{"id":7886,"date":"2024-08-11T09:40:26","date_gmt":"2024-08-11T09:40:26","guid":{"rendered":"https:\/\/longchangextracts.com\/?p=7886"},"modified":"2024-08-11T09:40:26","modified_gmt":"2024-08-11T09:40:26","slug":"bioinformatics-screening","status":"publish","type":"post","link":"https:\/\/longchangextracts.com\/tr\/bioinformatics-screening\/","title":{"rendered":"Biyoinformatik Taramaya Dayal\u0131 Olarak Pankreas Kanserinin Farkl\u0131 Genleri ve \u0130mm\u00fcn \u0130stila Mekanizmas\u0131 ile Hedeflenen Geleneksel \u00c7in T\u0131bb\u0131n\u0131n Tahmin Edilmesi"},"content":{"rendered":"<p>Biyoinformatik Taramaya Dayal\u0131 Olarak Pankreas Kanserinin Farkl\u0131 Genleri ve \u0130mm\u00fcn \u0130stila Mekanizmas\u0131 ile Hedeflenen Geleneksel \u00c7in T\u0131bb\u0131n\u0131n Tahmin Edilmesi<br \/>\nPankreatik duktal adenokarsinomun (PDAC) k\u00fcresel y\u00fck\u00fc son 25 y\u0131lda iki kattan fazla artm\u0131\u015ft\u0131r ve 2030 y\u0131l\u0131na kadar kansere ba\u011fl\u0131 \u00f6l\u00fcmlerin ikinci \u00f6nde gelen nedeni olmas\u0131 beklenmektedir. PDAC hastalar\u0131n\u0131n ortalama be\u015f y\u0131ll\u0131k sa\u011fkal\u0131m oran\u0131 sadece 8%'dir ve hastalar\u0131n 71% gibi y\u00fcksek bir oran\u0131 tam cerrahi rezeksiyondan sonra bile n\u00fcks riskiyle kar\u015f\u0131 kar\u015f\u0131yad\u0131r. Y\u00fcksek \u00f6l\u00fcmc\u00fcll\u00fck ve y\u00fcksek n\u00fcks oran\u0131na sahip bu t\u00fcm\u00f6r \u00f6zelli\u011fi, PDAC'nin imm\u00fcn efekt\u00f6r h\u00fccrelerin t\u00fcm\u00f6r i\u00e7ine s\u0131zmas\u0131n\u0131 \u00f6nleyen ve pankreas kanseri h\u00fccrelerinin imm\u00fcn g\u00f6zetimden ka\u00e7mas\u0131n\u0131 sa\u011flayan s\u0131k\u0131 matris bile\u015feni (fiziksel bariyer) taraf\u0131ndan belirlenir. G\u00fcn\u00fcm\u00fczde bir\u00e7ok klinik \u00e7al\u0131\u015fma, imm\u00fcn kontrol noktas\u0131 inhibit\u00f6rleri, kanser a\u015f\u0131lar\u0131, adoptif h\u00fccre metastaz\u0131 vb. dahil olmak \u00fczere imm\u00fcnoterapi yoluyla PDAC hastalar\u0131n\u0131n genel etkinli\u011fini art\u0131rmaya \u00e7al\u0131\u015fmaktad\u0131r. Monoklonal antikor tedavisinin klinik etkinli\u011fi zay\u0131ft\u0131r ve herhangi bir ilerleme kaydedilmemi\u015ftir.<\/p>\n<p>Y\u00fcksek verimli genetik analizin ortaya \u00e7\u0131kmas\u0131yla birlikte, gen ekspresyon profili olu\u015fturma, \u00e7e\u015fitli hastal\u0131klarda farkl\u0131 \u015fekilde ifade edilen genleri tan\u0131mlamak i\u00e7in etkili bir y\u00f6ntem haline gelmi\u015ftir. CIBERSORT, bir numunedeki imm\u00fcn h\u00fccrelerin ekspresyonunu de\u011ferlendirmek ve \u00e7e\u015fitli imm\u00fcn h\u00fccre oranlar\u0131 elde etmek i\u00e7in mikroarray verilerini veya RNA dizileme verilerini kullanan analitik bir ara\u00e7t\u0131r. PDAC'de diferansiyel olarak ifade edilen genler \u00fczerinde \u00e7ok say\u0131da biyoinformatik analiz yap\u0131lm\u0131\u015f olmas\u0131na ra\u011fmen, \u00f6zellikle bitkisel ila\u00e7lar\u0131n terap\u00f6tik potansiyeli a\u00e7\u0131s\u0131ndan, ba\u011f\u0131\u015f\u0131kl\u0131k mekanizmalar\u0131 ve terap\u00f6tik hedef tahmini konusunda daha derinlemesine ara\u015ft\u0131rma eksikli\u011fi vard\u0131r. Geleneksel \u00c7in t\u0131bb\u0131, PDAC ile ili\u015fkili sar\u0131l\u0131k ve asit gibi yayg\u0131n hastal\u0131klar hakk\u0131nda sistematik bir anlay\u0131\u015f olu\u015fturmu\u015ftur. Ayn\u0131 zamanda, geleneksel \u00c7in t\u0131bb\u0131, \u00e7oklu hedefin do\u011fal avantaj\u0131yla, daha fazla ara\u015ft\u0131rmaya de\u011fer olan karma\u015f\u0131k ba\u011f\u0131\u015f\u0131kl\u0131k mikro ortamlar\u0131na etkili bir \u015fekilde m\u00fcdahale edebilir. Bu nedenle, bu \u00e7al\u0131\u015fmada korelasyon analizi i\u00e7in PDAC hastalar\u0131ndan e\u015fle\u015ftirilmi\u015f doku \u00f6rneklerini se\u00e7mek \u00fczere Gen Expression Omnibus (GEO) veri taban\u0131 kullan\u0131lm\u0131\u015ft\u0131r. Hastal\u0131k mekanizmas\u0131 genetik d\u00fczeyde ara\u015ft\u0131r\u0131lm\u0131\u015f, sa\u011fkal\u0131m farkl\u0131l\u0131klar\u0131 ve ba\u011f\u0131\u015f\u0131kl\u0131k ile ilgili analizler yap\u0131lm\u0131\u015ft\u0131r. PDAC dokular\u0131ndaki imm\u00fcn h\u00fccre infiltrasyon modelini g\u00f6stermek i\u00e7in CIBERSORT dekonvol\u00fcsyon algoritmas\u0131 kullan\u0131lm\u0131\u015ft\u0131r. Son olarak, potansiyel etkili geleneksel \u00c7in ila\u00e7lar\u0131 kapsaml\u0131 bir \u015fekilde tahmin edilmi\u015f ve taranarak klinik ila\u00e7 se\u00e7imi ve geli\u015ftirilmesi i\u00e7in bir temel sa\u011flanm\u0131\u015ft\u0131r.