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1.

001-es BibID:BIBFORM074282
Első szerző:Biró Orsolya (molekuláris biológus)
Cím:Non-invasive prenatal biomarkers for fetal heart defects : circulating nucleic acid and protein biomarkers in maternal blood / Orsolya Biró, Bálint Nagy
Dátum:2018
Megjegyzések:Background: Congenital heart defects (CHDs) are the most common fetal malformations. Prenatal ultrasonography is routinely applied for the screening of CHD but many factors influence its diagnostic accuracy. The introduction of new biomarkers could facilitate the identification of high-risk pregnancies.Objective: We reviewed expression studies of maternal blood-derived cell-free nucleic acids and proteins in pregnancies affected by CHD. NIPT techniques which enabled the detection of heart-related chromosomal aberrations were also discussed.Methods: Scientific literature databases were screened for studies where the levels of potential CHD biomarkers were measured in maternal blood samples. Available NIPT tests were collected from the providers' resources.Results: To date, there are nine CHD-associated chromosomal abnormalities (five aneuploidies, and four microdeletions) which are included in different NIPT panels. We found eight studies from which five included the analysis of specific cell-free RNA expression profile and three measurements of protein levels.Conclusion: Most of the common heart-related chromosomal aberrations can be diagnosed by NIPT. Specific cell-free RNAs and circulating proteins seem to be potential biomarkers for fetal CHDs. The application of these new biomarkers could improve the detection rate at early pregnancy, making it possible to provide optimal perinatal and perioperative management.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idézhető absztrakt
congenital heart disease
maternal circulation
cell-free nucleic acids
biomarkers
Megjelenés:Biomedical Papers. - 162 : Suppl. 1 (2018), p. S6. -
További szerzők:Nagy Bálint (1956-) (molekuláris genetikus)
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2.

001-es BibID:BIBFORM074283
Első szerző:Biró Orsolya (molekuláris biológus)
Cím:Maternal methylenetetrahydrofolate reductase (MTHFR) polymorphisms : risk factors for congenital heart disease? / Orsolya Biró, János Rigó Jr., Bálint Nagy
Dátum:2018
Megjegyzések:Background: Maternal MTHFR polymorphisms have been associated with higher risk for miscarriage, preeclampsia, spina bifida and congenital heart disease (CHD).MTHFR is responsible for the conversion of folic acid to the biologically active l-methylfolate (5-MTHF), thus reduced enzyme can have severe consequences. Our aims were to assess the frequency of the two most common MTHFR polymorphisms (C677T and A1298C) in our Hungarian study group and to evaluate the association between these alterations and the risk for CHD. Methods: Blood samples were collected from 40 pregnant women, 20 whose fetus was diagnosed with CHD and 20 healthy controls. DNA was isolated from buffy coat and FRET-based real-time PCR were performed using MTHFR C677T and A1298C specific probes. Genotypes were determined by melting curve analysis and frequencies were determined. The odds ratio (OR) and 95% confidence interval were calculated for CHD in each case.Results: The frequencies for each genotype in all samples were CT/aa: 22,5%, TT/aa: 15%, CC/ca: 15%, CC/cc: 22,5%, CT/ac: 12,5% ,and CC/aa: 12,5%. The frequencies for each genotype in CHD vs control group: CT/aa: 30% vs. 15%, TT/aa: 10% vs. 20%, TT/ca: 15% vs. 15%,CC/cc: 25% vs. 20%, CT/ac: 15% vs. 10%, and CC/aa: 5% vs. 20%. The combined OR of MTHFR heterozygous, compound heterozygous or homozygous vs. wild type genotype was 4.75 for CHD, but the finding was not statistically significant.Conclusion: We showed that MHTFR polymorphisms are relatively common in Hungarian women: only 12.5% of the samples were not affected by any of the alterations. The "less frequent" A1298C is occurred in 50% of the samples, at the same rate as C677T.We have not found significant associations between the investigated polymorphisms and CHD, which may be due to the protective effect of periconceptional maternal supplement of bioavailable 5-MTHF against fetal abnormalities.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idézhető absztrakt
congenital heart defects
maternal circulation
cell-free nucleic acids
Megjelenés:Biomedical Papers. - 162 : Suppl. 1 (2018), p. S6-S7. -
További szerzők:Rigó János (1958-) (szülész-nőgyógyász) Nagy Bálint (1956-) (molekuláris genetikus)
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3.

