Disease Markers - Volume 26, issue 3

Authors: Pinheiro, Céline | Longatto-Filho, Adhemar | Pereira, Sônia Maria Miranda | Etlinger, Daniela | Moreira, Marise A.R. | Jubé, Luiz Fernando | Queiroz, Geraldo Silva | Schmitt, Fernando | Baltazar, Fátima

Article Type: Research Article

Abstract: Due to the highly glycolytic metabolism of solid tumours, there is an increased acid production, however, cells are able to maintain physiological pH through plasma membrane efflux of the accumulating protons. Acid efflux through MCTs (monocarboxylate transporters) constitutes one of the most important mechanisms involved in tumour intracellular pH maintenance. Still, the molecular mechanisms underlying the regulation of these proteins are not fully understood. We aimed to evaluate the association between CD147 (MCT1 and …MCT4 chaperone) and MCT expression in cervical cancer lesions and the clinico-pathological significance of CD147 expression, alone and in combination with MCTs. The series included 83 biopsy samples of precursor lesions and surgical specimens of 126 invasive carcinomas. Analysis of CD147 expression was performed by immunohistochemistry. CD147 expression was higher in squamous and adenocarcinoma tissues than in the non-neoplastic counterparts and, importantly, both MCT1 and MCT4 were more frequently expressed in CD147 positive cases. Additionally, co-expression of CD147 with MCT1 was associated with lymph-node and/or distant metastases in adenocarcinomas. Our results show a close association between CD147 and MCT1 and MCT4 expressions in human cervical cancer and provided evidence for a prognostic value of CD147 and MCT1 co-expression. Show more

Keywords: CD147, monocarboxylate transporters, cervical carcinoma

DOI: 10.3233/DMA-2009-0596

Citation: Disease Markers, vol. 26, no. 3, pp. 97-103, 2009

Authors: de Lira Freire, Alzírton | Conde, Roseneide Aparecida | Bertolo, Manoel Barros | Costallat, Lílian Teresa Lavras | Levy-Neto, Maurício | Fernandes, Sandra Regina Muchinechi

Article Type: Research Article

Abstract: The aim of this study was to evaluate the frequency and clinical associations of HLA-DR alleles in Brazilian Caucasian patients with polyarteritis nodosa (PAN) or microscopic polyangiitis (MPA). We evaluated 29 Caucasian patients with vasculitis classified as PAN or MPA according to the American College of Rheumatology (ACR) 1990 Criteria, Chapel Hill Consensus Conference (CHCC) nomenclature for vasculitis and EULAR recommendations for conducting clinical studies in systemic vasculitis. HLA-DR alleles were typed …using polymerase chain reaction-amplified DNA, hybridized with sequence-specific low resolution primers. DNA obtained from 59 Caucasian healthy blood donors were used as control. In order to evaluate if a specific HLA may have influence on the clinical profile of those diseases, we also divided the patients according to Birmingham vasculitis score (BVAS) and Five-Factors Score (FFS) at the time of diagnosis. Increased frequency of HLA-DRB1*16 (p = 0.023) and DRB4*01 (p = 0.048) was found in patients with higher disease activity at the time of diagnosis (BVAS ⩾ 22). Patients with less severe disease (FFS = 0) had a higher frequency of HLA-DRB1*03 (p = 0.011). Patients with gastrointestinal tract involvement had significantly increased frequency of HLA-DRB1*11 or B1*12 (p = 0.046), B1*13 (p = 0.021) and B3 (p = 0.008). In contrast, patients with renal disease, had higher frequency of DRB1*15 or DRB1*16 (p = 0.035) and B5 (p = 0.035). In the subgroup of patients with MPA, increased frequency of HLA-DRB1*15 was found in patients with BVAS ⩾ 22 (p = 0.038) and FFS ⩾ 1 (p = 0.039) suggesting that this allele is associated with more aggressive disease. Antineutrophil cytoplasmic antibodies (ANCA) negative MPA patients had significantly increased frequency of HLA-DRB1*11 or DRB1*12 when compared to ANCA positive patients (p = 0.023). Our results suggest that HLA-DR alleles may influence PAN and MPA clinical expression and outcome and that in MPA they participate in the mechanisms involved in the development to ANCA. Show more

Keywords: Polyarteritis nodosa, microscopic polyangiitis, HLA, vasculitis, autoimmunity

DOI: 10.3233/DMA-2009-0616

Citation: Disease Markers, vol. 26, no. 3, pp. 105-109, 2009

Authors: Chistiakov, Dimitry A. | Spitsina, Ekaterina V. | Nikitin, Alexey G. | Strokov, Igor A. | Nosikov, Valery V.

