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Titolo:
Pharmacological determinants of 9-aminocamptothecin cytotoxicity
Autore:
Li, ML; Horn, L; Firby, PS; Moore, MJ;
Indirizzi:
Princess Margaret Hosp, Dept Med, Ontario Canc Inst, Toronto, ON M2G 2M9, Canada Princess Margaret Hosp Toronto ON Canada M2G 2M9 onto, ON M2G 2M9, Canada Univ Toronto, Dept Pharmacol, Toronto, ON M5G 2S2, Canada Univ Toronto Toronto ON Canada M5G 2S2 macol, Toronto, ON M5G 2S2, Canada
Titolo Testata:
CLINICAL CANCER RESEARCH
fascicolo: 1, volume: 7, anno: 2001,
pagine: 168 - 174
SICI:
1078-0432(200101)7:1<168:PDO9C>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
PERFORMANCE LIQUID-CHROMATOGRAPHY; COLLOIDAL DISPERSION FORMULATION; MAMMALIAN TOPOISOMERASE-I; PHASE-I; CAMPTOTHECIN DERIVATIVES; ANTITUMOR-ACTIVITY; CARBOXYLATE FORMS; ANTICANCER DRUGS; KINETIC-ANALYSIS; CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Moore, MJ Princess Margaret Hosp, Dept Med, Ontario Canc Inst, 610 Univ Ave, Toronto, ON M2G 2M9, Canada Princess Margaret Hosp 610 Univ Ave Toronto ON Canada M2G 2M9 da
Citazione:
M.L. Li et al., "Pharmacological determinants of 9-aminocamptothecin cytotoxicity", CLIN CANC R, 7(1), 2001, pp. 168-174

Abstract

The camptothecins are a group of anticancer agents with a unique mechanismof action: poisoning of eukaryotic DNA topoisomerase I. 9-aminocamptothecin (9-AC), a potent water-insoluble derivative of camptothecin, is currentlyundergoing clinical testing. The kinetics of the active derivative 9-AC lactone in cell culture media was defined, and then 9-AC cytotoxicity againsthuman breast (MCF-7), bladder (MGH-U1), and colon (HT-29) cancer cell lines was studied. The relationship between cytotoxic effects, drug concentration, and exposure time was then explored. For all of the three cell lines, 9-AC cytotoxicity increased with both higher drug concentrations and longer exposure times. However, when the duration of exposure was less than 24 h, cytotoxicity was limited and less than 1 log of cell killing occurred, evenwith very high drug concentrations. Minimal cell killing was also observedunless 9-AC concentrations exceeded a threshold of 2.7 nM, No fixed relationship between the survival fraction and the area under the drug concentration-time curve could be modeled that would fit all of the three cell lines. However, data for the three cell lines from the multiple exposure time experiments were fitted very well to the pharmacodynamic model C(n)t = k (r(2), 0.90-0.99), where C is the drug concentration, n is the drug concentration coefficient, and t is the exposure time. For the three cell lines, to kill 1 log of cells, 0.30 < n < 0.85, which indicated that duration of exposure was more important than concentration, Our data support the use of 9-AC by infusion for 24 h or longer in clinical studies providing target plasma concentrations can be achieved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/07/20 alle ore 07:31:56