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Titolo:
PHARMACOLOGICAL BASIS FOR A NOVEL THERAPEUTIC STRATEGY BASED ON THE USE OF AQUATED CISPLATIN
Autore:
ZHENG H; FINK D; HOWELL SB;
Indirizzi:
UNIV CALIF SAN DIEGO,DEPT MED,9500 GILMAN DR LA JOLLA CA 92093 UNIV CALIF SAN DIEGO,DEPT MED LA JOLLA CA 92093 UNIV CALIF SAN DIEGO,CTR CANC LA JOLLA CA 92093
Titolo Testata:
Clinical cancer research
fascicolo: 7, volume: 3, anno: 1997,
pagine: 1157 - 1165
SICI:
1078-0432(1997)3:7<1157:PBFANT>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
OVARIAN-CARCINOMA CELLS; DNA PLATINATION; ADVANCED HEAD; NECK-CANCER; PLATINUM; ACCUMULATION; LINES; CIS-DIAMMINEDICHLOROPLATINUM(II); TOXICITY; BINDING;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
39
Recensione:
Indirizzi per estratti:
Citazione:
H. Zheng et al., "PHARMACOLOGICAL BASIS FOR A NOVEL THERAPEUTIC STRATEGY BASED ON THE USE OF AQUATED CISPLATIN", Clinical cancer research, 3(7), 1997, pp. 1157-1165

Abstract

In pursuit of a strategy for increasing delivery of platinum drugs totumors, we compared the cytotoxicity, extent of cellular uptake, and DNA platination of native cisplatin (DDP) and aquated cisplatin (aqDDP) in human head and neck carcinoma UMSCC10b cells. AqDDP was 1.8-fold more toxic than DDP when tested against UMSCC10b cells in vitro. At high concentrations, aqDDP uptake was 3-fold more rapid than that of DDP; uptake of DDP and aqDDP was nonsaturable up to a concentration of 1600 mu m. AqDDP produced 6.4-fold more platination of DNA than did DDP at the same concentration, suggesting that once inside the cell, aqDDPwas 2-fold more effective at producing adducts in DNA than the nativedrug. Despite the paradox that aqDDP, which contains some charged species, entered the cell more rapidly than did neutral native DDP at high concentrations, studies on the effect of temperature, ATP depletion,and sulfhydryl group blockade did not provide evidence for uptake of aqDDP via a channel or transporter. AqDDP was more nephrotoxic to micethan DDP; however, s.c. administration of sodium thiosulfate protected against this toxicity and permitted a 7-fold escalation of aqDDP dose. These studies provide the preclinical basis for a novel therapeuticstrategy based on the regional intraarterial or intracavitary administration of aqDDP in combination with a systemic neutralizing agent.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/09/20 alle ore 03:08:37