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Titolo:
Gene therapy targeting for hepatocellular carcinoma: Selective and enhanced suicide gene expression regulated by a hypoxia-inducible enhancer linked to a human alpha-fetoprotein promoter
Autore:
Ido, A; Uto, H; Moriuchi, A; Nagata, K; Onaga, Y; Onaga, M; Hori, T; Hirono, S; Hayashi, K; Tamaoki, T; Tsubouchi, H;
Indirizzi:
Miyazaki Med Coll, Dept Internal Med 2, Miyazaki 8891692, Japan Miyazaki Med Coll Miyazaki Japan 8891692 Med 2, Miyazaki 8891692, Japan Univ Calgary, Dept Med Biochem, Calgary, AB T2N 4N1, Canada Univ Calgary Calgary AB Canada T2N 4N1 ochem, Calgary, AB T2N 4N1, Canada
Titolo Testata:
CANCER RESEARCH
fascicolo: 7, volume: 61, anno: 2001,
pagine: 3016 - 3021
SICI:
0008-5472(20010401)61:7<3016:GTTFHC>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
ENDOTHELIAL GROWTH-FACTOR; THYMIDINE KINASE GENE; ADENOVIRUS-MEDIATED TRANSFER; CLINICAL-SIGNIFICANCE; HEPATOMA-CELLS; RECEPTOR GENE; TUMOR-GROWTH; ANGIOGENESIS; PROTEIN; CANCER;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
54
Recensione:
Indirizzi per estratti:
Indirizzo: Tsubouchi, H Miyazaki Med Coll, Dept Internal Med 2, 5200 Kihara, Miyazaki8891692, Japan Miyazaki Med Coll 5200 Kihara Miyazaki Japan 8891692 , Japan
Citazione:
A. Ido et al., "Gene therapy targeting for hepatocellular carcinoma: Selective and enhanced suicide gene expression regulated by a hypoxia-inducible enhancer linked to a human alpha-fetoprotein promoter", CANCER RES, 61(7), 2001, pp. 3016-3021

Abstract

We previously reported that the retroviral vector expressing the herpes simplex virus-thymidine kinase gene under the control of 0,3-kb human a-fetoprotein (AFP) gene promoter (AF0.3) provided the cytotoxicity to ganciclovir(GCV) in high-AFP-producing human hepatoma cells hut not in low-AFP-producing cells. Therefore, specific enhancement of AFP promoter activity is likely to he required to induce enough cytotoxicity in low-AFP-producing hepatoma cells. Zn this study, we constructed a hybrid promoter, [HRE]AF, in which a 0,4-kb fragment of human vascular endothelial growth factor 5'-flankingsequences containing hypoxia-responsive element (HRE) was fused to AF0.3 promoter. By means of the reporter gene transfection assay, hypoxia-inducible transcriptions that were mediated by [[HRE]AF promoter were detected in low- and non-AFP-producing human hepatoma cells, but not in nonhepatoma cells. When the herpes simplex virus-thymidine kinase gene controlled by [HRE]AF promoter was transduced into hepatoma and nonhepatoma cells by a retroviral vector, the exposure to 1% O-2 induced GCV cytotoxicity specifically in the hepatoma cells. Moreover, in nude mice bearing solid tumor xenografts, only the tumors consisting of the virus-infected hepatoma cells gradually disappeared by GCV administration. These results indicate that the hypoxia-inducible enhancer of the human vascular endothelial growth factor gene, which is directly linked to human AFP promoter, involves selective and enhanced tumoricidal activity in gene therapy for hepatocellular carcinoma.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 09:33:39