Antiangiogenic Gene Therapy With Soluble VEGFR-1, -2, and -3 Reduces the Growth of Solid Human Ovarian Carcinoma in Mice
Identifieur interne : 006C22 ( Main/Exploration ); précédent : 006C21; suivant : 006C23Antiangiogenic Gene Therapy With Soluble VEGFR-1, -2, and -3 Reduces the Growth of Solid Human Ovarian Carcinoma in Mice
Auteurs : Hanna Sallinen [Finlande] ; Maarit Anttila [Finlande] ; Johanna Narvainen [Finlande] ; Jonna Koponen [Finlande] ; Kirsi Hamalainen [Finlande] ; Ivana Kholova [Finlande] ; Tommi Heikura [Finlande] ; Pyry Toivanen [Finlande] ; Veli-Matti Kosma [Finlande] ; Seppo Heinonen [Finlande] ; Kari Alitalo [Finlande] ; Seppo Yla-Herttuala [Finlande]Source :
- Molecular Therapy: the Journal of the American Society of Gene Therapy [ 1525-0016 ] ; 2008.
Abstract
We studied antiangiogenic and antilymphangiogenic effects of sVEGFR-1 (sFlt-1), sVEGFR-2 (sFlk-1/KDR), and sVEGFR-3 (sFlt-4) gene transfers and their combinations in intraperitoneal ovarian cancer xenograft mice (Balb/c-Anu,
Url:
DOI: 10.1038/mt.2008.258
PubMed: 19050699
PubMed Central: 2835051
Affiliations:
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Virtanen Institute, University of Kuopio</institution> Kuopio,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Institute of Clinical Medicine, Gynaecology, and Pathology and Forensic Medicine, University of Kuopio</institution> Kuopio,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Department of Gynaecology, Kuopio University Hospital</institution> Kuopio,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Anttila, Maarit" sort="Anttila, Maarit" uniqKey="Anttila M" first="Maarit" last="Anttila">Maarit Anttila</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Molecular Medicine, A.I. 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Virtanen Institute, University of Kuopio</institution> Kuopio,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Toivanen, Pyry" sort="Toivanen, Pyry" uniqKey="Toivanen P" first="Pyry" last="Toivanen">Pyry Toivanen</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Molecular Medicine, A.I. 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Virtanen Institute, University of Kuopio</institution> Kuopio,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">19050699</idno><idno type="pmc">2835051</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835051</idno><idno type="RBID">PMC:2835051</idno><idno type="doi">10.1038/mt.2008.258</idno><date when="2008">2008</date><idno type="wicri:Area/Pmc/Corpus">000069</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000069</idno><idno type="wicri:Area/Pmc/Curation">000069</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000069</idno><idno type="wicri:Area/Pmc/Checkpoint">003A28</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">003A28</idno><idno type="wicri:Area/Ncbi/Merge">003088</idno><idno type="wicri:Area/Ncbi/Curation">003088</idno><idno type="wicri:Area/Ncbi/Checkpoint">003088</idno><idno type="wicri:doubleKey">1525-0016:2008:Sallinen H:antiangiogenic:gene:therapy</idno><idno type="wicri:Area/Main/Merge">006D29</idno><idno type="wicri:Area/Main/Curation">006C22</idno><idno type="wicri:Area/Main/Exploration">006C22</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Antiangiogenic Gene Therapy With Soluble VEGFR-1, -2, and -3 Reduces the Growth of Solid Human Ovarian Carcinoma in Mice</title><author><name sortKey="Sallinen, Hanna" sort="Sallinen, Hanna" uniqKey="Sallinen H" first="Hanna" last="Sallinen">Hanna Sallinen</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Molecular Medicine, A.I. Virtanen Institute, University of Kuopio</institution> Kuopio,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Institute of Clinical Medicine, Gynaecology, and Pathology and Forensic Medicine, University of Kuopio</institution> Kuopio,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Department of Gynaecology, Kuopio University Hospital</institution> Kuopio,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Anttila, Maarit" sort="Anttila, Maarit" uniqKey="Anttila M" first="Maarit" last="Anttila">Maarit Anttila</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Molecular Medicine, A.I. Virtanen Institute, University of Kuopio</institution> Kuopio,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Institute of Clinical Medicine, Gynaecology, and Pathology