title: In vivo studies of the new gonadotropin-releasing hormone antagonist--copolymer conjugates having antitumor activity.
abstract: The aim of the study was to test in vivo the gonadotropin-releasing hormone (GnRH) antagonists and their conjugates showing antitumor activities in vitro. The in vivo experiments with the human GnRH antagonist MI-1544 (Ac-D-Trp1,3,D-Cpa2,D-Lys6,D-Ala10)-GnRH, the chicken GnRH antagonist MI-1892 (Ac-D-Trp1,3,D-Cpa2,Lys5,/beta-Asp(DEA)/6,Gln8,D-Al a10)-GnRH, and their copolymer conjugates were carried out on MCF-7 and MDA-MB-231 human breast tumors xenografted in immunosuppressed CBA/Ca HRIJ-T6 female mice and on MXT mouse mammary tumors in BDF1 mice. The P-X-1544 and P-X-1892 conjugates were prepared by coupling the GnRH antagonists to macromolecule copolymer through biodegradable spacers. MI-1544 and its conjugate had strong, whereas MI-1892 and its conjugate had slight, castration effect in rats. All of them showed selective antitumor activity. The conjugates, given daily, inhibited both types of xenografts by 42 to 49%. Their activity was stronger in MXT mammary tumor (72 to 61%). The in vivo effect of GnRH antagonists was largely increased by coupling them to nonbiodegradable macromolecule carriers of polyanionic character. P-X-1544 and P-X-1892 GnRH antagonist-macromolecule conjugates might become important therapeutic agents for the treatment of breast cancer.
authors.affiliation: Department of Experimental Clinical Laboratory, National Institute of Oncology, Budapest, Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Vincze
authors.forename: I
authors.initials: I
authors.lastname: Pályi
authors.forename: D
authors.initials: D
authors.lastname: Gaál
authors.forename: J
authors.initials: J
authors.lastname: Pató
authors.forename: M
authors.initials: M
authors.lastname: Móra
authors.forename: I
authors.initials: I
authors.lastname: Mezõ
authors.forename: I
authors.initials: I
authors.lastname: Teplán
authors.forename: J
authors.initials: J
authors.lastname: Seprõdi
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D018450:Disease Progression; D004337:Drug Carriers; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006727:Hormone Antagonists / Q000627:therapeutic use; D006801:Humans; D008325:Mammary Neoplasms, Experimental; D051379:Mice; D008808:Mice, Inbred CBA; D009368:Neoplasm Transplantation; D013934:Thymectomy; D014183:Transplantation, Heterologous
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004337:Drug Carriers; D006727:Hormone Antagonists; C100780:MI 1892; C100781:P-X 1544; C100782:P-X 1892; D007987:Gonadotropin-Releasing Hormone; C040278:MI 1544