{"id":2367,"date":"2023-03-31T11:27:24","date_gmt":"2023-03-31T14:27:24","guid":{"rendered":"https:\/\/ibyme.org.ar\/investigacion\/?page_id=2367"},"modified":"2023-07-11T15:32:18","modified_gmt":"2023-07-11T18:32:18","slug":"lineas-de-investigacion","status":"publish","type":"page","link":"https:\/\/ibyme.org.ar\/investigacion\/laboratorios\/hormonas-y-cancer\/lineas-de-investigacion\/","title":{"rendered":"L\u00edneas de Investigaci\u00f3n"},"content":{"rendered":"<p><div class=\"fusion-fullwidth fullwidth-box fusion-builder-row-1 fusion-flex-container has-pattern-background has-mask-background fusion-parallax-none hundred-percent-fullwidth non-hundred-percent-height-scrolling\" 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style=\"--awb-bg-size:cover;--awb-width-large:100%;--awb-margin-top-large:0px;--awb-spacing-right-large:1.92%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:1.92%;--awb-width-medium:100%;--awb-order-medium:0;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-order-small:0;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;\"><div class=\"fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column\"><nav class=\"fusion-breadcrumbs awb-yoast-breadcrumbs fusion-breadcrumbs-1\" style=\"--awb-alignment:left;--awb-breadcrumb-sep:&#039;\/&#039;;text-align:left;\" aria-label=\"Breadcrumb\"><span><span><a href=\"https:\/\/ibyme.org.ar\/investigacion\/en\/laboratories\/\">Inicio<\/a><\/span><\/span><\/nav><div class=\"fusion-title title fusion-title-1 fusion-sep-none fusion-title-text fusion-title-size-one\" style=\"--awb-text-color:var(--awb-color8);--awb-margin-top-small:10px;--awb-margin-right-small:0px;--awb-margin-bottom-small:10px;--awb-margin-left-small:0px;\"><h1 class=\"fusion-title-heading title-heading-left\" style=\"margin:0;\">Hormonas y C\u00e1ncer<\/h1><\/div><\/div><\/div><\/div><\/div><div class=\"fusion-fullwidth fullwidth-box fusion-builder-row-4 fusion-flex-container has-pattern-background has-mask-background nonhundred-percent-fullwidth non-hundred-percent-height-scrolling\" style=\"--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-flex-wrap:wrap;\" ><div class=\"fusion-builder-row fusion-row fusion-flex-align-items-flex-start fusion-flex-content-wrap\" style=\"max-width:1248px;margin-left: calc(-4% \/ 2 );margin-right: calc(-4% \/ 2 );\"><div class=\"fusion-layout-column fusion_builder_column fusion-builder-column-2 fusion_builder_column_1_1 1_1 fusion-flex-column\" style=\"--awb-bg-size:cover;--awb-width-large:100%;--awb-margin-top-large:0px;--awb-spacing-right-large:1.92%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:1.92%;--awb-width-medium:100%;--awb-order-medium:0;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-order-small:0;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;\"><div class=\"fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column\"><div class=\"fusion-title title fusion-title-2 fusion-sep-none fusion-title-text fusion-title-size-two\" style=\"--awb-text-color:var(--awb-color5);--awb-margin-top-small:10px;--awb-margin-right-small:0px;--awb-margin-bottom-small:10px;--awb-margin-left-small:0px;--awb-font-size:22px;\"><h2 class=\"fusion-title-heading title-heading-left\" style=\"font-family:&quot;Red Hat Display&quot;;font-style:normal;font-weight:700;margin:0;font-size:1em;\">L\u00edneas de Investigaci\u00f3n<\/h2><\/div><\/div><\/div><\/div><\/div><div class=\"fusion-fullwidth fullwidth-box fusion-builder-row-5 fusion-flex-container has-pattern-background has-mask-background nonhundred-percent-fullwidth non-hundred-percent-height-scrolling\" style=\"--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-flex-wrap:wrap;\" ><div class=\"fusion-builder-row