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Titolo:
Induction of Epstein-Barr virus kinases to sensitize tumor cells to nucleoside analogues
Autore:
Moore, SM; Cannon, JS; Tanhehco, YC; Hamzeh, FM; Ambinder, RF;
Indirizzi:
Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21231 USA Johns Hopkins Univ Baltimore MD USA 21231 Oncol, Baltimore, MD 21231 USA Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21231 USA Johns Hopkins Univ Baltimore MD USA 21231 pt Med, Baltimore, MD 21231 USA
Titolo Testata:
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
fascicolo: 7, volume: 45, anno: 2001,
pagine: 2082 - 2091
SICI:
0066-4804(200107)45:7<2082:IOEVKT>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
HERPES-SIMPLEX VIRUS; NARROW SUBSTRATE-SPECIFICITY; LATENT MEMBRANE-PROTEIN; BURKITT-LYMPHOMA LINES; REED-STERNBERG CELLS; OPEN READING FRAME; THYMIDINE KINASE; HODGKINS-DISEASE; NUCLEAR ANTIGEN-2; INFECTED-CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Ambinder, RF 1650 Orleans St,Canc Res Bldg,Rm 389, Baltimore, MD 21231 USA 1650 Orleans St,Canc Res Bldg,Rm 389 Baltimore MD USA 21231
Citazione:
S.M. Moore et al., "Induction of Epstein-Barr virus kinases to sensitize tumor cells to nucleoside analogues", ANTIM AG CH, 45(7), 2001, pp. 2082-2091

Abstract

The presence of Epstein-Barr virus (EBV) in the tumor cells of some EBV-associated malignancies may facilitate selective killing of these tumor cells. We show that treatment of an EBV+ Burkitt's lymphoma cell line with 5-azacytidine led to a dose-dependent induction of EBV lytic antigen expression,including expression of the viral thymidine kinase (TK) and phosphotransferase (PT). Azacytidine treatment for 24 h modestly sensitized the cell lineto all nucleosides tested. To better characterize EBV TK with regard to various nucleoside analogues, we expressed EBV TK in stable cell clones. Two EBV TK expressing clones were moderately sensitive to high doses of acyclovir and penciclovir (PCV) (62.5 to 500 muM) and to lower doses of ganciclovir (GCV) and bromovinyldeoxyuridine (BVdU) (10 to 100 muM) compared to a control clone and were shown to phosphorylate GCV. Similar experiments in a transient overexpression system showed more killing of cells transfected withthe EBV TK expression vector than of cells transfected with the control mutant vector (50 muM GCV for 4 days). A putative PT was also studied in the transient transfection system and appeared similar to the TK in phosphorylating GCV and conferring sensitivity to GCV, but not in BVdU or PCV-mediatedcell killing. Induction of EBV kinases in combination with agents such as GCV merits further evaluation as an alternative strategy to gene therapy for selective killing of EBV-infected cells.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/09/20 alle ore 00:56:19