Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1998-9-16
pubmed:abstractText
p53 tumor suppressor gene therapy has been proposed for cancers characterized by inactivation of p53 function, and successful therapy will require efficient strategies for gene delivery. To maximize transgene expression in tumors, a clinical strategy has been proposed to treat neoplasms in the liver via hepatic artery administration of a recombinant adenovirus encoding wild-type p53 (rAd-p53). We have developed a syngeneic rat model using a p53mut hepatocellular carcinoma cell line (McA-RH7777) that results in multifocal liver tumor nodules to provide experimental support for this strategy. Treatment of McA-RH7777 cells with rAd-p53 in vitro resulted in efficient transgene expression, growth suppression, and apoptosis. Intrahepatic artery dosing with rAd-p53 or an adenovirus encoding beta-galactosidase (rAd-betagal) increased transgene expression in tumor tissue and decreased systemic exposure when compared with i.v. dosing. Daily hepatic artery dosing of rAd-p53 suppressed tumor growth when compared with untreated rats or animals treated with rAd-betagal. These data demonstrate the potential for arterial gene delivery to tumors using recombinant adenoviruses, and support continued investigation of rAd-p53 gene therapy for liver malignancies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1078-0432
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1649-59
pubmed:dateRevised
2006-4-21
pubmed:meshHeading
pubmed-meshheading:9676839-Adenoviridae, pubmed-meshheading:9676839-Animals, pubmed-meshheading:9676839-Apoptosis, pubmed-meshheading:9676839-Carcinoma, Hepatocellular, pubmed-meshheading:9676839-Defective Viruses, pubmed-meshheading:9676839-Female, pubmed-meshheading:9676839-Gene Expression, pubmed-meshheading:9676839-Gene Therapy, pubmed-meshheading:9676839-Genes, p53, pubmed-meshheading:9676839-Genetic Vectors, pubmed-meshheading:9676839-Hepatic Artery, pubmed-meshheading:9676839-Humans, pubmed-meshheading:9676839-Infusions, Intra-Arterial, pubmed-meshheading:9676839-Infusions, Intravenous, pubmed-meshheading:9676839-Liver Neoplasms, Experimental, pubmed-meshheading:9676839-Neoplasm Proteins, pubmed-meshheading:9676839-Rats, pubmed-meshheading:9676839-Transgenes, pubmed-meshheading:9676839-Tumor Cells, Cultured, pubmed-meshheading:9676839-Tumor Suppressor Protein p53
pubmed:year
1998
pubmed:articleTitle
p53 gene therapy in a rat model of hepatocellular carcinoma: intra-arterial delivery of a recombinant adenovirus.
pubmed:affiliation
Canji Inc., San Diego, California 92121, USA.
pubmed:publicationType
Journal Article