| Combined endostatin/sFlt-1 antiangiogenic gene therapy is highly effective in a rat model of HCC. | |
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MedLine Citation:
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PMID: 15739185 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Hepatocellular carcinoma (HCC) is regarded as a suitable target for antiangiogenic strategies. However, antiangiogenic agents aimed at single targets can be neutralized by upregulation of other proangiogenic factors. Therefore, combined approaches addressing at least two angiogenic targets should be more effective. Employing an appropriate rat hepatoma model, we examined the effects of sFlt-1 (soluble vascular endothelial growth factor [VEGF] receptor 1 as an indirect inhibitor of angiogenesis) and endostatin (a direct inhibitor of angiogenesis) in both single-agent as well as combined approaches under in vitro and in vivo conditions. Similar to human HCC, rat Morris hepatoma (MH) cells secreted high levels of VEGF, but no endogenous sFlt-1. Parental MH or MHES(r) cells, stably expressing rat endostatin, were adenovirally transduced either with AdsFlt-1 (encoding sFlt-1) or control vector Adnull (containing no transgene), followed by subcutaneous inoculation into syngeneic ACI rats. Compared with MH/Adnull cells, expressing no antiangiogenic factors at all, tumor weights were reduced fourfold in the MHES(r)/Adnull group, 19-fold in the MH/AdsFlt-1-group, and 77-fold in the MHES(r)/AdsFlt-1 combination therapy group. Analysis of variance did not show a significant interaction between the effects of the two factors ES(r) and sFlt-1; their effects multiplied. In conclusion, combined expression of sFlt-1 and endostatin effectively suppresses HCC growth under in vivo conditions. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html). |
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Authors:
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Florian Graepler; Barbara Verbeek; Tilmann Graeter; Irina Smirnow; Hwai Loong Kong; Detlef Schuppan; Michael Bauer; Reinhard Vonthein; Michael Gregor; Ulrich M Lauer |
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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: Hepatology (Baltimore, Md.) Volume: 41 ISSN: 0270-9139 ISO Abbreviation: Hepatology Publication Date: 2005 Apr |
Date Detail:
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Created Date: 2005-04-05 Completed Date: 2005-04-19 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 8302946 Medline TA: Hepatology Country: United States |
Other Details:
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Languages: eng Pagination: 879-86 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, University Clinic Tübingen, D-72076 Tübingen, Germany. florian.graepler@uni-tuebingen.de |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angiogenesis Inhibitors
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genetics* Animals Cell Line, Tumor Endostatins / genetics* Gene Therapy* Liver Neoplasms, Experimental / blood supply, pathology, therapy* Male Neovascularization, Pathologic / pathology Rats Solubility Treatment Outcome Vascular Endothelial Growth Factor Receptor-1 / chemistry, genetics* |
| Chemical | |
Reg. No./Substance:
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0/Angiogenesis Inhibitors; 0/Endostatins; 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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