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Patai A.V.,Semmelweis University | Valcz G.,Hungarian Academy of Sciences | Hollosi P.,Semmelweis University | Hollosi P.,Hungarian Academy of Sciences | And 17 more authors.
PLoS ONE | Year: 2015

Microarray analysis of promoter hypermethylation provides insight into the role and extent of DNA methylation in the development of colorectal cancer (CRC) and may be co-monitored with the appearance of driver mutations. Colonic biopsy samples were obtained endoscopically from 10 normal, 23 adenoma (17 low-grade (LGD) and 6 high-grade dys-plasia (HGD)), and 8 ulcerative colitis (UC) patients (4 active and 4 inactive). CRC samples were obtained from 24 patients (17 primary, 7 metastatic (MCRC)), 7 of them with synchronous LGD. Field effects were analyzed in tissues 1 cm (n = 5) and 10 cm (n = 5) from the margin of CRC. Tissue materials were studied for DNA methylation status using a 96 gene panel and for KRAS and BRAF mutations. Expression levels were assayed using whole genomic mRNA arrays. SFRP1 was further examined by immunohistochem-istry. HT29 cells were treated with 5-aza-2' deoxycytidine to analyze the reversal possibility of DNA methylation. More than 85% of tumor samples showed hypermethylation in 10 genes (SFRP1, SST, BNC1, MAL, SLIT2, SFRP2, SLIT3, ALDH1A3, TMEFF2, WIF1), whereas the frequency of examined mutations were below 25%. These genes distinguished precancerous and cancerous lesions from inflamed and healthy tissue. The mRNA alterations that might be caused by systematic methylation could be partly reversed by demethylation treatment. Systematic changes in methylation patterns were observed early in CRC carcinogenesis, occuring in precursor lesions and CRC. Thus we conclude that DNA hypermethylation is an early and systematic event in colorectal carci-nogenesis, and it could be potentially reversed by systematic demethylation therapy, but it would need more in vitro and in vivo experiments to support this theory. Copyright: © 2015 Patai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Source


Fata E.,Markusovszky Lajos Egyetemi Oktato Korhaz | Agota K.,Markusovszky Lajos Egyetemi Oktato Korhaz | Horvath D.E.,Markusovszky Lajos Egyetemi Oktato Korhaz | Viragh E.,Markusovszky Lajos Egyetemi Oktato Korhaz | And 11 more authors.
Lege Artis Medicinae | Year: 2014

Recent studies have shown that adequate vitamin D level is essential in the maintenance of normal immunological status and presumably, it has a remarkable role even in the healing of some diseases. Vitamin D deficiency is a common phenomenon worldwide. Presently, the accepted marker of vitamin-D status is the total-25-hydroxy-D-vitamin [t-25(OH)D], its level depends on the specific (DBP) and aspecific (albumin) binding proteins. As known, the level of binding proteins may change in the hospitalised patients therefore, the presently used marker could not be reliable for the vitamin status in these cases. Our aim was to measure the D-vitamin supply among hospitalized patients, taking into account the level of binding proteins. METHODS - 401 cases (average age 70±14 years) were sorted from Internal Medicine (IM; 68), Intensiv Care Unit (ICU; 58), Traumatology (203 patients suffered hip fracture) and Dialysis Center (72 patients with end stage renal disease). 127 age and sex matched persons with active lifestyle served as control group. We determined t-25(OH)D, DBP, parathormon (PTHi), albumin and the albumin corrected Ca level. The bioavailable and free vitamin fractions and the free index were calculated. RESULTS - Based on the measured t-25(OH)D, patients have more frequently suboptimal D-vitamin levels, compared to the control group (66% vs. 97%). Severe D-vitamin deficiency occured nearly 8 times more likely (6% vs. 47%) in the hospitalized patients. Chronic renal failure and malignant diseases seem to be significantly negative influencing factors in the metabolism of the vitamin D. The level of DBP, albumin, t-25(OH)D, Bio-25(OH)D was significantly lower in the patients who died. CONCLUSION - In most cases, t-25(OH)D levels show similar results about the vitamin-D supply than other calculated 25(OH)D fraction ,except for the patients of ICU and IM. The t-25(OH)D, the Bio-25(OH)D, the DBP and the albumin levels seem to be a good prognostic marker of the outcome. Source


Patai A.,Sopron Elizabeth Teaching Hospital | Patai A.,Markusovszky University Teaching Hospital | Solymosi N.,Eotvos Lorand University | Patai A.V.,Semmelweis University
Medicine (United States) | Year: 2014

