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001-es BibID:BIBFORM023718
035-os BibID:(cikkazonosító)M111.010298 (WoS)000298290300017 (Scopus)83055168546
Első szerző:Guergova-Kuras, Mariana
Cím:Discovery of lung cancer biomarkers by profiling the plasma proteome with monoclonal antibody libraries / Mariana Guergova-Kuras, István Kurucz, William Hempel, Nadege Tardieu, János Kádas, Carole Malderez-Bloes, Anne Jullien, Yann Kieffer, Marina Hincapie, András Guttman, Eszter Csánky, Balázs Dezső, Barry L. Karger, László Takács
Dátum:2011
ISSN:1535-9476 1535-9484
Megjegyzések:A challenge in the treatment of lung cancer is the lack of early diagnostics. Here, we describe the application of monoclonal antibody (mAb) proteomics for discovery of a panel of biomarkers for early detection (stage I) of non small cell lung cancer (NSCLC). We produced large monoclonal antibody libraries directed against the natural form of protein antigens present in the plasma of NSCLC patients. Plasma biomarkers associated with the presence of lung cancer were detected via high throughput ELISA. Differential profiling of plasma proteomes of four clinical cohorts, totalling 301 patients with lung cancer and 235 healthy controls, identified 13 lung cancer associated (p<0.05) monoclonal antibodies. The mAbs recognize five different cognate proteins identified using immunoprecipitation followed by mass spectrometry. Four of the five antigens were present in non-small cell lung cancer cells in-situ. The approach is capable of generating independent antibodies against different epitopes of the same proteins, allowing fast translation to multiplexed sandwich assays. Based on these results, we have verified in two independent clinical collections a panel of five biomarkers for classifying patient disease status with a diagnostics performance of 77% sensitivity and 87% specificity. Combining CYFRA, an established cancer marker, with the panel resulted in a performance of 83 % sensitivity at 95 % specificity for stage I NSCLC.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Molecular and Cellular Proteomics. - 10 : 12 (2011), p. 1-14. -
További szerzők:Kurucz István Hempel, William Tardieu, Nadège Kádas János (1976-) (molekuláris biológus, biokémikus, kertészmérnök) Malderez-Bloes, Carole Jullien, Anne Kieffer, Yann Hincapie, Marina Guttman András (1954-) (vegyészmérnök) Csánky Eszter (1959-) (tüdőgyógyász, klinikai immunológus, allergológus) Karger, Barry Takács László (1955-) Dezső Balázs (1951-) (pathológus)
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2.

001-es BibID:BIBFORM016390
Első szerző:Penyige András (molekuláris genetikus)
Cím:Analyses of association between PPAR gamma and EPHX1 polymorphisms and susceptibility to COPD in a Hungarian cohort, a case-control study / Penyige András, Póliska Szilárd, Csánky Eszter, Scholtz Beáta, Dezső Balázs, Schmelczer Iván, Kilty Iain, Takács László, Nagy László
Dátum:2010
ISSN:1471-2350
Megjegyzések:In addition to smoking, genetic predisposition is believed to play a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Genetic association studies of new candidate genes in COPD may lead to improved understanding of the pathogenesis of the disease.Methods: Two proposed casual single nucleotide polymorphisms (SNP) (rs1051740, rs2234922) in microsomal epoxide hydrolase (EPHX1) and three SNPs (rs1801282, rs1800571, rs3856806) in peroxisome proliferator-activated receptor gamma (PPARG), a new candidate gene, were genotyped in a case-control study (272 COPD patients and 301 controls subjects) in Hungary. Allele frequencies and genotype distributions were compared between the two cohorts and trend test was also used to evaluate association between SNPs and COPD. To estimate the strength of association, odds ratios (OR) (with 95% CI) were calculated and potential confounding variables were tested in logistic regression analysis. Association between haplotypes and COPD outcome was also assessed.Results: The distribution of imputed EPHX1 phenotypes was significantly different between the COPD and the control group (P = 0.041), OR for the slow activity phenotype was 1.639 (95% CI = 1.08- 2.49; P = 0.021) in our study. In logistic regression analysis adjusted for both variants, also age and pack-year, the rare allele of His447His of PPARG showed significant association with COPD outcome (OR = 1.853, 95% CI = 1.09-3.14, P = 0.0218). In haplotype analysis the GC haplotype of PPARG (OR = 0.512, 95% CI = 0.27-0.96, P = 0.035) conferred reduced risk for COPD.Conclusions: The "slow" activity-associated genotypes of EPHX1 were associated with increased risk of COPD. The minor His447His allele of PPARG significantly increased; and the haplotype containing the minor Pro12Ala and the major His447His polymorphisms of PPARG decreased the risk of COPD.
Tárgyszavak:Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:BMC Medical Genetics [electronic resource]. - 11 (2010), p. 152. -
További szerzők:Póliska Szilárd (1978-) (biológus) Csánky Eszter (1959-) (tüdőgyógyász, klinikai immunológus, allergológus) Scholtz Beáta (1967-) (biokémikus, molekuláris biológus) Dezső Balázs (1951-) (pathológus) Schmelczer Iván Kilty, Iain Takács László (1955-) Nagy László (1966-) (molekuláris sejtbiológus, biokémikus)
Pályázati támogatás:NKFP 1/007/01
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3.

