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001-es BibID:BIBFORM033548
035-os BibID:(Scopus)39049196032 (WoS)000239132600020 (PMID)16820890
Első szerző:Halmos Gábor (gyógyszerész, receptorfarmakológus, experimentális onkológus)
Cím:Characterization of receptors for growth hormone-releasing hormone in human osteosarcomas and Ewing's sarcomas / Gabor Halmos, Andrew V. Schally, Andrea L. F. Bernardino, Jozsef L. Varga
Dátum:2006
Megjegyzések:Antagonists of growth hormone-releasing hormone (GH-RH) inhibit growth of various human can s including osteosarcomas and Ewing's sarcomas, xenografted into nude mice or cultured in vitro. The antiproliferative effect of GH-RH antagonists could be mediated. in part. through the splice variants (SVs) of receptors for GH-RH which have been found in several human cancers and cancer cell lines. In this study we investigated the expression of SVs of GH-RH receptors and the binding, characteristics of these receptor isoforms in MNNG/HOS human osteosarcoma and SK-ES-1 human Ewing's sarcoma grown in nude mice. RT-PCR revealed the presence of mRNA for SVs of GH-RH receptors in both human malignant bone cancer models. Using ligand competition assays with I-125-labeled GH-RH antacyonist JV-1-42. we demonstrated in MNNG/HOS and SK-ES-I tumors the presence of specific high affinity binding sites for GH-RH (K-d=5.83 nM and K-d=2.76 nM) with a maximal binding capacity (B-max) of 552.1 fmol/mg protein and 371.9 fmol/mg protein, respectively. We also investigated the effect of GH-RH antagonist JV-1-38. administered s.c. at a dose of 20 mu g, twice daily for 4 weeks on the gene expression, affinity and concentration of receptors for GH-RH in MNNG/HOS human osteosarcomas xenografted into nude mice. Treatment with JV-1-38 did not affect the expression and binding characteristics of GH-RH receptors. High affinity binding of JV-1-38 to GH-RH receptors on MNNG/HOS tumors was characterized by an IC50 value of 1.04 nM. The presence of GH-RH receptors in human bone tumors provides a rationale for new approaches to the therapy of this malignancy based on GH-RH antagonists.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
egyetemen (Magyarországon) készült közlemény
Megjelenés:International journal of oncology. - 29 : 2 (2006), p. 463-469. -
További szerzők:Schally, Andrew Victor Bernardino, Andrea L. F. Varga József L.
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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