and Forensic Medicine, University of Kuopio</institution> Kuopio,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Department of Gynaecology, Kuopio University Hospital</institution> Kuopio,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Narvainen, Johanna" sort="Narvainen, Johanna" uniqKey="Narvainen J" first="Johanna" last="Narvainen">Johanna Narvainen</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>National BIO-NMR Facility, A.I. Virtanen Institute, University of Kuopio</institution> Kuopio,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Koponen, Jonna" sort="Koponen, Jonna" uniqKey="Koponen J" first="Jonna" last="Koponen">Jonna Koponen</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Molecular Medicine, A.I. Virtanen Institute, University of Kuopio</institution> Kuopio,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Hamalainen, Kirsi" sort="Hamalainen, Kirsi" uniqKey="Hamalainen K" first="Kirsi" last="Hamalainen">Kirsi Hamalainen</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Institute of Clinical Medicine, Gynaecology, and Pathology and Forensic Medicine, University of Kuopio</institution> Kuopio,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Department of Pathology, Kuopio University Hospital</institution> Kuopio,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kholova, Ivana" sort="Kholova, Ivana" uniqKey="Kholova I" first="Ivana" last="Kholova">Ivana Kholova</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Molecular Medicine, A.I. Virtanen Institute, University of Kuopio</institution> Kuopio,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Institute of Clinical Medicine, Gynaecology, and Pathology and Forensic Medicine, University of Kuopio</institution> Kuopio,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Department of Pathology, Kuopio University Hospital</institution> Kuopio,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Heikura, Tommi" sort="Heikura, Tommi" uniqKey="Heikura T" first="Tommi" last="Heikura">Tommi Heikura</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Molecular Medicine, A.I. Virtanen Institute, University of Kuopio</institution> Kuopio,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Toivanen, Pyry" sort="Toivanen, Pyry" uniqKey="Toivanen P" first="Pyry" last="Toivanen">Pyry Toivanen</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Molecular Medicine, A.I. Virtanen Institute, University of Kuopio</institution> Kuopio,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kosma, Veli Matti" sort="Kosma, Veli Matti" uniqKey="Kosma V" first="Veli-Matti" last="Kosma">Veli-Matti Kosma</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Institute of Clinical Medicine, Gynaecology, and Pathology and Forensic Medicine, University of Kuopio</institution> Kuopio,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Department of Pathology, Kuopio University Hospital</institution> Kuopio,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Heinonen, Seppo" sort="Heinonen, Seppo" uniqKey="Heinonen S" first="Seppo" last="Heinonen">Seppo Heinonen</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Institute of Clinical Medicine, Gynaecology, and Pathology and Forensic Medicine, University of Kuopio</institution> Kuopio,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Department of Gynaecology, Kuopio University Hospital</institution> Kuopio,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Molecular/Cancer Biology Laboratory Biomedicum Helsinki and Haartman Institute, University of Helsinki</institution> Helsinki,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName><orgName type="university">Université d'Helsinki</orgName></affiliation></author><author><name sortKey="Yla Herttuala, Seppo" sort="Yla Herttuala, Seppo" uniqKey="Yla Herttuala S" first="Seppo" last="Yla-Herttuala">Seppo Yla-Herttuala</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Molecular Medicine, A.I. Virtanen Institute, University of Kuopio</institution> Kuopio,<country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Molecular Therapy: the Journal of the American Society of Gene Therapy</title><idno type="ISSN">1525-0016</idno><idno type="eISSN">1525-0024</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>We studied antiangiogenic and antilymphangiogenic effects of sVEGFR-1 (sFlt-1), sVEGFR-2 (sFlk-1/KDR), and