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Titolo:
Non-steroidal anti-inflammatory drugs with activity against either cyclooxygenase 1 or cyclooxygenase 2 inhibit colorectal cancer in a DMH rodent model by inducing apoptosis and inhibiting cell proliferation
Autore:
Brown, WA; Skinner, SA; Malcontenti-Wilson, C; Vogiagis, D; OBrien, PE;
Indirizzi:
Monash Univ, Alfred Hosp, Dept Surg, Melbourne, Vic 3181, Australia MonashUniv Melbourne Vic Australia 3181 , Melbourne, Vic 3181, Australia
Titolo Testata:
GUT
fascicolo: 5, volume: 48, anno: 2001,
pagine: 660 - 666
SICI:
0017-5749(200105)48:5<660:NADWAA>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ABERRANT CRYPT FOCI; PROSTAGLANDIN G/H SYNTHASE-1; COLON CARCINOGENESIS; RAT COLON; DIFFERENTIAL INHIBITION; GASTROINTESTINAL-TRACT; SELECTIVE-INHIBITION; SULINDAC; TUMORS;
Keywords:
non-steroidal anti-inflammatory drugs; chemoprevention; colorectal cancer; apoptosis; bromodexoyuridine;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: Brown, WA Monash Univ, Alfred Hosp, Dept Surg, Commercial Rd, Prahran, Vic3181, Australia Monash Univ Commercial Rd Prahran Vic Australia 3181 , Australia
Citazione:
W.A. Brown et al., "Non-steroidal anti-inflammatory drugs with activity against either cyclooxygenase 1 or cyclooxygenase 2 inhibit colorectal cancer in a DMH rodent model by inducing apoptosis and inhibiting cell proliferation", GUT, 48(5), 2001, pp. 660-666

Abstract

Background-Standard non-steroidal anti-inflammatory drugs (NSAIDs) reduce the risk of colorectal cancer by 40-60% but the mechanism by which this occurs is uncertain. Selective cyclooxygenase2inhibitors arepotentiallyidealchemopreventive agents as they are less toxic than standard NSAIDs. No study has compared the efficacy of these drugs at clinically relevant doses in a tumour model. Aims-To assess the efficacy of a range of NSAIDs with varying activity against the two cyclooxygenase isoforms in a rodent colorectal carcinogen model at antiinflammatory doses and to explore the effect of NSAIDs on the rateof tumour apoptosis and proliferation. Methods-Colorectal tumours were induced in six week old Sprague-Dawley rats with five weekly doses of 1,2 dimethylhydrazine. Test agents were: indomethacin 2 mg/kg/day, meloxicam 0.6 mg/kg/ day, celecoxib 6 mg/kg/day, and sulindac sulphone 40 mg/kg/day. Sulindac was tested at its chemoprotective dose of 20 mg/kg/day. After 23 weeks the number and volume of tumours per animal were recorded. Histology was performed. Tumour apoptosis was quantifiedon haematoxylin-eosin sections. Tumour proliferation was quantified using an immunohistochemical stain for bromodexoyuridine incorporation. Results-Test agents effectively reduced the number and volume of tumours developing in the treatment period. In all groups there was an increase in the rate of tumour apoptosis and a reduced rate of proliferation. Conclusions-These data suggest that the chemopreventive effect of NSAIDs is independent of their cyclooxygenase inhibitory profile. One potential mechanism for their action may be through induction of apoptosis and inhibition of proliferation.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/05/20 alle ore 15:04:37