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001-es BibID:	BIBFORM082276
Első szerző:	Guergova-Kuras, Mariana
Cím:	Discovery and validation of a plasma protein biomarker panel for early detection of non small cell lung cancer / Mariana Guergova-Kuras, Istvan Kurucz, William Hempel, Nadège Tardieu, János Kádas, Carole Malderez-Bloes, Yann Kieffer, Anne Jullien, Eszter Csanky, Laszlo Takacs
Dátum:	2011
ISSN:	1556-0864
Tárgyszavak:	Orvostudományok Elméleti orvostudományok poszter folyóiratcikk
Megjelenés:	Journal of Thoracic Oncology. - 6 : 6 (2011), p. S1339-S1339. -
További szerzők:	Kurucz István Hempel, William Tardieu, Nadège Kádas János (1976-) (molekuláris biológus, biokémikus, kertészmérnök) Malderez-Bloes, Carole Kieffer, Yann Jullien, Anne Csánky Eszter (1959-) (tüdőgyógyász, klinikai immunológus, allergológus) Takács László (1955-)
Internet cím:	Szerző által megadott URL Intézményi repozitóriumban (DEA) tárolt változat
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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)
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat DOI
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001-es BibID:	BIBFORM111963
035-os BibID:	(cikkazonosító)100580 (Scopus)85165521769
Első szerző:	Lázár József
Cím:	Large-scale plasma proteome epitome profiling is an efficient tool for the discovery of cancer biomarkers / Lazar Jozsef, Antal-Szalmas Peter, Kurucz Istvan, Ferenczi Annamaria, Jozsi Mihaly, Tornyi Ilona, Muller Monika, Fekete Janos Tibor, Lamont John, FitzGerald Peter, Gall-Debreceni Anna, Kadas Janos, Vida Andras, Tardieu Nadege, Kieffer Yann, Jullien Anne, Guergova-Kuras Mariana, Hempel William, Kovacs Andras, Kardos Tamas, Bittner Nora, Csanky Eszter, Szilasi Maria, Losonczy Gyorgy, Szondy Klara, Galffy Gabriella, Csada Edit, Szalontai Klara, Somfay Attila, Malka David, Cottu Paul, Bogos Krisztina, Takacs Laszlo
Dátum:	2023
ISSN:	1535-9476
Megjegyzések:	Current proteomic technologies focus on the quantification of protein levels, while little effort is dedicated to the development of systems approaches to simultaneously monitor proteome variability and abundance. Protein variants may display different immunogenic epitopes detectable by monoclonal antibodies. Epitope variability results from alternative splicing, posttranslational modifications, processing, degradation, and complex formation and possess dynamically changing availability of interacting surface structures frequently serve as reachable epitopes, and often carry different functions. Thus, it is highly likely, that the presence of some of the accessible epitopes correlate with function under physiological and pathological conditions. To enable the exploration of the impact of protein variation on the immunogenic epitome first; here, we present a robust and analytically validated protein epitome profiling (PEP) technology for characterizing immunogenic epitopes of the plasma. To this end we prepared mAb libraries directed against the normalized human plasma proteome as a complex natural immunogen. Resulting hybridoma supernatants were selected for mAb production and the corresponding hybridomas were cloned. Monoclonal antibodies react with single epitopes, thus profiling with the libraries is expected to profile many epitopes which we define by the mimotopes, as we present here. Screening blood plasma samples from control subjects (n = 558) and cancer patients (n = 598) for merely 69 native epitopes displayed by 20 abundant plasma proteins resulted in distinct cancer-specific epitope panels that showed high accuracy (AUC 0.826?0.966) and specificity for lung, breast, and colon cancer. Deeper profiling (?290 epitopes of approximately 100 proteins) showed unexpected granularity of the epitope-level expression data and detected neutral and lung-cancer associated epitopes of individual proteins. Biomarker epitope panels selected from a pool of 21 epitopes of 12 proteins were validated in independent clinical cohorts. The results demonstrate the value of PEP as a rich and thus far unexplored source of protein biomarkers with diagnostic potential.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Molecular & Cellular Proteomics. - 22 : 7 (2023), p. 1-18. -
További szerzők:	Antal-Szalmás Péter (1968-) (laboratóriumi szakorvos) Kurucz István Ferenczi Annamária (1986-) (molekuláris biológus, mikrobiológus) Józsi Mihály Tornyi Ilona (1982-) (molekuláris biológus) Müller Mónika Fekete János Tibor Lamont, John FitzGerald, Peter Gall-Debreceni Anna Kádas János (1976-) (molekuláris biológus, biokémikus, kertészmérnök) Vida András (1979-) (molekuláris biológus, genetikus) Tardieu, Nadège Kieffer, Yann Jullien, Anne Guergova-Kuras, Mariana Hempel, William Kovács András László (1969-) (biológus, biológia-kémia tanár) Kardos Tamás (1980-) (pulmonológus, klinikai onkológus) Bittner Nóra (1963-) (orvos) Csánky Eszter (1959-) (tüdőgyógyász, klinikai immunológus, allergológus) Szilasi Mária (1953-) (tüdőgyógyász, klinikai immunológus, allergológus, belgyógyász) Losonczy György Szondy Klára Gálffy Gabriella Csada Edit Szalontai Klára Somfay Attila Malka, David Cottu, Paul Bogos Krisztina Takács László (1955-) (orvos)
Pályázati támogatás:	TECH-09-A1-2009-0113; mAbCHIC Egyéb GOP-1.2.1-09-2010-0019 Egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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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
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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