| pubmed-article:11859419 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:11859419 | lifeskim:mentions | umls-concept:C0040649 | lld:lifeskim |
| pubmed-article:11859419 | lifeskim:mentions | umls-concept:C0599894 | lld:lifeskim |
| pubmed-article:11859419 | lifeskim:mentions | umls-concept:C1515035 | lld:lifeskim |
| pubmed-article:11859419 | pubmed:issue | 3 | lld:pubmed |
| pubmed-article:11859419 | pubmed:dateCreated | 2002-2-22 | lld:pubmed |
| pubmed-article:11859419 | pubmed:abstractText | Transcriptional targeting of gene expression has been plagued by the weakness of tissue-specific promoters. Thus, to increase promoter strength while maintaining tissue specificity, we constructed a recombinant adenovirus containing a binary promoter system with a tumor-specific promoter (CEA; carcinoembryonic antigen) driving a transcription transactivator, which then activates a minimal promoter to express a suicide gene (HSV-tk; herpes simplex virus thymidine kinase). This ADV/binary-tk induced equal or greater cell killing in a CEA-specific manner in vitro compared with the CEA-independent killing of a vector with a constitutive viral promoter driving HSV-tk (ADV/RSV-tk). To monitor adenovirus-mediated HSV-tk gene expression in vivo, we employed noninvasive nuclear imaging using a radioiodinated nucleoside analog ([((1)31)I]-FIAU) serving as a substrate for HSV-tk. [((1)31)I]-FIAU-derived radioactivity accumulated after intratumoral injection of ADV/binary-tk only in the area of CEA-positive tumors with significantly less spread to the adjacent liver tissue than after administration of the universally expressed ADV/RSV-tk. Both viruses exhibited similar antitumor efficacy upon injection of liver metastases. Importantly, in vivo dose escalation studies demonstrated significantly reduced toxicity after intravenous administration of ADV/binary-tk versus ADV/RSV-tk. In summary, the increased therapeutic index of this novel, amplified CEA-driven suicide gene therapy vector is a proof of principle for the powerful enhancement of a weak tissue-specific promoter for effective tumor restricted gene expression. | lld:pubmed |
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| pubmed-article:11859419 | pubmed:language | eng | lld:pubmed |
| pubmed-article:11859419 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11859419 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:11859419 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:11859419 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11859419 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:11859419 | pubmed:month | Feb | lld:pubmed |
| pubmed-article:11859419 | pubmed:issn | 0969-7128 | lld:pubmed |
| pubmed-article:11859419 | pubmed:author | pubmed-author:BlasbergR GRG | lld:pubmed |
| pubmed-article:11859419 | pubmed:author | pubmed-author:HuangYY | lld:pubmed |
| pubmed-article:11859419 | pubmed:author | pubmed-author:GuoZ SZS | lld:pubmed |
| pubmed-article:11859419 | pubmed:author | pubmed-author:QiaoJJ | lld:pubmed |
| pubmed-article:11859419 | pubmed:author | pubmed-author:ConnJ BJB | lld:pubmed |
| pubmed-article:11859419 | pubmed:author | pubmed-author:TjuvajevJ GJG | lld:pubmed |
| pubmed-article:11859419 | pubmed:author | pubmed-author:AkhurstTT | lld:pubmed |
| pubmed-article:11859419 | pubmed:author | pubmed-author:SauterB VBV | lld:pubmed |
| pubmed-article:11859419 | pubmed:author | pubmed-author:BalatoniJJ | lld:pubmed |
| pubmed-article:11859419 | pubmed:author | pubmed-author:DoubrovinMM | lld:pubmed |
| pubmed-article:11859419 | pubmed:author | pubmed-author:WooS L CSL | lld:pubmed |
| pubmed-article:11859419 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:11859419 | pubmed:volume | 9 | lld:pubmed |
| pubmed-article:11859419 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:11859419 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:11859419 | pubmed:pagination | 168-75 | lld:pubmed |
| pubmed-article:11859419 | pubmed:dateRevised | 2008-11-21 | lld:pubmed |
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| pubmed-article:11859419 | pubmed:year | 2002 | lld:pubmed |
| pubmed-article:11859419 | pubmed:articleTitle | Tumor-specific transcriptional targeting of suicide gene therapy. | lld:pubmed |
| pubmed-article:11859419 | pubmed:affiliation | Institute for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA. | lld:pubmed |
| pubmed-article:11859419 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:11859419 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| pubmed-article:11859419 | pubmed:publicationType | Research Support, U.S. Gov't, Non-P.H.S. | lld:pubmed |
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