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Titolo:
DNA-TOPOISOMERASE-I, A NEW TARGET FOR THE TREATMENT OF NEUROBLASTOMA
Autore:
VASSAL G; PONDARRE C; CAPPELLI C; TERRIERLACOMBE MJ; BOLAND I; MORIZET J; BENARD J; VENUAT AM; ARDOUIN P; HARTMANN O; GOUYETTE A;
Indirizzi:
INST GUSTAVE ROUSSY,LAB PHARMACOTOXICOL & PHARMACOGENET,CNRS,URA 147,RUE CAMILLE DESMOULINS F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,DEPT PAEDIAT F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,DEPT HISTOPATHOL F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,LAB CLIN & MOL PHARMACOL F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,LAB CYTOGENET,CNRS,URA 1967 F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,ANIM EXPERIMENTAT UNIT F-94805 VILLEJUIF FRANCE
Titolo Testata:
European journal of cancer
fascicolo: 12, volume: 33, anno: 1997,
pagine: 2011 - 2015
SICI:
0959-8049(1997)33:12<2011:DANTFT>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR XENOGRAFTS; CAMPTOTHECIN; 9-DIMETHYLAMINOMETHYL-10-HYDROXYCAMPTOTHECIN; INHIBITOR; CELLS; CHEMOTHERAPY; EXPRESSION; EFFICACY; CPT-11; ADULT;
Keywords:
TOPOISOMERASE I; IRINOTECAN; TOPOTECAN; NEUROBLASTOMA; XENOGRAFTS;
Tipo documento:
Article
Natura:
Periodico
Citazioni:
24
Recensione:
Indirizzi per estratti:
Citazione:
G. Vassal et al., "DNA-TOPOISOMERASE-I, A NEW TARGET FOR THE TREATMENT OF NEUROBLASTOMA", European journal of cancer, 33(12), 1997, pp. 2011-2015

Abstract

DNA-topoisomerase I is the nuclear target of new anticancer drugs, namely camptothecin and its derivatives. In order to establish the rational basis for their clinical development in paediatric oncology, the antitumour activity of irinotecan (CPT-11) and topotecan, two camptothecin water-soluble derivatives, was studied in nude mice bearing neuroblastoma xenografts. The panel was composed of 4 previously establishedsubcutaneous xenograft lines (IGR-N835, IGR-N91, IGR-NB3, IGR-NB8) that exhibited the common biological markers of poor prognosis in children (MYCN amplification, 1p deletion, paradiploidy and/or MDR1 overexpression). Irinotecan and topotecan were administered i.v. or i.p. over 5 consecutive days in animals bearing tumours. Irinotecan (40 mg/kg/day) induced 20-100% complete regressions with tumour growth delays ranging from 20 to 46 days. Two out of 10 IGR-N91 bearing animals were tumour free more than 120 days after treatment with the top dose (50 mg/kg/day). Topotecan (2.7 mg/kg/day) induced 0-67% complete regressions with tumour growth delays ranging from 23 to 50 days. One out of 8 IGR-NB3 bearing mice was tumour free at the end of the experiment. The antitumour activity of both drugs was clearly sustained at a lower dose level. Topoisomerase I activity was assayed in 15 neuroblastomas, 3 ganglioneuroblastomas and 2 normal adrenal glands, using a DNA relaxationassay. Topoisomerase I activity ranged from 69 to 1304 arbitrary units/mg of protein, and was significantly higher in immature neuroblastomas than in ganglioneuroblastomas and adrenal glands. In conclusion, irinotecan and topotecan are active against neuroblastoma xenografts. Their target is expressed in patients' tumour samples. Clinical development of topoisomerase I inhibitors in children with neuroblastoma is warranted. (C) 1997 Published by Elsevier Science Ltd.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/11/20 alle ore 04:44:16