001-es BibID:BIBFORM074289
Első szerző:Buglyó Gergely (genetikus)
Cím:Novel miRNA downregulations in blastemal Wilms' tumor : an FFPE-based study / Gergely Buglyó, Zsófia Magyar, Éva Romicsné Görbe, Rita Bánusz, Monika Csóka, Tamás Micsik, Zsanett Berki, Péter Varga, Zoltán Sápi, Bálint Nagy
Dátum:2018
Megjegyzések:According to the SIOP protocol, Wilms' tumor histology is assessed from the surgical sample, after pre-operative chemotherapy. The two most common subtypes are regressive and blastemal. As the presence of blastema is a sign of adverse prognosis, recent efforts have focused on revealing molecular features of blastemal Wilms' tumors that may be responsible for poor chemo-responsiveness. Characteristic miRNA-signatures can be identified from tumor tissue as well as circulating miRNA from serum. In our study, we investigated miRNA expression in 8 patients using FFPE samples from tumor and control tissues. After identifying miRNAs of interest in the first sample by aqRT-PCR Array, 4 chosen miRNAs (miR-184, miR-203a, miR-34c-5p and miR-194-5p) were studied in all samples using individual primers. Results were comparable to previous reports based on fresh frozen tissue, but also showed a deregulation of miR-203a as a novel finding, and an underexpression of miR-184 at a previously unreported magnitude that may be present in a subset of blastemal or other Wilms' tumors. As a conclusion, we may note that further investigation of miRNA expression patterns in Wilms' tumor subtypes may be warranted, and FFPE samples (not older than 7-10 years) are excellent miRNA sources to increase sample count for high-scale studies.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idézhető absztrakt
miRNA
Wilms tumor
FFPE
Megjelenés:Biomedical Papers. - 162 : Suppl. 1 (2018), p. S15. -
További szerzők:Magyar Zsófia Görbe Éva Bánusz Rita Csóka Mónika Micsik Tamás Berki Zsanett Varga Péter (szülész-nőgyógyász) Sápi Zoltán Nagy Bálint (1956-) (molekuláris genetikus)
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4.

001-es BibID:BIBFORM074281
Első szerző:Grendar, Marian
Cím:Decreasing the no call rate of Non-Invasive Prenatal Testing / Marian Grendar, Dusan Loderer, Iveta Svecova, Zuzana Laucekova, Michaela Hrtankova, Andrea Hornakova, Balint Nagy, Zora Lasabova, Jan Danko
Dátum:2018
Megjegyzések:The no call (or failure) rate is an important characteristics of any diagnostic, testing, or screening method. Failures of the read counting approach to Non-Invasive Prenatal Testing (NIPT) are primarily caused by the low fetal fraction. If fetal fraction is below a value, known as the Limit of Detection (LoD), then NIPT cannot determine the aneuploidy status of a fetus. The LoD can be estimated experimentally or by the coverage method. The coverage method implies that the LoD, and hence also the no call rate due to the low fetal fraction, can be made arbitrarily small by increasing the sequencing depth. The no call rate can be made arbitrarily small also by excluding from NIPT the pregnancies suspect of having fetal fraction below the LoD (e.g., due to the low gestational age, high maternal BMI, etc.). These methods of decreasing the no call rate have obvious drawbacks.Explorations of the quantitative foundations of NIPT lead a variant of NIPT that for a fixed sequencing depth attains the no call rate lower than the conventional NIPT and is particularly useful for the subpopulation of pregnancies with the high maternal BMI, and/or low gestational week.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idézhető absztrakt
Non-Invasive Prenatal Testing
quantitative foundations
Megjelenés:Biomedical Papers. - 162 : Suppl. 1 (2018), p. S3. -
További szerzők:Loderer, Dusan Svecova, Iveta Laucekova, Zuzana Hrtankova, Michaela Hornakova, Andrea Nagy Bálint (1956-) (molekuláris genetikus) Lasabova, Zora Danko, Jan
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5.

