{"id":100537,"date":"2018-03-11T10:22:02","date_gmt":"2018-03-11T10:22:02","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/inactivacion-terapeutica-del-oncogen-ccnd1-en-modelos-celulares-humanos-y-murinos-de-linfoma-de-celulas-del-manto\/"},"modified":"2018-03-11T10:22:02","modified_gmt":"2018-03-11T10:22:02","slug":"inactivacion-terapeutica-del-oncogen-ccnd1-en-modelos-celulares-humanos-y-murinos-de-linfoma-de-celulas-del-manto","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/farmacologia\/inactivacion-terapeutica-del-oncogen-ccnd1-en-modelos-celulares-humanos-y-murinos-de-linfoma-de-celulas-del-manto\/","title":{"rendered":"Inactivaci\u00f3n terap\u00e9utica del oncog\u00e9n ccnd1 en modelos celulares humanos y murinos de linfoma de c\u00e9lulas del manto"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Elena Beltr\u00e1n De Miguel <\/strong><\/h2>\n<p>Targeting ccnd1 oncogene to treat mantle cell lymphoma in human and mouse models  abstract mantle cell lymphoma (mcl) is initiated by cyclin-d1 activation followed by genetic changes involving survival and dna-repair machineries. Because mcl is incurable with current treatments, the use of drugs targeting cyclin-d1 and\/or other molecular pathways may be of clinical benefit. Here, we screened for predictors of response to target-directed therapies in human mcl-derived cell lines and in a human-like mcl mouse model generated by co-expressing cyclin-d1 and bcl2 in na\u00ed\u00afve b lymphocytes engrafted in immunodeficient rag2-\/-il2&#61543;c-\/- mice. In these lymphomas, cyclin-d1 can be repressed by administering doxicycline-containing water to mice. We show that individual blockade of cyclin-d1 or bcl2 had moderate effects on cell survival, but the simultaneous inhibition of both proteins induced prominent cell proliferative arrest and apoptosis in human and mouse lymphomas. This therapeutic synergy was further enhanced by mcl1 depletion. Mechanistically, cyclin-d1 silencing released the pro-apoptotic final effector bax, thus sensitizing cells to bcl2-mediated apoptosis. Finally, we show that the dual cyclin-d1 and mcl1 inhibitor roscovitine, combined with the bh3 mimetic abt-737, was an effective therapy for primary mcl samples. These findings illustrate the potential benefit of combining therapies modulating cell-cycle and survival pathways aiming to cure patients with mcl.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Inactivaci\u00f3n terap\u00e9utica del oncog\u00e9n ccnd1 en modelos celulares humanos y murinos de linfoma de c\u00e9lulas del manto<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Inactivaci\u00f3n terap\u00e9utica del oncog\u00e9n ccnd1 en modelos celulares humanos y murinos de linfoma de c\u00e9lulas del manto <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Elena Beltr\u00e1n De Miguel <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Navarra<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 27\/04\/2010<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Jos\u00e9 \u00e1ngel Mart\u00ednez Climent<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Mar\u00eda  jose Calasanz abinzano <\/li>\n<li>Miguel angel Piris pinilla (vocal)<\/li>\n<li>eduardo Olavarria l\u00f3pez-arostegui (vocal)<\/li>\n<li>isidro Javier S\u00e1nchez Garc\u00eda (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Elena Beltr\u00e1n De Miguel Targeting ccnd1 oncogene to treat mantle cell lymphoma in human and mouse models [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center 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