Disease Markers - Volume 33, issue 2

Authors: Zavalhia, Lisiane Silveira | Romitti, Mirian | Netto, Gabriel Corteze | dos Santos, Giovana Tavares | Meurer, Rosalva Thereza | Hilbig, Arlete | Michalowski, Mariana Bohns | de Castro Ribeiro, Marlise

Article Type: Research Article

Abstract: C-kit is a proto-oncogene located on the long arm of chromosome 4. Its product, CD117, is a specific immunohistochemical (IHQ) marker that is associated with response to a potent tyrosine kinase inhibitor therapy with STI-571 (Gleevec®) in chronic myelogenous leukemia and GISTs. In our study, we aimed to evaluate the expression of CD117 in glial tumors as this finding may guide therapeutic approaches for these brain tumors. Ependymomas and oligodendrogliomas, in formalin fixed and …paraffin embedded blocks were assayed for CD117 immunoreactivity using anti-c-kit (CD117, DAKO). GISTs were used as positive control. We observed immunoreactivity of CD117 protein in 25.5% of tumors in both histological types. In oligodendrogliomas, there was an association between older age at diagnosis and positivity for CD117 (P=0.039). In addition, we observed an association between higher tumor grade (grade III) and positivity for CD117 (P=0.007). No clinical association was observed in ependymomas (P>0.05). This study encourages further investigations, considering that CD117 may be a possible oncogenic factor in some glial tumors. In this case, tumors that express this marker may eventually benefit from a therapy with selective inhibitors of receptor kinases. Show more

Keywords: CD117 c-kit, ependymomas, glial tumors, oligodendrogliomas

DOI: 10.3233/DMA-2012-0905

Citation: Disease Markers, vol. 33, no. 2, pp. 61-68, 2012

Authors: Sulicka, Joanna | Surdacki, Andrzej | Strach, Magdalena | Kwater, Aleksander | Gryglewska, Barbara | Ćwiklińska, Magdalena | Balwierz, Walentyna | Grodzicki, Tomasz K.

Article Type: Research Article

Abstract: Background: Adult survivors of childhood malignancy are predisposed to late cardiovascular (CV) complications. Our aim was to estimate plasma levels of the endogenous nitric oxide formation inhibitor asymmetric dimethylarginine (ADMA), in long-term survivors of childhood acute lymphoblastic leukemia (ALL) treated with only chemotherapy. Methods: ADMA and its isomer symmetric dimethylarginine (SDMA) were measured in 25 former ALL patients (aged 18–28 years) who had survived without recurrent disease ⩾ 5 years from completing chemotherapy without …cranial irradiation, and in 20 healthy controls (aged 20–31 years). Results: Characteristics of the both groups were similar, except for lower high-density lipoproteins-cholesterol (HDL-C) in ALL survivors. Compared to controls, the former ALL patients exhibited significant, albeit small, rises in levels of ADMA (0.63 ± 0.09 [SD] vs. 0.57 ± 0.07 μ mol/L; p=0.016), but not SDMA, with a consequently increased ADMA to SDMA ratio (1.08 ± 0.22 vs. 0.91 � 0.16; p=0.004). The effect of former ALL on ADMA was attenuated (intergroup p=0.10 [ANCOVA]) upon adjustment for HDL-C (ADMA vs. HDL-C regression coefficient: −0.065 ± 0.030 [SEM]; p=0.03). Conclusions: ADMA is elevated in adult childhood ALL survivors, which can reflect late detrimental chemotherapy effects, partially related to minor lipid profile changes. Whether these subtle ADMA elevations might herald future CV morbidity, remains to be elucidated. Show more

Keywords: Acute lymphoblastic leukemia, asymmetric dimethylarginine, late effects, long-term survivors of childhood malignancy

DOI: 10.3233/DMA-2012-0906

Citation: Disease Markers, vol. 33, no. 2, pp. 69-76, 2012

Authors: Colak, Yasar | Senates, Ebubekir | Coskunpinar, Ender | Oltulu, Yasemin Musteri | Zemheri, Ebru | Ozturk, Oguzhan | Doganay, Levent | Mesci, Banu | Yilmaz, Yusuf | Enc, Feruze Yilmaz | Kiziltas, Safak | Ulasoglu, Celal | Tuncer, Ilyas

Article Type: Research Article

Abstract: Aim: In this study, we aimed to investigate the relationship between the histological fibrosis stage of nonalcoholic fatty liver disease (NAFLD) and serum connective tissue growth factor (CTGF) to determine the usefulness of this relationship in clinical practice. Methods: Serum samples were collected from 51 patients with biopsy-proven NAFLD and 28 healthy controls, and serum levels of CTGF were assayed by ELISA. Results: Levels of CTGF were significantly higher in patients with …NAFLD compared with controls (P=0.001). The serum CTGF levels were significantly increased, that correlated with histological fibrosis stage, in patients with NAFLD [in patients with no fibrosis (stage 0) 308.2 ± 142.9, with mild fibrosis (stage 1–2) 519.9 ± 375.2 and with advanced fibrosis (stage 3–4) 1353.2 ± 610 ng/l, P < 0.001]. Also serum level of CTGF was found as an independent predictor of histological fibrosis stage in patients with NAFLD (β = 0.662, t=5.6, P <0.001). The area under the ROC curve was estimated 0.931 to separate patients with severe fibrosis from patients with other fibrotic stages. Conclusion: Serum levels of CTGF may be a clinical utility for distinguishing NAFLD patients with and without advanced fibrosis. Show more