Rectal indomethacin has been proven to be effective for prevention of post-ERCP pancreatitis (PEP) but its impact on bleeding after biliary sphincterotomy (BABES) and cardiovascular mortality has not been extensively studied. We aimed to assess the effect of indomethacin on the rate of BABES and short-term cardiovascular mortality, particularly in patients receiving antiplatelet therapy (APT). In this double-blind, randomized, placebo-controlled, single-center study, 100mg indomethacin or placebo was given within 1 hour before biliary endoscopic sphincterotomy to in-patients including those who are receiving APT (acetylsalicylic acid [ASA] and/or clopidogrel). Cardiovascular mortality and BABES were observed for 30 days. Of 576 randomized patients (289 indomethacin, 287 placebo), 87 patients used 100mg/day ASA and 29 patients took 75mg/day clopidogrel, among them 5 patients were on dual APT. The ASA and clopidogrel taking patients were older than patients without APT (P<0.001), but these groups were similar in other parameters. BABES occurred similarly in different subgroups: indomethacin (8.0%) vs placebo (9.4%) (P=0.56), ASA (10.3%) vs non-ASA (8.4%) (P=0.54), clopidogrel (6.9%) vs nonclopidogrel (8.8%) (P>0.99). No BABES was observed among patients on dual APT. There was no difference in cardiovascular mortality between subgroups (P>0.99). Results indicate that single dose of 100mg indomethacin does not increase BABES rate and cardiovascular mortality. This result is independent from administering antiplatelet agents. Source


Eder K.,Markusovszky University Teaching Hospital | Kalman B.,Markusovszky University Teaching Hospital | Kalman B.,University of Pecs
Pathology & Oncology Research | Year: 2014

Glioblastoma is the most common intracranial malignancy and constitutes about 50 % of all gliomas. Both inter-tumor and intra-tumor histological heterogeneity had been recognized by the early 1980-ies. Recent works using novel molecular platforms provided molecular definitions of these tumors. Based on comprehensive genomic sequence analyses, The Cancer Genome Atlas Research Network (TCGA) cataloged somatic mutations and recurrent copy number alterations in glioblastoma. Robust transcriptome and epigenome studies also revealed inter-tumor heterogeneity. Integration and cluster analyses of multi-dimensional genomic data lead to a new classification of glioblastoma tumors into subtypes with distinct biological features and clinical correlates. However, multiple observations also revealed tumor area-specific patterns of genomic imbalance. In addition, genetic alterations have been identified that were common to all areas analyzed and other alterations that were area specific. Analyses of intra-tumor transcriptome variations revealed that in more than half of the examined cases, fragments from the same tumor mass could be classified into at least two different glioblastoma molecular subgroups. Intra-tumor heterogeneity of molecular genetic profiles in glioblastoma may explain the difficulties encountered in the validation of oncologic biomarkers, and contribute to a biased selection of patients for single target therapies, treatment failure or drug resistance. In this paper, we summarize the currently available literature concerning inter- and intra-tumor molecular heterogeneity of glioblastomas, and call attention to the importance of this topic in relation to the growing efforts in routine molecular diagnostics and personalized therapy. © 2014 Arányi Lajos Foundation. Source


Plander M.,Markusovszky University Teaching Hospital | Kalman B.,Markusovszky University Teaching Hospital | Kalman B.,University of Pecs
Autoimmunity | Year: 2016

Autoimmune diseases represent a heterogeneous group of common disorders defined by complex trait genetics and environmental effects. The genetic variants usually align in immune and metabolic pathways that affect cell survival or apoptosis and modulate leukocyte function. Nevertheless, the exact triggers of disease development remain poorly understood and the current therapeutic interventions only modify the disease course. Both the prevention and the cure of autoimmune disorders are beyond our present medical capabilities. In contrast, a growing number of single gene autoimmune disorders have also been identified and characterized in the last few decades. Mutations and other gene alterations exert significant effects in these conditions, and often affect genes involved in central or peripheral immunologic tolerance induction. Even though a single genetic abnormality may be the disease trigger, it usually upsets a number of interactions among immune cells, and the biological developments of these monogenic disorders are also complex. Nevertheless, identification of the triggering molecular abnormalities greatly contributes to our understanding of the pathogenesis of autoimmunity and facilitates the development of newer and more effective treatment strategies. © 2016 Informa UK Limited, trading as Taylor & Francis Group. Source

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