001-es BibID:BIBFORM074284
Első szerző:Keserű Judit (molekuláris genetikus)
Cím:Correlation of plasma mitochondrial DNA copy number and status of ovarian cancer patients / Judit Keserű, Beáta Soltész, János Lukács, Róbert Póka, Bálint Nagy
Dátum:2018
Megjegyzések:Introduction: Mitochondria are important organelles in ATP synthesis of cells in aerobic conditions, and are involved in various different cell processes like cell proliferation, and apoptosis. Their copy number variations were connected to many different pathological conditions like development of many types of cancer, e.g. ovarian cancer. That is why we measured the mtDNA copy numbers in the plasma in ovarian cancer patients and healthy controls.Materials and methods: We involved 53 healthy controls (avarage age 57.45?10.61 years) and 24 ovarian cancer patients (average age 61.33?12.72 years) in the study. Blood was drawn into EDTA tubes and plasma was separated by centrifugations. MtDNA copy numbers were determined by Human Mitochondrial DNA (mtDNA) Monitoring Primer Set kit (Takara, Japan) with real-time PCR.Results: The mtDNA copy number was 43.55?13.69 in the healthy control group. We divided the ovarian cancer patients into groups according to their FIGO classification and their cancer stage. The copy numbers were the followings: FIGO I. (early-stage ovarian cancer) 32?8.27; FIGO III. and IV (advanced-stage ovarian cancer) 37.19?13.75 (FIGO III. 33?5.66; FIGO IV. 42?18.87). Student's unpaired t-test was performed. No significant difference was found among the early-stage and advanced-stage patients or control group and advanced stage patients (p=0.3740 and p=0.1084, respectively) but significant difference was found among control group and early-stage patients (p=0.0290) in the plasma cell-free mtDNA copy numbers.Conclusion: We determined the cell-free mtDNA copy numbers in the plasma of ovarian cancer patients and healthy controls and we found significant difference among control group and early-stage patients. We plan to extend the study to more ovarian cancer patients and also we plan exosome encapsulated mtDNA measurements.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idézhető absztrakt
mitochondrial DNA
ovarian cancer
cell-free mtDNA
Megjelenés:Biomedical Papers. - 162 : Suppl. 1 (2018), p. S11. -
További szerzők:Soltész Beáta (1987-) (molekuláris biológus) Lukács János (1975-) (szülész-nőgyógyász, genetikus) Póka Róbert (1960-) (szülész-nőgyógyász, klinikai onkológus) Nagy Bálint (1956-) (molekuláris genetikus)
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6.

001-es BibID:BIBFORM074290
Első szerző:Márton Éva (biológus)
Cím:Study the role of miR141 and miR429 in the diagnosis of epithelial ovarian cancer / Éva Márton, János Lukács, Réka Szabó, Beáta Soltész, Eszter Janka, Róbert Póka, Bálint Nagy, Melinda Szilágyi-Bónizs
Dátum:2018
Megjegyzések:Ovarian cancer is the most lethal form of gynecological malignancy that is mostly due to the difficulty of early diagnosis. Developing a fast, non-invasive diagnostic test would greatly facilitate the early detection and survival chances of ovarian cancer. Circulating miRNAs proved to be promising biomarkers in various cancers, including breast, prostate, pancreatic or colon cancer. However, only few publications focus on circulating miRNAs in ovarian cancer especially in European populations.Here we studied the expression levels of miR141 and miR429 in the plasma samples of healthy (n=17), and previously untreated epithelial ovarian carcinoma patients (n=17, FIGO stages III or IV) in a Hungarian cohort. The relative amount of miRNAs was detected by qRT-PCR.The expression levels of miR141 and miR429 proved to be higher in the malignant samples compared to the healthy donors (p<0.05). ROC-AUC proved to be good in the case of both miR141 (0.737, 95%CI=0.565-0.909) and miR429 (0.727, 95%CI=0.552-0.901). Sensitivity and negative predictive value were higher in the case of miR429(76.47% and 75%) than in the case of miR141 (64.71% and 68.42%). However, specificity and positive predictive value proved to be higher in the case of miR141 (76.47% and 73.33%) than in the case of miR429 (70.59% and 72.22%). Diagnostic accuracy was higher in the case of miR429 (73.53%) than in the case of miR141 (70.59%).We conclude that the miR200 family member miR141 and miR429 might be promising candidate biomarkers in the diagnosis of ovarian cancer. Further studies are needed to test our hypothesis.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idézhető absztrakt
miRNA
Wilms tumor
FFPE
Megjelenés:Biomedical Papers. - 162 : Suppl. 1 (2018), p. S17. -
További szerzők:Lukács János (1975-) (szülész-nőgyógyász, genetikus) Szabó Réka Soltész Beáta (1987-) (molekuláris biológus) Janka Eszter Anna (1989-) (bőrgyógyász, népegészségügyi szakember) Póka Róbert (1960-) (szülész-nőgyógyász, klinikai onkológus) Nagy Bálint (1956-) (molekuláris genetikus) Szilágyi Melinda (1984-) (biológus)
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7.

