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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:	BIBFORM047176
035-os BibID:	PMID:23744510
Első szerző:	Szepesházi Károly
Cím:	Powerful Inhibition of Experimental Human Pancreatic Cancers by Receptor Targeted Cytotoxic LH-RH analog AEZS-108 / Karoly Szepeshazi, Andrew V. Schally, Norman L. Block, Gabor Halmos, Mehrdad Nadji, Luca Szalontay, Irving Vidaurre, Andrew Abi-Chaker, Ferenc G. Rick
Dátum:	2013
Megjegyzések:	Pancreatic carcinoma is one of the cancers with the worse prognosis, thus any therapeutic improvement is imperative. Cytotoxic LH-RH analog, AN-152 (proprietary designation, AEZS-108), consisting of doxorubicin (DOX) conjugated to D-Lys6LH-RH, is now in clinical trials for targeted therapy of several sex hormone-dependent tumors that express LH-RH receptors. We investigated LH-RH receptors in human pancreatic carcinoma and the effects of AN-152 (AEZS-108) on experimental pancreatic cancers. We determined LH-RH receptor presence in human pancreatic cancer samples by immunohistochemistry and, in three human pancreatic cancer lines (SW-1990, Panc-1 and CFPAC-1), by binding assays and Western blotting. The effects of the cytotoxic LH-RH analog were investigated on growth of these same cancer lines xenografted into nude mice. We also analyzed differences between the antitumor effects of the cytotoxic analog and its cytotoxic radical alone, doxorubicin (DOX), on the expression of cancer-related genes by PCR arrays. LH-RH receptors were expressed in two randomly selected surgically removed human pancreatic cancer samples and in all three cancer lines. Cytotoxic LH-RH analogs powerfully inhibited growth of all three tumor lines in nude mice; AN-152 was significantly stronger than DOX on Panc-1 and CFPAC-1 cancers. PCR array showed that cytotoxic LH-RH analog AN-152 affected the expression of genes associated with cellular migration, invasion, metastasis and angiogenesis more favorably than DOX, however the changes in gene expression varied considerably among the three cancer lines. Cytotoxic LH-RH analog, AEZS-108, may be a useful agent for the treatment of LH-RH receptor positive advanced pancreatic carcinoma.
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban Molekulatudomány
Megjelenés:	Oncotarget (electronic resources). - 4 : 5 (2013), p. 751-760. -
További szerzők:	Schally, Andrew Victor Block, Norman L. Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Nadji, Mehrdad Szalontay Luca Vidaurre, Irving Abi-Chaker, Andrew Rick Ferenc G.
Pályázati támogatás:	K81596 OTKA 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:	Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM036738
035-os BibID:	PMID:22824624
Első szerző:	Szepesházi Károly
Cím:	Receptor-targeted therapy of human experimental urinary bladder cancers with cytotoxic LH-RH analog AN-152 [AEZS- 108] / Karoly Szepeshazi, Andrew V. Schally, Gunhild Keller, Norman L. Block, Daniel Benten, Gabor Halmos, Luca Szalontay, Irving Vidaurre, Miklos Jaszberenyi, Ferenc G. Rick
Dátum:	2012
Megjegyzések:	Many bladder cancers progress to invasion with poor prognosis; new therapeutic methods are needed. We developed a cytotoxic LH-RH analog, AN-152 (AEZS-108) containing doxorubicin (DOX), for targeted therapy of cancers expressing LHRH receptors. We investigated the expression of LH-RH receptors in clinical bladder cancers and in HT-1376, J82, RT-4 and HT-1197 human bladder cancer lines. The effect of analog, AN-152, on growth of these tumor lines xenografted into nude mice was analyzed. Using molecular and functional assays, we also evaluated the differences between the effects of AN-152, and DOX alone. We demonstrated the expression of LH-RH receptors on 18 clinical bladder cancers by immunohistochemistry and on four human urinary bladder cancer lines HT-1376, J82, RT-4 and HT-1197 by Western blotting and binding assays. AN-152 powerfully inhibited growth of these bladder cancers in nude mice. AN-152 exerted greater effects than DOX and was less toxic. DOX activated strong multidrug resistance mechanisms in RT-4 and HT-1197 cancers, while AN-152 had no or less such effect. PCR assays and in vitro studies revealed differences in the action of AN-152 and DOX on the expression of genes involved in apoptosis. These results suggest that targeted cytotoxic LH-RH analog, AN-152 (AEZS- 108), should be examined for treatment of patients with LH-RH receptor positive invasive bladder cancers.
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban Molekulatudomány külföldön készült közlemény
Megjelenés:	Oncortarget (electronic resources). - 3 : 7 (2012), p. 686-699. -
További szerzők:	Schally, Andrew Victor Keller, Gunhild Block, Norman L. Benten, Daniel Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Szalontay Luca Vidaurre, Irving Jászberényi Miklós Rick Ferenc G.
Pályázati támogatás:	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
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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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