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001-es BibID:	BIBFORM083143
Első szerző:	Molnár-Fodor Klára (biotechnológus)
Cím:	The targeted LHRH analog AEZS-108 alters expression of genes related to angiogenesis and development of metastasis in uveal melanoma / Klara Fodor, Nikoletta Dobos, Andrew Schally, Zita Steiber, Gabor Olah, Eva Sipos, Lorant Szekvolgyi, Gabor Halmos
Dátum:	2020
ISSN:	1949-2553 1949-2553
Megjegyzések:	Uveal melanoma (UM) is the most common malignant tumor of the eye. Recently, we have established that 46% of UM specimens express LHRH receptors. This finding supports the idea of a LHRH receptor-targeted therapy of UM patients. Cytotoxic analog of LHRH, AEZS-108 exhibits effective anti-cancer activity in LHRH-receptor positive cancers. AEZS-108 is a hybrid molecule, composed of a synthetic peptide carrier and the cytotoxic doxorubicin (DOX). In the present study, we investigated AEZS-108 induced cytotoxicity and the altered mRNA expression profile of regulatory factors related to angiogenesis and metastasis in LHRH receptor positive OCM3 cells. Our results show that AEZS-108 upregulates the expression of MASPIN/SERPINB5 tumor suppressor gene, which is downregulated in normal uvea and UM specimens independently from the LHRH receptor-ligand interaction. AEZS-108 also substantially downregulates hypoxia-inducible factor 1 alpha (HIF1A) expression. In order to investigate the mechanism of the induction of MASPIN by AEZS-108, OCM3 cells were treated with free DOX, D-Lys6 LHRH analog, or AEZS-108. qRT- PCR analysis revealed in OCM3 cells that AEZS-108 is a more potent inducer of MASPIN than free DOX. In conclusion, we show for the first time that AEZS-108 has a major impact in the regulation of angiogenesis thus plays a potential role in tumor suppression. Taken together, our results support the development of novel therapeutic strategies for UM focusing on LHRH receptors.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk uveal melanoma luteinizing hormone-releasing hormone (LHRH) receptor angiogenesis MASPIN/SERPINB5 AEZS-108 (AN-152/Zoptarelin Doxorubicin Acetate)
Megjelenés:	Oncotarget. - 11 : 2 (2020), p. 175-187. -
További szerzők:	Dobos Nikoletta (1981-) (biológus) Schally, Andrew Victor Steiber Zita (1977-) (orvos, szemész) Oláh Gábor (1987-) (gyógyszerész) Sipos Éva (1989-) (gyógyszerész) Székvölgyi Lóránt (1977-) (biofizikus, biokémikus, sejtbiológus) Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
Pályázati támogatás:	GINOP-2.3.2-15-2016-00024 GINOP MTA-DE Lendület MTA Élettudományok - Orvosi tudományok OTKA-K 81596 OTKA TÁMOP-4.2.2.A-11/1/KONV-2012-0025 TÁMOP GINOP-2.3.2-15-2016-00043 GINOP GINOP-2.3.2-15-2016-00024 GINOP TÁMOP-4.2.4.A/2-11-1-2012-0001 TÁMOP
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001-es BibID:	BIBFORM048907
035-os BibID:	(PMID)24077773
Első szerző:	Treszl Andrea (molekuláris biológus)
Cím:	Substantial expression of luteinizing hormone-releasing hormone (LHRH) receptor type I in human uveal melanoma / Andrea Treszl, Zita Steiber, Andrew V. Schally, Norman L. Block, Balazs Dezso, Gabor Olah, Bernadett Rozsa, Klara Fodor, Armin Buglyo, Janos Gardi, Andras Berta, Gabor Halmos
Dátum:	2013
ISSN:	1949-2553
Megjegyzések:	Uveal melanoma is the most common primary intraocular malignancy in adults, with a very high mortality rate due to frequent liver metastases. Consequently, the therapy of uveal melanoma remains a major clinical challenge and new treatment approaches are needed. For improving diagnosis and designing a rational and effective therapy, it is essential to elucidate molecular characteristics of this malignancy. The aim of this study therefore was to evaluate as a potential therapeutic target the expression of luteinizing hormone-releasing hormone (LHRH) receptor in human uveal melanoma. The expression of LHRH ligand and LHRH receptor transcript forms was studied in 39 human uveal melanoma specimens by RT-PCR using gene specific primers. The binding charachteristics of receptors for LHRH on 10 samples were determined by ligand competition assays. The presence of LHRH receptor protein was further evaluated by immunohistochemistry. The expression of mRNA for type I LHRH receptor was detected in 18 of 39 (46%) of tissue specimens. mRNA for LHRH-I ligand could be detected in 27 of 39 (69%) of the samples. Seven of 10 samples investigated showed high affinity LHRH-I receptors. The specific presence of full length LHRH receptor protein was further confirmed by immunohistochemistry. A high percentage of uveal melanomas express mRNA and protein for type-I LHRH receptors. Our results support the merit of further investigation of LHRH receptors in human ophthalmological tumors. Since diverse analogs of LHRH are in clinical trials or are already used for the treatment of various cancers, theseanalogs could be considered for the LHRH receptor-based treatment of uveal melanoma.
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban uveal melanoma luteinizing hormone-releasing hormone (LHRH) receptor
Megjelenés:	Oncotarget. - 4 : 10 (2013), p. 1721-1728. -
További szerzők:	Steiber Zita (1977-) (orvos, szemész) Schally, Andrew Victor Block, Norman L. Dezső Balázs (1951-) (pathológus) Oláh Gábor (1987-) (gyógyszerész) Rózsa Bernadett (1981-) (molekuláris biológus) Molnár-Fodor Klára (1989-) (biotechnológus) Buglyó Armin Gardi János Berta András (1955-) (szemész, gyermekszemész) Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
Pályázati támogatás:	TÁMOP-4.2.2.A-11/1/KONV-2012-0025 TÁMOP K81596 OTKA
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat
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