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Titolo:
5-Fluorouracil induced Fas upregulation associated with apoptosis in livermetastases of colorectal cancer patients
Autore:
Backus, HHJ; Dukers, DF; van Groeningen, CJ; Vos, W; Bloemena, E; Wouters, D; van Riel, JMGH; Smid, K; Giaccone, G; Pinedo, HM; Peters, GJ;
Indirizzi:
Free Univ Amsterdam, Univ Hosp, Dept Med Oncol, NL-1081 BT Amsterdam, Netherlands Free Univ Amsterdam Amsterdam Netherlands NL-1081 BT terdam, Netherlands Free Univ Amsterdam, Univ Hosp, Dept Pathol, NL-1081 BT Amsterdam, Netherlands Free Univ Amsterdam Amsterdam Netherlands NL-1081 BT terdam, Netherlands
Titolo Testata:
ANNALS OF ONCOLOGY
fascicolo: 2, volume: 12, anno: 2001,
pagine: 209 - 216
SICI:
0923-7534(200102)12:2<209:5IFUAW>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
COLON-CARCINOMA CELLS; THYMIDYLATE SYNTHASE INHIBITION; IN-VIVO; IMMUNOHISTOCHEMICAL ANALYSIS; RETINOBLASTOMA PROTEIN; REGULATING APOPTOSIS; GENE-EXPRESSION; CYCLE CONTROL; DEATH FACTOR; UNIQUE ROLE;
Keywords:
apoptosis; cell-cycle arrest; colorectal cancer; Fas; 5-fluorouracil; thymidylate synthase;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
66
Recensione:
Indirizzi per estratti:
Indirizzo: Peters, GJ Free Univ Amsterdam, Univ Hosp, Dept Med Oncol, De Boelelaan 1117, NL-1081BT Amsterdam, Netherlands Free Univ Amsterdam De Boelelaan 1117 Amsterdam Netherlands NL-1081 BT
Citazione:
H.H.J. Backus et al., "5-Fluorouracil induced Fas upregulation associated with apoptosis in livermetastases of colorectal cancer patients", ANN ONCOL, 12(2), 2001, pp. 209-216

Abstract

Background: In vitro, thymidylate synthase (TS) inhibition by 5-fluorouracil (5-FU) induces thymineless apoptosis possibly via Fas receptor-Fas ligand interactions and cell-cycle arrest. In colorectal cancer patients we evaluated whether 5-FU administration also resulted in apoptosis and cell-cyclearrest and which proteins might be involved. Patients and methods: Biopsy specimens were taken from 36 patients 2, 22 or 46 hours after administration of 500 mg/m(2) 5-FU, and from 12 control patients who did not receive 5-FU. In frozen tissue-sections from liver metastases immunohistochemistry was performed with antibodies directed against p53, p21, E2F2, Rb, Ki67 and TS (cell-cycle related) and bax, BCL-2, BCL-x, mcl-1, PARP, caspase-3, Fas receptor and Fas ligand (apoptosis related). Apoptosis was determined by M30 immunostaining, which recognises a cleavage product of cytokeratin 18. Results: Fas receptor expression was 50% higher (P = 0.036) 46 hours after5-FU administration compared to the control group. This was associated with a 12% increase (P < 0.02) in M30 positive tumour cells and with elevationof caspase-3 and PARP expression. The expression of Ki67 and E2F2 was 30% lower after 46 hours compared to the control group, whereas TS was 56% lower after 2 hours and 32% higher again after 46 hours. No differences in the expression of the other proteins were found. Conclusions: These results suggest that 5-FU decreases proliferation status and induces apoptosis possibly via the Fas pathway. Since Fas mediated cell killing is important for cytotoxic T cells this indicates that clinical studies combining immunotherapy for activation of T cells and chemotherapy using 5-FU might be very effective.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/09/20 alle ore 18:00:24