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Titolo:
An advanced generation of adenoviral vectors selectively enhances gene transfer for ovarian cancer gene therapy approaches
Autore:
Vanderkwaak, TJ; Wang, MH; Gomez-Navarro, J; Rancourt, C; Dmitriev, I; Krasnykh, V; Barnes, M; Siegal, GP; Alvarez, R; Curiel, DT;
Indirizzi:
Univ Alabama, Dept Obstet & Gynecol, Div Gynecol Oncol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 ecol Oncol, Birmingham, AL 35294 USA Univ Alabama, Gene Therapy Ctr, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 herapy Ctr, Birmingham, AL 35294 USA Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 ept Pathol, Birmingham, AL 35294 USA Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 Cell Biol, Birmingham, AL 35294 USA Univ Alabama, Dept Surg, Birmingham, AL 35294 USA Univ Alabama BirminghamAL USA 35294 Dept Surg, Birmingham, AL 35294 USA
Titolo Testata:
GYNECOLOGIC ONCOLOGY
fascicolo: 2, volume: 74, anno: 1999,
pagine: 227 - 234
SICI:
0090-8258(199908)74:2<227:AAGOAV>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
PREVIOUSLY TREATED OVARIAN; COXSACKIE-B VIRUSES; PHASE-I; ALPHA(V)BETA(3) INTEGRIN; MODIFIED FIBERS; EXPRESSION; RECEPTOR; CARCINOMAS; DELIVERY; ANTIBODY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Vanderkwaak, TJ Univ Alabama, Dept Obstet & Gynecol, Div Gynecol Oncol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 ingham, AL 35294 USA
Citazione:
T.J. Vanderkwaak et al., "An advanced generation of adenoviral vectors selectively enhances gene transfer for ovarian cancer gene therapy approaches", GYNECOL ONC, 74(2), 1999, pp. 227-234

Abstract

Objective. We hypothesized that incorporation of an integrin binding Arg-Gly-Asp (RGD)-containing peptide to the HI loop of the adenovirus fiber knobwould allow enhanced, coxsackie-adenovirus receptor-independent gene transfer by modified Ad vector in the context of ovarian cancer. Methods. Ovarian cancer cell lines, primary ovarian cancer cells, primary tumor explants, and mesothelial tissue were transfected with luciferase encoding adenovirus (AdCMVLuc) or a genetically modified adenovirus (Ad5lucRGD) which contained an RGD motif within the HI loop of the knob. The luciferase activity was measured and the transduction efficiencies of both viruses were compared. Results. In all established ovarian cell lines and primary tumor cell samples there was dramatically augmented gene transfer observed with the Ad5lucRGD compared to AdCMVLuc. The enhanced gene transfer in ovarian cancer celllines ranged from 2.5- to 471.6-fold, in ascites samples from 26.1- to 64.0-fold, and in tumor explants from 1.6- to 11.1-fold. Although gene transfer to normal mesothelial tissue was slightly augmented by RGD retargeting, the level of gene transfer was much lower than that seen in ovarian cancer cells. Conclusion. This study demonstrates that genetically altered adenoviruses with modified tropism are capable of more efficient gene transfer in the context of ovarian cancer. The higher level of transfer with respect to peritoneal mesothelium can be exploited to enhance the therapeutic index of interventions using adenoviral vectors. Studies are warranted, therefore, to determine the in vivo utility of this targeted vector approach in the contextof gene therapeutic strategies for cancer of the ovary. (C) 1999 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 16:21:50