{"id":10460,"date":"2024-03-26T14:37:32","date_gmt":"2024-03-26T14:37:32","guid":{"rendered":"https:\/\/planescomplementariossalud.es\/stop-dmg\/"},"modified":"2025-09-08T09:49:45","modified_gmt":"2025-09-08T09:49:45","slug":"stop-dmg","status":"publish","type":"post","link":"https:\/\/planescomplementariossalud.es\/ca\/stop-dmg\/","title":{"rendered":"STOP-DMG"},"content":{"rendered":"\n<div style=\"height:2px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-28f84493 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<div class=\"wp-block-cover alignfull wp-duotone-unset-1\" style=\"margin-top:0;padding-top:48px;padding-right:48px;padding-bottom:48px;padding-left:48px;min-height:430px;aspect-ratio:unset;\"><span aria-hidden=\"true\" class=\"wp-block-cover__background has-background-dim-30 has-background-dim\" style=\"background-color:#1b305a\"><\/span><img fetchpriority=\"high\" decoding=\"async\" width=\"837\" height=\"510\" src=\"https:\/\/planescomplementariossalud.es\/wp-content\/uploads\/2024\/03\/Image-STOP-DMG.png\" class=\"wp-block-cover__image-background wp-post-image\" alt=\"\" data-object-fit=\"cover\" data-object-position=\"36% 72%\" style=\"object-position:36% 72%;\" srcset=\"https:\/\/planescomplementariossalud.es\/wp-content\/uploads\/2024\/03\/Image-STOP-DMG.png 837w, https:\/\/planescomplementariossalud.es\/wp-content\/uploads\/2024\/03\/Image-STOP-DMG-300x183.png 300w, https:\/\/planescomplementariossalud.es\/wp-content\/uploads\/2024\/03\/Image-STOP-DMG-768x468.png 768w\" sizes=\"(max-width: 837px) 100vw, 837px\" \/><div class=\"wp-block-cover__inner-container is-layout-flow wp-block-cover-is-layout-flow\">\n<div class=\"wp-block-group is-content-justification-left is-layout-constrained wp-container-core-group-is-layout-0b562c1c wp-block-group-is-layout-constrained\">\n<h2 class=\"wp-block-heading has-text-align-left has-white-color has-text-color\" style=\"font-size:100px;font-style:normal;font-weight:700;letter-spacing:0px;line-height:1;text-transform:uppercase\">\n          STOP-DMG\n          <\/h2>\n<\/div>\n<\/div><\/div>\n\n\n\n<h2 class=\"wp-block-heading\">Identificaci\u00f3n y validaci\u00f3n de dianas terap\u00e9uticas para el glioma difuso de l\u00ednea media (DMG) basada en cribado de alto rendimiento<\/h2>\n\n\n\n<p class=\"has-ast-global-color-6-background-color has-background\"><strong>LINEA DE ACTUACI\u00d3N 3:<\/strong> PLATAFORMA DE CRIBADO DE F\u00c1RMACOS Y AN\u00c1LISIS INTERACCIONES F\u00c1RMACO-DIANA<br><br><strong>Palabras clave:<\/strong> Gliomas Difusos de L\u00ednea Media; dianas terap\u00e9uticas; xeno-injectos derivados de pacientes; cribado de alto rendimiento<br><strong>Coordina:<\/strong> Fundaci\u00f3 Centre de Regulaci\u00f3 Gen\u00f2mica (CRG) (Barcelona)<br><strong>Participa:<\/strong> Hospital Sant Joan de D\u00e9u (Catalunya), Centro Singular de Investigaci\u00f3n en Medicina Molecular e Enfermedades Cr\u00f3nicas (CiMUS) (Galicia)<br><strong>Persona de contacto:<\/strong> Luciano Di Croce (Luciano.dicroce@crg.eu)<\/p>\n<\/div>\n<\/div>\n\n\n<div class=\"responsive-tabs\">\n<h2 class=\"tabtitle\">RESUMEN PROYECTO<\/h2>\n<div class=\"tabcontent\">\n\n\n\n\n<p>Los gliomas difusos de l\u00ednea media (DMG) son tumores primarios que afectan el sistema nervioso central. Es un c\u00e1ncer agresivo que afecta a ni\u00f1os de entre seis y doce a\u00f1os. Unos 80% de los DMG tienen una mutaci\u00f3n al nivel de la Histona H3 que afecta a las modificaciones epigeneticas de esta histona por el complejo Polycomb. Esta mutaci\u00f3n no solo afecta a la organizaci\u00f3n general y a la proliferaci\u00f3n de las c\u00e9lulas tumorales, pero tambi\u00e9n modifica la arquitectura de la cromatina, su composici\u00f3n y el transcriptoma. Los objetivos de este proyecto son validar in vivo la influencia de varias prote\u00ednas enriquecidas en la cromatina de los H3K27M DMG, usando xeno-injectos derivados de pacientes (PDX) y identificar nuevas dianas involucradas en la progresi\u00f3n de la enfermedad con un cribado de alto rendimiento\u202fusando l\u00edneas de c\u00e9lulas derivadas de pacientes.