Keywords: Nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), connective tissue growth factor (CTGF), fibrosis

DOI: 10.3233/DMA-2012-0907

Citation: Disease Markers, vol. 33, no. 2, pp. 77-83, 2012

Authors: Yasar, Ali | Gunduz, Kamer | Onur, Ece | Calkan, Mehmet

Article Type: Research Article

Abstract: The aim of this study was to determine serum vitamin B12, folic acid and homocysteine (Hcy) levels as well as MTHFR (C677, A1298C) gene polymorphisms in patients with vitiligo, and to compare the results with healthy controls. Forty patients with vitiligo and 40 age and sex matched healthy subjects were studied. Serum vitamin B12 and folate levels were determined by enzyme-linked immunosorbent assay. Plasma Hcy levels and MTHFR polymorphisms were determined by chemiluminescence and real time …PCR methods, respectively. Mean serum vitamin B12 and Hcy levels were not significantly different while folic acid levels were significantly lower in the control group. There was no significant relationship between disease activity and vitamin B12, folic acid and homocystein levels. No significant difference in C677T gene polymorphism was detected. Heterozygote A1298C gene polymorphism in the patient group was statistically higher than the control group. There was no significant relationship between MTHFR gene polymorphisms and vitamin B12, folic acid and homocysteine levels. In conclusion, vitamin B12, folate and Hcy levels are not altered in vitiligo and MTHFR gene mutations (C677T and A1298C) do not seem to create susceptibility for vitiligo. Show more

Keywords: Vitiligo, homocysteine, methylenetetrahydrofolate reductase, gene polymorphism, vitamin B12, folic acid

DOI: 10.3233/DMA-2012-0908

Citation: Disease Markers, vol. 33, no. 2, pp. 85-89, 2012

Authors: Shakoori, Tania A. | Sin, Don D. | Bokhari, S. Nazim Hussain | Ghafoor, Farkhanda | Shakoori, A.R.

Article Type: Research Article

Abstract: Introduction: There are limited data linking serum levels of surfactant protein D, its genetic polymorphisms to the risk of Chronic Obstructive Pulmonary Disease (COPD). Objectives: We sought to investigate these relationships using a case control study design. Methods: Post bronchodilator values of FEV1/FVC < 0.7 were used to diagnose COPD patients (n=115). Controls were healthy subjects with normal spirometry (n=106) Single nucleotide polymorphisms (rs721917, rs2243639, rs3088308) were genotyped using polymerase chain reaction …(PCR) and restriction analysis. Serum SP-D levels were measured using a specific immunoassay. Results: Allele 'A' at rs3088308 (p < 0.00, B= −0.41) and 'C' allele at rs721917 (p=0.03; B= −0.30) were associated with reduced serum SP-D levels. Genotype 'T/T' at rs721917 was significantly associated with risk of COPD (p=0.01). Patients with repeat exacerbations had significantly higher serum SP-D even after adjusting for genetic factors. Conclusions: We report for the first time that rs3088308 is an important factor influencing systemic SP-D levels and confirm the previous association of rs721917 to the risk of COPD and serum SP-D levels. Show more

Keywords: Surfactant protein D, SP-D SNPs, serum SP-D levels, COPD risk, SP-D haplotypes

DOI: 10.3233/DMA-2012-0909

Citation: Disease Markers, vol. 33, no. 2, pp. 91-100, 2012

Authors: Mackness, Bharti | Marsillach, Judit | Elkeles, Robert S. | Godsland, Ian F. | Feher, Michael D. | Rubens, Michael B. | Flather, Marcus D. | Humphries, Steve E. | Cooper, Jackie | Mackness, Mike

Article Type: Research Article

Abstract: Objectives: To determine any association between serum paraoxonase-1 (PON1) activity, protein and coding region genetic polymorphisms and coronary artery calcification (CACS) and to determine factors which modulate serum PON1 in type 2 diabetes (T2DM). Methods and results: 589 patients (419 Caucasian, 120 South Asian, 50 other) from the PREDICT Study were investigated. All patients were asymptomatic for coronary disease and had established T2DM. CACS, lipids, lipoproteins, inflammatory markers, insulin resistance and PON1 activity, concentration and Q192R and L55M …genotypes were measured. Independent associations were: 1) PON1 activity negatively with insulin resistance, triglycerides and PON1-55 genotype and positively with PON1-192 genotype; 2) PON1 concentration negatively with Caucasian ethnicity, duration of diabetes and statin use and positively with plasma creatinine and PON1-192 genotype. There was no association between CACS and any of the PON1 activity, concentration or genotype and this finding was not different in the various ethnic groups within the PREDICT study. Conclusion: PON1 is modulated by a number of factors, some of which are reported here for the first time, including ethnicity and insulin resistance in subjects with T2DM. No association between CACS and PON1 was found. Show more

Keywords: Paraoxonase-1, coronary calcification, insulin resistance, Type 2 diabetes

DOI: 10.3233/DMA-2012-0910

Citation: Disease Markers, vol. 33, no. 2, pp. 101-112, 2012