{"id":35687,"date":"2019-07-29T03:20:04","date_gmt":"2019-07-29T00:20:04","guid":{"rendered":"https:\/\/bilimvegelecek.com.tr\/?p=35687"},"modified":"2019-07-28T08:53:21","modified_gmt":"2019-07-28T05:53:21","slug":"epigenetik-degisiklikler-kanser-hucrelerinin-tedaviye-karsi-direnc-gelistirmelerine-neden-oluyor","status":"publish","type":"post","link":"https:\/\/bilimvegelecek.com.tr\/index.php\/2019\/07\/29\/epigenetik-degisiklikler-kanser-hucrelerinin-tedaviye-karsi-direnc-gelistirmelerine-neden-oluyor","title":{"rendered":"Epigenetik de\u011fi\u015fiklikler, kanser h\u00fccrelerinin tedaviye kar\u015f\u0131 diren\u00e7 geli\u015ftirmelerine neden oluyor!"},"content":{"rendered":"

Bellvitge Biyomedikal Ara\u015ft\u0131rma Enstit\u00fcs\u00fc\u2019nde \u00e7al\u0131\u015fma y\u00fcr\u00fcten ara\u015ft\u0131rmac\u0131lar, meme kanserinin farkl\u0131 tiplerine y\u00f6nelik ara\u015ft\u0131rmalar\u0131yla kanserin epigenetik mekanizmas\u0131na ili\u015fkin yeni bir model olu\u015fturdular. Bu \u00e7al\u0131\u015fma s\u0131ras\u0131nda biliminsanlar\u0131, hastal\u0131k seyri b\u00fcy\u00fck oranda k\u00f6t\u00fcye do\u011fru ilerleyen ve \u201c3\u2019l\u00fc Negatif\u201d olarak tan\u0131mlanan meme kanserinin alt s\u0131n\u0131flar\u0131n\u0131 bulduklar\u0131n\u0131 da a\u00e7\u0131klad\u0131lar.<\/p>\n

Kanserin epigenetik mekanizmas\u0131na dair yeni \u00e7al\u0131\u015fmaya ge\u00e7meden \u00f6nce, \u201cepigenetik\u201d kavram\u0131na bakal\u0131m ve bu kavram \u00fczerinden kanserin epigenetik mekanizmas\u0131n\u0131 a\u00e7\u0131klayal\u0131m. Epigenetik, temelde bir canl\u0131n\u0131n genetik materyalinde bir de\u011fi\u015fiklik ger\u00e7ekle\u015fmeden bu genetik materyalin okunmas\u0131 s\u0131ras\u0131nda ya\u015fanan de\u011fi\u015fikliklerin canl\u0131n\u0131n fenotipi dedi\u011fimiz d\u0131\u015f g\u00f6r\u00fcn\u00fcm\u00fcne yans\u0131mas\u0131 durumudur. Yani genleri, genomu ifade eden genotipte temelde bir de\u011fi\u015fim g\u00f6zlenmezken; gen anlat\u0131m\u0131 s\u0131ras\u0131nda ya\u015fanan de\u011fi\u015fimler canl\u0131da normal giden s\u00fcre\u00e7lerin seyrini de\u011fi\u015ftirebilir. Epigenetik de\u011fi\u015fiklikler, \u00e7o\u011fu kez \u00e7evrenin etkisiyle g\u00f6zlenir. Canl\u0131n\u0131n ya\u015f\u0131, \u00e7evresi, ya\u015fam tarz\u0131 ve hastal\u0131k durumu gibi \u00e7e\u015fitli fakt\u00f6rler epigenetik de\u011fi\u015fimlerin ya\u015fanmas\u0131nda etkili olabilir. Alana dair yeni \u00e7al\u0131\u015fmalarda, \u00e7e\u015fitli hastal\u0131klarda epigeneti\u011fin rol\u00fc incelenmektedir. Epigenetik de\u011fi\u015fimlerin, kanser gibi hastal\u0131klarla sonu\u00e7lanan daha zararl\u0131 etkilerinin olabilece\u011fi d\u00fc\u015f\u00fcn\u00fclmektedir.<\/p>\n

