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001-es BibID:	BIBFORM033618
035-os BibID:	WOS:000089931600051 PMID:11051271
Első szerző:	Chatzistamou, Ioulia
Cím:	Effective treatment of metastatic MDA-MB-435 human estrogen-independent breast carcinomas with a targeted cytotoxic analogue of luteinizing hormone-releasing hormone AN-207 / Ioulia Chatzistamou, Andrew V. Schally, Attila Nagy, Patricia Armatis, Karoly Szepeshazi, Gabor Halmos
Dátum:	2000
Megjegyzések:	A highly potent derivative of doxorubicin, 2-pyrrolinod-oxorubicin (AN-201), was linked to [D-Lys(6)]luteinizing hormone-releasing hormone (LH-RH) to form a cytotoxic analogue, AN-207, that can be targeted to LH-RT-I receptors, The effects of AN-207 were investigated in MDA-MB-435 human estrogen-independent breast carcinomas, which express LB-RH receptors, In experiment I, nude mice bearing orthotopically implanted tumors received a single i.v. injection of AN-207, AN-201, or the carrier at 250 nmol/kg, Five weeks after administration of AN-207, tumor volume was significantly decreased by 66% (P < 0.001) and tumor burden by 71% (P < 0.05) as compared with controls, but no significant effects occurred in other groups. Six of eight (75%) control animals and 37.5% of mice treated with AN-201 developed metastases in the lymph nodes, whereas no lymphatic spread was found in any of the mice that received injections of AN-207, The antitumor effect of AN-207 could be partially blocked by pretreatment of the tumor-bearing mice with high doses of agonist [D-Trp(6)]LH-RH,which suggests that AN-207 acts on LH-RH receptors on tumors. The mortality due to toxicity was 25% in the group receiving AN-201 and 12.5% in the AN-207-treated group. Radioligand binding assays revealed the presence of high-affinity binding sites for LH-RH on tumor membranes, and mRNA for LH-RH receptors was demonstrated by reverse transcription-PCR, In experiment 2, two i.v. injections of AN-207 or AN-201 at 150 nmol/kg were given on days 0 and 28 to mice bearing orthotopic xenografts of MDA-MB-435, The outcome of the treatment was similar to that observed in experiment 1, but without any toxicity-related deaths, Tumor growth inhibition and prevention of metastatic disease suggest that cytotoxic LH-RH analogue AN-207 could be considered for the treatment of human estrogen-independent breast cancers expressing receptors for LH-RH.
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban külföldön készült közlemény
Megjelenés:	Clinical Cancer Research. - 6 : 10 (2000), p. 4158-4165. -
További szerzők:	Schally, Andrew Victor Nagy Attila Armatis, Patricia Szepesházi Károly Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus)
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat
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