| |  Online-Ressource |
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| Verfasst von: | Singhal, Mahak [VerfasserIn]  |
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| | Gengenbacher, Nicolas [VerfasserIn] |
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| | La Porta, Silvia [VerfasserIn] |
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| | Gehrs, Stephanie [VerfasserIn] |
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| | Shi, Jingjing [VerfasserIn] |
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| | Kamiyama, Miki [VerfasserIn] |
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| | Bodenmiller, Diane M [VerfasserIn] |
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| | Fischl, Anthony [VerfasserIn] |
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| | Schieb, Benjamin [VerfasserIn] |
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| | Besemfelder, Eva [VerfasserIn] |
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| | Chintharlapalli, Sudhakar [VerfasserIn] |
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| | Augustin, Hellmut [VerfasserIn] |
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| Titel: | Preclinical validation of a novel metastasis-inhibiting Tie1 function-blocking antibody |
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| Verf.angabe: | Mahak Singhal, Nicolas Gengenbacher, Silvia La Porta, Stephanie Gehrs, Jingjing Shi, Miki Kamiyama, Diane M Bodenmiller, Anthony Fischl, Benjamin Schieb, Eva Besemfelder, Sudhakar Chintharlapalli & Hellmut G Augustin |
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| E-Jahr: | 2020 |
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| Jahr: | 17 April 2020 |
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| Umfang: | 9 S. |
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| Fussnoten: | Gesehen am 05.10.2020 |
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| Titel Quelle: | Enthalten in: European Molecular Biology OrganizationEMBO molecular medicine |
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| Ort Quelle: | [London] : Nature Publishing Group UK, 2009 |
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| Jahr Quelle: | 2020 |
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| Band/Heft Quelle: | 12(2020,6) Artikel-Nummer e11164, 9 Seiten |
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| ISSN Quelle: | 1757-4684 |
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| Abstract: | Abstract The angiopoietin (Ang)?Tie pathway has been intensely pursued as candidate second-generation anti-angiogenic target. While much of the translational work has focused on the ligand Ang2, the clinical efficacy of Ang2-targeting drugs is limited and failed to improve patient survival. In turn, the orphan receptor Tie1 remains therapeutically unexplored, although its endothelial-specific genetic deletion has previously been shown to result in a strong reduction in metastatic growth. Here, we report a novel Tie1 function-blocking antibody (AB-Tie1-39), which suppressed postnatal retinal angiogenesis. During primary tumor growth, neoadjuvant administration of AB-Tie1-39 strongly impeded systemic metastasis. Furthermore, the administration of AB-Tie1-39 in a perioperative therapeutic window led to a significant survival advantage as compared to control-IgG-treated mice. Additional in vivo experimental metastasis and in vitro transmigration assays concurrently revealed that AB-Tie1-39 treatment suppressed tumor cell extravasation at secondary sites. Taken together, the data phenocopy previous genetic work in endothelial Tie1 KO mice and thereby validate AB-Tie1-39 as a Tie1 function-blocking antibody. The study establishes Tie1 as a therapeutic target for metastasis in a perioperative or neoadjuvant setting. |
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| DOI: | doi:10.15252/emmm.201911164 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.15252/emmm.201911164 |
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| | Volltext: https://www.embopress.org/doi/full/10.15252/emmm.201911164 |
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| | DOI: https://doi.org/10.15252/emmm.201911164 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | angiogenesis |
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| | angiopoietin-Tie signaling |
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| | cancer |
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| | endothelial cells |
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| | metastasis |
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| K10plus-PPN: | 1734613661 |
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| Verknüpfungen: | → Zeitschrift |
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Preclinical validation of a novel metastasis-inhibiting Tie1 function-blocking antibody / Singhal, Mahak [VerfasserIn]; 17 April 2020 (Online-Ressource)