Article Type: Research Article

Abstract: Abnormalities in G protein-mediated signal transduction could be involved in the pathogenesis of diabetic polyneuropathy (DPN). Here we test whether the GNB3 C825T variant confers susceptibility to DPN in type 1 diabetes (T1D) mellitus. The C825T marker of GNB3 was genotyped in genomic DNA from blood isolated from a total of 213 Russian T1D patients 100 of whom had DPN. Compared to carriers of the wild-type genotype C/C, diabetic subjects with genotypes T/T had significantly increased …risk to develop DPN (Odds Ratio (OR) of 4.4 (p = 0.001). The adjustment for confounders (age, sex, body mass index, cigarette smoking, and level of reduced glutathione) resulted in increase of the OR value up to 4.72 (p = 8.9 × 10^{-3} ). The further adjustment for hypertension abolished the association between the GNB3 C825T variant and DPN (OR = 1.95, p = 0.18). Non-complicated subjects homozygous for T/T showed decreased levels of reduced glutathione (T/T: 69 ± 19 vs. C/T: 74 ± 19 vs. C/C: 77 ± 17 μmol/l, p = 0.009). Compared to other GNB3 variants, carriers of the T/T genotype had elevated systolic blood pressure (SBP) in complicated (T/T: 115.8 ± 9.1 vs. C/T: 113.3 ± 8.2 vs. C/C: 109.5 ± 8.7 mm/Hg, p = 0.036) and non-complicated T1D patients (T/T: 118.1 ± 8.4 vs. C/T: 116.9 ± 7.9 vs. C/C: 112.1 ± 7.2 mm/Hg, p = 0.02). However, the significance of association between the C825T polymorphism was lost after adjustment for confounding risk factors. In conclusion, the 825T allele of GNB3 is likely to accelerate the development of DPN through primary effects to SBP and hypertension in subgroups of diabetic patients with impaired neurovascular function and advanced oxidative stress. Show more

Keywords: GNB3, C825T polymorphism, peripheral polyneuropathy, type 1 diabetes, susceptibility

DOI: 10.3233/DMA-2009-0620

Citation: Disease Markers, vol. 26, no. 3, pp. 111-117, 2009

Authors: Navarro-Hernández, Rosa Elena | Oregon-Romero, Edith | Mercado, Mónica Vázquez-Del | Rangel-Villalobos, Héctor | Palafox-Sánchez, Claudia Azucena | Muñoz-Valle, José Francisco

Article Type: Research Article

Abstract: To investigate the association of sICAM-1 and sVCAM-1 with ICAM1 721G>A and VCAM1 1238G>C polymorphisms and rheumatoid arthritis (RA) clinical activity, sixty RA patients and 60 healthy non-related subjects (HS) matched for age and sex were recruited. Soluble adhesion molecules were determined by ELISA technique. Rheumatoid factor (RF), C reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were measured by routine methods. Disability and clinical activity was measured with Spanish-HAQ-DI and DAS28 …scores, respectively. The ICAM1 and VCAM1 polymorphism were identified using the PCR-RFLP procedure. Inter-group comparison showed increased levels of sICAM-1 and sVCAM-1 in RA patients (284 and 481 ng/mL) versus HS (132 and 280 ng/mL); in the RA group, significant correlations between sVCAM-1 and RF (r = 0.402), ESR (r = 0.426), Spanish-HAQ-DI (r = 0.276), and DAS28 (r = 0.342) were found, whereas sICAM-1 only correlated with RF (r = 0.445). In RA patients, a significant association with the 721A allele of ICAM1 polymorphism (p = 0.04), was found. In addition, the allele impact (G/A+A/A) of this polymorphism was confirmed, (p = 0.038, OR = 2.3, C.I. 1.1–5.0). sVCAM-1 and sICAM-1 serum levels reflected the clinical status in RA, independently of the ICAM1 and VCAM1 polymorphism. However, the ICAM1 721A allele could be a genetic marker to RA susceptibility. Show more

Keywords: Rheumatoid arthritis, polymorphism, soluble adhesion molecules, ICAM-1, VCAM-1

DOI: 10.3233/DMA-2009-0621

Citation: Disease Markers, vol. 26, no. 3, pp. 119-126, 2009

Authors: Swellam, Menha | Samy, Nervana | Wahab, Susan Abdl | Ibrahim, Mohamed Saeed

