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The onset of PI3K-r...
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Kobialka, PiotrJosep Carreras Leukaemia Res Inst, Endothelial Pathobiol & Microenvironm, Barcelona, Spain.
(author)
The onset of PI3K-related vascular malformations occurs during angiogenesis and is prevented by the AKT inhibitor miransertib
- Article/chapterEnglish2022
Publisher, publication year, extent ...
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2022-06-13
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EMBO Press,2022
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electronicrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-485842
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-485842URI
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https://doi.org/10.15252/emmm.202115619DOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Low-flow vascular malformations are congenital overgrowths composed of abnormal blood vessels potentially causing pain, bleeding and obstruction of different organs. These diseases are caused by oncogenic mutations in the endothelium, which result in overactivation of the PI3K/AKT pathway. Lack of robust in vivo preclinical data has prevented the development and translation into clinical trials of specific molecular therapies for these diseases. Here, we demonstrate that the Pik3caH1047R activating mutation in endothelial cells triggers a transcriptome rewiring that leads to enhanced cell proliferation. We describe a new reproducible preclinical in vivo model of PI3K-driven vascular malformations using the postnatal mouse retina. We show that active angiogenesis is required for the pathogenesis of vascular malformations caused by activating Pik3ca mutations. Using this model, we demonstrate that the AKT inhibitor miransertib both prevents and induces the regression of PI3K-driven vascular malformations. We confirmed the efficacy of miransertib in isolated human endothelial cells with genotypes spanning most of human low-flow vascular malformations.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Sabata, HelenaJosep Carreras Leukaemia Res Inst, Endothelial Pathobiol & Microenvironm, Barcelona, Spain.
(author)
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Vilalta, OdenaJosep Carreras Leukaemia Res Inst, Endothelial Pathobiol & Microenvironm, Barcelona, Spain.
(author)
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Gouveia, LeonorUppsala universitet,Vaskulärbiologi,Josep Carreras Leukaemia Res Inst, Endothelial Pathobiol & Microenvironm, Barcelona, Spain(Swepub:uu)margo865
(author)
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Angulo-Urarte, AnaJosep Carreras Leukaemia Res Inst, Endothelial Pathobiol & Microenvironm, Barcelona, Spain.
(author)
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Muixi, LaiaJosep Carreras Leukaemia Res Inst, Endothelial Pathobiol & Microenvironm, Barcelona, Spain.
(author)
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Zanoncello, JasminaJosep Carreras Leukaemia Res Inst, Endothelial Pathobiol & Microenvironm, Barcelona, Spain.
(author)
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Muñoz-Aznar, OscarInst Recerca St Joan de Deu, Dev Tumor Biol Lab, Barcelona, Spain.
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Olaciregui, Nagore G.Inst Recerca St Joan de Deu, Dev Tumor Biol Lab, Barcelona, Spain.
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Fanlo, LuciaJosep Carreras Leukaemia Res Inst, 3D Chromatin Org, Barcelona, Spain.
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Esteve-Codina, AnnaBarcelona Inst Sci & Technol, Ctr Genom Regulat, CNAG CRG, Barcelona, Spain.;Univ Pompeu Fabra UPF, Barcelona, Spain.
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Lavarino, CinziaInst Recerca St Joan de Deu, Dev Tumor Biol Lab, Barcelona, Spain.
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Javierre, Biola M.Josep Carreras Leukaemia Res Inst, 3D Chromatin Org, Barcelona, Spain.
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Celis, VeronicaHosp St Joan de Deu Barcelona, Pediat Canc Ctr Barcelona, Barcelona, Spain.
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Rovira, CarlotaHosp St Joan de Deu Barcelona, Dept Pathol, Barcelona, Spain.
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López-Fernández, SusanaHosp Santa Creu & Sant Pau, Dept Plast Surg, Barcelona, Spain.
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Baselga, EulàliaHosp St Joan de Deu, Dept Dermatol, Barcelona, Spain.
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Mora, JaumeInst Recerca St Joan de Deu, Dev Tumor Biol Lab, Barcelona, Spain.;Hosp St Joan de Deu Barcelona, Pediat Canc Ctr Barcelona, Barcelona, Spain.
(author)
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Castillo, Sandra D.Josep Carreras Leukaemia Res Inst, Endothelial Pathobiol & Microenvironm, Barcelona, Spain.
(author)
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Graupera, MarionaJosep Carreras Leukaemia Res Inst, Endothelial Pathobiol & Microenvironm, Barcelona, Spain.;Inst Salud Carlos III, CIBERONC, Madrid, Spain.
(author)
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Josep Carreras Leukaemia Res Inst, Endothelial Pathobiol & Microenvironm, Barcelona, Spain.Vaskulärbiologi
(creator_code:org_t)
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In:EMBO Molecular Medicine: EMBO Press14:71757-46761757-4684
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Kobialka, Piotr
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Sabata, Helena
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Vilalta, Odena
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Gouveia, Leonor
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Angulo-Urarte, A ...
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Muixi, Laia
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Zanoncello, Jasm ...
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Muñoz-Aznar, Osc ...
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Olaciregui, Nago ...
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Fanlo, Lucia
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Esteve-Codina, A ...
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Lavarino, Cinzia
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Javierre, Biola ...
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Celis, Veronica
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Rovira, Carlota
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López-Fernández, ...
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Baselga, Eulàlia
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Mora, Jaume
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Castillo, Sandra ...
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Graupera, Marion ...
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