD patients with at least one >98% stenosis in a coronary vessel vs those with no >98% stenosis in a coronary vessel (respectively: 0.425 and 0.365, p<0.05$). Conclusions: these results support the increased risk of developing early CAD and of having rapid progression of coronary stenosis in subjects carrying the C242T nucleotide transition among the Italian population. Show more

Keywords: Oxidative stress, cardiovascular, gene, variant, NAD(P)H oxidase

Citation: Disease Markers, vol. 22, no. 3, pp. 167-173, 2006

Authors: Carrillo, Esmeralda | Prados, José | Marchal, Juan Antonio | Boulaiz, Houria | Martínez, Antonio | Rodríguez-Serrano, Fernando | Caba, Octavio | Serrano, Salvio | Aránega, Antonia

Article Type: Research Article

Abstract: Malignant melanoma (MM) prognosis has been related to tumour thickness and clinical stage and metastasis risk has been associated with presence of tumour cells in peripheral blood. The aim of this study was to determine the relationship between presence of tyrosinase in peripheral blood of MM patients and their clinical prognosis. Blood samples from 58 MM patients (stage I–IV) were analysed, using RT-PCR assay to detect tyrosinase mRNA. The results showed that positive RT-PCR assay for …tyrosinase were significantly associated with clinical status and tumour thickness. After a median follow-up of 24 months, RT-PCR results were found to be significant correlated with recurrence (p<0.05) and clinical stage III (p<0.05). Separate analysis of stage III tumours to determine the prognostic value of tyrosinase presence in peripheral blood showed an overall 24-month survival rate of 70% in the RT-PCR negative group versus 10% in the positive group (p<0.02). These results suggest that detection of circulating melanoma cells may be especially relevant in stage III patients, in whom RT-PCR positivity defines a subpopulation at high risk of recurrence. Show more

Citation: Disease Markers, vol. 22, no. 3, pp. 175-181, 2006