<\/p>\n\n\n\n<figure class=\"wp-block-embed is-type-video is-provider-youtube wp-block-embed-youtube wp-embed-aspect-16-9 wp-has-aspect-ratio\"><div class=\"wp-block-embed__wrapper\">\n<div class=\"ast-oembed-container \" style=\"height: 100%;\"><iframe title=\"STOP DMG - Identificaci\u00f3n y validaci\u00f3n de dianas terap\u00e9uticas para el glioma difuso de l\u00ednea media\" width=\"500\" height=\"281\" src=\"https:\/\/www.youtube.com\/embed\/rpXyWcxZRBU?feature=oembed\" frameborder=\"0\" allow=\"accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture; web-share\" referrerpolicy=\"strict-origin-when-cross-origin\" allowfullscreen><\/iframe><\/div>\n<\/div><\/figure>\n\n\n\n<\/div><h2 class=\"tabtitle\">RESULTADOS DEL PROYECTO<\/h2>\n<div class=\"tabcontent\">\n\n\n\n\n<figure class=\"wp-block-image size-large\"><img decoding=\"async\" width=\"1024\" height=\"458\" src=\"https:\/\/planescomplementariossalud.es\/wp-content\/uploads\/2024\/03\/Screenshot-2025-09-08-at-11.56.30-1024x458.png\" alt=\"\" class=\"wp-image-22084\" srcset=\"https:\/\/planescomplementariossalud.es\/wp-content\/uploads\/2024\/03\/Screenshot-2025-09-08-at-11.56.30-1024x458.png 1024w, https:\/\/planescomplementariossalud.es\/wp-content\/uploads\/2024\/03\/Screenshot-2025-09-08-at-11.56.30-300x134.png 300w, https:\/\/planescomplementariossalud.es\/wp-content\/uploads\/2024\/03\/Screenshot-2025-09-08-at-11.56.30-768x344.png 768w, https:\/\/planescomplementariossalud.es\/wp-content\/uploads\/2024\/03\/Screenshot-2025-09-08-at-11.56.30-1536x687.png 1536w, https:\/\/planescomplementariossalud.es\/wp-content\/uploads\/2024\/03\/Screenshot-2025-09-08-at-11.56.30-2048x916.png 2048w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><figcaption class=\"wp-element-caption\"><strong>Figura 1:<\/strong> Desarrollo de modelos de DMG en xenoinjertos derivados de pacientes. Se inyectaron c\u00e9lulas HSJD-DIPG-007-Luciferasa dise\u00f1adas ortot\u00f3picamente en cerebros de ratones. (A) La expresi\u00f3n de luciferasa permite monitorizar el crecimiento de los tumores in vivo a lo largo del tiempo (el panel superior muestra la actividad de la luciferasa medida mediante el Sistema de Imagenolog\u00eda In Vivo (IVIS) durante varios d\u00edas tras la implantaci\u00f3n (PI)). El desarrollo de los tumores cerebrales se confirma adem\u00e1s por la p\u00e9rdida de peso de los animales a lo largo del tiempo en comparaci\u00f3n con los ratones control no inyectados (panel inferior). (B) El uso de anticuerpos espec\u00edficos contra el marcador de proliferaci\u00f3n Ki67 (rojo) o el marcador de n\u00facleos humanos (verde) en secciones de cerebros incluidos en parafina muestra la distribuci\u00f3n de las c\u00e9lulas DMG humanas en el cerebro de un rat\u00f3n receptor, recapitulando el fenotipo difuso de los tumores DMG.\u00a0<\/figcaption><\/figure>\n\n\n\n<p>El glioma difuso de la l\u00ednea media (DMG) es un tumor cerebral pedi\u00e1trico altamente agresivo que se presenta principalmente en la protuberancia anular y afecta com\u00fanmente a ni\u00f1os de 6 a 12 a\u00f1os. Aproximadamente el 80% de los DMG presentan mutaciones en los genes de la histona H3, en particular H3K27M, que alteran la arquitectura de la cromatina y la regulaci\u00f3n g\u00e9nica a trav\u00e9s de las prote\u00ednas del grupo Polycomb. Este estudio busca identificar nuevas dianas terap\u00e9uticas y evaluar su potencial en modelos precl\u00ednicos.