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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2003-7-1
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pubmed:abstractText |
Multiple myeloma is a disseminated neoplasm of terminally differentiated plasma cells that is incurable with currently available therapies. Although the disease is radiosensitive, external beam radiation leads to significant toxicity due to sensitive end-organ damage. Thus, genetic approaches for therapy are required. We hypothesized that the incorporation of immunoglobulin promoter and enhancer elements in a self-inactivating (SIN) lentiviral vector should lead to specific and high-level transgene expression in myeloma cells. A SIN lentivector with enhanced green fluorescent protein (EGFP) expression under the control of a minimal immunoglobulin promoter as well as the Kappa light chain intronic and 3' enhancers transduced myeloma cell lines with high efficiency (30%-90%). EGFP was expressed at a high level in myeloma cells but silent in all nonmyeloma cell lines tested compared with the cytomegalovirus (CMV) promoter/enhancer. Transduction of myeloma cells with the targeted vector coding for the human sodiumiodide symporter (hNIS) led to hNIS expression by these cells allowing them to concentrate radioiodine up to 18-fold compared with controls. Tumor xenografts in severe combined immunodeficiency mice expressing hNIS could be imaged using iodine-123 (123I) and shown to retain iodide for up to 48 hours. These tumor xenografts were completely eradicated by a single dose of the therapeutic isotope iodine-131 (131I) without evidence of recurrence up to 5 months after therapy. We conclude that lentivectors can be transcriptionally targeted for myeloma cells and the use of hNIS as a therapeutic gene for myeloma in combination with 131I needs further exploration.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
102
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
489-96
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12649158-Animals,
pubmed-meshheading:12649158-Cytomegalovirus,
pubmed-meshheading:12649158-Defective Viruses,
pubmed-meshheading:12649158-Drug Delivery Systems,
pubmed-meshheading:12649158-Enhancer Elements, Genetic,
pubmed-meshheading:12649158-Genes, Immunoglobulin,
pubmed-meshheading:12649158-Genes, Reporter,
pubmed-meshheading:12649158-Genes, Synthetic,
pubmed-meshheading:12649158-Genetic Vectors,
pubmed-meshheading:12649158-Green Fluorescent Proteins,
pubmed-meshheading:12649158-Humans,
pubmed-meshheading:12649158-Immunoglobulin kappa-Chains,
pubmed-meshheading:12649158-Introns,
pubmed-meshheading:12649158-Iodine Radioisotopes,
pubmed-meshheading:12649158-Lentivirus,
pubmed-meshheading:12649158-Luminescent Proteins,
pubmed-meshheading:12649158-Mice,
pubmed-meshheading:12649158-Mice, SCID,
pubmed-meshheading:12649158-Multiple Myeloma,
pubmed-meshheading:12649158-Myeloma Proteins,
pubmed-meshheading:12649158-Promoter Regions, Genetic,
pubmed-meshheading:12649158-Radiopharmaceuticals,
pubmed-meshheading:12649158-Recombinant Fusion Proteins,
pubmed-meshheading:12649158-Symporters,
pubmed-meshheading:12649158-Transcription, Genetic,
pubmed-meshheading:12649158-Transduction, Genetic,
pubmed-meshheading:12649158-Tumor Cells, Cultured,
pubmed-meshheading:12649158-Xenograft Model Antitumor Assays
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pubmed:year |
2003
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pubmed:articleTitle |
Genetically targeted radiotherapy for multiple myeloma.
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pubmed:affiliation |
Mayo Clinic and Foundation, Rochester, MN, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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