fusion-row fusion-flex-align-items-flex-start fusion-flex-content-wrap\" style=\"max-width:1248px;margin-left: calc(-4% \/ 2 );margin-right: calc(-4% \/ 2 );\"><div class=\"fusion-layout-column fusion_builder_column fusion-builder-column-3 fusion_builder_column_1_1 1_1 fusion-flex-column\" style=\"--awb-bg-size:cover;--awb-width-large:100%;--awb-margin-top-large:0px;--awb-spacing-right-large:1.92%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:1.92%;--awb-width-medium:100%;--awb-order-medium:0;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-order-small:0;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;\"><div class=\"fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column\"><div class=\"fusion-text fusion-text-1\"><p>Receptores adren\u00e9rgicos y c\u00e1ncer de mama:<br \/>\nLos compuestos adren\u00e9rgicos, adrenalina y noradrenalina son importantes hormonas\/ neurotransmisores liberados durante el estr\u00e9s. Sus respuestas est\u00e1n mediadas por la activaci\u00f3n de receptores adren\u00e9rgicos. Nuestro grupo ha descripto la expresi\u00f3n de receptores \u03b12-adren\u00e9rgicos en l\u00edneas tumorales y no tumorales de mama humano y murino. Su estimulaci\u00f3n est\u00e1 asociada a un aumento significativo de la proliferaci\u00f3n celular y del crecimiento tumoral en diferentes modelos experimentales de c\u00e1ncer de mama. Hemos encontrado adem\u00e1s que un antagonista \u03b12 y un agonista \u03b22-adren\u00e9rgico (este \u00faltimo usualmente utilizado para el tratamiento del asma) inhiben estos par\u00e1metros.<br \/>\nDescribimos que los agonistas \u03b2-adren\u00e9rgicos tienen un importante efecto sobre el desarrollo de la gl\u00e1ndula mamaria normal de rat\u00f3n y producen diferenciaci\u00f3n en modelos experimentales de c\u00e1ncer de mama. Estudiamos estos compuestos in vitro e in vivo en cuanto a su efecto biol\u00f3gico y a los mecanismos de se\u00f1alizaci\u00f3n intracelulares implicados en estas respuestas. Comprendiendo estos mecanismos, se podr\u00eda determinar qu\u00e9 compuestos (agonistas y antagonistas) pueden ser \u00fatiles como tratamiento adyuvante del c\u00e1ncer de mama. Se trata de hallazgos prometedores con posibilidades de utilizaci\u00f3n cl\u00ednica ya que muchos de estos compuestos se utilizan ampliamente para otras especificaciones con efectos secundarios m\u00ednimos. Podr\u00edan eventualmente complementar terapias existentes, sobre todo en aquellos casos en los que se desarrolla resistencia a las mismas. Otra posibilidad que estamos analizando es la disminuci\u00f3n de las dosis de drogas que poseen efectos secundarios importantes (como es la quimioterapia) mediante la administraci\u00f3n conjunta de las mismas con agentes adren\u00e9rgicos de muy baja toxicidad.<br \/>\nPor otro lado, hemos encontrado en estudios in silico que algunos de estos receptores est\u00e1n relacionados con una mejor sobrevida libre de enfermedad en algunos subtipos de tumores de mama en pacientes, mientras que otros subtipos poseen el efecto contrario. En este momento estamos completando estos hallazgos mediante experimentaci\u00f3n del comportamiento biol\u00f3gico de cada subtipo de receptor adren\u00e9rgico (mediante transfecciones estables) en modelos experimentales de c\u00e1ncer de mama en c\u00e9lulas en cultivo. Por otro lado, estudiamos la conformaci\u00f3n de estos receptores con el objetivo de comprender su estructura e interacci\u00f3n con sus ligandos para permitir la s\u00edntesis de nuevos ligandos espec\u00edficos. Esta l\u00ednea es llevada a cabo por los Dres. Carlos David Bruque e Isabel L\u00fcthy.