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Titolo:
Thymidylate synthase (TS) and ribonucleotide reductase (RNR) may be involved in acquired resistance to 5-fluorouracil (5-FU) in human cancer xenografts in vivo
Autore:
Fukushima, M; Fujioka, A; Uchida, J; Nakagawa, F; Takechi, T;
Indirizzi:
Taisho Pharmaceut Co Ltd, Canc Lab 2, Hanno, Saitama 3578527, Japan TaishoPharmaceut Co Ltd Hanno Saitama Japan 3578527 itama 3578527, Japan
Titolo Testata:
EUROPEAN JOURNAL OF CANCER
fascicolo: 13, volume: 37, anno: 2001,
pagine: 1681 - 1687
SICI:
0959-8049(200109)37:13<1681:TS(ARR>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
DIHYDROPYRIMIDINE DEHYDROGENASE-ACTIVITY; CELL-LINES; GENE AMPLIFICATION; ANTITUMOR-ACTIVITY; COLORECTAL TUMORS; INHIBITION; EXPRESSION; CHEMOTHERAPY; SYNTHETASE; 5-FLUORO-2'-DEOXYURIDYLATE;
Keywords:
thymidylate synthase; ribonucleotide reductase; dihydropyrimidine dehydrogenase; orotate phosphoribosyltransferase; mRNA; 5-fluorouracil; acquired resistance; 5-fluorouracil metabolism; colorectal carcinoma; human xenograft; S-1;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Fukushima, M Taisho Pharmaceut Co Ltd, Canc Lab 2, 1-27 Misugidai, Hanno, Saitama 3578527, Japan Taisho Pharmaceut Co Ltd 1-27 Misugidai Hanno Saitama Japan 3578527
Citazione:
M. Fukushima et al., "Thymidylate synthase (TS) and ribonucleotide reductase (RNR) may be involved in acquired resistance to 5-fluorouracil (5-FU) in human cancer xenografts in vivo", EUR J CANC, 37(13), 2001, pp. 1681-1687

Abstract

A human tumour sub-line resistant to 5-fluorouracil (5-FU) was establishedby once a day and every 5, with at least 50 administrations of 5-FU to KM12C human colorectal xenografts in nude mice. KM12C tumours treated with 5-FU showed less sensitivity to 5-FU with an inhibition rate (IR) of 7.9%, while non-treated tumours were highly sensitive to 5-FU with an IR of 81.8%. To clarify the mechanism of 5-FU-resistance, the activities of various enzymes and gene expressions involved in the metabolism of 5-FU in both parentaland 5-FU-treated KM12C tumours were measured. A 2- to 3-fold increase in thymidylate synthase (TS) activity and 4- to 5-fold decrease in ribonucleotide reductase (RNR) activity were observed in 5-FU-resistant KM12C tumours, while the activities of orotate phosphoribosyltransferase (OPRT) thymidine and uridine phosphorylases (TP,UP) and thymidine kinase (TK) were not markedly changed as a consequence of repeated treatment of KM12C tumours with 5-FU. The expression of TS mRNA was also amplified in accordance with the increased TS activity in a 5-FU-treated tumour sub-line (KM12C/5-FU) compared with that in parental tumours, but changed expressions of both RNR-R1 and RNA-R2 mRNA could not be detected in the 5-FU-resistant tumour sub-line compared with the parental tumours, suggesting possible post-transcriptional regulation of RNR. Moreover, RNR, in addition to TS and OPRT, seemed to be related to the inherent insensitivity to 5-FU in human cancer xenografts. From these results, it may be concluded that RNR activity is one of the acquired or inherent resistant factors, including TS, to 5-FU in human cancer xenografts in vivo. (C) 2001 Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 10:22:43