| Suppression of ovarian cancer by muscle-mediated expression of soluble VEGFR-1/Flt-1 using adeno-associated virus serotype 1-derived vector. | |
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MedLine Citation:
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PMID: 17066424 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Vascular endothelial growth factor (VEGF) is known to play a major role in angiogenesis in a variety of tumors. A soluble form of Flt-1 (sFlt-1), a VEGF receptor, is potentially useful as an antagonist of VEGF, and accumulating evidences suggest the applicability of sFlt-1 in tumor suppression by means of anti-angiogenesis. We previously demonstrated the efficacy of sflt-1 gene expression in situ to suppress tumor growth and ascites in ovarian cancer. Here, we demonstrate the therapeutic applicability of muscle-mediated expression of sFlt-1 in tumor-bearing mice. Initially, tumor suppressive action was confirmed by inoculating sFlt-1-expressing ovarian cancer (SHIN-3) cells into mice, both subcutaneously and intraperitoneally. To validate the therapeutic efficacy in a more clinically relevant model, adeno-associated virus vectors encoding sflt-1 were introduced into mouse skeletal muscles and were subsequently inoculated with tumor cells. As a result, high serum sFlt-1 levels were constantly observed, and the growth of both subcutaneously- and intraperitoneally-inoculated tumors was significantly suppressed. No delay in wound healing or adverse events of neuromuscular damage were noted, body weight did not change, and laboratory data, such as those representing liver and renal functions, were not affected. These results indicate that sFlt-1 suppresses growth and peritoneal dissemination of ovarian cancer by the inhibition of angiogenesis, and thus suggest the usefulness of gene therapy for ovarian cancer. |
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Authors:
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Yuji Takei; Hiroaki Mizukami; Yasushi Saga; Ichiro Yoshimura; Yoko Hasumi; Takeshi Takayama; Takahiro Kohno; Takashi Matsushita; Takashi Okada; Akihiro Kume; Mitsuaki Suzuki; Keiya Ozawa |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: International journal of cancer. Journal international du cancer Volume: 120 ISSN: 0020-7136 ISO Abbreviation: Int. J. Cancer Publication Date: 2007 Jan |
Date Detail:
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Created Date: 2006-12-04 Completed Date: 2007-02-23 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: United States |
Other Details:
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Languages: eng Pagination: 278-84 Citation Subset: IM |
Copyright Information:
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(c) 2006 Wiley-Liss, Inc. |
Affiliation:
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Division of Genetics Therapeutics, Center for Molecular Medicine, Jichi Medical School, Tochigi, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Proliferation Dependovirus / genetics Female Gene Therapy* Genetic Vectors / genetics Humans Mice Muscle, Skeletal / metabolism Neoplasm Transplantation Neovascularization, Pathologic / pathology, therapy* Ovarian Neoplasms / blood supply*, pathology, therapy* Suppression, Genetic Transduction, Genetic Vascular Endothelial Growth Factor A / blood Vascular Endothelial Growth Factor Receptor-1 / blood, genetics* Xenograft Model Antitumor Assays |
| Chemical | |
Reg. No./Substance:
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0/Vascular Endothelial Growth Factor A; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-1 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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