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-7887\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/1-334.png\" alt=\"\" width=\"905\" height=\"830\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/1-334.png 905w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/1-334-768x704.png 768w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/1-334-785x720.png 785w\" sizes=\"(max-width: 905px) 100vw, 905px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-7888\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/2-280.png\" alt=\"\" width=\"904\" height=\"876\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/2-280.png 904w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/2-280-768x744.png 768w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/2-280-743x720.png 743w\" sizes=\"(max-width: 904px) 100vw, 904px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-7889\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/3-261.png\" alt=\"\" width=\"905\" height=\"506\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/3-261.png 905w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/3-261-768x429.png 768w\" sizes=\"(max-width: 905px) 100vw, 905px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-7890\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/4-242.png\" alt=\"\" width=\"905\" height=\"557\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/4-242.png 905w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/4-242-768x473.png 768w\" sizes=\"(max-width: 905px) 100vw, 905px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-7891\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/5-217.png\" alt=\"\" width=\"905\" height=\"628\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/5-217.png 905w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/5-217-768x533.png 768w\" sizes=\"(max-width: 905px) 100vw, 905px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-7892\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/6-198.png\" alt=\"\" width=\"905\" height=\"396\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/6-198.png 905w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/6-198-768x336.png 768w\" sizes=\"(max-width: 905px) 100vw, 905px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-7893\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/7-181.png\" alt=\"\" width=\"905\" height=\"502\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/7-181.png 905w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/7-181-768x426.png 768w\" sizes=\"(max-width: 905px) 100vw, 905px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-7894\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/8-162.png\" alt=\"\" width=\"905\" height=\"625\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/8-162.png 905w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/8-162-768x530.png 768w\" sizes=\"(max-width: 905px) 100vw, 905px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-7895\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/9-147.png\" alt=\"\" width=\"905\" height=\"677\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/9-147.png 905w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/9-147-768x575.png 768w\" sizes=\"(max-width: 905px) 100vw, 905px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-7896\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/10-117.png\" alt=\"\" width=\"905\" height=\"487\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/10-117.png 905w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/10-117-768x413.png 