<\/p>\n<p>Rol de FGFR2 y RUNX2 en el desarrollo de resistencia a la terapia endocrina en modelos experimentales de c\u00e1ncer de mama humano:<br \/>\nAproximadamente un 70% de los carcinomas mamarios expresan receptores hormonales y son susceptibles a una terapia endocrina. Sin embargo, la mayor\u00eda de las pacientes desarrolla resistencia a la terapia. Un posible mecanismo involucrado en el desarrollo de resistencia es el aumento en la activaci\u00f3n de receptores de factores de crecimiento como la v\u00eda de receptor de crecimiento fibrobl\u00e1stico (FGFR). A partir de evidencias bibliogr\u00e1ficas, sabemos que la v\u00eda de FGFR induce la expresi\u00f3n y activaci\u00f3n del factor de transcripci\u00f3n RUNX2, que se asocia al establecimiento de met\u00e1stasis. Recientemente demostramos en un modelo resistente endocrino, una regulaci\u00f3n cruzada entre el FGFR2 y RUNX2 y, que la sobreexpresi\u00f3n de RUNX2 induce un aumento en el crecimiento tumoral y en las met\u00e1stasis. En estudios preliminares, observamos que la sobreexpresi\u00f3n de RUNX2 induce resistencia al tratamiento hormonal en un modelo sensible a la terapia endocrina. Nuestra hip\u00f3tesis es que en el c\u00e1ncer de mama luminal, el aumento en los niveles de expresi\u00f3n de RUNX2 favorece el desarrollo de la resistencia endocrina y la diseminaci\u00f3n metast\u00e1sica. El objetivo general de nuestro trabajo es determinar el rol de RUNX2 en la resistencia endocrina y los mecanismos involucrados en su activaci\u00f3n a trav\u00e9s de su interacci\u00f3n con la v\u00eda de FGFR, con el fin de establecer su participaci\u00f3n en la respuesta a la terapia endocrina en carcinomas mamarios. Para llevarlo a cabo, utilizaremos un modelo sensible endocrino para corroborar el rol de RUNX2 en la adquisici\u00f3n de resistencia hormonal y si las terapias dirigidas al FGFR y\/o RUNX2 revierten la resistencia endocrina. Asimismo, evaluamos los mecanismos moleculares involucrados en la activaci\u00f3n y regulaci\u00f3n de la transcripci\u00f3n de RUNX2. Realizamos ensayos de: proliferaci\u00f3n celular y crecimiento tumoral, sensibilidad endocrina, expresi\u00f3n de prote\u00ednas, expresi\u00f3n de luciferasa y ChIP, entre otros. Considerando que existe una regulaci\u00f3n cruzada entre las v\u00edas de FGFR2 y RUNX2, el bloqueo de las v\u00edas de FGFR combinado con la v\u00eda de RUNX2 constituye una alternativa terap\u00e9utica prometedora para tumores luminales resistentes a la terapia endocrina.<br \/>\nEsta l\u00ednea de trabajo es llevada a cabo por la Dra. Cecilia P\u00e9rez Pi\u00f1ero y la Lic. Mar\u00eda Sol Rodr\u00edguez en estrecha colaboraci\u00f3n con las Dras. Claudia Lanari y Caroline Lamb, del Laboratorio de Carcinog\u00e9nesis Hormonal.<\/p>\n<\/div><\/div><\/div><\/div><\/div><\/p>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":43,"featured_media":0,"parent":2364,"menu_order":2,"comment_status":"closed","ping_status":"closed","template":"100-width.php","meta":{"_acf_changed":false,"inline_featured_image":false,"wpupg_custom_link":[],"wpupg_custom_link_behaviour":["default"],"wpupg_custom_link_nofollow":[],"wpupg_custom_image":[],"wpupg_custom_image_id":[],"footnotes":""},"page_category":[],"class_list":["post-2367","page","type-page","status-publish","hentry"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.7 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>L\u00edneas de Investigaci\u00f3n - IBYME<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/ibyme.org.ar\/investigacion\/laboratorios\/hormonas-y-cancer\/lineas-de-investigacion\/\" \/>\n<meta property=\"og:locale\" content=\"es_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"L\u00edneas de Investigaci\u00f3n - 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