{"id":7407,"date":"2019-10-24T00:00:00","date_gmt":"2019-10-23T22:00:00","guid":{"rendered":"https:\/\/idibell.cat\/blog\/2019\/10\/24\/humanitzen-cucs-per-fer-sensibles-a-un-farmac-contra-el-cancer-i-identificar-els-punts-febles-de-cel%c2%b7lules-tumorals\/"},"modified":"2020-05-13T19:45:48","modified_gmt":"2020-05-13T17:45:48","slug":"humanitzen-cucs-per-fer-sensibles-a-un-farmac-contra-el-cancer-i-identificar-els-punts-febles-de-cel%c2%b7lules-tumorals","status":"publish","type":"post","link":"https:\/\/idibell.cat\/2019\/10\/humanitzen-cucs-per-fer-sensibles-a-un-farmac-contra-el-cancer-i-identificar-els-punts-febles-de-cel%c2%b7lules-tumorals\/","title":{"rendered":"Humanitzen cucs per fer-sensibles a un f\u00e0rmac contra el c\u00e0ncer i identificar els punts febles de c\u00e8l\u00b7lules tumorals"},"content":{"rendered":"<p>A primera vista, un cuc que mesura un mil\u00b7l\u00edmetre i que cal observar amb lupa no s&#8217;assembla en res a un \u00e9sser hum\u00e0. No obstant aix\u00f2, el nematode <em>Caenorhabditis elegans<\/em>, un animal model usat en investigaci\u00f3 biom\u00e8dica per centenars de laboratoris al m\u00f3n, t\u00e9 aproximadament el mateix nombre de gens que tenim els humans, uns 20.000. A m\u00e9s, la majoria dels gens humans que estan relacionats amb malalties tenen un gen molt semblant, u ort\u00f2leg, en el cuc <em>C. elegans<\/em>. Aix\u00ed, per exemple, el gen hum\u00e0 SF3B1 que es troba mutat en diferents tipus de c\u00e0ncer, principalment en leuc\u00e8mies, per\u00f2 tamb\u00e9 en alguns tumors de mama o pr\u00f2stata, \u00e9s molt similar al gen sftb-1 de <em>C. elegans<\/em>. S\u00f3n tan similars que quan s&#8217;observa la seq\u00fc\u00e8ncia d&#8217;amino\u00e0cids de la prote\u00efna humana SF3B1 en les seves regions m\u00e9s afectades per mutacions de c\u00e0ncer, el 89% dels amino\u00e0cids s\u00f3n id\u00e8ntics. Precisament algun d&#8217;aquests amino\u00e0cids conservats des cucs fins humans s\u00f3n els que es troben mutats en alguns tumors.<\/p>\n<p>Un grup d&#8217;investigadors dirigit pel Dr Juli\u00e1n Cer\u00f3n, de l&#8217;Institut d&#8217;Investigacions Biom\u00e8diques de Bellvitge (IDIBELL), ha aprofitat la similitud entre aquests amino\u00e0cids i la seva experi\u00e8ncia en la t\u00e8cnica d&#8217;edici\u00f3 g\u00e8nica de CRISPR per imitar en <em>C. elegans<\/em> les mutacions del gen SF3B1 que es troben en tumors humans.<\/p>\n<p>Aquestes investigacions han perm\u00e8s utilitzar cucs per identificar possibles punts febles o vulnerabilitats de les c\u00e8l\u00b7lules canceroses que tenen mutacions en SF3B1. Aix\u00ed, els investigadors apunten a tres factors de splicing, que funcionen al costat de SF3B1 en el processament de l&#8217;ARN missatger, com a dianes per a mol\u00e8cules terap\u00e8utiques que matin a les c\u00e8l\u00b7lules cancer\u00edgenes amb la mutaci\u00f3 en SF3B1 per\u00f2 no a les c\u00e8l\u00b7lules normals. El treball de recerca, que forma part de la tesi doctoral de X\u00e8nia Serrat i en el qual han col\u00b7laborat investigadors de l&#8217;Institut Pasteur de Paris, acaba de ser publicat a la revista <em>PLoS Genetics<\/em>.<\/p>\n<p>Els investigadors de l&#8217;IDIBELL no nom\u00e9s han reprodu\u00eft les mutacions de pacients de c\u00e0ncer en el genelegoma de cucs, sin\u00f3 que tamb\u00e9 han humanitzat la regi\u00f3 de la prote\u00efna SF3B1 que s&#8217;uneix a Pladienolide B, una mol\u00e8cula de la qual deriva un f\u00e0rmac que est\u00e0 en fase d&#8217;assaig cl\u00ednic per al tractament del c\u00e0ncer. Aquest avan\u00e7 permetr\u00e0 provar moltes m\u00e9s mol\u00e8cules derivades del Pladienolide B, per a seleccionar la m\u00e9s eficient com a agent anti-tumoral.<\/p>\n<p>Gr\u00e0cies a la tecnologia de CRISPR, en la qual el grup del Dr Cer\u00f3n \u00e9s especialista, el reempla\u00e7ament funcional de prote\u00efnes de <em>C. elegans<\/em> per les seves hom\u00f2logues humanes permetr\u00e0 usar aquests cucs humanitzats per investigar mecanismes de malaltia i pronosticar la implicaci\u00f3 certes mutacions en el desenvolupament de malalties. Aquest sistema tamb\u00e9 serviria per buscar noves f\u00e0rmacs d&#8217;una manera r\u00e0pida, eficient, i \u00e8ticament responsable.<br \/>\u00a0<\/p>\n","protected":false},"excerpt":{"rendered":"<p>A primera vista, un cuc que mesura un mil\u00b7l\u00edmetre i que cal observar amb lupa no s&#8217;assembla en res a un \u00e9sser hum\u00e0. No obstant aix\u00f2, el nematode Caenorhabditis elegans, un animal model usat en investigaci\u00f3 biom\u00e8dica per centenars de laboratoris al m\u00f3n, t\u00e9 aproximadament el mateix nombre de gens que tenim els humans, uns [&hellip;]<\/p>\n","protected":false},"author":6,"featured_media":7408,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"no-sidebar","site-content-layout":"page-builder","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":"default","adv-header-id-meta":"","stick-header-meta":"default","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":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","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-opacity":"","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-opacity":"","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-opacity":"","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-opacity":"","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-opacity":"","overlay-gradient":""}},"footnotes":""},"categories":[334,355],"tags":[],"class_list":["post-7407","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-medicina-translacional","category-models-de-malaltia-en-c-elegans"],"publishpress_future_action":{"enabled":false,"date":"2025-01-29 05:06:45","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category"},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"_links":{"self":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/7407","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/comments?post=7407"}],"version-history":[{"count":0,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/posts\/7407\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/media\/7408"}],"wp:attachment":[{"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/media?parent=7407"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/categories?post=7407"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/idibell.cat\/wp-json\/wp\/v2\/tags?post=7407"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}