001-es BibID:BIBFORM016135
Első szerző:Póliska Szilárd (biológus)
Cím:Chronic Obstructive Pulmonary Disease-Specific Gene Expression Signatures of Alveolar Macrophages as well as Peripheral Blood Monocytes Overlap and Correlate with Lung Function / Poliska Szilard, Csanky Eszter, Szanto Attila, Szatmari Istvan, Mesko Bertalan, Szeles Lajos, Dezso Balazs, Scholtz Beata, Podani Janos, Kilty Iain, Takacs Laszlo, Nagy Laszlo
Dátum:2011
ISSN:0025-7931
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Respiration. - 81 : 6 (2011), p. 499-510. -
További szerzők:Csánky Eszter (1959-) (tüdőgyógyász, klinikai immunológus, allergológus) Szántó Attila (1976-) (orvos, biokémikus) Szatmári István (1971-) (biológus) Meskó Bertalan (1984-) (kutatóorvos) Széles Lajos (1971-) (molekuláris biológus) Dezső Balázs (1951-) (pathológus) Scholtz Beáta (1967-) (biokémikus, molekuláris biológus) Podani János Kilty, Iain Takács László (1955-) Nagy László (1966-) (molekuláris sejtbiológus, biokémikus)
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4.

001-es BibID:BIBFORM082285
Első szerző:Takács László
Cím:Non-small cell lung cancer biomarkers : discovery using mab proteomics / L. Takacs, M. Guergova-Kuras, I. Kurucz, N. Tardieu, J. Kadas, C. Malderez-Bloes, A. Jullien, Y. Kieffer, B. Dezso, B. Karger
Dátum:2011
ISSN:0732-183X 1527-7755
Megjegyzések:Background: A challenge in the treatment of lung cancer is the lack of early, pre-symptomatic diagnosis. Here, we describe the application of monoclonal antibody proteomics approach to profile the natural plasma proteome for the discovery of lung cancer biomarkers. Methods: We produced large monoclonal antibody (mAb) libraries directed against the natural form of complex mixtures of protein antigens present in the plasma of non-small cell lung cancer (NSCLC) patients. Lung cancer specific biomarkers in the plasma were detected via high throughput ELISA with mAbs. Antigen identification and specificity of the selected antibodies was determined using immunoprecipitation followed by mass spectrometric analysis. The presence of the biomarkers in non-small cell lung cancer tissues was validated by immunohistochemistry. Results: Differential profiling of plasma proteomes of four clinical collections, totalling 301 patients with lung cancer and 235 healthy controls, identified twenty four monoclonal antibodies recognizing protein biomarkers specific for NSCLC. The majority of the selected mAbs detect antigens present in non-small cell lung cancer cells in-situ. Our study confirms previously reported circumstantial evidences for the association with lung cancer for four of the identified biomarkers and provides an independent validation in larger multi-centric clinical collection for the association of their plasma concentrations to the presence of lung cancer. Multivariate analysis of the biomarker results generated with one of these collections (214 NSCLC cases of which 128 in stage I and 169 healthy controls) yielded a five biomarkers classifier that could discriminate NSCLC cases from healthy controls with 77% sensitivity and 87% specificity. The performance of the classifier was validated in an independent collection and combination with well known a NSCLC biomarkers showed additive effect and combined performance of 84 % sensitivity at 95 % specificity. Conclusions: Using the mAb proteomics approach we have identified a panel of monoclonal antibodies associated with specific protein biomarkers that could be readily transferred to a simple screening test for the early detection of non-small cell lung cancer.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idézhető absztrakt
folyóiratcikk
Megjelenés:Journal of Clinical Oncology. - 29 : 15 suppl. (2011), p. 10561-10561. -
További szerzők:Guergova-Kuras, Mariana Kurucz István Tardieu, Nadège Kádas János (1976-) (molekuláris biológus, biokémikus, kertészmérnök) Malderez-Bloes, Carole Jullien, Anne Kieffer, Yann Dezső Balázs (1951-) (pathológus) Karger, Barry
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