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10.1007/s00401-017-1799-2 http://scihub22266oqcxt.onion/10.1007/s00401-017-1799-2 C5904229!5904229!29305721     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Acta+Neuropathol 2018 ; 135 (5): 779-98 Nephropedia Template TP {{tp|p=29305721|t=2018. Paragangliomas arise through an autonomous vasculo-angio-neurogenic program inhibited by imatinib |pdf=|usr=}}{{29305721}} gab.com Text Paragangliomas arise through an autonomous vasculo-angio-neurogenic program inhibited by imatinib JO: Acta Neuropathol http://www.kidney.de/pget.php?&tw=1&pmid=29305721 #FOAvip Tumours can be viewed as aberrant tissues or organs sustained by tumorigenic stem-like cells that engage into dysregulated histo/organogenetic processes. Paragangliomas, prototypical organoid tumours constituted by dysmorphic variants of the vascular and neural tissues found in normal paraganglia, provide a model to test this hypothesis. To understand the origin of paragangliomas, we built a biobank comprising 77 cases, 18 primary cultures, 4 derived cell lines, 80 patient-derived xenografts and 11 cell-derived xenografts. We comparatively investigated these unique complementary materials using morphofunctional, ultrastructural and flow cytometric assays accompanied by microRNA studies. We found that paragangliomas contain stem-like cells with hybrid mesenchymal/vasculoneural phenotype, stabilized and expanded in the derived cultures. The viability and growth of such cultures depended on the downregulation of the miR-200 and miR-34 families, which allowed high PDGFRA and ZEB1 protein expression levels. Both tumour tissue- and cell culture-derived xenografts recapitulated the vasculoneural paraganglioma structure and arose from mesenchymal-like cells through a fixed developmental sequence. First, vasculoangiogenesis organized the microenvironment, building a perivascular niche which in turn supported neurogenesis. Neuroepithelial differentiation was associated with severe mitochondrial dysfunction, not present in cultured paraganglioma cells, but acquired in vivo during xenograft formation. Vasculogenesis was the Achilles? heel of xenograft development. In fact, imatinib, that targets endothelial-mural signalling, blocked paraganglioma xenograft formation (11 xenografts from 12 cell transplants in the control group versus 2 out of 10 in the treated group, P = 0.0015). Overall our key results were unaffected by the SDHx gene carrier status of the patient, characterized for 70 out of 77 cases. In conclusion, we explain the biphasic vasculoneural structure of paragangliomas and identify an early and pharmacologically actionable phase of paraganglioma organization.Electronic supplementary material: The online version of this article (10.1007/s00401-017-1799-2) contains supplementary material, which is available to authorized users. Twit Text FOAVip Paragangliomas arise through an autonomous vasculo-angio-neurogenic program inhibited by imatinib ????Acta Neuropathol http://www.kidney.de/pget.php?&tw=1&pmid=29305721 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29305721 #FOAvip English Wikipedia <ref>{{Cite pmid|29305721}}</ref> Paragangliomas arise through an autonomous vasculo-angio-neurogenic program inhibited by imatinib #MMPMID29305721 Verginelli F; Perconti S; Vespa S; Schiavi F; Prasad SC; Lanuti P; Cama A; Tramontana L; Esposito DL; Guarnieri S; Sheu A; Pantalone MR; Florio R; Morgano A; Rossi C; Bologna G; Marchisio M; D?Argenio A; Taschin E; Visone R; Opocher G; Veronese A; Paties CT; Rajasekhar VK; Söderberg-Nauclér C; Sanna M; Lotti LV; Mariani-Costantini R Acta Neuropathol 2018[]; 135 (5): 779-98 PMID29305721show ga Tumours can be viewed as aberrant tissues or organs sustained by tumorigenic stem-like cells that engage into dysregulated histo/organogenetic processes. Paragangliomas, prototypical organoid tumours constituted by dysmorphic variants of the vascular and neural tissues found in normal paraganglia, provide a model to test this hypothesis. To understand the origin of paragangliomas, we built a biobank comprising 77 cases, 18 primary cultures, 4 derived cell lines, 80 patient-derived xenografts and 11 cell-derived xenografts. We comparatively investigated these unique complementary materials using morphofunctional, ultrastructural and flow cytometric assays accompanied by microRNA studies. We found that paragangliomas contain stem-like cells with hybrid mesenchymal/vasculoneural phenotype, stabilized and expanded in the derived cultures. The viability and growth of such cultures depended on the downregulation of the miR-200 and miR-34 families, which allowed high PDGFRA and ZEB1 protein expression levels. Both tumour tissue- and cell culture-derived xenografts recapitulated the vasculoneural paraganglioma structure and arose from mesenchymal-like cells through a fixed developmental sequence. First, vasculoangiogenesis organized the microenvironment, building a perivascular niche which in turn supported neurogenesis. Neuroepithelial differentiation was associated with severe mitochondrial dysfunction, not present in cultured paraganglioma cells, but acquired in vivo during xenograft formation. Vasculogenesis was the Achilles? heel of xenograft development. In fact, imatinib, that targets endothelial-mural signalling, blocked paraganglioma xenograft formation (11 xenografts from 12 cell transplants in the control group versus 2 out of 10 in the treated group, P = 0.0015). Overall our key results were unaffected by the SDHx gene carrier status of the patient, characterized for 70 out of 77 cases. In conclusion, we explain the biphasic vasculoneural structure of paragangliomas and identify an early and pharmacologically actionable phase of paraganglioma organization.Electronic supplementary material: The online version of this article (10.1007/s00401-017-1799-2) contains supplementary material, which is available to authorized users. äParagangliomas arise through an autonomous vasculo-angio-neurogenic pr(epmc).pdf DeepDyve Pubget Overpricing