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Titolo:
Prevention and inhibition of nasopharyngeal carcinoma growth by antiviral phosphonated nucleoside analogs
Autore:
Murono, S; Raab-Traub, N; Pagano, JS;
Indirizzi:
Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USAUniv N Carolina Chapel Hill NC USA 27599 c Ctr, Chapel Hill, NC 27599 USA Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA Univ N Carolina Chapel Hill NC USA 27599 munol, Chapel Hill, NC 27599 USA Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA Univ N Carolina Chapel Hill NC USA 27599 t Med, Chapel Hill, NC 27599 USA
Titolo Testata:
CANCER RESEARCH
fascicolo: 21, volume: 61, anno: 2001,
pagine: 7875 - 7877
SICI:
0008-5472(20011101)61:21<7875:PAIONC>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
EPSTEIN-BARR-VIRUS; POLY(ADP-RIBOSE) POLYMERASE; LATENT MEMBRANE-PROTEIN-1; NUDE-MICE; CIDOFOVIR; APOPTOSIS; CELLS; REPLICATION; DNA; (S)-1-(3-HYDROXY-2-PHOSPHONYLMETHOXYPROPYL)CYTOSINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
23
Recensione:
Indirizzi per estratti:
Indirizzo: Pagano, JS Univ N Carolina, Lineberger Comprehens Canc Ctr, CB 7295, Chapel Hill, NC 27599 USA Univ N Carolina CB 7295 Chapel Hill NC USA 27599 , NC 27599 USA
Citazione:
S. Murono et al., "Prevention and inhibition of nasopharyngeal carcinoma growth by antiviral phosphonated nucleoside analogs", CANCER RES, 61(21), 2001, pp. 7875-7877

Abstract

Nasopharyngeal carcinoma (NPC) is universally associated with EBV infection. We have shown that the phosphonated nucleoside analog, (S)-1-[3-hydroxy-2-(phosphonylmethoxy)-propyl]cytosine (HPMPC) strongly inhibits growth of NPC xenografts in nude mice by causing apoptosis (J. Neyts et al., Cancer Res., 58, 384-388, 1998). We, therefore, tested two additional members of this drug family that have different degrees of antiviral activity, 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) and 9-2-(R)-(phosphonomethoxy)propyladenine (PMEA). Intratumoral injection of PMEA (75 mul of 2% solution) in C15 NPC xenografts, which are latently infected with EBV, slowed tumor growth moderately, whereas PMPA (75 mul of 2% solution) slowed tumor growth only marginally. Compared with the previous results showing complete regression of tumor, PMEA had less antitumoral effect than HPMPC, and PMPA had the least. After 4 weeks of preventive treatments tumors formed in 12.5, 50, and 100% of mice treated with HPMPC, PMEA, and PMPA, respectively, in contrast to the development of tumors in all of the PBS-treated control mice. We also investigated the effect of each drug on the EBV-positive epithelial cell line NPC-KT in vitro. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed inhibition of growth of NPC-KT cells by HPMPC and PMEA, but not by PMPA, which correlates with the results observed in tumor xenografts. Growth inhibition was attributable to induction of apoptosis in NPC-KT cells as indicated by a DNA fragmentation assay. Cleavage of poly(ADP-ribose) polymerase after treatment of NPC-KT cells with HPMPC was observed,which suggested that the apoptosis may be mediated by caspase(s). The apoptotic effects of the drugs are independent of any effects on EBV DNA polymerase, which is not expressed in these latently infected NPCs. These resultssuggest that HPMPC as well as PMEA could provide an adjunctive treatment for NPC.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/07/20 alle ore 01:35:22