Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Buthionine sulfoximine and myeloablative concentrations of melphalan overcome resistance in a melphalan-resistant neuroblastoma cell line
Autore:
Anderson, CP; Seeger, RC; Satake, N; Monforte-Munoz, HL; Keshelava, N; Bailey, HH; Reynolds, CP;
Indirizzi:
Childrens Hosp Los Angeles, Div Hematol Oncol, Los Angeles, CA 90027 USA Childrens Hosp Los Angeles Los Angeles CA USA 90027 Angeles, CA 90027 USA Univ So Calif, Keck Sch Med, Dept Pediat, Los Angeles, CA USA Univ So Calif Los Angeles CA USA h Med, Dept Pediat, Los Angeles, CA USA Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA USA Univ So Calif Los Angeles CA USA h Med, Dept Pathol, Los Angeles, CA USA Univ Wisconsin, Dept Med, Ctr Comprehens Canc, Madison, WI USA Univ Wisconsin Madison WI USA Med, Ctr Comprehens Canc, Madison, WI USA
Titolo Testata:
JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
fascicolo: 8, volume: 23, anno: 2001,
pagine: 500 - 505
SICI:
1077-4114(200111)23:8<500:BSAMCO>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
BONE-MARROW TRANSPLANTATION; CHILDRENS CANCER GROUP; PHASE-I TRIAL; STAGE-4 NEUROBLASTOMA; GLUTATHIONE DEPLETION; 13-CIS-RETINOIC ACID; RISK NEUROBLASTOMA; DRUG-RESISTANCE; CYTO-TOXICITY; CHEMOTHERAPY;
Keywords:
neuroblastoma; buthionine sulfoximine; melphalan; alkylator resistance; myeloablative therapy; P-glycoprotein;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Reynolds, CP Childrens Hosp Los Angeles, Div Hematol Oncol, MS-57,4650 Sunset Blvd, LosAngeles, CA 90027 USA Childrens Hosp Los Angeles MS-57,4650 Sunset Blvd Los Angeles CA USA 90027
Citazione:
C.P. Anderson et al., "Buthionine sulfoximine and myeloablative concentrations of melphalan overcome resistance in a melphalan-resistant neuroblastoma cell line", J PED H ONC, 23(8), 2001, pp. 500-505

Abstract

Background: Alkylator resistance contributes to treatment failure in high-risk neuroblastoma. Buthionine sulfoximine (BSO) can deplete glutathione and synergistically enhance in vitro sensitivity to the alkylating agent melphalan (L-PAM) for many neuroblastoma cell lines, but optimal use of this combination needs to be defined because clinical responses have been less frequent and not durable. Patients and Methods: The authors established and characterized a neuroblastoma cell line (CHLA-171) from a patient who died of progressive disease after treatment with BSO and low-dose L-PAM. Results: CHLA-171 lacks MYCN amplification, expresses PGP (P-glycoprotein)9.5 RNA, and shows cell surface antigen expression (human leukocyte antigen class I weakly positive, but HSAN 1.2 (hybridoma, SAN 1.2) and anti-GD2 (anti-ganglioside GD2 antibody) strongly positive) characteristic of neuroblastoma cell lines. Twenty-four hours of BSO treatment (0-1,000 mu mol/L) maximally depleted CHLA-171 glutathione to 36% of baseline. The cytotoxic response of CHLA-171 to BSO and L-PAM, alone and in combination, was measured by digital image microscopy (DIMSCAN) over a range of drug concentrations and compared with drug levels obtained in the patient during BSO/L-PAM therapy. As single agents, CHLA-171 was highly resistant to L-PAM (LD90 = 42 mu mol/L; peak plasma concentration in the patient equals 3.9 mu mol/L) and moderately resistant to BSO (LD90 = 509 mu mol/L steady-state concentration in the patient equals 397 mu mol/L). Treatment with a 10:1 (BSO:L-PAM) fixedratio combination synergistically overcame resistance (3-4 logs of cell kill, combination index <1) at clinically achievable levels of BSO (100-400 <mu>mol/L) and levels of L-PAM (10-40 mu mol/L) clinically achievable only with hematopoietic stern cell support. Conclusions: The in vitro results obtained for CHLA-171 suggest that BSO/L-PAM therapy may be optimally effective for drug-resistant neuroblastoma using myeloablative doses of L-PAM.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 13:30:46