\u201cEpigenetik\u201d terimi, genetik ve geli\u015fim biyolojisini kapsayan bir alan olarak 20\u2019nci y\u00fczy\u0131l\u0131n ortalar\u0131nda ilk defa kullan\u0131lmaya ba\u015fland\u0131. Yunanca\u2019daki \u201cepigenesis\u201d kelimesinden t\u00fcretilen \u201cepigenetik\u201d terimi; 1990\u2019larda alana dair ilginin yeniden artmas\u0131yla birlikte, Drosophila meyve sinekleri \u00fczerinde yap\u0131lan \u00e7al\u0131\u015fmalar yoluyla yeniden biliminsanlar\u0131n\u0131n g\u00fcndemine yerle\u015fti. 1969 y\u0131l\u0131nda yap\u0131lan \u00e7al\u0131\u015fmayla ortaya konan ve epigenetik de\u011fi\u015fikliklerin ilk s\u0131ras\u0131nda yer alan DNA metilasyonu, ard\u0131ndan gelen s\u00fcre\u00e7te daha iyi \u015fekilde ara\u015ft\u0131r\u0131lm\u0131\u015f ve \u00f6nemi ortaya konmu\u015ftur. Zamanla epigeneti\u011fe olan ilginin artmas\u0131yla kanserin ba\u015f\u0131n\u0131 \u00e7ekti\u011fi bir dizi hastal\u0131\u011fa ili\u015fkin \u00e7al\u0131\u015fmalarda epigenetik de\u011fi\u015fimlerin etkisi aranm\u0131\u015ft\u0131r. Bu \u00e7al\u0131\u015fmalar bu hastal\u0131klarla ilgili daha yeni bulgular\u0131n ortaya \u00e7\u0131kar\u0131lmas\u0131yla sonu\u00e7lanm\u0131\u015ft\u0131r.<\/p>\n

\"\"
Metil gruplar\u0131 yoluyla epigenetik de\u011fi\u015fim<\/figcaption><\/figure>\n

Epigenetik de\u011fi\u015fiklikler kal\u0131t\u0131m yoluyla aktar\u0131labilir ancak epigenetik de\u011fi\u015fiklikler s\u00fcrekli ya\u015fanabilir ve ebeveynden \u00e7ocu\u011fa ge\u00e7en epigenetik de\u011fi\u015fiklikler yeniden de\u011fi\u015fim g\u00f6sterebilir. Bu nedenle epigenetik de\u011fi\u015fiklikler nesiller aras\u0131nda aktar\u0131labilir diyebilsek de, bu de\u011fi\u015fiklikler i\u00e7in \u201ckal\u0131tsal\u201d demek b\u00fct\u00fcn\u00fcyle do\u011fru olmayabilir. Bu noktada epigenetik de\u011fi\u015fikliklerin hastal\u0131klara etkisini irdeleyelim ve kanserin epigenetik mekanizmas\u0131na bakal\u0131m.<\/p>\n

Genomu olu\u015fturan kromatin yap\u0131lar\u0131 stabil kalma e\u011filimi g\u00f6sterirler. De\u011fi\u015fime kar\u015f\u0131 direnen kromatin yap\u0131lar\u0131, bu diren\u00e7leri yoluyla canl\u0131lardaki \u201cnormal geli\u015fimi\u201d korumu\u015f olur. Bu durumda de\u011fi\u015fiklik oldu\u011fu takdirde yani epigenetik de\u011fi\u015fiklikler, genomun \u00e7al\u0131\u015fma prensiplerini etkiledi\u011fi anlarda kansere kap\u0131 aralayacak durumlar g\u00f6zlenebilir. Kar\u015f\u0131la\u015f\u0131lan bir di\u011fer durum ise epigenetik de\u011fi\u015fimlerin kansere kar\u015f\u0131 kullan\u0131lan ila\u00e7lara diren\u00e7 sa\u011flanmas\u0131na neden olmas\u0131, b\u00f6ylelikle ilac\u0131n kendi etkisinin g\u00f6r\u00fclememesi durumudur.<\/p>\n

