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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0017296,
umls-concept:C0038661,
umls-concept:C0086222,
umls-concept:C0086860,
umls-concept:C0208973,
umls-concept:C0599894,
umls-concept:C0851285,
umls-concept:C1307640,
umls-concept:C1517892,
umls-concept:C1704666,
umls-concept:C1705733,
umls-concept:C2239176,
umls-concept:C2349975
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pubmed:issue |
7
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pubmed:dateCreated |
2001-4-18
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pubmed:abstractText |
We previously reported that the retroviral vector expressing the herpes simplex virus-thymidine kinase gene under the control of 0.3-kb human alpha-fetoprotein (AFP) gene promoter (AF0.3) provided the cytotoxicity to ganciclovir (GCV) in high-AFP-producing human hepatoma cells but not in low-AFP-producing cells. Therefore, specific enhancement of AFP promoter activity is likely to be required to induce enough cytotoxicity in low-AFP-producing hepatoma cells. In this study, we constructed a hybrid promoter, [HRE]AF, in which a 0.4-kb fragment of human vascular endothelial growth factor 5'-flanking sequences 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% O2 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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0008-5472
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pubmed:author |
pubmed-author:HayashiKK,
pubmed-author:HironoSS,
pubmed-author:HoriTT,
pubmed-author:IdaSS,
pubmed-author:MoriuchiAA,
pubmed-author:NagataKK,
pubmed-author:OnagaMM,
pubmed-author:OnagaYY,
pubmed-author:TamaokiTT,
pubmed-author:TsubouchiHH,
pubmed-author:UttMM
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
61
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3016-21
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11306481-Animals,
pubmed-meshheading:11306481-Carcinoma, Hepatocellular,
pubmed-meshheading:11306481-Cell Hypoxia,
pubmed-meshheading:11306481-Endothelial Growth Factors,
pubmed-meshheading:11306481-Enhancer Elements, Genetic,
pubmed-meshheading:11306481-Ganciclovir,
pubmed-meshheading:11306481-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:11306481-Gene Therapy,
pubmed-meshheading:11306481-Genetic Vectors,
pubmed-meshheading:11306481-Humans,
pubmed-meshheading:11306481-Liver Neoplasms,
pubmed-meshheading:11306481-Lymphokines,
pubmed-meshheading:11306481-Male,
pubmed-meshheading:11306481-Mice,
pubmed-meshheading:11306481-Mice, Inbred BALB C,
pubmed-meshheading:11306481-Mice, Nude,
pubmed-meshheading:11306481-Promoter Regions, Genetic,
pubmed-meshheading:11306481-Retroviridae,
pubmed-meshheading:11306481-Simplexvirus,
pubmed-meshheading:11306481-Thymidine Kinase,
pubmed-meshheading:11306481-Transcriptional Activation,
pubmed-meshheading:11306481-Transduction, Genetic,
pubmed-meshheading:11306481-Vascular Endothelial Growth Factor A,
pubmed-meshheading:11306481-Vascular Endothelial Growth Factors,
pubmed-meshheading:11306481-alpha-Fetoproteins
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pubmed:year |
2001
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pubmed:articleTitle |
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.
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pubmed:affiliation |
Department of Internal Medicine II, Miyazaki Medical College, Kiyotake, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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