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001-es BibID:	BIBFORM033598
035-os BibID:	WOS:000185548300031
Első szerző:	Bajo, Ana-Maria
Cím:	Targeted doxorubicin-containing luteinizing hormone-releasing hormone analogue AN-152 inhibits the growth of doxorubicin-resistant MX-1 human breast cancers / Ana M. Bajo, Andrew V. Schally, Gabor Halmos, Attila Nagy
Dátum:	2003
Megjegyzések:	Purpose: The receptors for luteinizing hormone-releasing hormone receptor (LHRH-R) are found in >50% of human breast cancers. Doxorubicin (DOX) was linked to [D-Lys(6)]LHRH to form a cytotoxic conjugate, AN-152, which can be targeted to tumor cells expressing LHRH-R. We evaluated the effects of AN-152 on the estrogen-independent, DOX-resistant human mammary carcinoma line MX-1, xenografted into nude mice. Experimental Design: Nude mice bearing MX-1 tumors were administered five i.v. injections of AN-152 or DOX at doses equivalent to 3 mg/kg DOX. Tumor growth was followed, and changes in the expression of LHRH-R on tumors were evaluated by radioreceptor assays, reverse transcription-PCR, and Western blotting. The effects of AN-152 on the expression of human epidermal growth factor receptor (HER)-2 were investigated. Because LHRH-R are coupled to various G proteins, which are involved in mitogenic signaling, we determined the outcome of treatment with AN-152 on the levels of mRNA for different G proteins. Results: Treatment with AN-152 significantly (P < 0.05) decreased the final tumor volume to 978.56 +/- 176.85 mm(3), compared with the control tumors, which measured 2837.38 +/- 515.38 mm(3). Tumor doubling time was likewise significantly (P < 0.05) extended by AN-152 to 12.01 +/- 1.99 days from 6.45 +/- 0.36 days for the controls. Therapy with AN-152, but not with DOX, resulted in a significant decrease of LHRH-R levels on MX-1 tumors. The expression of mRNAs for HER-2, HER-3, Galpha(i2), and Galpha(11) and the levels of HER-2 and HER-3 proteins were also significantly reduced by AN-152. Conclusions: Cytotoxic LHRH analogue AN-152 could be considered for targeted chemotherapy of DOX-resistant breast cancers expressing LHRH-R.
Tárgyszavak:	Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban külföldön készült közlemény
Megjelenés:	Clinical Cancer Research. - 9 : 10 (2003), p. 3742-3748. -
További szerzők:	Schally, Andrew Victor Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Nagy Attila
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat
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