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001-es BibID:BIBFORM033559
035-os BibID:(Scopus)27644545827 (WoS)000233103000027 (PMID)16211544
Első szerző:Keller, Gunhild
Cím:Targeted chemotherapy with cytotoxic bombesin analogue AN-215 can overcome chemoresistance in experimental renal cell carcinomas / Gunhild Keller, Andrew V. Schally, Attila Nagy, Gabor Halmos, Benjamin Baker, Jorg B. Engel
Dátum:2005
ISSN:0008-543X
Megjegyzések:BACKGROUND. Multidrug resistance (MDR) mediated by membrane transporters, such as P-glycoprotein (MDR-1) and MDR-associated protein (MRP), remains a challenge in the therapy of renal cell carcinoma (RCC). Chemotherapy targeted to hormone receptors may provide a new approach to overcome chemoresistance. The cytotoxic analogue of bombesin/gastrin-releasing peptide (GRP), AN-215, consists of a superactive derivative of doxorubicin, AN-201, which is linked to a bombesin analogue carrier: RC-3094. METHODS. The authors examined the expression of bombesin/GRP receptors in 3 human RCC cell lines (A-498, ACHN. and 786-0) by using reverse - transcriptase polymerase chain reaction (ET-PCR) analysis and radioligand-binding assays. They also evaluated the effects of AN-215 and its cytotoxic radical AN-201 in the same RCC models in vivo, and they studied the effects of AN-215 and AN-201 on the expression levels of MDR-1 and subtype 1 of MRP (MRP-1) by using real-time PCR. RESULTS. A N-215 significantly (P < 0.05) inhibited the growth of A-498, ACHN, and 786-0 RCC xenografted into nude mice by 59.2-67.6%, whereas the cytotoxic radical AN-201 alone had no significant antitumor effects. The efficacy of AN-215 was independent of the expression patterns of MDR-1 and MRP-1 in these RCC cell lines. The induction of MDR-1 by AN-215 was similar (Experiment 2) or weaker (Experiment 1) compared with AN-201. Both AN-215 and AN-201 caused only a minor induction of MRP-1. CONCLUSIONS. The current findings indicated that targeted chemotherapy with cytotoxic bombesin/GRP analogue AN-215 can inhibit the growth of RCC, providing a new treatment modality for patients with advanced RCC.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
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Megjelenés:Cancer. - 104 : 10 (2005), p. 2266-2274. -
További szerzők:Schally, Andrew Victor Nagy Attila Halmos Gábor (1962-) (gyógyszerész, receptorfarmakológus, experimentális onkológus) Baker, Benjamin Engel, Jörg B.
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