Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
An adenovirus encoding proapoptotic Bax induces apoptosis and enhances theradiation effect in human ovarian cancer
Autore:
Arafat, WO; Gomez-Navarro, J; Xiang, JL; Barnes, MN; Mahasreshti, P; Alvarez, RD; Siegal, GP; Badib, AO; Buchsbaum, D; Curiel, DT; Stackhouse, MA;
Indirizzi:
Univ Alabama, Wallace Tumor Inst 620, Dept Med, Div Human Gene Therapy, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 ne Therapy, Birmingham, AL 35294 USA Univ Alabama, Dept Pathol, Div Human Gene Therapy, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 ne Therapy, Birmingham, AL 35294 USA Univ Alabama, Dept Surg, Div Human Gene Therapy, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 ne Therapy, 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 Obstet & Gynecol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 & Gynecol, 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 Univ Alabama, Dept Radiat Oncol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 diat Oncol, Birmingham, AL 35294 USA Univ Alexandria, Dept Clin Oncol, Alexandria, Egypt Univ Alexandria Alexandria Egypt ia, Dept Clin Oncol, Alexandria, Egypt
Titolo Testata:
MOLECULAR THERAPY
fascicolo: 6, volume: 1, anno: 2000,
pagine: 545 - 554
SICI:
1525-0016(200006)1:6<545:AAEPBI>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
SINGLE-CHAIN ANTIBODY; BREAST-CANCER; IN-VIVO; CELL-LINES; FRAMESHIFT MUTATIONS; MEDIATED DELIVERY; MCF-7 CELLS; EXPRESSION; BCL-2; GENE;
Keywords:
gene therapy; adenovirus; apoptosis; radiosensitization; Bax; ovarian cancer;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Curiel, DT Univ Alabama, Wallace Tumor Inst 620, Dept Med, Div Human Gene Therapy, 1824 6th Ave S, Birmingham, AL 35294 USA Univ Alabama 1824 6th AveS Birmingham AL USA 35294 L 35294 USA
Citazione:
W.O. Arafat et al., "An adenovirus encoding proapoptotic Bax induces apoptosis and enhances theradiation effect in human ovarian cancer", MOL THER, 1(6), 2000, pp. 545-554

Abstract

Overexpression of proapoptotic Bar favors death in cells resistant to ionizing radiation. We hypothesized that expression of Bar via adenoviral-mediated gene delivery could sensitize radiation-refractory cells to radiotherapy. An inducible Bar recombinant adenovirus (Ad/Bax) had been generated using the Cre/loxp system. Human ovarian cancer cell lines and primary, patient-derived cancer cells from ascites were irradiated and infected with the Ad/Bar and an expression-inducing vector, Ad/Cre. Cell death was evaluated bycrystal violet staining, fluorescence-activated cell sorter analysis of Annexin V, and colony formation assay (cell lines only). To further characterize the mechanism of death, cell morphology was examined by nuclear staining with Hoechst 33258. Lastly, to evaluate the capacity of the combined treatment to inhibit tumor growth, mice were injected subcutaneously with ovarian cancer cells exposed to Bar, radiation therapy (RT), or both, and tumor size was measured periodically. Infection of the cancer cell lines and primary cells with both Ad/Bar and Ad/Cre significantly enhanced sensitivity toionizing radiation, achieving high levels of cell killing in short-term assays. In addition, the combination of Bar and radiotherapy reduced the survival fraction of cell lines 2 logs in standard colony-forming assays. Investigation into the involved mechanism suggests that Bar-mediated radiosensitization occurs through both apoptosis and necrosis pathways. Further, mice subcutaneously injected with ovarian tumor cells previously treated with radiation, or with radiation and irrelevant viruses, consistently developed tumor nodules. In addition, approximately 80% of injections were followed bytumor formation after treatment with Ad/Bar and Ad/Cre alone. In contrast,tumor formation was completely inhibited after combined treatment with Ad/Bar and Ad/Cre and radiation. Augmentation of the effect of radiotherapy onhuman ovarian cancer cells and primary cancer cells from patients via a recombinant adenovirus encoding Bar is feasible.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/05/20 alle ore 02:49:34