{"id":1184,"date":"2020-07-01T14:35:07","date_gmt":"2020-07-01T13:35:07","guid":{"rendered":"http:\/\/www-b3.ijs.si\/?page_id=1184"},"modified":"2020-07-01T14:35:07","modified_gmt":"2020-07-01T13:35:07","slug":"rak","status":"publish","type":"page","link":"https:\/\/www-b3.ijs.si\/index.php\/raziskave\/podrocja-raziskav\/rak\/?lang=sl","title":{"rendered":"Rak"},"content":{"rendered":"<p><section class=\"kc-elm kc-css-149607 kc_row\"><div class=\"kc-row-container  kc-container\"><div class=\"kc-wrap-columns\"><div class=\"kc-elm kc-css-388610 kc_col-sm-12 kc_column kc_col-sm-12\"><div class=\"kc-col-container\">\n<div class=\"kc-elm kc-css-534852 kc-blog-posts kc-blog-posts-3 kc-blog-grid kc_blog_masonry kc-image-align-both\">\n\t\n\t\t<h3>Blog Post: Nothing not found.<\/h3>\n\n\t\n<\/div>\n<\/div><\/div><\/div><\/div><\/section><section class=\"kc-elm kc-css-584638 kc_row\"><div class=\"kc-row-container  kc-container\"><div class=\"kc-wrap-columns\"><div class=\"kc-elm kc-css-59406 kc_col-sm-12 kc_column kc_col-sm-12\"><div class=\"kc-col-container\"><div class=\"kc-elm kc-css-896632 kc_text_block\"><\/p>\n<h2>Proteolizni sistem pri raku<br \/><\/h2>\n<p>Motnje v proteoliznem sistemu so zna\u010dilne za vrsto bolezni, ki vklju\u010dujejo rak, imunske in nevrodegenerativne bolezni. Na\u0161a raziskovalna skupina \u017ee vrsto let raziskuje molekularne mehanizme napredovanja teh bolezni, v katerih sodelujejo razli\u010dni proteolizni encimi in\u00a0 njihovi zaviralci. Pri tem \u017eelimo opredeliti primerne tar\u010de za razvoj novih diagnosti\u010dnih in terapevtskih pristopov. Kot pomembne dejavnike smo opredelili cisteinske katepsine, predvsem katepsina B in X. Za inaktivacijo njune kvarne patolo\u0161ke aktivnosti smo razvili specifi\u010dne\u00a0 zaviralce in dokazali, da in vitro in in vivo u\u010dinkovito zmanj\u0161ajo tumorsko rast in metastaziranje. Cisteinske peptidaze so zelo pomembne tudi pri regulaciji protitumorskega imunskega odziva, saj omogo\u010dajo predstavitev antigenov imunskim celicam, pospe\u0161ujejo\u00a0 njihovo adhezijo in migracijo, vplivajo na aktivnost kemokinov in prek aktivacije grancimov zagotavljajo citotoksi\u010dnost limfocitov T ter naravnih celic ubijalk (NK). Pomemben del na\u0161ih raziskav obsegajo interakcije med tumorskimi celicami in citotoksi\u010dnimi celicami v tumorskem mikrookolju. Pri tem ima zelo pomembno vlogo proteinski inhibitor cisteinskih peptidaz cistatin F, ki z inhibicijo katepsinov C in H prepre\u010di aktivacijo grancimov, peptidaz, ki se nahajajo v sekretornih granulah citotoksi\u010dnih celic. Aktivni grancimi vstopijo v tar\u010dne celice in spro\u017eijo njihovo uni\u010denje z apoptozo. Tumorske celice in imunske celice v tumorskem mikrookolju izlo\u010dajo neaktivno dimerno obliko cistatina F, ki se potem internalizira v citotoksi\u010dne celice in inhibira aktivacijo grancimov. Dokazali smo, da je citotoksi\u010dnost NK celic in citotoksi\u010dnih limfocitov T odvisna od koncentracije aktivne oblike cistatina F v teh celicah. Z nevtralizacijo delovanja cistatina F posku\u0161amo izbolj\u0161ati terapevtsko uporabo citotoksi\u010dnih celic v imunoterapiji raka. <\/p>\n<p>\n<\/div><div class=\"kc-elm kc-css-317515\" style=\"height: 30px; clear: both; width:100%;\"><\/div><\/div><\/div><\/div><\/div><\/section><section class=\"kc-elm kc-css-962873 kc_row\"><div class=\"kc-row-container  kc-container\"><div class=\"kc-wrap-columns\"><div class=\"kc-elm kc-css-187609 kc_col-sm-12 kc_column kc_col-sm-12\"><div class=\"kc-col-container\"><div class=\"kc-elm kc-css-664300 kc_shortcode kc_single_image\">\n\n        <img src=\"https:\/\/www-b3.ijs.si\/wp-content\/uploads\/2020\/05\/Cancer-scheme-eng.jpg\" class=\"\" alt=\"\" \/>    <\/div>\n<div class=\"kc-elm kc-css-654673\" style=\"height: 30px; clear: both; width:100%;\"><\/div><\/div><\/div><\/div><\/div><\/section><section class=\"kc-elm kc-css-365745 kc_row\"><div class=\"kc-row-container  kc-container\"><div class=\"kc-wrap-columns\"><div class=\"kc-elm kc-css-7449 kc_col-sm-12 kc_column kc_col-sm-12\"><div class=\"kc-col-container\"><div class=\"kc-elm kc-css-11199 kc_text_block\"><\/p>\n<h4>Izbrane objave<\/h4>\n<ul>\n<li>PERI\u0160I\u0106, Milica, PAWELEC, Graham, KOS, Janko. <a href=\"https:\/\/www.mdpi.com\/1422-0067\/22\/16\/8408\" target=\"_blank\" rel=\"noopener\"><strong>Human CD4+ T-cell clone expansion leads to the expression of the cysteine peptidase inhibitor cystatin F<\/strong><\/a>. International journal of molecular sciences, 2021, 16, 8408-1-8408-15.