&nbsp;<\/p>\n\n\n\n<p>Se emple\u00f3 un enfoque de varios pasos que incluy\u00f3: (i) validaci\u00f3n in vivo de dianas previamente identificadas mediante xenoinjertos ortot\u00f3picos derivados de pacientes (PDOX); (ii) cribado qu\u00edmico de alto rendimiento (HTS) de 4800 compuestos en neuroesferas de DMG para descubrir nuevos candidatos a tratamiento; y (iii) cribado combinatorio para explorar interacciones farmacol\u00f3gicas sin\u00e9rgicas. La l\u00ednea celular DMG HSJD-DIPG-007 se dise\u00f1\u00f3 para expresar los reporteros de luciferasa y GFP, lo que permite el seguimiento in vivo y la capacidad de HTS. Estas c\u00e9lulas establecieron con \u00e9xito tumores cerebrales en ratones, lo que permiti\u00f3 el monitoreo del tumor en tiempo real a trav\u00e9s de im\u00e1genes IVIS y validaci\u00f3n histol\u00f3gica utilizando marcadores nucleares y de proliferaci\u00f3n espec\u00edficos de humanos.&nbsp;<\/p>\n\n\n\n<p>El estudio HTS realizado por INNOPHARMA condujo a la identificaci\u00f3n de 112 compuestos que redujeron la proliferaci\u00f3n de neuroesferas, 22 de los cuales fueron validados en un cribado secundario. Los compuestos seleccionados se est\u00e1n sometiendo a an\u00e1lisis dosis-respuesta, y los candidatos m\u00e1s prometedores se est\u00e1n evaluando in vivo mediante la inhibici\u00f3n de shRNA o inhibidores disponibles. Los primeros resultados in vivo muestran que las l\u00edneas de shRNA inducibles replican los resultados fenot\u00edpicos observados en los ensayos de neuroesferas.&nbsp;<\/p>\n\n\n\n<p>Esta plataforma integrada, que combina el cribado gen\u00e9tico y qu\u00edmico con robustos modelos in vivo, allana el camino para la identificaci\u00f3n de estrategias terap\u00e9uticas eficaces para la DMG. La colaboraci\u00f3n entre el CRG, el HSJD (Barcelona) e INNOPHARMA (Universidad de Santiago de Compostela) es prometedora para traducir estos hallazgos en intervenciones cl\u00ednicas.&nbsp;<\/p>\n\n\n\n<div class=\"wp-block-file alignwide\"><a id=\"wp-block-file--media-67891bbf-0982-42d2-8d4e-c72067b9b204\" href=\"https:\/\/planescomplementariossalud.es\/wp-content\/uploads\/2024\/03\/Resumen-cast_web.pdf\">Descargar ficha de resultados<\/a><\/div>\n\n\n<\/div><\/div>\n\n\n\n<hr class=\"wp-block-separator has-text-color has-ast-global-color-6-color has-alpha-channel-opacity has-ast-global-color-6-background-color has-background\"\/>\n\n\n\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-28f84493 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<p class=\"has-text-align-center\">COORDINA:<\/p>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<p class=\"has-text-align-center\">PARTICIPA:<\/p>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<p class=\"has-text-align-center\"><\/p>\n<\/div>\n<\/div>\n\n\n\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-28f84493 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<figure class=\"wp-block-image aligncenter size-full is-resized\"><img decoding=\"async\" width=\"1864\" height=\"904\" src=\"https:\/\/planescomplementariossalud.es\/wp-content\/uploads\/2024\/03\/LOGOs-CRG-CAST_2014.jpg\" alt=\"\" class=\"wp-image-9394\" style=\"width:185px;height:auto\" srcset=\"https:\/\/planescomplementariossalud.es\/wp-content\/uploads\/2024\/03\/LOGOs-CRG-CAST_2014.jpg 1864w, https:\/\/planescomplementariossalud.es\/wp-content\/uploads\/2024\/03\/LOGOs-CRG-CAST_2014-300x145.jpg 300w, https:\/\/planescomplementariossalud.es\/wp-content\/uploads\/2024\/03\/LOGOs-CRG-CAST_2014-1024x497.jpg 1024w, https:\/\/planescomplementariossalud.es\/wp-content\/uploads\/2024\/03\/LOGOs-CRG-CAST_2014-768x372.jpg 768w, https:\/\/planescomplementariossalud.es\/wp-content\/uploads\/2024\/03\/LOGOs-CRG-CAST_2014-1536x745.jpg 1536w\" sizes=\"(max-width: 1864px) 100vw, 1864px\" \/><\/figure>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<figure class=\"wp-block-image