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Titolo:
ACTIVITY OF FOTEMUSTINE IN MEDULLOBLASTOMA AND MALIGNANT GLIOMA XENOGRAFTS IN RELATION TO O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE AND ALKYLPURINE-DNA N-GLYCOSYLASE ACTIVITY
Autore:
VASSAL G; BOLAND I; TERRIERLACOMBE MJ; WATSON AJ; MARGISON GP; VENUAT AM; MORIZET J; PARKER F; LACROIX C; LELLOUCHTUBIANA A; PIERREKAHN A; POULLAIN MG; GOUYETTE A;
Indirizzi:
INST GUSTAVE ROUSSY,CNRS URA 147,LAB PHARMACOTOXICOL & PHARMACOGENET,RUE CAMILLE DESMOULINS F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,DEPT PEDIAT F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,DEPT ANATOMOPATHOL F-94805 VILLEJUIF FRANCE CHRISTIE HOSP NHS TRUST,PATERSON INST CANC RES,DEPT CARCINOGENESIS,CANC RES CAMPAIGN MANCHESTER M20 9BX LANCS ENGLAND INST GUSTAVE ROUSSY,CNRS URA 1967,LAB CYTOGENET F-94805 VILLEJUIF FRANCE HOP BICETRE,DEPT NEUROSURG F-94000 LE KREMLIN BICETR FRANCE HOP BICETRE,NEUROPATHOL LAB F-94000 LE KREMLIN BICETR FRANCE HOP NECKER ENFANTS MALAD,DEPT ANATOMOPATHOL F-75015 PARIS FRANCE HOP NECKER ENFANTS MALAD,DEPT PEDIAT NEUROSURG F-75015 PARIS FRANCE INST RECH INT SERVIER F-92415 COURBEVOIE FRANCE
Titolo Testata:
Clinical cancer research
fascicolo: 2, volume: 4, anno: 1998,
pagine: 463 - 468
SICI:
1078-0432(1998)4:2<463:AOFIMA>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
BRAIN-TUMOR XENOGRAFTS; PHASE-II; NITROSOUREA; AGENTS; 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA; THIOTEPA; CHILDREN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
26
Recensione:
Indirizzi per estratti:
Citazione:
G. Vassal et al., "ACTIVITY OF FOTEMUSTINE IN MEDULLOBLASTOMA AND MALIGNANT GLIOMA XENOGRAFTS IN RELATION TO O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE AND ALKYLPURINE-DNA N-GLYCOSYLASE ACTIVITY", Clinical cancer research, 4(2), 1998, pp. 463-468

Abstract

Fotemustine is a chloroethylnitrosourea with antitumor activity in disseminated melanoma and adult primary brain tumors, Because new drugs are required for the treatment of medulloblastoma in children, we evaluated the preclinical antitumor activity of fotemustine in four s.c. medulloblastoma xenografts, in comparison with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), Both drugs were administered as a single i.p. injection to nude mice bearing advanced-stage tumor, Fotemustine displayed significant antitumor activity in three of four medulloblastoma xenografts; two, IGRM34 and IGRM57, were highly sensitive, with 37 and 100% tumor-free survivors, respectively, more than 120 days after treatment at the highest nontoxic dose (50 mg/kg), Fotemustine was also highly active in a malignant glioma xenograft (IGRG88; five of six tumor-free survivors on day 177), Fotemustine proved to be significantly more active than BCNU in IGRM34 and the glioma xenograft IGRG88, The DNA repair protein O-6-alkylguanine-DNA alkyltransferase (ATase) was detected in all tumor xenografts, ranging in activity from 6 to 892 fmol/mg protein, The high in vivo sensitivity to fotemustine and BCNU observed in three xenografts was clearly associated with a low ATase activity (<20 fmol/mg), whereas the two poorly sensitive or refractory medulloblastoma xenografts showed high ATase activity (>500 fmol/mg), Alkylpurine-DNA N-glycosylase activity was detected in all tumor xenografts butat levels ranging only from 513 to 1105 fmol/mg/h; no consistent relationship was found between alkylpurine-DNA N-glycosylase activity and the in vivo sensitivity to the two chloroethylnitrosoureas. The improved activity and tolerance of fotemustine in comparison with BCNU in pediatric medulloblastoma xenografts strongly support the clinical development of this agent in children with brain tumors, in which ATase should be examined as a potential prognostic indicator.

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Documento generato il 02/12/20 alle ore 05:37:22