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001-es BibID:	BIBFORM048273
Első szerző:	Meskó Bertalan (kutatóorvos)
Cím:	Peripheral blood derived gene panels predict response to infliximab in rheumatoid arthritis and Crohn's disease / Bertalan Mesko, Szilard Poliska, Andrea Váncsa, Zoltan Szekanecz, Karoly Palatka, Zsolt Hollo, Attila Horvath, Laszlo Steiner, Gabor Zahuczky, Janos Podani, Laszlo Nagy
Dátum:	2013
ISSN:	1756-994X
Megjegyzések:	Biological therapies have been introduced for the treatment of chronic inflammatory diseases including rheumatoid arthritis (RA) and Crohn's disease (CD). The efficacy of biologics differs from patient to patient. Moreover these therapies are rather expensive, therefore treatment of primary non-responders should be avoided.METHOD:We addressed this issue by combining gene expression profiling and biostatistical approaches. We performed peripheral blood global gene expression profiling in order to filter the genome for target genes in cohorts of 20 CD and 19 RA patients. Then RT-quantitative PCR validation was performed, followed by multivariate analyses of genes in independent cohorts of 20 CD and 15 RA patients, in order to identify sets ofinterrelated genes that can separate responders from non-responders to the humanized chimeric anti-TNFalpha antibody infliximab at baseline.RESULTS:Gene panels separating responders from non-responders were identified using leave-one-out cross-validation test, and a pool of genes that should be tested on larger cohorts was created in both conditions.CONCLUSIONS:Our data show that peripheral blood gene expression profiles are suitable for determining gene panels with high discriminatory power to differentiate responders from non-responders in infliximab therapy at baseline in CD and RA, which could be cross-validated successfully. Biostatistical analysis of peripheral blood gene expression data leads to the identification of gene panels that can help predict responsiveness of therapy and support the clinical decision-making process.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban RA patient Crohn's disease chronic inflammatory diseases
Megjelenés:	Genome Medicine. - 5 : 6 (2013), p. 59-69. -
További szerzők:	Póliska Szilárd (1978-) (biológus) Váncsa Andrea (1972-) (orvos) Szekanecz Zoltán (1964-) (reumatológus, belgyógyász, immunológus) Palatka Károly (1961-) (belgyógyász, gasztroenterológus) Holló Zsolt Horváth Attila (1988-) (programtervező informatikus) Steiner László Zahuczky Gábor (1975-) (molekuláris biológus, biokémikus, vegyész) Podani János Nagy László (1966-) (molekuláris sejtbiológus, biokémikus)
Pályázati támogatás:	NK72730 OTKA K100196 OTKA REGPOT-2008-1-01/MOLMEDREX/229920 FP7 TÁMOP-4.2.2/08/1 TÁMOP ETT 294-07 Egyéb K 105073 OTKA TÁMOP-4.2.2.A-11/1/KONV-2012-0031 TÁMOP
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001-es BibID:	BIBFORM037888
035-os BibID:	PMID:22467923 WOS:000303975300009
Első szerző:	Meskó Bertalan (kutatóorvos)
Cím:	Peripheral blood gene expression and IgG glycosylation profiles as markers of tocilizumab treatment in rheumatoid arthritis / Bertalan Mesko, Szilárd Póliska, Szilvia Szamosi, Zoltán Szekanecz, János Podani, Csaba Váradi, András Guttman, László Nagy
Dátum:	2012
ISSN:	0315-162X
Megjegyzések:	Objective. Tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, has recentlybeen approved as a biological therapy for rheumatoid arthritis (RA) and other diseases. It is not knownif there are characteristic changes in gene expression and immunoglobulin G glycosylation during therapyor in response to treatment.Methods. Global gene expression profiles from peripheral blood mononuclear cells of 13 patients withRA and active disease at Week 0 (baseline) and Week 4 following treatment were obtained together withclinical measures, serum cytokine levels using ELISA, and the degree of galactosylation of the IgG Nglycanchains. Gene sets separating responders and nonresponders were tested using canonical variatesanalysis. This approach also revealed important gene groups and pathways that differentiate respondersfrom nonresponders.Results. Fifty-nine genes showed significant differences between baseline and Week 4 and thus correlatedwith treatment. Significantly, 4 genes determined responders after correction for multiple testing. Tenof the 12 genes with the most significant changes were validated using real-time quantitative polymerasechain reaction. An increase in the terminal galactose content of N-linked glycans of IgG was observed inresponders versus nonresponders, as well as in treated samples versus samples obtained at baseline.Conclusion. As a preliminary report, gene expression changes as a result of tocilizumab therapy in RAwere examined, and gene sets discriminating between responders and nonresponders were found andvalidated. A significant increase in the degree of galactosylation of IgG N-glycans in patients with RAtreated with tocilizumab was documented.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban egyetemen (Magyarországon) készült közlemény
Megjelenés:	The Journal of Rheumatology 39 : 5 (2012), p. 916-928. -
További szerzők:	Póliska Szilárd (1978-) (biológus) Szamosi Szilvia (1975-) (belgyógyász, reumatológus) Szekanecz Zoltán (1964-) (reumatológus, belgyógyász, immunológus) Podani János Váradi Csaba (1988-) (molekuláris biológus) Guttman András (1954-) (vegyészmérnök) Nagy László (1966-) (molekuláris sejtbiológus, biokémikus)
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