sVEGFR-3 (sFlt-4) gene transfers and their combinations in intraperitoneal ovarian cancer xenograft mice (Balb/c-Anu, <italic>n</italic> = 55). Gene therapy was initiated when the presence of sizable tumors was confirmed in magnetic resonance imaging (MRI). Adenovirus-mediated gene transfer was performed intravenously via tail vein as follows: Ad<italic>Lac</italic>Z as a control (group I), AdsFlt-1 (group II), AdsKDR (group III), AdsFlt-4 (group IV) and two combination groups of AdsFlt-1 and AdsFlt-4 (group V) and AdsFlt-1, AdsKDR, and AdsFlt-4 (group VI). Antitumor effectiveness was assessed by sequential MRI, immunohistochemistry, microvessel density, overall tumor growth, and survival time. In combination group VI, intraperitoneal tumors were significantly smaller than in the control group at the end of the follow-up (<italic>P</italic> < 0.001). Furthermore, in group VI the microvessel density (microvessels/mm<sup>2</sup>) in tumor tissue and the total area of tumors covered by microvessels were significantly smaller than in the controls. One mouse in group V was cured. The combined antiangiogenic gene therapy with soluble VEGFRs reduced tumor growth, tumor vascularity, and ascites formation in ovarian cancer xenografts. The results suggest that the combined antiangiogenic gene therapy is a potential approach for the treatment of ovarian cancer patients.</p></div></front></TEI><affiliations><list><country><li>Finlande</li></country><region><li>Uusimaa</li></region><settlement><li>Helsinki</li></settlement><orgName><li>Université d'Helsinki</li></orgName></list><tree><country name="Finlande"><noRegion><name sortKey="Sallinen, Hanna" sort="Sallinen, Hanna" uniqKey="Sallinen H" first="Hanna" last="Sallinen">Hanna Sallinen</name></noRegion><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><name sortKey="Anttila, Maarit" sort="Anttila, Maarit" uniqKey="Anttila M" first="Maarit" last="Anttila">Maarit Anttila</name><name sortKey="Anttila, Maarit" sort="Anttila, Maarit" uniqKey="Anttila M" first="Maarit" last="Anttila">Maarit Anttila</name><name sortKey="Anttila, Maarit" sort="Anttila, Maarit" uniqKey="Anttila M" first="Maarit" last="Anttila">Maarit Anttila</name><name sortKey="Hamalainen, Kirsi" sort="Hamalainen, Kirsi" uniqKey="Hamalainen K" first="Kirsi" last="Hamalainen">Kirsi Hamalainen</name><name sortKey="Hamalainen, Kirsi" sort="Hamalainen, Kirsi" uniqKey="Hamalainen K" first="Kirsi" last="Hamalainen">Kirsi Hamalainen</name><name sortKey="Heikura, Tommi" sort="Heikura, Tommi" uniqKey="Heikura T" first="Tommi" last="Heikura">Tommi Heikura</name><name sortKey="Heinonen, Seppo" sort="Heinonen, Seppo" uniqKey="Heinonen S" first="Seppo" last="Heinonen">Seppo Heinonen</name><name sortKey="Heinonen, Seppo" sort="Heinonen, Seppo" uniqKey="Heinonen S" first="Seppo" last="Heinonen">Seppo Heinonen</name><name sortKey="Kholova, Ivana" sort="Kholova, Ivana" uniqKey="Kholova I" first="Ivana" last="Kholova">Ivana Kholova</name><name sortKey="Kholova, Ivana" sort="Kholova, Ivana" uniqKey="Kholova I" first="Ivana" last="Kholova">Ivana Kholova</name><name sortKey="Kholova, Ivana" sort="Kholova, Ivana" uniqKey="Kholova I" first="Ivana" last="Kholova">Ivana Kholova</name><name sortKey="Koponen, Jonna" sort="Koponen, Jonna" uniqKey="Koponen J" first="Jonna" last="Koponen">Jonna Koponen</name><name sortKey="Kosma, Veli Matti" sort="Kosma, Veli Matti" uniqKey="Kosma V" first="Veli-Matti" last="Kosma">Veli-Matti Kosma</name><name sortKey="Kosma, Veli Matti" sort="Kosma, Veli Matti" uniqKey="Kosma V" first="Veli-Matti" last="Kosma">Veli-Matti Kosma</name><name sortKey="Narvainen, Johanna" sort="Narvainen, Johanna" uniqKey="Narvainen J" first="Johanna" last="Narvainen">Johanna Narvainen</name><name sortKey="Sallinen, Hanna" sort="Sallinen, Hanna" uniqKey="Sallinen H" first="Hanna" last="Sallinen">Hanna Sallinen</name><name sortKey="Sallinen, Hanna" sort="Sallinen, Hanna" uniqKey="Sallinen H" first="Hanna" last="Sallinen">Hanna Sallinen</name><name sortKey="Toivanen, Pyry" sort="Toivanen, Pyry" uniqKey="Toivanen P" first="Pyry" last="Toivanen">Pyry Toivanen</name><name sortKey="Yla Herttuala, Seppo" sort="Yla Herttuala, Seppo" uniqKey="Yla Herttuala S" first="Seppo" last="Yla-Herttuala">Seppo Yla-Herttuala</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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