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Titolo:
Using a tropism-modified adenoviral vector to circumvent inhibitory factors in ascites fluid
Autore:
Blackwell, JL; Li, H; Gomez-Navarro, J; Dmitriev, I; Krasnykh, V; Richter, CA; Shaw, DR; Alvarez, RD; Curiel, DT; Strong, TV;
Indirizzi:
Univ Alabama, Ctr Comprehens Canc, Dept Med, Div Hematol & Oncol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 ol & Oncol, Birmingham, AL 35294 USA Univ Alabama, Ctr Comprehens Canc, Dept Surg, Div Otolaryngol, Birmingham,AL 35294 USA Univ Alabama Birmingham AL USA 35294 Otolaryngol, Birmingham,AL 35294 USA Univ Alabama, Ctr Comprehens Canc, Gene Therapy Ctr, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 herapy Ctr, Birmingham, AL 35294 USA Univ Alabama, Ctr Comprehens Canc, Dept Obstet & Gynecol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 & Gynecol, Birmingham, AL 35294 USA
Titolo Testata:
HUMAN GENE THERAPY
fascicolo: 12, volume: 11, anno: 2000,
pagine: 1657 - 1669
SICI:
1043-0342(20000810)11:12<1657:UATAVT>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
CANCER GENE-THERAPY; SQUAMOUS-CELL CARCINOMA; HUMAN OVARIAN-CARCINOMA; GROWTH-FACTOR RECEPTOR; I CLINICAL-TRIAL; MOUSE-LIVER; TRANSGENE EXPRESSION; IMMUNE-RESPONSES; PHASE-I; RECOMBINANT ADENOVIRUSES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
62
Recensione:
Indirizzi per estratti:
Indirizzo: Strong, TV Univ Alabama, Ctr Comprehens Canc, Dept Med, Div Hematol & Oncol, WTI 520,1824 6th Ave S, Birmingham, AL 35294 USA Univ Alabama WTI 520,1824 6th Ave S Birmingham AL USA 35294 USA
Citazione:
J.L. Blackwell et al., "Using a tropism-modified adenoviral vector to circumvent inhibitory factors in ascites fluid", HUM GENE TH, 11(12), 2000, pp. 1657-1669

Abstract

Peritoneal compartmentalization of advanced stage ovarian cancer provides a rational scenario for gene therapy strategies. Several groups are exploring intraperitoneal administration of adenoviral (Ad) vectors for this purpose. We examined in vitro gene transfer in the presence of ascites fluid from ovarian cancer patients and observed significant inhibition of Ad-mediated gene transfer. The inhibitory activity was not identified as either complement or cellular factors, but depletion of IgG from ascites removed the inhibitory activity, implicating neutralizing anti-Ad antibodies. A wide range of preexisting anti-Ad antibody titers in patient ascites fluid was measured by ELISA, Western blot analysis demonstrated that the antibodies mere directed primarily against the Ad fiber protein. To circumvent inhibition byneutralizing antibodies, a genetically modified adenoviral vector was tested. The Ad5Luc,RGD vector has an Arg-Gly-Asp (RGD) peptide sequence inserted into the fiber knob domain and enters cells through a nonnative pathway, Compared with the conventional Ad5 vector, Ad5Luc,RGD directed efficient gene transfer to cell lines and primary ovarian cancer cells in the presence of ascites fluid containing high-titer neutralizing anti-Ad antibodies. These results suggest that such modified Ad vectors will be needed to achieve efficient gene transfer in the clinical setting.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/06/20 alle ore 03:03:21