Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
p27-p16 chimera: A superior antiproliferative for the prevention of neointimal hyperplasia
Autore:
McArthur, JG; Qian, HS; Citron, D; Banik, GG; Lamphere, L; Gyuris, J; Tsui, L; George, SE;
Indirizzi:
Cell Genesys Inc, Dept Preclin Biol & Immunol, Foster City, CA 94404 USA Cell Genesys Inc Foster City CA USA 94404 unol, Foster City, CA 94404 USA Duke Univ, Med Ctr, Durham, NC 27710 USA Duke Univ Durham NC USA 27710Duke Univ, Med Ctr, Durham, NC 27710 USA GPC Biotech Inc, Cambridge, MA 02139 USA GPC Biotech Inc Cambridge MA USA02139 otech Inc, Cambridge, MA 02139 USA
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 1, volume: 3, anno: 2001,
pagine: 8 - 13
SICI:
1525-0016(200101)3:1<8:PCASAF>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
MUSCLE CELL-PROLIFERATION; DEPENDENT KINASE INHIBITOR; GENE-THERAPY; ARTERIAL INJURY; IN-VITRO; MODEL; VIVO; CDK4; OLIGONUCLEOTIDES; EXPRESSION;
Keywords:
p16; p27; vascular gene therapy; adenoviral gene therapy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: McArthur, JG Cell Genesys Inc, Dept Preclin Biol & Immunol, 344 Lakeside Dr, Foster City, CA 94404 USA Cell Genesys Inc 344 Lakeside Dr Foster City CA USA 94404 USA
Citazione:
J.G. McArthur et al., "p27-p16 chimera: A superior antiproliferative for the prevention of neointimal hyperplasia", MOL THER, 3(1), 2001, pp. 8-13

Abstract

Cyclin-dependent kinase inhibitors (CDKi's) may be useful to treat hyperproliferative vascular disorders, such as restenosis induced following angioplasty or vein engraftment. We have shown that a novel fusion protein of theCDKi's p27 and p16, named W9, significantly reduces proliferation of humancoronary smooth muscle cells in vitro, by blocking cell proliferation without inducing apoptosis. We have now evaluated the efficacy of adenovirus-mediated gene transfer of W9 (AV-W9) in a balloon-injury model, in the carotid arteries of cholesterol-fed rabbits. We observed that intravascular delivery of 2 x 10(11) viral particles of AV-W9 3 days following balloon injury inhibited intimal hyperplasia by 60% compared to a control virus (P > 0.001). PCNA expression in the AV-W9-treated vessels, a marker of injury-inducedcell proliferation, was also reduced compared to the control virus-treatedvessels. Direct comparison of the efficacy of AV-W9 and AV-p16 and AV-p27 in this model indicated that delivery of either of the parental genes was significantly less effective in inhibiting intimal thickening compared to the AV-W9 treatment. We conclude that combining the activities of multiple cell cycle regulatory proteins greatly increases the potency of cytostatic gene therapy in the treatment of balloon injury-induced intimal hyperplasia and represents a promising potential approach to preventing postangioplasty restenosis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 15:29:02