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Titolo:
Increased cytotoxicity and bystander effect of 5-fluorouracil and 5 '-deoxy-5-fluorouridine in human colorectal cancer cells transfected with thymidine phosphorylase
Autore:
Evrard, A; Cuq, P; Ciccolini, J; Vian, L; Cano, JP;
Indirizzi:
Fac Pharm Montpellier, Lab Toxicol Medicament, F-34060 Montpellier 02, France Fac Pharm Montpellier Montpellier France 02 34060 Montpellier 02, France Lab Toxicocinet & Pharmacocinet, F-13385 Marseille, France Lab Toxicocinet& Pharmacocinet Marseille France F-13385 rseille, France
Titolo Testata:
BRITISH JOURNAL OF CANCER
fascicolo: 11, volume: 80, anno: 1999,
pagine: 1726 - 1733
SICI:
0007-0920(199908)80:11<1726:ICABEO>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
COLON-CARCINOMA CELLS; EXPRESS CYTOSINE DEAMINASE; GROWTH-FACTOR; GENE-THERAPY; IN-VITRO; PYRIMIDINE ANTIMETABOLITES; ANTITUMOR-ACTIVITY; ESCHERICHIA-COLI; BLOOD-PLATELETS; NORMAL-TISSUES;
Keywords:
cancer gene therapy; thymidine phosphorylase; 5-FU; 5 '-DFUR; bystander effect;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Cuq, P Fac Pharm Montpellier, Lab Toxicol Medicament, 15 Av Charles Flahault, F-34060 Montpellier 02, France Fac Pharm Montpellier 15 Av Charles Flahault Montpellier France 02
Citazione:
A. Evrard et al., "Increased cytotoxicity and bystander effect of 5-fluorouracil and 5 '-deoxy-5-fluorouridine in human colorectal cancer cells transfected with thymidine phosphorylase", BR J CANC, 80(11), 1999, pp. 1726-1733

Abstract

5-Fluorouracil (5-FU) and 5'-deoxy-5-fluorouridine (5'-DFUR), a prodrug of5-FU, are anticancer agents activated by thymidine phosphorylase (TP). Transfecting the human TP cDNA into cancer cells in order to sensitize them tothese pyrimidine antimetabolites may he an important approach in human cancer gene therapy research. In this study, an expression vector containing the human TP cDNA (pcTP5) was transfected into LS174T human colon carcinoma cells. Eight stable transfectants were randomly selected and analysed. The cytotoxic effects of 5-FU and 5'-DFUR were higher in TP;transfected cells as compared to wild-type cells. The maximal decreases in the IC50 were 80-fold for 5-FU and 40-fold for 5'-DFUR. The increase in sensitivity to these pyrimidines of TP-transfected cells significantly correlated with the increase in both TP activity and TP expression. Transfected clone LS174T-c2 but not wild-type cells exhibited formation of [H-3]FdUMP from [H-3]5-FU. in addition the LS174T-c2 clone enhanced the cytotoxic effect of 5'-DFUR, but also that of 5-FU, towards co-cultured parental cells. For both anti-cancer agents, this bystander effect did not require cell-cell contact. These results show that both 5-FU or 5'-DFUR could be used together with a TP-suicide Vector in cancer gene therapy.

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Documento generato il 24/11/20 alle ore 08:31:28