Article Type: Research Article

Abstract: Objectives: Endothelial disturbance and excess inflammatory response are pathogenic mechanisms in pre-eclampsia (PE). Authors determine the clinical diagnostic role for thrombomodulin (TM), plasminogen activator inhibitor-1 (PAI-1) as endothelial markers and C-reactive protein (CRP), and interlukin-6 (IL-6) as inflammatory markers when tested independently or in combinations. Materials and methods: We conducted a retrospective study in a cohort of 185 women grouped as 80 women with PE, 55 normotensive pregnant and 50 …healthy non-pregnant. Plasma levels of TM, PAI-1, CRP and IL-6 were examined using enzyme linked immunosorbent assays. Results: Median levels and the positivity rates for the investigated markers were higher in PE as compared to the other groups (P < 0.0001). Using linear regression analysis, the investigated markers were significantly correlated regarding healthy non-pregnant vs PE or normotensive pregnant vs PE. The sensitivity of PAI-1 was the highest (98%) among the tested biomarkers. Combination between the investigated markers revealed absolute sensitivity (100%) and reliable specificity especially when PAI-1 was combined with CRP at 83% specificity. Conclusions: Investigated endothelial and inflammatory markers revealed sensitive diagnostic test for PE. However, coupled combination between PAI-1 with CRP showed superior both sensitivity and specificity which represent a promising new approach for detection of PE. Show more

Keywords: Pre-eclampsia, thrombomodulin, CRP, IL-6, PAI-1, inflammatory markers, adhesion molecules

DOI: 10.3233/DMA-2009-0622

Citation: Disease Markers, vol. 26, no. 3, pp. 127-133, 2009

Authors: Al-Daghri, Nasser M. | Al-Attas, Omar S. | Alokail, Majed | Draz, Hossam M. | Bamakhramah, Ahmed | Sabico, Shaun

Article Type: Research Article

Abstract: We studied the association between RBP4 and various markers related to insulin resistance and diabetic complications as well as inflammatory markers in Saudi population suffering from type 2 diabetes and coronary heart disease. Patients with type 2 diabetes were divided into 3 groups according to the type of treatment and involvement of coronary artery disease. Serum RBP4, TNF-α, insulin, CRP, resistin, leptin and adiponectin were analysed in all samples. RBP4 levels increased significantly in the group …of diabetic subjects treated with oral hypoglycemic agents and diabetic patients with coronary heart disease (30.2 ± 11.8; 33.4 ± 13.6 respectively), while there was no significant change in the other group for diabetic subjects on low-carbohydrate diet (25.1 ± 10.9) compared to control group (22.6 ± 9.5). RPB4 levels were positively correlated with TNF-α in the group of diabetic subjects on oral hypoglycemic agents and diabetic patients with coronary heart disease (r = 0.52, P < 0.05; r = 0.58, P < 0.05 respectively). No correlations were found between RBP4 levels and insulin resistance in all studied groups. Our findings suggest that serum RBP4 levels is associated with pro-inflammatory cytokine (TNF-α) and is not associated with insulin resistance among patients with type 2 diabetes and coronary heart disease. Show more

Keywords: Retinol-binding protein 4, TNF-α, insulin resistance, type 2 diabetes, coronary heart diseases

DOI: 10.3233/DMA-2009-0623

Citation: Disease Markers, vol. 26, no. 3, pp. 135-140, 2009

Authors: Varga, Éva | Seres, Ildikó | Harangi, Mariann | Sztanek, Ferenc | Asztalos, László | Lõcsey, Lajos | Borbás, Béla | Szegedi, János | Kárpáti, István | Paragh, Gyórgy

Article Type: Research Article

Abstract: Background: Human paraoxonase-1 (PON1) inhibits LDL-oxidation and atherogenesis, and possesses lactonase activity. Decreased PON1 activity was found in hemodialyzed and renal transplanted patients. Cystatin C plays a protective role in atherosclerosis, and is a new, sensitive marker of renal function. The relationship between these two markers in renal failure has not been investigated. Aims: The goal of this study was to clarify the relationship between PON1 activity, cystatin C and homocysteine in chronic renal …failure. We also determined the levels of oxidatively modified LDL (oxLDL) and thiobarbituric acid reactive substances (TBARS) to characterize lipid peroxidation. Patients and methods: 74 hemodialized (HD), 171 renal transplanted patients (TRX), and 110 healthy controls (C) were involved in the study. PON1 activity and TBARS levels were measured spectrophotometrically. OxLDL level was determined with sandwich ELISA. Results: There was a negative correlation between PON1 activity and cystatin C level. Homocysteine level correlated negatively with PON1 activity, and positively with cystatin C level. OxLDL and TBARS levels were significantly higher in the HD and TRX groups compared to C. Conclusions: Cystatin C may be a good predictive factor not only for homocysteine levels but for the antioxidant status in patients with renal failure and renal transplantation. Show more

Keywords: Cystatin C, homocysteine, paraoxonase, renal failure, oxidative stress

DOI: 10.3233/DMA-2009-0624

Citation: Disease Markers, vol. 26, no. 3, pp. 141-148, 2009