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001-es BibID:BIBFORM033620
035-os BibID:WOS:000089341400049
Első szerző:Halmos Gábor (gyógyszerész, receptorfarmakológus, experimentális onkológus)
Cím:Human renal cell carcinoma expresses distinct binding sites for growth hormone-releasing hormone / Gabor Halmos, Andrew V. Schally, Jozsef L. Varga, Artur Plonowski, Zoltan Rekasi, Tamas Czompoly
Dátum:2000
Megjegyzések:Antagonists of growth hormone-releasing hormone (GHRH) inhibit the proliferation of various human cancers in vitro and in vivo by mechanisms that include apparent direct effects through specific binding sites expressed on tumors and that differ from pituitary human GHRH (hGHRH) receptors. In this study, GHRH antagonist JV-1-38 (20 mu g/day per animal s.c,) inhibited the growth of orthotopic CAKI-1 human renal cell carcinoma (RCC) by 83% and inhibited the development of metastases to lung and lymph nodes. Using ligand competition assays with I-125-labeled GHRH antagonist JV-1-42. we demonstrated the presence of specific high-affinity (K-d = 0.25 +/- 0.03 nM) binding sites for GHRH with a maximal binding capacity (B-max) Of 70.2 +/- 4.1 fmol/mg of membrane protein in CAKI-1 tumors. These receptors bind GHRH antagonists preferentially and display a lower affinity for hGHRH. The binding of I-125-JV-1-42 is not inhibited by vasoactive intestinal peptide (VIP)-related peptides sharing structural homology with hGHRH. The receptors for GHRH antagonists on CAKI-1 tumors are distinct from binding sites detected with I-125-VIP (K-d = 0.89 +/- 0.14 nM; B-max = 183.5 +/- 2.6 fmol/mg of protein) and also have different characteristics from GHRH receptors on rat pituitary as documented by the insignificant binding of [His(1),I-125-Tyr(10),Nle(27)]hGHRH(1-32)NH2. Reverse transcription-PCR revealed the expression of splice variants of hGHRH receptor in CAKI-1 RCC. Biodistribution studies demonstrate an in vivo uptake of I-125-JV-1-42 by the RCC tumor tissue. The presence of specific receptor proteins that bind GHRH antagonists in CAKI-1 RCC supports the view that distinct binding sites that mediate the inhibitory effect of GHRH antagonists are present on various human cancers.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:Proceedings of The National Academy of Sciences of The United States Of America. - 97 : 19 (2000), p. 10555-10560. -
További szerzők:Schally, Andrew Victor Varga József L. Plonowski, Artur Rékási Zoltán Czompoly Tamás
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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2.

001-es BibID:BIBFORM033602
035-os BibID:PMID:12364462 WOS:000178649800050
Első szerző:Halmos Gábor (gyógyszerész, receptorfarmakológus, experimentális onkológus)
Cím:Expression of growth hormone-releasing hormone and its receptor splice variants in human prostate cancer / Gabor Halmos, Andrew V. Schally, Tamas Czompoly, Magdalena Krupa, Jozsef L. Varga, Zoltan Rekasi
Dátum:2002
ISSN:0021-972X
Megjegyzések:Antagonists of GHRH inhibit the growth of various human tumors, including prostate cancer, but the tumoral receptors mediating the antiproliferative effect of GHRH antagonists have not been clearly identified. Recently, we demonstrated that human cancer cell lines express splice variants (SVs) of receptors for GHRH, of which SV1 exhibits the greatest similarity to the pituitary GHRH receptors. In this study we investigated the expression of GHRH and SVs of GHRH receptor and the binding characteristics of the GHRH receptor isoform in 20 surgical specimens of organ-confined and locally advanced human prostatic adenocarcinomas. The mRNA expression of GHRH and SVs of GHRH receptor was investigated by RT-PCR. The affinity and density of receptors for GHRH were determined by ligand competition assays based on binding of (125)I-labeled GHRH antagonist JV-1-42 to tumor membranes. Twelve of 20 tumors (60%) exhibited specific, high affinity binding for JV-1-42, with a mean dissociation constant (K(d)) of 0.81 nmol/liter and a mean maximal binding capacity of 185.2 fmol/mg membrane protein. The mRNA of SV1 was detected in 13 of 20 (65%) prostate cancer specimens and was consistent with the presence of GHRH binding. RT-PCR analyses also revealed the expression of mRNA for GHRH in 13 of 15 (86%) prostatic carcinoma specimens examined. The presence of GHRH and its tumoral receptor SVs in prostate cancers suggests the possible existence of an autocrine mitogenic loop. The antitumor effects of GHRH antagonists in prostate cancer could be exerted in part by interference with this local GHRH system.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:Journal of Clinical Endocrinology & Metabolism. - 87 : 10 (2002), p. 4707-4714. -
További szerzők:Schally, Andrew Victor Czompoly Tamás Krupa, Magdalena Varga József L. Rékási Zoltán
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3.