001-es BibID:BIBFORM074287
Első szerző:Soltész Beáta (molekuláris biológus)
Cím:Cell-free miRNAs as potential biomarkers in the diagnosis of ovarian cancer / Beáta Soltész, Orsolya Biró, János Lukács, András Penyige, Róbert Póka, Bálint Nagy
Dátum:2018
Megjegyzések:cause of cancer mortality among women due to the poor early diagnostic tools for the detection of this type of aggressive tumour. Cell-free microRNAs appear to be potential candidate biomarker in this early diagnosis.Materials and methods: Eleven ovarian cancer patients and 11 healthy controls were involved into the study. EDTA-anticoagulated blood was drawn; the microRNA was isolated with miRNeasy Mini kit (Qiagen, Germany) and cDNA was synthesised. The miR-103; miR-125, miR-193b and miR-200b expression were determined by miRCURY Universal RT microRNA PCR Starter kit (Exiqon, USA). The results were normalised to the miRNA-93 reference gene. Student t-test was used for the statistical calculations.Results: Significant difference in the expression of miR-103 (p=0.001), miR-193b (p=0.0236), miR-125 (p=0.029) and miR-200b (p=0.0273) was detected among the cancer patients and controls.Conclusion: The expression of four different cell-free microRNAs was determined from the plasma of patients with ovarian cancer and healthy controls. Significant difference was found in the expression of the analysed microRNAs. In the near future, our study will be extended on higher number of cases.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idézhető absztrakt
ovarian cancer
mirNA
cell-free
Megjelenés:Biomedical Papers. - 162 : Suppl. 1 (2018), p. S13. -
További szerzők:Biró Orsolya (molekuláris biológus) Lukács János (1975-) (szülész-nőgyógyász, genetikus) Penyige András (1954-) (molekuláris genetikus) Póka Róbert (1960-) (szülész-nőgyógyász, klinikai onkológus) Nagy Bálint (1956-) (molekuláris genetikus)
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8.

001-es BibID:BIBFORM074292
Első szerző:Soltész Beáta (molekuláris biológus)
Cím:Cell-free, long non-coding RNA as novel biomarker in the diagnosis of ovarian cancer / B. Soltesz, J. Lukács, E. Szilágyi, R. Póka, B. Nagy
Dátum:2018
ISSN:1018-4813
Megjegyzések:Background: Ovarian cancer is the fifth leading cause of cancer-associated mortality among women. A reliable, non-invasive diagnostic method may contribute to the early detection of this malignancy. The long non-coding RNAs (lncRNAs) have a significant role in the oncogenesis, metastasis and chemoresistance. The upregulation of Hox transcript antisense intergenic RNA (HOTAIR) was determined in the development of ovarian cancer cells, however, the cell-free HOTAIR expression was not detected from the plasma until now.Materials and methods: Twenty previously untreated ovarian cancer patients (60.60?10.84y; FIGO stages III or IV) and 20 healthy controls (56.70?14.51y) were involved in the study. EDTA blood was drawn; RNA was isolated; cDNA was synthesised and the HOTAIR lncRNA expression were determined by using ExiLERATE LNA? qPCR,for mRNA and long non-coding RNA (Exiqon, USA). ACTB was used as reference gene. Student t-test was applied for the statistical calculations.Results: Higher expression of HOTAIR was detected in the samples of patients with ovarian cancer (1.89?2.39) than in healthy controls (1.39?1.48) but the difference was no significant (p=0.432).Conclusion: We determined the concentration of the cell free HOTAIR lncRNA from the plasma of ovarian cancer patients and healthy controls. There was no significant difference in the expression of the analysed lncRNA; but this is the first study to analyse the cell-free HOTAIR expression among Hungarian ovarian cancer patients. We would like to extend our study on higher number of cases as this lncRNA seem to be novel biomarker for the diagnosis of ovarian cancer.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idézhető absztrakt
ovarian cancer
cell-free
long-noncoding RNA
Megjelenés:Biomedical Papers. - 162 : Suppl. 1 (2018), p. S12. -
További szerzők:Lukács János (1975-) (szülész-nőgyógyász, genetikus) Szilágyi Edina (1993-) (laboratóriumi analitikus) Póka Róbert (1960-) (szülész-nőgyógyász, klinikai onkológus) Nagy Bálint (1956-) (molekuláris genetikus)
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9.

