{"id":90606,"date":"2008-12-12T00:00:00","date_gmt":"2008-12-12T00:00:00","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/analisis-de-la-funcion-de-ews-fl11-en-la-patogenia-del-sarcoma-de-ewing\/"},"modified":"2008-12-12T00:00:00","modified_gmt":"2008-12-12T00:00:00","slug":"analisis-de-la-funcion-de-ews-fl11-en-la-patogenia-del-sarcoma-de-ewing","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/salamanca\/analisis-de-la-funcion-de-ews-fl11-en-la-patogenia-del-sarcoma-de-ewing\/","title":{"rendered":"An\u00e1lisis de la funci\u00f3n de ews-fl11 en la patogenia del sarcoma de ewing"},"content":{"rendered":"<h2>Tesis doctoral de <strong> David Herrero Mart\u00edn <\/strong><\/h2>\n<p>El sarcoma de ewing es una neoplasia pedi\u00e1trica de huesos y tejidos blandos que se caracteriza por la presencia de una translocaci\u00f3n cromos\u00f3mica que da lugar a la formaci\u00f3n de prote\u00ednas quim\u00e9ricas. La mayor\u00eda de estas prote\u00ednas de fusi\u00f3n son factores transcripcionales aberrantes, cuyos genes diana est\u00e1n relacionados con el ciclo celular, la proliferaci\u00f3n, la apoptosis o el desarrollo. La fusi\u00f3n g\u00e9nica mayoritaria es la que une el extremo amino-terminal de la prote\u00edna de uni\u00f3n a arn, ews con el dominio carboxi-terminal de un factor de transcripci\u00f3n de la familia ets, fli-1 en el 90% los casos (translocaci\u00f3n (11;22)(q24;q12)). El contexto celular es fundamental dado que la introducci\u00f3n de las fusiones en diferentes modelos celulares genera fenotipos muy diferentes. Se desconoce la c\u00e9lula de origen aunque se cree que puede ser de la cresta neural o por contra c\u00e9lulas madre mesenquimales. El uso de la t\u00e9cnica de arn de interferencia en l\u00edneas celulares de sarcoma de ewing nos ha permitido analizar la fusi\u00f3n y sus dianas identificando nuevas dianas directas como topk, una quinasa involucrada en la proliferaci\u00f3n y motilidad celular. A su vez hemos descrito a lrrc48 como una nueva diana directa de topk. Topk y ews-fli1 reprimen la expresi\u00f3n de lrrc48. La inhibici\u00f3n de ews-fli1 reduce el potencial tumorig\u00e9nico celular, disminuye el crecimiento tumoral in vivo, impide la migraci\u00f3n celular y hace que las c\u00e9lulas sean m\u00e1s sensibles a la apoptosis y a la acci\u00f3n de inhibidores de la v\u00eda de igf-1\/igf-1r. Hemos tratado de determinar si las c\u00e9lulas madre humanas mesenquimales adultas obtenidas de m\u00e9dula \u00f3sea eran el nicho celular propicio para la generaci\u00f3n del sarcoma de ewing. La introducci\u00f3n de las fusiones ews-ets en las mismas no ha logrado per se reproducir el fenotipo tumoral in vitro as\u00ed como tampoco la inhici\u00f3n de p16 lo que demuestra que las fusiones, si bien son imprescindibles en la patog\u00e9nesis den esta sarcoma, necesitan la colaboraci\u00f3n de un evento adicional, que no es la p\u00e9rdida de p16. As\u00ed mismo hemos comparado los perfiles de expresi\u00f3n gen\u00f3mica y prote\u00f3mica de las c\u00e9lulas madre mesenquinales adultas de m\u00e9dula \u00f3sea de pacientes con sarcoma de ewing y donantes sanos de cara a identificar eventos oncog\u00e9nicos tempranos.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>An\u00e1lisis de la funci\u00f3n de ews-fl11 en la patogenia del sarcoma de ewing<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 An\u00e1lisis de la funci\u00f3n de ews-fl11 en la patogenia del sarcoma de ewing <\/li>\n<li><strong>Autor:<\/strong>\u00a0 David Herrero Mart\u00edn <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Salamanca<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 12\/12\/2008<\/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>Enrique De \u00e1lava Casado<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Juan  pedro Bola\u00f1os hernandez <\/li>\n<li>rosa Noguera salv\u00e1 (vocal)<\/li>\n<li>dionisio Miguel Mart\u00edn zanca (vocal)<\/li>\n<li>ren\u00e9 Rodr\u00edguez gonz\u00e1lez (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de David Herrero Mart\u00edn El sarcoma de ewing es una neoplasia pedi\u00e1trica de huesos y tejidos blandos que [&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 center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"footnotes":""},"categories":[9386],"tags":[187966,29677,17769,57945,56897,135682],"class_list":["post-90606","post","type-post","status-publish","format-standard","hentry","category-salamanca","tag-david-herrero-martin","tag-dionisio-miguel-martin-zanca","tag-enrique-de-alava-casado","tag-juan-pedro-bolanos-hernandez","tag-rene-rodriguez-gonzalez","tag-rosa-noguera-salva"],"_links":{"self":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/90606","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/comments?post=90606"}],"version-history":[{"count":0,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/90606\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/media?parent=90606"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/categories?post=90606"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/tags?post=90606"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}