Linked Life Data

17653245

Source:http://linkedlifedata.com/resource/pubmed/id/17653245

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pubmed-article:17653245pubmed:abstractTextTreatments 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.lld:pubmed
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pubmed-article:17653245pubmed:authorpubmed-author:KimS WSWlld:pubmed
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pubmed-article:17653245pubmed:dateRevised2009-11-19lld:pubmed
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pubmed-article:17653245pubmed:articleTitleNon-viral delivery of interleukin-2 and soluble Flk-1 inhibits metastatic and primary tumor growth in renal cell carcinoma.lld:pubmed
pubmed-article:17653245pubmed:affiliationDepartment of Pharmaceutics and Pharmaceutical Chemistry, Center for Controlled Chemical Delivery, University of Utah, Salt Lake City, UT 84112, USA.lld:pubmed
pubmed-article:17653245pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:17653245pubmed:publicationTypeResearch Support, N.I.H., Extramurallld:pubmed
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