Source:http://linkedlifedata.com/resource/pubmed/id/19887556
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
11
|
| pubmed:dateCreated |
2009-11-12
|
| pubmed:abstractText |
Thymidine kinase (TK)-mediated suicide gene therapy has been considered for the treatment of pancreatic cancer. However, despite a bystander effect, the proportion of transduced tumor cells has proven too low to result in efficacy. We propose the use of a drug-selectable marker (MDR1) to enrich TK-expressing cells using chemotherapy. This enrichment or positive selection phase may increase the efficacy of suicide gene therapy. To test this strategy, we generated stable NP18MDR/TK-GFP transfectants and showed docetaxel resistance in vivo. Mixed tumors of MDR/TK-expressing cells and parental NP18 cells were established and docetaxel was used to increase the proportion of TK-expressing cells. After this positive selection phase, suicide gene therapy with ganciclovir was applied. Upon positive selection, the proportion of TK-expressing cells increased from 4% to 22%. Subsequent suicide gene therapy was more effective compared with a control group without positive selection. Starting with 10% of TK-expressing cells the positive-negative selection strategy completely inhibited tumor growth. Taken together, these results suggest that a positive-negative selection strategy based on MDR and TK genes represents an efficient way to increase the proportion of TK-expressing cells in the tumor and the efficacy of TK-mediated suicide gene therapy.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ABCB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Ganciclovir,
http://linkedlifedata.com/resource/pubmed/chemical/P-Glycoprotein,
http://linkedlifedata.com/resource/pubmed/chemical/Taxoids,
http://linkedlifedata.com/resource/pubmed/chemical/Thymidine Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/docetaxel
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
|
| pubmed:issn |
1538-8514
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| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:volume |
8
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
3098-107
|
| pubmed:meshHeading |
pubmed-meshheading:19887556-Adenocarcinoma,
pubmed-meshheading:19887556-Animals,
pubmed-meshheading:19887556-Antineoplastic Agents,
pubmed-meshheading:19887556-Cell Line, Tumor,
pubmed-meshheading:19887556-Combined Modality Therapy,
pubmed-meshheading:19887556-Ganciclovir,
pubmed-meshheading:19887556-Gene Therapy,
pubmed-meshheading:19887556-Genes, Transgenic, Suicide,
pubmed-meshheading:19887556-Genetic Vectors,
pubmed-meshheading:19887556-Humans,
pubmed-meshheading:19887556-Male,
pubmed-meshheading:19887556-Mice,
pubmed-meshheading:19887556-Mice, Inbred BALB C,
pubmed-meshheading:19887556-P-Glycoprotein,
pubmed-meshheading:19887556-Pancreatic Neoplasms,
pubmed-meshheading:19887556-Taxoids,
pubmed-meshheading:19887556-Thymidine Kinase,
pubmed-meshheading:19887556-Transfection,
pubmed-meshheading:19887556-Xenograft Model Antitumor Assays
|
| pubmed:year |
2009
|
| pubmed:articleTitle |
Positive selection of gene-modified cells increases the efficacy of pancreatic cancer suicide gene therapy.
|
| pubmed:affiliation |
Gene and Viral Therapy Group, IDIBELL-Catalan Institute of Oncology (ICO), L'Hospitalet de Llobregat, UPF, Parc de Recerca Biomédica de Barcelona and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER-ISCIII), Barcelona, Spain.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|