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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
1995-2-24
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pubmed:abstractText |
We have constructed recombinant human adenoviruses that express wild-type human p53 under the control of either the Ad 2 major late promoter (MLP) or the human cytomegalovirus (CMV) immediate early gene promoter. Each construct replaces the Ad 5 E1a and E1b coding sequences necessary for viral replication with the p53 cDNA and MLP or CMV promoter. These p53/Ad recombinants are able to express p53 protein in a dose-dependent manner in infected human cancer cells. Tumor suppressor activity of the expressed p53 protein was assayed by several methods. [3H]Thymidine incorporation assays showed that the recombinant adenoviruses were capable of inhibiting DNA synthesis in a p53-specific, dose-dependent fashion. Ex vivo treatment of Saos-2 tumor cells, followed by injection of the treated cells into nude mice, led to complete tumor suppression using the MLP/p53 recombinant. Following a single injection of CMV/p53 recombinant adenovirus into the peritumoral space surrounding an in vivo established tumor derived from a human small cell lung carcinoma cell line (NIH-H69), we were able to detect p53 mRNA in the tumors at 2 and 7 days post-injection. Continued treatment of established H69 tumors with MLP/p53 recombinant led to reduced tumor growth and increased survival time compared to control treated animals. These results indicate that recombinant adenoviruses expressing wild-type p53 may be useful vectors for gene therapy of human cancer.
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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 |
Sep
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pubmed:issn |
1043-0342
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
5
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pubmed:owner |
NLM
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pubmed:authorsComplete |
N
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pubmed:pagination |
1079-88
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:7833367-Adenoviruses, Human,
pubmed-meshheading:7833367-Animals,
pubmed-meshheading:7833367-Base Sequence,
pubmed-meshheading:7833367-Carcinoma, Small Cell,
pubmed-meshheading:7833367-Cytomegalovirus,
pubmed-meshheading:7833367-DNA, Complementary,
pubmed-meshheading:7833367-DNA, Recombinant,
pubmed-meshheading:7833367-DNA, Viral,
pubmed-meshheading:7833367-DNA Replication,
pubmed-meshheading:7833367-Defective Viruses,
pubmed-meshheading:7833367-Female,
pubmed-meshheading:7833367-Gene Therapy,
pubmed-meshheading:7833367-Genes, p53,
pubmed-meshheading:7833367-Genetic Vectors,
pubmed-meshheading:7833367-Humans,
pubmed-meshheading:7833367-Lung Neoplasms,
pubmed-meshheading:7833367-Mice,
pubmed-meshheading:7833367-Mice, Inbred BALB C,
pubmed-meshheading:7833367-Mice, Nude,
pubmed-meshheading:7833367-Molecular Sequence Data,
pubmed-meshheading:7833367-Neoplasm Transplantation,
pubmed-meshheading:7833367-Neoplasms,
pubmed-meshheading:7833367-Promoter Regions, Genetic,
pubmed-meshheading:7833367-Recombinant Fusion Proteins,
pubmed-meshheading:7833367-Transplantation, Heterologous,
pubmed-meshheading:7833367-Tumor Cells, Cultured,
pubmed-meshheading:7833367-Tumor Suppressor Protein p53
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pubmed:year |
1994
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pubmed:articleTitle |
Development and characterization of recombinant adenoviruses encoding human p53 for gene therapy of cancer.
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pubmed:affiliation |
CANJI, Inc., San Diego, CA 92121.
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pubmed:publicationType |
Journal Article
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