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Titolo:
Pro-apoptotic treatment with an adenovirus encoding Bax enhances the effect of chemotherapy in ovarian cancer
Autore:
Xiang, J; Gomez-Navarro, J; Arafat, W; Liu, B; Barker, SD; Alvarez, RD; Siegal, GP; Curiel, DT;
Indirizzi:
Univ Alabama, Gene Therapy Ctr, Birmingham, AL 35233 USA Univ Alabama Birmingham AL USA 35233 herapy Ctr, Birmingham, AL 35233 USA Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35233 USA Univ Alabama Birmingham AL USA 35233 & Gynecol, Birmingham, AL 35233 USA Univ Alabama, Dept Pathol, Birmingham, AL 35233 USA Univ Alabama Birmingham AL USA 35233 ept Pathol, Birmingham, AL 35233 USA Univ Alabama, Dept Cell Biol, Birmingham, AL 35233 USA Univ Alabama Birmingham AL USA 35233 Cell Biol, Birmingham, AL 35233 USA Univ Alabama, Dept Surg, Birmingham, AL 35233 USA Univ Alabama BirminghamAL USA 35233 Dept Surg, Birmingham, AL 35233 USA
Titolo Testata:
JOURNAL OF GENE MEDICINE
fascicolo: 2, volume: 2, anno: 2000,
pagine: 97 - 106
SICI:
1099-498X(200003/04)2:2<97:PTWAAE>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
RADIATION-INDUCED APOPTOSIS; PROAPOPTOTIC GENE BAX; INDUCED CELL-DEATH; IN-VIVO; ANTITUMOR-ACTIVITY; HUMAN BREAST; MCF-7 CELLS; P53; EXPRESSION; THERAPY;
Keywords:
Bax; apoptosis; chemotherapy; taxol; adenovirus; ovarian cancer;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
64
Recensione:
Indirizzi per estratti:
Indirizzo: Curiel, DT Univ Alabama, Gene Therapy Ctr, Wallace Tumor Inst 620, 1824 6th Ave S, Birmingham, AL 35294 USA Univ Alabama 1824 6th Ave S Birmingham ALUSA 35294 L 35294 USA
Citazione:
J. Xiang et al., "Pro-apoptotic treatment with an adenovirus encoding Bax enhances the effect of chemotherapy in ovarian cancer", J GENE MED, 2(2), 2000, pp. 97-106

Abstract

Background Tumor cell heterogeneity and resistance to chemotherapy-mediated cell death are major obstacles in cancer therapy. It has been reported that expression of the pro-apoptotic molecule Bar can induce cell death or sensitize tumor cells to chemotherapy in stable cell clones derived from tumor cells. However, these studies are limited in that they cannot represent the heterogeneity of cancer cells observed in vivo. In this study, we have further explored the therapeutic potential of Bar. Methods Using an inducible recombinant Bar adenovirus, we screened a panelof ovarian cancer cell lines and primary patient-derived ovarian tumor cells for their sensitivity to Bar-mediated cytotoxicity. Apoptotic cell deathwas evaluated qualitatively with Hoechst staining and quantitatively with MTS and Annexin V-based assays. Endogenous levels of both Bcl-2 and Bar protein and p53 status were evaluated. The potential of bax to sensitize ovarian cancer lines to chemotherapy was also tested. Dose-response curves were generated to evaluate cell death. Results Overexpression of Bar directly induced apoptosis in both ovarian cancer cell lines and the patient-derived primary cancer cells. However, thesensitivity of these cells to Bar varied and appeared to be independent ofboth the status of p53 and the endogenous levels of bcl-2 or Bar, criticalmolecules in the apoptotic pathway. Importantly, overexpression of Bar significantly enhanced chemotherapy-induced cytotoxicity in both established cell lines and primary ovarian carcinoma cells. Conclusions These studies suggest that overexpression of Bar alone or in combination with chemotherapy may provide a means to overcome the problems imposed by the heterogeneous nature of tumors, ultimately augmenting the efficacy of chemotherapy in patients suffering from ovarian cancer. Copyright (C) 2000 John Wiley & Sons, Ltd.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/05/20 alle ore 19:54:07