001-es BibID:BIBFORM033638
Első szerző:Rékási Zoltán
Cím:Antagonistic actions of analogs related to growth hormone-releasing hormone (GHRH) on receptors for GHRH and vasoactive intestinal peptide on rat pituitary and pineal cells in vitro / Zoltan Rekasi, Jozsef L. Varga, Andrew V. Schally, Gabor Halmos, Kate Groot, Tamas Czompoly
Dátum:2000
ISSN:0027-8424
Megjegyzések:Peptide analogs of growth hormone-releasing hormone (GHRH) can potentially interact with vasoactive intestinal peptide (VIP) receptors (VPAC(1)-R and VPAC(2)-R) because of the structural similarities of these two hormones and their receptors. We synthesized four new analogs related to GHRH (JV-1-50, JV-1-51, JV-1-52, and JV-1-53) with decreased GHRH antagonistic activity and increased VIP antagonistic potency. To characterize various peptide analogs for their antagonistic activity on receptors for GHRH and VIP, we developed assay systems based on superfusion of rat pituitary and pineal cells. Receptor-binding affinities of peptides to the membranes of these cells were also evaluated by radioligand competition assays. Previously reported GHRH antagonists JV-1-36, JV-1-38, and JV-1-42 proved to be selective for GHRH receptors, because they did not influence VIP-stimulated VPAC(2) receptor-dependent prolactin release from pituitary cells or VPAC(1) receptor-dependent cAMP efflux from pinealocytes but strongly inhibited GHRH-stimulated growth hormone (GH) release. Analogs JV-1-50, JV-1-51, and JV-1-52 showed various degrees of VPAC(1)-R and VPAC(2)-R antagonistic potency, although also preserving a substantial GHRH antagonistic effect. Analog JV-1-53 proved to be a highly potent VPAC(1) and VPAC(2) receptor antagonist, devoid of inhibitory effects on GHRH-evoked GH release. The antagonistic activity of these peptide analogs on processes mediated by receptors for GHRH and VIP was consistent with the binding affinity. The analogs with antagonistic effects on different types of receptors expressed on tumor cells could be utilized for the development of new approaches to treatment of various human cancers.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:Proceedings of The National Academy of Sciences of The United States of America. - 97 : 3 (2000), p. 1218-1223. -
További szerzők:Varga József L. Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Groot, Kate Czompoly Tamás
Internet cím:Szerző által megadott URL
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Intézményi repozitóriumban (DEA) tárolt változat
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4.