\u0130fade edildi\u011fi gibi, kromatin yap\u0131s\u0131n\u0131n i\u00e7 ve d\u0131\u015f tehditlere kar\u015f\u0131 kendi yap\u0131s\u0131n\u0131 koruma e\u011filimi olarak tan\u0131mlanan \u201chomeostatik denge\u201d bozuldu\u011fu takdirde, yani h\u00fccre genomu \u201csavunmas\u0131z ve diren\u00e7siz\u201d kald\u0131\u011f\u0131 durumlarda h\u00fccreyi hastal\u0131kl\u0131 bir yap\u0131ya s\u00fcr\u00fckleyen durumlar ya\u015fanabilir. Bu noktada ise h\u00fccreleri kanserle\u015fmeye g\u00f6t\u00fcren de\u011fi\u015fiklikler; genetik, \u00e7evresel ve metabolik uyaranlar\u0131n etkisiyle g\u00f6zlenebilir. Bu noktada en \u00e7ok \u00f6ne \u00e7\u0131kan epigenetik de\u011fi\u015fiklik \u201cmetillenme\u201ddir. Metillenme genellikle; DNA, RNA ve Histon proteinleri \u00fczerinde g\u00f6zlenir. Bu noktalardan hareketle, epigenetik de\u011fi\u015fikliklerin kanserle\u015fmeye etkisi \u00fczerine yap\u0131lan yeni \u00e7al\u0131\u015fmaya d\u00f6nelim ve \u00e7al\u0131\u015fman\u0131n \u00f6nemini kavramaya \u00e7al\u0131\u015fal\u0131m.<\/p>\n

Epigenetik de\u011fi\u015fiklikler, gen anlat\u0131m\u0131n\u0131 de\u011fi\u015ftirebilir<\/strong>
\nBellvitge Biyomedikal Ara\u015ft\u0131rma Enstit\u00fcs\u00fc\u2019nde transformasyon ve metastaz \u00fczerine \u00e7al\u0131\u015fma y\u00fcr\u00fcten ekip taraf\u0131ndan ortaya konulan ara\u015ft\u0131rmada, kanserin epigenetik mekanizmas\u0131na ek olarak kansere kar\u015f\u0131 yayg\u0131n bir tedavi olarak kullan\u0131lan Dosetaksel\u2019in metabolizma yan\u0131t\u0131 ile DNA metilasyonundaki de\u011fi\u015fikliklerin ili\u015fkisi tan\u0131mland\u0131. \u00c7al\u0131\u015fman\u0131n y\u00fcr\u00fct\u00fcc\u00fcl\u00fc\u011f\u00fcn\u00fc ise Dr. Eva Gonz\u00e1lez-Surez yapt\u0131.<\/p>\n

\u00c7al\u0131\u015fman\u0131n \u00e7\u0131kt\u0131lar\u0131n\u0131n yer ald\u0131\u011f\u0131 makaleye g\u00f6re; metilasyon, metil gruplar\u0131 olarak adland\u0131r\u0131lan molek\u00fcllerin DNA\u2019ya ba\u011flanmas\u0131yla olu\u015fur. Bu epigenetik i\u015flem \u00fczerinden gen anlat\u0131m\u0131 yeniden d\u00fczenlenir. Bu molek\u00fcller, belirli bi\u00e7imlerde DNA\u2019ya ba\u011flan\u0131r ve genetik materyalin diziliminde farkl\u0131la\u015fmaya neden olmaks\u0131z\u0131n gen anlat\u0131m\u0131nda de\u011fi\u015fime neden olur. B\u00f6ylelikle gen anlat\u0131m\u0131 ya artt\u0131r\u0131l\u0131r ya da azalt\u0131l\u0131r.<\/p>\n

Bir hastadan al\u0131nan t\u00fcm\u00f6r h\u00fccrelerinden implantasyon yoluyla PDX maddeleri t\u00fcretilir. \u00c7al\u0131\u015fman\u0131n yazarlar\u0131, iki ana meme kanseri alt tipine ait t\u00fcm\u00f6r \u00f6rneklerinin metilasyon modellerini ilk kez raporlad\u0131. Bu \u00e7al\u0131\u015fmada PDX\u2019lerdeki ile hastalarda g\u00f6zlenen modellerin ayn\u0131 oldu\u011fu ortaya \u00e7\u0131kar\u0131ld\u0131. Bu y\u00f6n\u00fcyle \u00e7al\u0131\u015fma, ilaca diren\u00e7 ve metilasyon \u00fczerine yap\u0131lan klinik \u00f6ncesi \u00e7al\u0131\u015fmalar\u0131 da do\u011frulamaktad\u0131r.<\/p>\n

