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Titolo:
THERAPEUTIC ACTIVITY OF CPT-11, A DNA-TOPOISOMERASE-I INHIBITOR, AGAINST PERIPHERAL PRIMITIVE NEUROECTODERMAL TUMOR AND NEUROBLASTOMA XENOGRAFTS
Autore:
VASSAL G; TERRIERLACOMBE MJ; BISSERY MC; VENUAT AM; GYERGYAY F; BENARD J; MORIZET J; BOLAND I; ARDOUIN P; BRESSACDEPAILLERETS B; GOUYETTE A;
Indirizzi:
INST GUSTAVE ROUSSY,CNRS URA 147,LAB PHARMACOTOXICOL & PHARMACOGENET,RUE CAMILLE DESMOULINS F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,DEPT PEDIAT ONCOL F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,DEPT PATHOL ANAT F-94805 VILLEJUIF FRANCE RHONE POULENC RORER SA F-9440 VITRY SUR SEINE FRANCE INST GUSTAVE ROUSSY,LAB CYTOGENET,CNRS URA 1967 F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,LAB CLIN & MOL PHARMACOL F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,ANIM EXPT UNIT F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,LAB CLIN BIOL F-94805 VILLEJUIF FRANCE
Titolo Testata:
British Journal of Cancer
fascicolo: 4, volume: 74, anno: 1996,
pagine: 537 - 545
SICI:
0007-0920(1996)74:4<537:TAOCAD>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
FRANCAISE-DONCOLOGIE-PEDIATRIQUE; NEURO-BLASTOMA; PHASE-II; ANTITUMOR-ACTIVITY; NUDE-MICE; N-MYC; CAMPTOTHECIN; AMPLIFICATION; CHEMOTHERAPY; CHROMOSOME-1;
Keywords:
CPT-11; PERIPHERAL PRIMITIVE NEUROECTODERMAL TUMOR; NEUROBLASTOMA; XENOGRAFT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
37
Recensione:
Indirizzi per estratti:
Citazione:
G. Vassal et al., "THERAPEUTIC ACTIVITY OF CPT-11, A DNA-TOPOISOMERASE-I INHIBITOR, AGAINST PERIPHERAL PRIMITIVE NEUROECTODERMAL TUMOR AND NEUROBLASTOMA XENOGRAFTS", British Journal of Cancer, 74(4), 1996, pp. 537-545

Abstract

The anti-tumour activity of CPT-11, a topoisomerase I inhibitor, was evaluated in four human neural-crest-derived paediatric tumour xenografts: one peripheral primitive neuroectodermal tumour (pPNET) (SK-N-MC)and three neuroblastomas. Two models, SK-N-MC and IGR-N835, were established in athymic mice from a previously established in vitro cell line. Two new neuroblastoma xenograft models, IGR-NB3 and IGR-NB8, were derived from previously untreated non-metastatic neuroblastomas. They exhibited the classic histological features of immature neuroblastoma along with N-myc amplification, paradiploidy, chromosome 1p deletions and overexpression of the human mdr 1 gene. These tumour markers have been shown to be poor prognostic factors in children treated for neuroblastoma. CPT-11 was tested against advanced stage subcutaneous tumours. CPT-II was administered i.v. using an intermittent (q4d x 3) and a daily x 5 schedule. The optimal dosage and schedule was 40 mg kg(-1) daily for 5 days. At this highest non-toxic dose, CPT-11 induced 100% tumour-free survivors on day 121 in mice bearing the pPNET SK-N-MC xenograft. For the three neuroblastoma xenografts, 38-100% complete tumourregressions were observed with a tumour growth delay from 38 to 42 days, and anti-tumour activity was clearly sustained al a lower dosage (27 mg kg(-1) day(-1)). The efficacy of five anti-cancer drugs commonlyused in paediatric oncology or in clinical development was evaluated against SK-N-MC and IGR-N835. The sensitivity of these two xenografts to cyclophosphamide, thiotepa and cisplatin was of the same order of magnitude as that of CPT-11, but they were refractory to etoposide and taxol. In conclusion, CPT-II demonstrated significant activity againstpPNET and neuroblastoma xenografts. Further clinical development of CPT-11 in paediatric oncology is warranted.

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Documento generato il 25/11/20 alle ore 03:44:56