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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
19
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pubmed:dateCreated |
2007-9-18
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pubmed:abstractText |
Treatments for renal cell carcinoma, while promising, are still limited by toxicity and cost. In the hopes of finding a novel compound or combination, we developed a plasmid containing the genes for interleukin-2 (IL-2) and soluble vascular endothelial growth factor receptor 2 (msFlk1). The plasmid, p2CMVIL2/msFlk1, demonstrated similar in vitro transgene expression of IL-2 or msFlk1 compared to their single-agent counterparts. Subcutaneous tumor growth was significantly inhibited in the p2CMVIL2/msFlk1 group when delivered locally by the non-viral water soluble polymer, WSLP and exhibited a 50% increase in survival over glucose and single-agent controls. In vivo experimentation demonstrated that WSLP/msFlk1 decreased microvessel density in pCMVmsFlk1 and p2CMVIL2/msFlk1 treated groups. Furthermore, tumor-infiltrating lymphocytes expressing CD45RO and CD68 were increased within the tumor microenvironment upon p2CMVIL2/msFlk1 treatment. To determine the effects of p2CMVIL2/msFlk1 in an experimental RENCA lung metastases model, therapeutic DNA was delivered systemically following complexation with the angiogenic endothelial-targeting polymer PEI-g-PEG-RGD. The p2CMVIL2/msFlk1 treatment significantly reduced metastases by 56% over single-agent therapy and increased survival proportions by 50% over all groups. Our work clearly demonstrates that non-viral delivery of p2CMVIL2/msFlk1 can inhibit RENCA growth in a synergistic manner and may represent a new treatment for renal carcinoma.
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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 |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD45,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation...,
http://linkedlifedata.com/resource/pubmed/chemical/CD68 antigen, human,
http://linkedlifedata.com/resource/pubmed/chemical/Drug Carriers,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Lipids,
http://linkedlifedata.com/resource/pubmed/chemical/PEI-g-PEG-RGD,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides, Cyclic,
http://linkedlifedata.com/resource/pubmed/chemical/Polyethylene Glycols,
http://linkedlifedata.com/resource/pubmed/chemical/Polyethyleneimine,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/poly(ethylenimine)-co-(N-(2-aminoeth...
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0969-7128
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
14
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1399-405
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17653245-Animals,
pubmed-meshheading:17653245-Antigens, CD,
pubmed-meshheading:17653245-Antigens, CD45,
pubmed-meshheading:17653245-Antigens, Differentiation, Myelomonocytic,
pubmed-meshheading:17653245-Carcinoma, Renal Cell,
pubmed-meshheading:17653245-Combined Modality Therapy,
pubmed-meshheading:17653245-Drug Carriers,
pubmed-meshheading:17653245-Female,
pubmed-meshheading:17653245-Gene Therapy,
pubmed-meshheading:17653245-Genetic Engineering,
pubmed-meshheading:17653245-Immunotherapy,
pubmed-meshheading:17653245-Interleukin-2,
pubmed-meshheading:17653245-Kidney Neoplasms,
pubmed-meshheading:17653245-Lipids,
pubmed-meshheading:17653245-Lung Neoplasms,
pubmed-meshheading:17653245-Mice,
pubmed-meshheading:17653245-Microcirculation,
pubmed-meshheading:17653245-Neoplasms, Experimental,
pubmed-meshheading:17653245-Neovascularization, Pathologic,
pubmed-meshheading:17653245-Peptides, Cyclic,
pubmed-meshheading:17653245-Polyethylene Glycols,
pubmed-meshheading:17653245-Polyethyleneimine,
pubmed-meshheading:17653245-Transfection,
pubmed-meshheading:17653245-Vascular Endothelial Growth Factor Receptor-2
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pubmed:year |
2007
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pubmed:articleTitle |
Non-viral delivery of interleukin-2 and soluble Flk-1 inhibits metastatic and primary tumor growth in renal cell carcinoma.
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pubmed:affiliation |
Department of Pharmaceutics and Pharmaceutical Chemistry, Center for Controlled Chemical Delivery, University of Utah, Salt Lake City, UT 84112, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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