{"id":103616,"date":"2018-03-11T10:26:17","date_gmt":"2018-03-11T10:26:17","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/uso-de-agentes-demetilantes-en-el-trasplante-alogenico\/"},"modified":"2018-03-11T10:26:17","modified_gmt":"2018-03-11T10:26:17","slug":"uso-de-agentes-demetilantes-en-el-trasplante-alogenico","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/bioquimica-molecular\/uso-de-agentes-demetilantes-en-el-trasplante-alogenico\/","title":{"rendered":"Uso de agentes demetilantes en el trasplante alog\u00e9nico"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Silvia Guti\u00e9rrez Cos\u00edo <\/strong><\/h2>\n<p>En linfocitos t, la expresi\u00f3n de ant\u00edgenos asociados a tumor y la producci\u00f3n decitoquinas est\u00e1n reguladas por m\u00faltiples mecanismos epigen\u00e9ticos. La 5-azacitidina (5-aza) es un an\u00e1logo nucleos\u00eddico que inhibe las dna-metiltransferasas (dnmt) generando regiones hipometiladas y por tanto activando la expresi\u00f3n de genes. En este estudio analizamos el efecto de la 5-aza en lt observamos c\u00f3mo la 5-aza inhibe la activaci\u00f3n y proliferaci\u00f3n celular adem\u00e1s de bloquear el ciclo celular en fase g0-g1, tambi\u00e9n disminuye la produci\u00f3n de citoquinas proinflamatorias como tnf\u00c2\u00bf e ifn\u00c2\u00bf. este efecto no es debido a un efecto pro-apopt\u00f3tico ya que este f\u00e1rmaco no modifica la viabilidad celular, sin embargo, disminuye la expresi\u00f3n de genes involucrados en la activaci\u00f3n como ccng2, mtcp1, cd58 y adk y aumenta la expresi\u00f3n de genes que inducen bloqueo y parada del ciclo celular como p27, p16, p53 \u00f3 p73. Una prolongada exposici\u00f3n al f\u00e1rmaco lleva a la demetilaci\u00f3n del promotor de foxp3 y sobreexpresi\u00f3n de foxp3. As\u00ed, hemos comprobado c\u00f3mo la 5-aza expande c\u00e9lulas t reguladoras. finalmente, la administraci\u00f3n de 5-aza post-trasplante previene el desarrollo de enfermedad injerto contra hu\u00e9sped (eich) y lleva a una mayor supervivencia de los ratones que han recibido un trasplante alog\u00e9nico. Este estudio muestra el efecto inmunomodulador en el trasplante alog\u00e9nico de la 5-aza describiendo un nuevo camino para prevenir la eich. Posteriormente, estudiamos el efecto de la 5-aza sobre la expresi\u00f3n de prame en blastos de lma y en c\u00e9lulas cd34+ de donantes sanos. previamente hab\u00edamos comprobado que el promotor de prame est\u00e1 muy metilado en c\u00e9lulas cd34+ sanas e hipometilado en blastos que sobreexpresan prame. As\u00ed, cuando tratamos estas c\u00e9lulas con 5-aza se demetila el promotor aumentando la expresi\u00f3n de prame en blastos pero no en c\u00e9lulas sanas. De esta forma justificar\u00edamos la utilizaci\u00f3n de prame como diana terap\u00e9utica frente a c\u00e9lulas tumorales.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Uso de agentes demetilantes en el trasplante alog\u00e9nico<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Uso de agentes demetilantes en el trasplante alog\u00e9nico <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Silvia Guti\u00e9rrez Cos\u00edo <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Salamanca<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 13\/09\/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 Antonio P\u00e9rez Sim\u00f3n<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: Mar\u00eda  consuelo Juan a Del ca\u00f1izo fernandez roldan <\/li>\n<li>\u00e1lvaro Urbano ispiz\u00faa (vocal)<\/li>\n<li>jordi Sierra gil (vocal)<\/li>\n<li>Manuel Ramirez orellan (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Silvia Guti\u00e9rrez Cos\u00edo En linfocitos t, la expresi\u00f3n de ant\u00edgenos asociados a tumor y la producci\u00f3n decitoquinas [&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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