001-es BibID:BIBFORM033636
035-os BibID:PMID:10830299 WOS:000088386100031
Első szerző:Rékási Zoltán
Cím:Antagonists of growth hormone-releasing hormone and vasoactive intestinal peptide inhibit tumor proliferation by different mechanisms : evidence from in vitro studies on human prostatic and pancreatic cancers / Zoltan Rekasi, Jozsef L. Varga, Andrew V. Schally, Gabor Halmos, Patricia Armatis, Kate Groot, Tamas Czompoly
Dátum:2000
ISSN:0013-7227
Megjegyzések:Antagonists of GH-releasing hormone (GHRH) and vasoactive intestinal peptide (VIP) inhibit the proliferation of various tumors in vitro and in vivo, but a comparison of their antitumor effects and mechanisms of action has not been reported to date. We recently synthesized and characterized a series of analogs, some of which are primarily GHRH antagonists (JV-1-36, JV-1-38, and JV-1-42), whereas others are more selective for VIP receptors (VPAC-R; JV-1-50, JV-1-51, JV-1-52, and JV-1-53). LNCaP human prostatic cancer cells express VPAC-R, with predominant subtype 1 determined by RT-PCR. Our studies show that GHRH antagonists significantly inhibit the proliferation of both VPAC-R positive LNCaP cells (P < 0.001) and VPAC-R negative MiaPaCa-2 human pancreatic cancer cells cultured in vitro (P < 0.05 to P < 0.001). Growth inhibition of LNCaP cells is accompanied by a proportional reduction in prostate-specific antigen (PSA) secretion (P < 0.001). In a superfusion system, the inhibitory activities of the analogs on the rate of VIP and GHRH-induced PSA secretion correlate well with their VPAC-R binding affinities to LNCaP cell membranes. Antagonists more selective for VPAC-R display a stronger inhibition of inducible PSA release than GHRH antagonists, but have smaller effects or no effects on proliferation and PSA secretion in culture. Collectively, our findings demonstrate that the antiproliferative activity of the analogs on cancer cells is not correlated to their VPAC-R antagonistic potencies. Because GHRH antagonists inhibit the proliferation of LNCaP cells more powerfully than VPAC-R antagonists and also suppress the growth ofVPAC-R-negative MiaPaCa-2 cells, it can be concluded that their antiproliferative effect is exerted through a mechanism independent of VPAC-R.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Endocrinology. - 141 : 6 (2000), p. 2120-2128. -
További szerzők:Varga József L. Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Armatis, Patricia Groot, Kate Czompoly Tamás
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DOI
Intézményi repozitóriumban (DEA) tárolt változat
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5.

001-es BibID:BIBFORM033622
035-os BibID:WOS:000089341400050 PMID:10962031
Első szerző:Rékási Zoltán
Cím:Isolation and sequencing of cDNAs for splice variants of growth hormone-releasing hormone receptors from human cancers / Zoltan Rekasi, Tamas Czompoly, Andrew V. Schally, Gabor Halmos
Dátum:2000
Megjegyzések:The proliferation of various tumors is inhibited by the antagonists of growth hormone-releasing hormone (GHRH) in vitro and in vivo, but the receptors mediating the effects of GHRH antagonists have not been identified so far. Using an approach based on PCR, we detected two major splice variants (SVs) of mRNA for human GHRH receptor (GHRH-R) in human cancer cell lines, including LNCaP prostatic. MiaPaCa-2 pancreatic. MDA-MB-468 breast, OV-1063 ovarian, and H-69 small-cell lung carcinomas. In addition, high-affinity, low-capacity binding sites for GHRH antagonists were found on the membranes of cancer cell lines such as MiaPaCa-2 that are negative for the vasoactive intestinal peptide/pituitary adenylate cyclase-activating polypeptide receptor (VPAC-R) or lines such as LNCaP that are positive for VPAC-R. Sequence analysis of cDNAs revealed that the first three exons in SV1 and SV2 are replaced by a fragment of retained intron 3 having a new putative in-frame start codon. The rest of the coding region of SV1 is identical to that of human pituitary GHRH-R. whereas in SV2 exon 7 is spliced out, resulting in a 1-nt upstream frameshift. which leads to a premature stop codon in exon 8. The intronic sequence may encode a distinct 25-aa fragment of the N-terminal extracellular domain, which could serve as a proposed signal peptide. The continuation of the deduced protein sequence coded by exons 4-13 in SV1 is identical to that of pituitary GHRH-R. SV2 may encode a GHRH-R isoform truncated after the second transmembrane domain. Thus SVs of GHRH-Rs have now been identified in human extrapituitary cells. The findings support the view that distinct receptors are expressed on human cancer cells, which may mediate the antiproliferative effect of GHRH antagonists.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
külföldön készült közlemény
Megjelenés:Proceedings of The National Academy of Sciences of The United States of America. - 97 : 19 (2000), p. 10561-10566. -
További szerzők:Czompoly Tamás Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
DOI
Borító:
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