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Titolo:
Strategies to accomplish targeted expression of transgenes in ovarian cancer for molecular therapeutic applications
Autore:
Casado, E; Gomez-Navarro, J; Yamamoto, M; Adachi, Y; Coolidge, CJ; Arafat, WO; Barker, SD; Wang, MH; Mahasreshti, PJ; Hemminki, A; Gonzalez-Baron, M; Barnes, MN; Pustilnik, TB; Siegal, GP; Alvarez, RD; Curiel, DT;
Indirizzi:
Univ Alabama, Div Human Gene Therapy, Gene Therapy Ctr, Dept Med, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 , Dept Med, 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 Surg, Birmingham, AL 35294 USA Univ Alabama BirminghamAL USA 35294 Dept Surg, 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 Obstet Gynecol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 et Gynecol, Birmingham, AL 35294 USA Hosp La Paz, Med Oncol Serv, Madrid 28046, Spain Hosp La Paz Madrid Spain 28046 Paz, Med Oncol Serv, Madrid 28046, Spain
Titolo Testata:
CLINICAL CANCER RESEARCH
fascicolo: 8, volume: 7, anno: 2001,
pagine: 2496 - 2504
SICI:
1078-0432(200108)7:8<2496:STATEO>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
VIRUS THYMIDINE KINASE; ENDOPEROXIDE SYNTHASE-2 GENE; CYTOSINE DEAMINASE GENE; ADENOVIRAL VECTORS; IN-VIVO; CARCINOEMBRYONIC ANTIGEN; MESOTHELIAL CELLS; MEDIATED TRANSFER; PROMOTER; CARCINOMA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Curiel, DT Univ Alabama, Div Human Gene Therapy, Gene Therapy Ctr, Dept Med, Wallace Tumor Inst Room 620,1824 6th Ave S, Birmingham, AL 35294 USA Univ Alabama Wallace Tumor Inst Room 620,1824 6th Ave S Birmingham AL USA 35294
Citazione:
E. Casado et al., "Strategies to accomplish targeted expression of transgenes in ovarian cancer for molecular therapeutic applications", CLIN CANC R, 7(8), 2001, pp. 2496-2504

Abstract

Purpose: The purpose of the study was to determine the capability of the midkine (MK) and cycooxygenase-2 (cox-2) gene promoter regions to function as tumor-specific promoters for use in targeted gene therapy of ovarian cancer. Experimental Design: Established and primary ovarian cancer and mesothelial cells were transduced by adenoviral vectors containing a reporter or thymidine kinase gene expressed under the control of the MK, cox-2, or cytomegalovirus (CMV) promoters. SCID or C57BL/6 mice were injected i.p. with thesesame vectors. In vitro reporter gene expression and cellular cytotoxicity was determined using luciferase and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, respectively. Acute toxicity in vivo was assessed by histological evaluation of harvested tissues. Results: Consistent activation of the MK and cox-2 promoters was noted in all of the ovarian cancer cell lines in addition to primary ovarian cancer cells. In contrast, reduced reporter activity was reported in mesothelial cells transduced with adenoviruses containing the test promoters, which was especially apparent for the cox-2 promoter. Additionally, the cox-2 promoter exhibited significantly lower reporter gene levels in liver and peritoneum than the control promoter in in vivo experiments. Tumor-cell killing induced by Adcox-2 MTK was comparable to that observed with AdCMVTK. However, aclear differential toxicity pattern was observed in favor of animals treated with Adcox-2 MTK when compared with controls. Conclusions: These data clearly demonstrate that the transcriptional control afforded by the cox-2 promoter is tumor-specific and is able to mitigateassociated toxicity in normal tissue while maintaining therapeutic efficacy in the context of an ovarian cancer molecular chemotherapeutic approach.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/06/20 alle ore 11:26:34