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Titolo:
Inhibition of glioma cells in vitro and in vivo using a recombinant adenoviral vector containing an astrocyte-specific promoter
Autore:
Vandier, D; Rixe, O; Besnard, F; Kim, M; Rikiyama, T; Goldsmith, M; Brenner, M; Gouyette, A; Cowan, KH;
Indirizzi:
Univ Nebraska, Med Ctr, Eppley Inst Res Canc, Eppley Canc Ctr, Omaha, NE 68198 USA Univ Nebraska Omaha NE USA 68198 nc, Eppley Canc Ctr, Omaha, NE 68198 USA NCI, Med Branch, Bethesda, MD 20892 USA NCI Bethesda MD USA 20892NCI, Med Branch, Bethesda, MD 20892 USA Clin Claude Bernard, Dept Oncol, Metz, France Clin Claude Bernard Metz France laude Bernard, Dept Oncol, Metz, France Sanofi Synthelabo, Rueil Malmaison, France Sanofi Synthelabo Rueil Malmaison France elabo, Rueil Malmaison, France Univ Alabama, Dept Neurobiol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 Neurobiol, Birmingham, AL 35294 USA Univ Alabama, Dept Phys Med & Rehabil, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 & Rehabil, Birmingham, AL 35294 USA Inst Gustave Roussy, Dept Pharmacotoxicol & Pharmacogenet, Unite Mixte Rech 8532, CNRS, Villejuif, France Inst Gustave Roussy Villejuif France Rech 8532, CNRS, Villejuif, France
Titolo Testata:
CANCER GENE THERAPY
fascicolo: 8, volume: 7, anno: 2000,
pagine: 1120 - 1126
SICI:
0929-1903(200008)7:8<1120:IOGCIV>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
FIBRILLARY ACIDIC PROTEIN; THYMIDINE KINASE GENE; BRAIN-TUMORS; TRANSGENIC MICE; THERAPY; EXPRESSION; SYSTEM; GFAP; MALIGNANCIES; REGRESSION;
Keywords:
gene therapy; glial fibrillary acidic protein; glioblastoma; adenovirus; herpes simplex virus thymidine kinase gene;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Cowan, KH Univ Nebraska, Med Ctr, Eppley Inst Res Canc, Eppley Canc Ctr, Room 2016, Omaha, NE 68198 USA Univ Nebraska Room 2016 Omaha NE USA 68198 , Omaha, NE 68198 USA
Citazione:
D. Vandier et al., "Inhibition of glioma cells in vitro and in vivo using a recombinant adenoviral vector containing an astrocyte-specific promoter", CANC GENE T, 7(8), 2000, pp. 1120-1126

Abstract

Gene therapy using the herpes simplex virus thymidine kinase (HSV-TK) genein combination with the drug ganciclovir (GCV) is a promising approach forthe treatment of cancer-inducing gliomas, a tumor with a poor prognosis. In an attempt to limit the toxic effects on normal tissues, we constructed arecombinant adenoviral vector, Adgfa2TK, in which the HSV-TK gene is driven by the promoter for the gene encoding glial fibrillary acidic protein, anintermediate filament protein expressed primarily in astrocytes. Infectionby Adgfa2TK of a glial cell line (C6) and a non-glial cell line (MDA-MB-231) revealed markedly increased expression of HSV-TK in glial cells as determined by Western blot. In comparison, high HSV-TK protein levels were produced in both cell lines after infection with a control virus, AdCMVTK, in which the constitutive cytomegalovirus viral promoter was used to direct HSV-TK expression. infection of two glial cell lines (C6, U251) and two non-glial cell lines (HepG2, MDA-MB-231) with Adgfa2TK followed by GCV treatment revealed high toxicity in glial cell lines (50% growth inhibitory concentration: <2 mu g/mL of GCV) with little or no toxicity (50% growth inhibitory concentration: >75 mu g/mL) in the non-glial cell lines. In vivo, injection of Adgfa2TK into CG tumors grown in nude mice followed by intraperitoneal GCV treatment significantly repressed tumor growth compared with the controls. Adgfa2TK may be useful for directing expression of the HSV-TK gene to gliomas.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/11/20 alle ore 04:20:15