<\/li>\n<li><u>SENJOR, Emanuela<\/u>, <u>PERI\u0160I\u0106, Milica<\/u>, BREZNIK, Barbara, <u>MITROVI\u0106, Ana<\/u>, MLAKAR, Jernej, ROTTER, Ana, POR\u010cNIK, Andrej, LAH TURN\u0160EK, Tamara, <u>KOS, Janko<\/u>. <a href=\"https:\/\/link.springer.com\/article\/10.1007%2Fs13402-021-00618-9\" target=\"_blank\" rel=\"noopener\"><strong>Cystatin F acts as a mediator of immune suppression in glioblastoma<\/strong><\/a>. Cellular oncology, 2021, 13.<\/li>\n<li>PRUNK, Mateja, PERI\u0160I\u0106 NANUT, Milica, JAKO\u0160, Tanja, SABOTI\u010c, Jerica, \u0160VAJGER, Urban, KOS, Janko. <a href=\"https:\/\/www.mdpi.com\/2072-6694\/12\/12\/3660?type=check_update&amp;version=1\" target=\"_blank\" rel=\"noopener noreferrer\"><strong>Extracellular Cystatin F Is Internalised by Cytotoxic T Lymphocytes and Decreases Their Cytotoxicity.<\/strong><\/a> Cancers, 2020, 12(12), 3660.<\/li>\n<li><span style=\"text-decoration: underline;\">MITROVI\u0106, Ana<\/span>, ZAVR\u0160NIK, Janja, MIKHAYLOV, Georgy, KNEZ, Damijan, PE\u010cAR FONOVI\u0106, Ur\u0161a, MATJAN-\u0160TEFIN, Petra, BUTINAR, Miha, GOBEC, Stanislav, TURK, Boris, <span style=\"text-decoration: underline;\">KOS, Janko<\/span>. <a href=\"https:\/\/link.springer.com\/article\/10.1007%2Fs00018-021-04117-w\" target=\"_blank\" rel=\"noopener\"><strong>Evaluation of novel cathepsin-X inhibitors in vitro and in vivo and their ability to improve cathepsin-B-directed antitumor therapy.<\/strong><\/a> Cellular and molecular life sciences. 2022, 79, 1, 34-1-34-14.<\/li>\n<li>MITROVI\u0106, Ana, KLJUN, Jakob, SOSI\u010c, Izidor, UR\u0160I\u010c, Matija, MEDEN, Anton, GOBEC, Stanislav, KOS, Janko, TUREL, Iztok. <a href=\"https:\/\/pubs.acs.org\/doi\/10.1021\/acs.inorgchem.9b01882\" target=\"_blank\" rel=\"noopener noreferrer\"><strong>Organoruthenated nitroxoline derivatives impair tumor cell invasion through inhibition of cathepsin B activity.<\/strong><\/a> Inorganic chemistry, 2019, 58, 18, 12334-12347.<\/li>\n<\/ul>\n<p>\n<\/div><div class=\"kc-elm kc-css-894683\" style=\"height: 30px; clear: both; width:100%;\"><\/div><\/div><\/div><\/div><\/div><\/section><section class=\"kc-elm kc-css-36181 kc_row\"><div class=\"kc-row-container  kc-container\"><div class=\"kc-wrap-columns\"><div class=\"kc-elm kc-css-482094 kc_col-sm-12 kc_column kc_col-sm-12\"><div class=\"kc-col-container\"><div class=\"kc-elm kc-css-866615\" style=\"height: 30px; clear: both; width:100%;\"><\/div><\/div><\/div><\/div><\/div><\/section><\/p>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":6,"featured_media":678,"parent":1183,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"_links":{"self":[{"href":"https:\/\/www-b3.ijs.si\/index.php\/wp-json\/wp\/v2\/pages\/1184"}],"collection":[{"href":"https:\/\/www-b3.ijs.si\/index.php\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www-b3.ijs.si\/index.php\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www-b3.ijs.si\/index.php\/wp-json\/wp\/v2\/users\/6"}],"replies":[{"embeddable":true,"href":"https:\/\/www-b3.ijs.si\/index.php\/wp-json\/wp\/v2\/comments?post=1184"}],"version-history":[{"count":1,"href":"https:\/\/www-b3.ijs.si\/index.php\/wp-json\/wp\/v2\/pages\/1184\/revisions"}],"predecessor-version":[{"id":1717,"href":"https:\/\/www-b3.ijs.si\/index.php\/wp-json\/wp\/v2\/pages\/1184\/revisions\/1717"}],"up":[{"embeddable":true,"href":"https:\/\/www-b3.ijs.si\/index.php\/wp-json\/wp\/v2\/pages\/1183"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www-b3.ijs.si\/index.php\/wp-json\/wp\/v2\/media\/678"}],"wp:attachment":[{"href":"https:\/\/www-b3.ijs.si\/index.php\/wp-json\/wp\/v2\/media?parent=1184"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}