Linked Life Data

12566311

Source:http://linkedlifedata.com/resource/pubmed/id/12566311

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-2-4
pubmed:abstractText
A major potential limitation to the success of enzyme prodrug gene therapy is the toxicity that could result from gene expression in normal tissues. In this study, we investigated the use of an enhanced human carcinoembryonic antigen (CEA) promoter for yeast cytosine deaminase (yCD), which converts 5-fluorocytosine to 5-fluorouracil, to increase targeting while maintaining activity both in cell culture and in nude rats bearing intrahepatic xenografts. We found that an enhanced CEA-yCD adenoviral vector can achieve significantly greater yCD expression in CEA-expressing colon carcinoma cell lines (LoVo, HT29, and CaCo2) compared with a nonspecific Rous sarcoma virus-yCD virus. In contrast, infection with CEA-yCD led to lower or equivalent yCD expression in normal hepatocytes or fibroblasts compared with that produced by the RSV-yCD. Adenovirus administered in the portal vein or the hepatic artery of nude rats bearing intrahepatic LoVo colon carcinomas could mediate beta-galactosidase expression equally in liver and tumors under the control of cytomegalovirus, a nonspecific promoter. However, infusion of CEA-yCD virus markedly increased yCD expression in tumors over normal liver (>4-fold) measured both by levels of mRNA and yCD activity. Moreover, the efficiency of 5-fluorocytosine conversion into 5-fluorouracil in tumors was significantly higher than that in normal liver ( approximately 3-fold) in rats receiving portal venous viral infusion of CEA-yCD and subsequent 5FC treatment. Thus, an enhanced CEA promoter can preferentially stimulate yCD gene expression in CEA-expressing cells in vivo. Such tumor-specific expression should prove useful in colorectal cancer gene therapy to achieve selective prodrug conversion in tumors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
658-63
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12566311-Adenoviridae, pubmed-meshheading:12566311-Animals, pubmed-meshheading:12566311-Antimetabolites, Antineoplastic, pubmed-meshheading:12566311-Carcinoembryonic Antigen, pubmed-meshheading:12566311-Colonic Neoplasms, pubmed-meshheading:12566311-Cytosine Deaminase, pubmed-meshheading:12566311-Flucytosine, pubmed-meshheading:12566311-Fluorouracil, pubmed-meshheading:12566311-Gene Expression, pubmed-meshheading:12566311-Gene Therapy, pubmed-meshheading:12566311-Genetic Vectors, pubmed-meshheading:12566311-Humans, pubmed-meshheading:12566311-Immunoblotting, pubmed-meshheading:12566311-Liver Neoplasms, pubmed-meshheading:12566311-Nucleoside Deaminases, pubmed-meshheading:12566311-Prodrugs, pubmed-meshheading:12566311-Promoter Regions, Genetic, pubmed-meshheading:12566311-Rats, pubmed-meshheading:12566311-Tumor Cells, Cultured, pubmed-meshheading:12566311-Xenograft Model Antitumor Assays
pubmed:year
2003
pubmed:articleTitle
Regional delivery and selective expression of a high-activity yeast cytosine deaminase in an intrahepatic colon cancer model.
pubmed:affiliation
Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. mingz@med.umich.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't