Linked Life Data

11745423

Source:http://linkedlifedata.com/resource/pubmed/id/11745423

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2001-12-17
pubmed:abstractText
Recent clinical trials of cancer gene therapy have shown encouraging results for controlling localized tumors. However, to control metastatic or disseminated tumor cells, further modification of vectors is required to enhance specificity and infectivity against targets. We investigated whether utilization of the Cre recombinase(Cre)/loxP system contributes to enhanced antitumor effects together with minimal adverse reactions in specific gene therapy against disseminated carcinoembryonic antigen (CEA)-producing cancer cells in the peritoneal cavity of mice. CEA-producing cancer would be a good therapeutic target because it is found in lung, stomach and colon sites, which account for most cancers. We constructed a pair of recombinant adenoviral vectors (Ads), one of which expresses the Cre gene under the control of the CEA promoter (Ad.CEA-Cre); the other expresses the herpes simplex virus thymidine kinase (HSV-TK) gene (Ad.lox-TK), or the beta-galactosidase gene (beta-gal) by Cre (Ad.lox-beta-gal). Intraperitoneal coinjection of Ad.CEA-Cre and Ad.lox-beta-gal into mice with peritonitis carcinomatosa by CEA-producing tumor cells showed selective expression of the beta-gal gene in tumor foci. Coinfection of Ad.CEA-Cre and Ad.lox-TK followed by ganciclovir (GCV) administration significantly suppressed the total tumor weight in the peritoneal cavity of the mice to 13% of that of the untreated mice and 22% of that of the mice treated with Ad.CEA-TK/GCV, an Ad that expressed the HSV-TK gene driven by the CEA promoter alone. Moreover, treatment with Ad.CEA-Cre and Ad.lox-TK/GCV completely suppressed tumors in 4 of 10 (40%) mice without significant weight loss, although 2 of 10 mice treated with Ad.CAG-TK/GCV, an adenovirus vector that strongly but nonspecifically expressed the TK gene, died due to severe side effects including diarrhea, weight loss and liver dysfunction. These findings suggest that cell type-specific gene therapy using the Cre/loxP system is effective against disseminated cancer cells without significant side effects.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
94
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
414-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11745423-Adenoviridae, pubmed-meshheading:11745423-Animals, pubmed-meshheading:11745423-Body Weight, pubmed-meshheading:11745423-Carcinoembryonic Antigen, pubmed-meshheading:11745423-Cell Division, pubmed-meshheading:11745423-Dose-Response Relationship, Drug, pubmed-meshheading:11745423-Ganciclovir, pubmed-meshheading:11745423-Gene Therapy, pubmed-meshheading:11745423-Genes, Reporter, pubmed-meshheading:11745423-Humans, pubmed-meshheading:11745423-Integrases, pubmed-meshheading:11745423-Mice, pubmed-meshheading:11745423-Mice, Nude, pubmed-meshheading:11745423-Neoplasm Transplantation, pubmed-meshheading:11745423-Neoplasms, pubmed-meshheading:11745423-Promoter Regions, Genetic, pubmed-meshheading:11745423-Time Factors, pubmed-meshheading:11745423-Tumor Cells, Cultured, pubmed-meshheading:11745423-Viral Proteins, pubmed-meshheading:11745423-beta-Galactosidase
pubmed:year
2001
pubmed:articleTitle
Gene therapy utilizing the Cre/loxP system selectively suppresses tumor growth of disseminated carcinoembryonic antigen-producing cancer cells.
pubmed:affiliation
Department of Molecular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't