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001-es BibID:	BIBFORM033758
035-os BibID:	(Scopus)0030656285 (WoS)A1997YH75900014
Első szerző:	Miyazaki, Masahiro
Cím:	Growth inhibition of human ovarian cancers by cytotoxic analogues of luteinizing hormone-releasing hormone / Masahiro Miyazaki, Attila Nagy, Andrew V. Schally, Najib Lamharzi, Gabor Halmos, Karoly Szepeshazi, Kate Groot, Patricia Armatis
Dátum:	1997
ISSN:	0027-8874
Megjegyzések:	Background: Receptors for luteinizing hormone-releasing hormone (LH-RH) are found in nearly 80% of human ovarian cancers. The chemotherapeutic agent doxorubicin can be linked to [D-lysine(6)]LH-RH to form a cytotoxic analogue (AN-152) that may have greater specificity for tumor cells. This study was conducted to investigate the effects of AN-152 on the growth of LH-RH receptor-positive OV-1063 human epithelial ovarian cancers. Methods: Nude mice bearing human ovarian tumors, OV-163 or UCI-107 (LH-RH recpetor negative), were injected intraperitoneally with saline (control) or with equimolar doses of AN-152 or doxorubicin; experiments involving mice with OV-1063 tumors also included groups that were administered [D-lysine(6)]LH-RH either alone or in combination with doxorubicin. Tumor volume, weight, doubling time, and burden (i.e, tumor weight/body weight) as well as tumor apoptotic and mitotic indices were determined. The levels of receptors for LH-RH and epidermal growth factor (EGF) and their messenger RNAs were measured by use of radioreceptor and reverse transcription-polymerase chain reaction assays respectively. Results: The growth of OV-1063 ovarian tumors in nude mice as based on reduction in tumor volume, was inhibited significantly (all P,.05, two-sided) 4 weeks after treatment with AN-152, even at the lowest dose tested (413 nmol/20g weight); the toxic effects of an equivalent dose of doxorubicin caused substantial mortality. High-affinity receptors for LH-RH and EGF were found on cell membranes of OV-1063 cancers; however, after in vivo treatment with AN-152, LH-RH receptor-binding sites were not detectable and EGF receptors were reduced in number. The growth of UCI-107 ovarian cancers was not inhibited by AN-152. Conclusions: In nude mice bearing LH-RH receptor positive OV-1063 epithelial ovarian cancers, systemic administration of AN-152 is less toxic and inhibits tumor growth better than equimolar doses of doxorubicin.
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban külföldön készült közlemény
Megjelenés:	Journal of The National Cancer Institute. - 89 : 23 (1997), p. 1803-1809. -
További szerzők:	Nagy Attila Schally, Andrew Victor Lamharzi, Najib Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Szepesházi Károly Groot, Kate Armatis, Patricia
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