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Titolo:
A hypoxia-regulated adeno-associated virus vector for cancer-specific genetherapy
Autore:
Ruan, HJ; Su, H; Hu, L; Lamborn, KR; Kan, YW; Deen, DF;
Indirizzi:
Univ Calif San Francisco, Dept Neurol Surg, Brain Tumor Res Ctr, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA
Titolo Testata:
NEOPLASIA
fascicolo: 3, volume: 3, anno: 2001,
pagine: 255 - 263
SICI:
1522-8002(200105/06)3:3<255:AHAVVF>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
INDUCIBLE FACTOR 1-ALPHA; GROWTH-FACTOR GENE; BRAIN-TUMORS; ISCHEMIC DISEASE; EXPRESSION; CELLS; FACTOR-1-ALPHA; ANGIOGENESIS; PROGRESSION; METASTASES;
Keywords:
hypoxia; brain tumor cells; hypoxia-responsive element; adeno-associated virus; gene therapy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Deen, DF Univ Calif San Francisco, Dept Neurol Surg, Brain Tumor Res Ctr, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 CA 94143 USA
Citazione:
H.J. Ruan et al., "A hypoxia-regulated adeno-associated virus vector for cancer-specific genetherapy", NEOPLASIA, 3(3), 2001, pp. 255-263

Abstract

The presence of hypoxic cells in human brain tumors is an important factorleading to resistance to radiation therapy. However, this physiological difference between normal tissues and tumors also provides the potential for designing cancer-specific gene therapy. We compared the increase of gene expression under anoxia (<0.01% oxygen) produced by 3, 6, and 9 copies of hypoxia-responsive elements (HRE) from the erythropoietin gene (Epo), which are activated through the transcriptional complex hypoxia-inducible factor 1 (HIF-1). Under anoxic conditions, nine copies of HIRE (9XHRE) yielded 27- to 37-fold of increased gene expression in U-251 MG and U-87 MG human brain tumor cell lines. Under the less hypoxic conditions of 0.3% and 1% oxygen, gene activation by 9XHRE increased expression 11- to 18-fold in these cell lines. To generate a recombinant adeno-associated virus (rAAV) in which thetransgene can be regulated by hypoxia, we inserted the DNA fragment containing 9XHRE and the LacZ reporter gene into an AAV vector. Under anoxic conditions, this vector produced 79- to 110-fold increase in gene expression. We believe this hypoxia-regulated rAAV vector will provide a useful deliveryvehicle for cancer-specific gene therapy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/03/20 alle ore 10:08:10