Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2001-6-4
pubmed:abstractText
A 2.4-kb truncated L-plastin promoter was inserted either 5' to the LacZ gene (Ad-Lp-LacZ) or 5' to the cytosine deaminase (CD) gene (Ad-Lp-CD) in a replication-incompetent adenoviral vector backbone. Infectivity and cytotoxicity experiments with the LacZ and CD vectors suggested that the L-plastin promoter-driven transcriptional units were expressed at much higher levels in explants of ovarian cancer cells from patients and in established ovarian or bladder cancer cell lines than they were in normal peritoneal mesothelial cells from surgical specimens, in organ cultures of normal ovarian cells, or in the established CCD minimal deviation fibroblast cell line. Control experiments showed that this difference was not attributable to the lack of infectivity of the normal peritoneal cells, the normal ovarian cells, or the minimal deviation CCD fibroblast cell line, because these cells showed expression of the LacZ reporter gene when exposed to the replication-incompetent adenoviral vector carrying the cytomegalovirus (CMV)-driven LacZ gene (Ad-CMV-LacZ). The Ovcar-5 and Skov-3 ovarian cancer cell lines exposed to the Ad-Lp-CD adenoviral vector were much more sensitive to the prodrug 5-fluorocytosine (5FC), which is converted from the 5FC prodrug into the toxic chemical 5-fluorouracil, than was the CCD minimal deviation fibroblast cell line after exposure to the same vector. A mouse xenograft model was used to show that the Ad-Lp-CD vector/5FC system could prevent engraftment of ovarian cancer cells in nude mice. Finally, injection of the Ad-Lp-CD vector into s.c. tumor nodules generated a greater reduction of the size of the tumor nodules than did injection of the Ad-CMV-LacZ vectors into tumor nodules. The Ad-Lp-CD vectors were as suppressive to tumor growth as the Ad-CMV-CD vectors. These results suggest that an adenoviral vector carrying the CD gene controlled by the L-plastin promoter (Ad-Lp-CD) may be of potential value for the i.p. therapy of ovarian cancer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4405-13
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11389068-Adenoviridae, pubmed-meshheading:11389068-Animals, pubmed-meshheading:11389068-Cytomegalovirus, pubmed-meshheading:11389068-Cytosine Deaminase, pubmed-meshheading:11389068-Female, pubmed-meshheading:11389068-Flucytosine, pubmed-meshheading:11389068-Fluorouracil, pubmed-meshheading:11389068-Gene Expression, pubmed-meshheading:11389068-Gene Therapy, pubmed-meshheading:11389068-Genetic Vectors, pubmed-meshheading:11389068-Humans, pubmed-meshheading:11389068-Inhibitory Concentration 50, pubmed-meshheading:11389068-Lac Operon, pubmed-meshheading:11389068-Membrane Glycoproteins, pubmed-meshheading:11389068-Mice, pubmed-meshheading:11389068-Mice, Nude, pubmed-meshheading:11389068-Microfilament Proteins, pubmed-meshheading:11389068-Nucleoside Deaminases, pubmed-meshheading:11389068-Ovarian Neoplasms, pubmed-meshheading:11389068-Phosphoproteins, pubmed-meshheading:11389068-Promoter Regions, Genetic, pubmed-meshheading:11389068-Tumor Cells, Cultured, pubmed-meshheading:11389068-Urinary Bladder Neoplasms, pubmed-meshheading:11389068-Xenograft Model Antitumor Assays
pubmed:year
2001
pubmed:articleTitle
The use of the L-plastin promoter for adenoviral-mediated, tumor-specific gene expression in ovarian and bladder cancer cell lines.
pubmed:affiliation
Genetic Therapy Program, Yale Cancer Center, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't