\"\"
Epigenetik de\u011fi\u015fiklikler, Dosetaksel gibi ila\u00e7lara diren\u00e7 kazan\u0131lmas\u0131nda \u00f6nemli bir rol oynuyor<\/figcaption><\/figure>\n

Ek olarak, ara\u015ft\u0131rmac\u0131lar olduk\u00e7a heterojen ve bir s\u0131n\u0131fland\u0131rmaya dahil edilemeyen kanser hastas\u0131 grubun, \u201c3\u2019l\u00fc Negatif\u201d olarak adland\u0131r\u0131lan meme kanseri alt s\u0131n\u0131fland\u0131rmas\u0131na izin verecek metilasyon modellerine sahip oldu\u011funu bu \u00e7al\u0131\u015fma yoluyla g\u00f6zlemlediler. Kanser hastal\u0131\u011f\u0131n\u0131n alt gruplar\u0131na ili\u015fkin bu s\u0131n\u0131fland\u0131rma, ara\u015ft\u0131rmac\u0131lar\u0131n hastal\u0131\u011fa \u00f6zg\u00fc tedavi geli\u015ftirmeleri i\u00e7in \u00f6n a\u00e7\u0131c\u0131 olabilir.<\/p>\n

Ara\u015ft\u0131rmac\u0131lar \u00e7al\u0131\u015fmada, t\u00fcm\u00f6r h\u00fccrelerinde metilasyon g\u00f6zlenmesinin, kemoterapide en yayg\u0131n kullan\u0131lan ila\u00e7lardan biri olan Dosetaksel gibi ila\u00e7lara diren\u00e7 kazan\u0131lmas\u0131nda \u00f6nemli bir rol oynad\u0131\u011f\u0131n\u0131 ortaya koydu.<\/p>\n

\n

Kaynak: https:\/\/medicalxpress.com\/news\/2019-07-epigenetic-docetaxel-resistant-breast-cancer.html
\nhttps:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1392256\/
\nhttps:\/\/science.sciencemag.org\/content\/357\/6348\/eaal2380<\/p>\n

Kanser epigeneti\u011fine ili\u015fkin ileri okumalar i\u00e7in:
\nhttps:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2802667\/
\nhttps:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5991666\/<\/p>\n","protected":false},"excerpt":{"rendered":"

Bellvitge Biyomedikal Ara\u015ft\u0131rma Enstit\u00fcs\u00fc\u2019nde \u00e7al\u0131\u015fma y\u00fcr\u00fcten ara\u015ft\u0131rmac\u0131lar, meme kanserinin farkl\u0131 tiplerine y\u00f6nelik ara\u015ft\u0131rmalar\u0131yla kanserin epigenetik mekanizmas\u0131na ili\u015fkin yeni bir model olu\u015fturdular. Bu \u00e7al\u0131\u015fma s\u0131ras\u0131nda biliminsanlar\u0131, hastal\u0131k seyri b\u00fcy\u00fck oranda k\u00f6t\u00fcye do\u011fru ilerleyen ve \u201c3\u2019l\u00fc Negatif\u201d olarak tan\u0131mlanan meme kanserinin alt s\u0131n\u0131flar\u0131n\u0131 bulduklar\u0131n\u0131 da a\u00e7\u0131klad\u0131lar. Kanserin epigenetik mekanizmas\u0131na dair yeni \u00e7al\u0131\u015fmaya ge\u00e7meden \u00f6nce, \u201cepigenetik\u201d kavram\u0131na bakal\u0131m […]<\/p>\n","protected":false},"author":1390,"featured_media":35690,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[19],"tags":[5101,272,2114,773,444,5100],"class_list":["post-35687","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-bilim-gundemi","tag-direnc","tag-dna","tag-epigenetik","tag-genom","tag-kanser","tag-metilasyon"],"acf":[],"aioseo_notices":[],"aioseo_head":"\n\t\t\n\t\n\t\n\t\n\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t\n\t\t