Linked Life Data

11012166

Source:http://linkedlifedata.com/resource/pubmed/id/11012166

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2000-10-19
pubmed:abstractText
Transfer of drug resistance genes to hematopoietic cells is being studied as a means to protect against the myelosuppression associated with cancer chemotherapy and as a strategy for the in vivo selection and amplification of genetically modified cells. The goal of this study was to test if retroviral-mediated gene transfer of a dihydrofolate reductase (DHFR) variant (L22Y) could be used for in vivo selection of transduced myeloid cells and to determine what proportion of transduced cells was required for protection from myelosuppression. Based on previous work suggesting that selection with antifolates may also require inhibition of nucleoside transport mechanisms, mice transplanted with DHFR-transduced bone marrow cells were treated with trimetrexate and the nucleoside transport inhibitor prodrug nitrobenzylmercaptopurine riboside phosphate. In vivo selection of transduced myeloid progenitors was seen in the bone marrow and in circulating mature peripheral blood cells following drug treatment. These results show that the novel combination of the L22Y-DHFR cDNA, trimetrexate and nitrobenzylmercaptopurine riboside phosphate can be used to select for transduced myeloid cells, and that this approach warrants further study in large animal models. A bicistronic vector containing a human CD24 reporter gene was used to determine the number of modified cells needed for chemoprotection. Partial protection from neutropenia was seen when greater than 10% of myeloid cells expressed the vector, and high levels of protection were obtained when the proportion exceeded 30%. These results suggest that gene transfer may be useful for myeloprotection in certain pediatric cancers, but that more efficient gene transfer will be required to apply this approach to adult cancer patients.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1066-5099
pubmed:author
pubmed:issnType
Print
pubmed:volume
16 Suppl 1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
223-33
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11012166-Adult, pubmed-meshheading:11012166-Amino Acid Substitution, pubmed-meshheading:11012166-Animals, pubmed-meshheading:11012166-Antigens, CD, pubmed-meshheading:11012166-Antigens, CD24, pubmed-meshheading:11012166-Bone Marrow Cells, pubmed-meshheading:11012166-Encephalomyocarditis virus, pubmed-meshheading:11012166-Female, pubmed-meshheading:11012166-Gene Therapy, pubmed-meshheading:11012166-Gene Transfer Techniques, pubmed-meshheading:11012166-Genes, Reporter, pubmed-meshheading:11012166-Genetic Variation, pubmed-meshheading:11012166-Genetic Vectors, pubmed-meshheading:11012166-Harvey murine sarcoma virus, pubmed-meshheading:11012166-Hematopoietic Stem Cell Transplantation, pubmed-meshheading:11012166-Hematopoietic Stem Cells, pubmed-meshheading:11012166-Humans, pubmed-meshheading:11012166-Membrane Glycoproteins, pubmed-meshheading:11012166-Mice, pubmed-meshheading:11012166-Recombinant Proteins, pubmed-meshheading:11012166-Tetrahydrofolate Dehydrogenase, pubmed-meshheading:11012166-Thioinosine, pubmed-meshheading:11012166-Thionucleotides, pubmed-meshheading:11012166-Transfection, pubmed-meshheading:11012166-Trimetrexate
pubmed:year
1998
pubmed:articleTitle
Retroviral vectors containing a variant dihydrofolate reductase gene for drug protection and in vivo selection of hematopoietic cells.
pubmed:affiliation
Department of Hematology and Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't