001-es BibID:BIBFORM074288
Első szerző:Szemes, Tomas (biológus)
Cím:Are phages part of our immunity? / Tomas Szemes, Andrej Balaz, Michal Kajsik, Iveta Gazdaricova, Orsolya Biro, Balint Nagy, Jan Turna, Jaroslav Budis
Dátum:2018
Megjegyzések:Introduction: Several non-invasive prenatal tests (NIPT) use total DNA massively parallel sequencing. A portion of sequences are not mapped to human genome reference sequence and is filtered out in the NIPT analysis. Our aim was to determine source of unmapped reads. Preliminary data suggests presence of bacteriophage DNA in human circulation. Materials and methods: We carried out massively parallel sequencing of total DNA from plasma from group of healthy individuals and individuals undergoing antiviral treatment. DNA fragments which mapped to the human reference genome (version hg38) were filtered. We assigned each unmapped fragment a taxonomic label using metagenomic classifier Clark. Taxonomic composition of samples was compared and visualized using Krona graphs. We assembled filtered reads using assembler specialized for assembly of viral genomes called Savage.Results: We identified presence of phage sequences in a small number of reads in studied samples of healthy individuals. In addition, we observed significant drop in phage sequences in individuals undergoing antiviral treatment. In the results we present breakdown of the identified phage data.Conclusions: Preliminary data suggest presence of phage DNA in circulating free nucleic acids. We hypothesize that host immune system tolerates phages to assist in control and stabilization of microenvironment. More rigorous analysis needs to be carried out and supportive experiments are needed to confirm the finding as well as to study our hypotheses.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idézhető absztrakt
DNA
phage
MPS
Megjelenés:Biomedical Papers. - 162 : Suppl. 1 (2018), p. S14. -
További szerzők:Balaz, Andrej Kajsik, Michal Gazdaricova, Iveta Biró Orsolya (molekuláris biológus) Nagy Bálint (1956-) (molekuláris genetikus) Turna, Jan Budis, Jaroslav
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10.

001-es BibID:BIBFORM074285
Első szerző:Szilágyi Melinda (biológus)
Cím:MiR200a, miR200b and miR200c are promising candidate biomarkers in epithelial ovarian cancer / Melinda Szilágyi-Bónizs, Éva Márton, János Lukács, Beáta Soltész, Eszter Janka, András Penyige, Róbert Póka, Bálint Nagy
Dátum:2018
Megjegyzések:Ovarian cancer is the fifth most common form of cancer death among women. Developing a fast, reliable blood test would facilitate the early detection of ovarian cancer, which would also contribute to the improvement of survival chances. Screening circulating miRNAs proved to be reliable biomarkers in various cancers. MiRNAs are also dysregulated in ovarian cancer, however, only a few publications focus on their diagnostic role. We screened 6 miRNAs in the plasma samples of healthy (n=30), previously untreated epithelial ovarian carcinoma patients (n=21, FIGO stages III or IV) and patients with benign masses (n=14). The relative amount of miRNAs was detected by qRT-PCR.The expression levels of miR200a, miR200b and miR200c were elevated in the malignant samples compared to the healthy donors (p<0.001). The level of miR200a was also higher in malignant than benign samples (p<0.01). However, no significant difference was detected in the expression of miR205, miR483 and let7f. ROC-AUC was the highest in the case of miR200a (0.875, 95%CI=0.76-0.99) and it was still promising in the case of miR200b (0.85, 95%CI=0.72-0.98) and miR200c (0.83, 95%CI=0.70-0.97). Spearman's rank correlation was relatively high between the expression values of miR200b and miR200c (rs = 0.858; p<0.001) and these miRNAs shared several target genes involved in cancer development according to target prediction analysis. The agreement of diagnostic tests based on miR200s and CA125 or HE4 proved to be weak according to Cohen's kappa values.We conclude that miR200a, miR200b and miR200c might be promising complementary markers of CA125 and HE4 in ovarian cancer. Moreover miR200a is also a reliable biomarker in the differential diagnosis of benign tumors.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idézhető absztrakt
ovarian cancer
cell-free mtDNA
miRNA
Megjelenés:Biomedical Papers. - 162 : Suppl. 1 (2018), p. S11. -
További szerzők:Márton Éva (1992-) (biológus) Lukács János (1975-) (szülész-nőgyógyász, genetikus) Soltész Beáta (1987-) (molekuláris biológus) Janka Eszter Anna (1989-) (bőrgyógyász, népegészségügyi szakember) Penyige András (1954-) (molekuláris genetikus) Póka Róbert (1960-) (szülész-nőgyógyász, klinikai onkológus) Nagy Bálint (1956-) (molekuláris genetikus)
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