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001-es BibID:	BIBFORM114434
035-os BibID:	(Scopus)85169116190 (WoS)001063702100001
Első szerző:	Csizmarik Anita
Cím:	Comparative proteome and serum analysis identified FSCN1 as a marker of abiraterone resistance in castration-resistant prostate cancer / Csizmarik Anita, Nagy Nikolett, Keresztes Dávid, Váradi Melinda, Bracht Thilo, Sitek Barbara, Witzke Kathrin, Puhr Martin, Tornyi Ilona, Lázár József, Takács László, Kramer Gero, Sevcenco Sabina, Maj-Hes Agnieszka, Hadaschik Boris, Nyirády Péter, Szarvas Tibor
Dátum:	2023
ISSN:	1365-7852
Megjegyzések:	Background: Abiraterone (Abi) is an androgen receptor signaling inhibitor that significantly improves patients' life expectancy in metastatic prostate cancer (PCa). Despite its beneficial effects, many patients have baseline or acquired resistance against Abi. The aim of this study was to identify predictive serum biomarkers for Abi treatment. Methods: We performed a comparative proteome analysis on three Abi sensitive (LNCaPabl, LAPC4, DuCaP) and resistant (LNCaPabl-Abi, LAPC4-Abi, DuCaP-Abi) PCa cell lines using liquid chromatography tandem mass spectrometry (LC-MS/MS) technique. Two bioinformatic selection workflows were applied to select the most promising candidate serum markers. Serum levels of selected proteins were assessed in samples of 100 Abi-treated patients with metastatic castration-resistant disease (mCRPC) using ELISA. Moreover, FSCN1 serum concentrations were measured in samples of 69 Docetaxel (Doc) treated mCRPC patients. Results: Our proteome analysis identified 68 significantly, at least two-fold upregulated proteins in Abi resistant cells. Using two filtering workflows four proteins (AMACR, KLK2, FSCN1 and CTAG1A) were selected for ELISA analyses. We found high baseline FSCN1 serum levels to be significantly associated with poor survival in Abi-treated mCRPC patients. Moreover, the multivariable analysis revealed that higher ECOG status (>1) and high baseline FSCN1 serum levels (>10.22 ng/ml by ROC cut-off) were independently associated with worse survival in Abi-treated patients (p < 0.001 and p = 0.021, respectively). In contrast, no association was found between serum FSCN1 concentrations and overall survival in Doc-treated patients. Conclusions: Our analysis identified baseline FSCN1 serum levels to be independently associated with poor survival of Abi-treated, but not Doc-treated mCRPC patients, suggesting a therapy specific prognostic value for FSCN1.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Prostate Cancer And Prostatic Diseases. - [Epub ahead of print] (2023). -
További szerzők:	Nagy Nikoletta Keresztes Dávid Váradi Melinda Bracht, Thilo Sitek Barbara Witzke, Kathrin Puhr, Martin Tornyi Ilona (1982-) (molekuláris biológus) Lázár József Takács László (1955-) (orvos) Kramer, Gero Sevcenko, Sabina Maj-Hes, Agnieszka Hadaschik, Boris Nyirády Péter Szarvas Tibor (urológus)
Pályázati támogatás:	NKFIH / FK 124431 Egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM017037
Első szerző:	Rózsa Bernadett (molekuláris biológus)
Cím:	Receptors for Luteinizing Hormone-Releasing Hormone (LHRH) in Benign Prostatic Hyperplasia (BPH) as Potential Molecular Targets for Therapy with LHRH Antagonist Cetrorelix / Bernadett Rozsa, Mehrdad Nadji, Andrew V. Schally, Balazs Dezso, Tibor Flasko, Gyorgy Toth, Melinda Mile, Norman L. Block, Gabor Halmos
Dátum:	2011
ISSN:	0270-4137
Megjegyzések:	The majority of men will develop symptoms of benign prostatic hyperplasia (BPH) after 70 years of age. Various studies indicate that antagonists of LHRH, such as cetrorelix, exert direct inhibitory effects on BPH mediated by specific LHRH receptors. Our aim was to investigate the mRNA for LHRH and LHRH receptors and the expression of LHRH receptors in specimens of human BPH.METHODSThe expression of mRNA for LHRH (n?=?35) and LHRH receptors (n?=?55) was investigated by RT-PCR in surgical specimens of BPH, using specific primers. The characteristics of binding sites for LHRH on 20 samples were determined by ligand competition assays. The LHRH receptor expression was also examined in 64 BPH specimens by immunohistochemistry.RESULTSPCR products for LHRH were found in 18 of 35 (51%) BPH tissues and mRNA for LHRH receptors was detected in 39 of 55 (71%) BPH specimens. Eighteen of 20 (90%) samples showed a single class of high affinity binding sites for [D-Trp6]LHRH with a mean Kd of 4.04?nM and a mean Bmax of 527.6?fmol/mg membrane protein. LHRH antagonist cetrorelix showed high affinity binding to LHRH receptors in BPH. Positive immunohistochemical reaction for LHRH receptors was present in 42 of 64 (67%) BPH specimens.CONCLUSIONA high incidence of LHRH receptors in BPH supports the use of LHRH antagonists such as cetrorelix, for treatment of patients with lower urinary tract symptoms from BPH.
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban human benign prostatic hyperplasia luteinizing hormone-releasing hormone (LHRH) receptors LHRH antagonist Molekulatudomány
Megjelenés:	Prostate. - 71 : 5 (2011), p. 445-452. -
További szerzők:	Nadji, Mehrdad Schally, Andrew Victor Dezső Balázs (1951-) (pathológus) Flaskó Tibor (1960-) (urológus) Tóth György (1965-) (urológus) Mile Melinda (1983-) (gyógyszerész) Block, Norman L. Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
Pályázati támogatás:	K81596 OTKA ETT 240/2006 Egyéb TÁMOP-4.2.1/B-09/1/KONV-2010-0007 TÁMOP Peptid hormon és növekedési faktor receptorok mint molekuláris célpontok a humán rosszindulatú daganatok diagnosztikájában és terápiájában
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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