aligncenter size-full is-resized\"><img loading=\"lazy\" decoding=\"async\" width=\"520\" height=\"270\" src=\"https:\/\/planescomplementariossalud.es\/wp-content\/uploads\/2024\/03\/sant_joan_de_deu_1669114427.png\" alt=\"\" class=\"wp-image-9254\" style=\"width:214px;height:auto\" srcset=\"https:\/\/planescomplementariossalud.es\/wp-content\/uploads\/2024\/03\/sant_joan_de_deu_1669114427.png 520w, https:\/\/planescomplementariossalud.es\/wp-content\/uploads\/2024\/03\/sant_joan_de_deu_1669114427-300x156.png 300w\" sizes=\"(max-width: 520px) 100vw, 520px\" \/><\/figure>\n\n\n\n<div style=\"height:20px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n<\/div>\n\n\n\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<figure class=\"wp-block-image aligncenter size-full is-resized\"><img loading=\"lazy\" decoding=\"async\" width=\"415\" height=\"85\" src=\"https:\/\/planescomplementariossalud.es\/wp-content\/uploads\/2024\/03\/logocimus_0.jpg\" alt=\"\" class=\"wp-image-9404\" style=\"width:243px;height:auto\" srcset=\"https:\/\/planescomplementariossalud.es\/wp-content\/uploads\/2024\/03\/logocimus_0.jpg 415w, https:\/\/planescomplementariossalud.es\/wp-content\/uploads\/2024\/03\/logocimus_0-300x61.jpg 300w\" sizes=\"(max-width: 415px) 100vw, 415px\" \/><\/figure>\n\n\n\n<div style=\"height:20px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n<\/div>\n<\/div>\n\n\n\n<hr class=\"wp-block-separator has-text-color has-ast-global-color-6-color has-alpha-channel-opacity has-ast-global-color-6-background-color has-background\"\/>\n\n\n\n<p><\/p>\n","protected":false},"excerpt":{"rendered":"<p><i>L\u00ednea de actuaci\u00f3n 3 (LA3)<\/i><\/p>\n<p><&#038;nbsp><br \/>\n<\/p>\n<p>Identificaci\u00f3n y validaci\u00f3n de dianas terap\u00e9uticas para el glioma difuso de l\u00ednea media (DMG) basada en cribado de alto rendimiento.<\/p>\n<p><&#038;nbsp><br \/>\n<strong>Palabras clave:<\/strong> Gliomas Difusos de L\u00ednea Media; dianas terap\u00e9uticas; xeno-injectos derivados de pacientes; cribado de alto rendimiento.<\/p>\n","protected":false},"author":15,"featured_media":10348,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","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":"","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":[245],"tags":[196,86,133],"class_list":["post-10460","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-proyecto-ca","tag-catalunya-ca","tag-cribado-de-farmacos-ca","tag-proyecto-colaborativo-ca"],"_links":{"self":[{"href":"https:\/\/planescomplementariossalud.es\/ca\/wp-json\/wp\/v2\/posts\/10460","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/planescomplementariossalud.es\/ca\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/planescomplementariossalud.es\/ca\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/planescomplementariossalud.es\/ca\/wp-json\/wp\/v2\/users\/15"}],"replies":[{"embeddable":true,"href":"https:\/\/planescomplementariossalud.es\/ca\/wp-json\/wp\/v2\/comments?post=10460"}],"version-history":[{"count":6,"href":"https:\/\/planescomplementariossalud.es\/ca\/wp-json\/wp\/v2\/posts\/10460\/revisions"}],"predecessor-version":[{"id":22091,"href":"https:\/\/planescomplementariossalud.es\/ca\/wp-json\/wp\/v2\/posts\/10460\/revisions\/22091"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/planescomplementariossalud.es\/ca\/wp-json\/wp\/v2\/media\/10348"}],"wp:attachment":[{"href":"https:\/\/planescomplementariossalud.es\/ca\/wp-json\/wp\/v2\/media?parent=10460"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/planescomplementariossalud.es\/ca\/wp-json\/wp\/v2\/categories?post=10460"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/planescomplementariossalud.es\/ca\/wp-json\/wp\/v2\/tags?post=10460"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}