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Titolo:
Enhanced antitumor activity of 5-fluorouracil in combination with 2 '-deoxyinosine in human colorectal cell lines and human colon tumor xenografts
Autore:
Ciccolini, J; Peillard, L; Evrard, A; Cuq, P; Aubert, C; Pelegrin, A; Formento, P; Milano, G; Catalin, J;
Indirizzi:
Fac Pharm, Lab Toxicocinet & Pharmacocinet, F-13385 Marseille 05, France Fac Pharm Marseille France 05 harmacocinet, F-13385 Marseille 05, France Fac Med Montpellier, Toxicol Lab, F-34000 Montpellier, France Fac Med Montpellier Montpellier France F-34000 34000 Montpellier, France CRLC Val Daurelle, F-34000 Montpellier, France CRLC Val Daurelle Montpellier France F-34000 F-34000 Montpellier, France Ctr Antoine Lacassagne, Lab Oncopharmacol, F-06000 Nice, France Ctr Antoine Lacassagne Nice France F-06000 armacol, F-06000 Nice, France
Titolo Testata:
CLINICAL CANCER RESEARCH
fascicolo: 4, volume: 6, anno: 2000,
pagine: 1529 - 1535
SICI:
1078-0432(200004)6:4<1529:EAAO5I>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
THYMIDINE PHOSPHORYLASE; CARCINOMA CELLS; CYTO-TOXICITY; GROWTH-FACTOR; CANCER; SENSITIVITY; INTERFERON; APOPTOSIS; ANGIOGENESIS; 5'-DEOXY-5-FLUOROURIDINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Ciccolini, J Fac Pharm, Lab Toxicocinet & Pharmacocinet, 27 Bd Jean Moulin, F-13385 Marseille 05, France Fac Pharm 27 Bd Jean Moulin Marseille France 05 e 05, France
Citazione:
J. Ciccolini et al., "Enhanced antitumor activity of 5-fluorouracil in combination with 2 '-deoxyinosine in human colorectal cell lines and human colon tumor xenografts", CLIN CANC R, 6(4), 2000, pp. 1529-1535

Abstract

We investigated the effects of 2'-deoxyinosine (d-Ino), a modulator yielding thymidine phosphorylase activity, on cellular pharmacology of 5-fluorouracil (FUra) in various human colorectal cell lines and its antitumoral activity when combined with FUra in human xenografts. Associating d-Ino with FUra increased by 38 up to 700 times the sensitivity of HT29 and FUra-resistant SW620 lines, respectively, but not of CaCo2 cells, although high levels of intracellular FdUMP and subsequent higher thymidylate synthase inhibition were observed. Cell death studies confirmed the ability of d-Ino to enhance both early and late apoptosis induced by FUra in HT29 and SW620 but not in CaCo2, Similarly, we showed that associating d-Ino increased by 68 up to101% the Fas overexpression induced by FUra in HT29 and SW620 but not in CaCo2 cells. Anti-Fas and anti-Fast antibodies both partly reversed this increase of cell sensitivity, thus confirming the role Fas plays in the modulation of FUra toxicity by d-Ino. This Fas component could explain the discrepancy between the lines because CaCo2 has been described as insensitive to Fas-mediated apoptosis, Antitumor activity of the combination was next investigated in nude mice transplanted with SW620, Results showed that althoughFUra alone has little effect on SW620 xenografts (P > 0.05), associating d-Ino significantly reduced the tumor growth by 57% (P < 0.05). This study suggests that it is possible to reduce both in vitro mid in vivo resistance to FUra by modulating the way the drug, is converted after cellular uptake.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 19:38:20