768w\" sizes=\"(max-width: 905px) 100vw, 905px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-7897\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/11-110.png\" alt=\"\" width=\"905\" height=\"440\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/11-110.png 905w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/11-110-768x373.png 768w\" sizes=\"(max-width: 905px) 100vw, 905px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-7898\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/12-91.png\" alt=\"\" width=\"905\" height=\"851\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/12-91.png 905w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/12-91-768x722.png 768w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/12-91-766x720.png 766w\" sizes=\"(max-width: 905px) 100vw, 905px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-7899\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/13-77.png\" alt=\"\" width=\"905\" height=\"598\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/13-77.png 905w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/13-77-768x507.png 768w\" sizes=\"(max-width: 905px) 100vw, 905px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-7900\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/14-59.png\" alt=\"\" width=\"905\" height=\"492\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/14-59.png 905w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/14-59-768x418.png 768w\" sizes=\"(max-width: 905px) 100vw, 905px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-7901\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/15-42.png\" alt=\"\" width=\"905\" height=\"673\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/15-42.png 905w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/15-42-768x571.png 768w\" sizes=\"(max-width: 905px) 100vw, 905px\" \/><br \/>\nG\u00fcn\u00fcm\u00fczde, pankreas kanserinin imm\u00fcnoterapisi baz\u0131 ilerlemeler kaydetmi\u015f ve bu da pankreas kanserinin klinik tedavisine umut getirmi\u015ftir. Bununla birlikte, pankreas kanserinin mikro ortam\u0131 genellikle imm\u00fcnosupresif h\u00fccre \u00e7o\u011falmas\u0131, imm\u00fcn h\u00fccre inaktivasyonu ve d\u00fc\u015f\u00fck t\u00fcm\u00f6r mutasyon y\u00fck\u00fc i\u00e7erdi\u011finden, imm\u00fcnoterapi sonu\u00e7lar\u0131n\u0131n \u00e7o\u011fu tatmin edici de\u011fildir. Y\u00fcksek verimli teknolojinin geli\u015fmesiyle birlikte, Lv ve arkada\u015flar\u0131 pankreas kanserinin diferansiyel \u00e7ekirdek genlerini \u00e7\u0131karmak i\u00e7in \u00e7oklu veri setleri kullanm\u0131\u015f, Xiao ve arkada\u015flar\u0131 geleneksel \u00c7in t\u0131bb\u0131n\u0131 \u00e7\u0131karmak i\u00e7in \"inflamasyon kanseri\" diferansiyel genlerini kullanm\u0131\u015f, vb. bunlar\u0131n hepsi pankreas kanserinin molek\u00fcler mekanizmas\u0131na ili\u015fkin anlay\u0131\u015flar\u0131n\u0131 derinle\u015ftirmi\u015ftir. Bununla birlikte, bu hastal\u0131\u011f\u0131n ba\u011f\u0131\u015f\u0131kl\u0131kla ilgili mekanizmalar\u0131 \u00fczerine yap\u0131lan \u00e7al\u0131\u015fmalar yetersizdir ve bu da hastalar\u0131n uzun vadeli sa\u011fkal\u0131m prognozunu iyile\u015ftirmeye elveri\u015fli de\u011fildir. Bu nedenle, bu \u00e7al\u0131\u015fma, mekanizmalar\u0131 iyile\u015ftirmeyi ve ila\u00e7 geli\u015ftirmeyi te\u015fvik etmeyi ama\u00e7layan, ilgili ba\u011f\u0131\u015f\u0131kl\u0131k infiltrasyon mekanizmalar\u0131n\u0131 ve diferansiyel genlere dayal\u0131 potansiyel etkili geleneksel \u00c7in t\u0131bb\u0131n\u0131 daha fazla ara\u015ft\u0131ran ilk \u00e7al\u0131\u015fmad\u0131r. \u0130lk olarak, bu \u00e7al\u0131\u015fma GEO veri taban\u0131 arac\u0131l\u0131\u011f\u0131yla uygun gen \u00e7iplerini taram\u0131\u015f ve ayn\u0131 hastadan al\u0131nan pankreas t\u00fcm\u00f6r\u00fc ve normal doku \u00f6rneklerinin gen ekspresyon profillerini kar\u015f\u0131la\u015ft\u0131rarak 2653 diferansiyel olarak ifade edilen gen elde etmi\u015ftir. H\u00fccre d\u0131\u015f\u0131 matris dokusu ve kolajen lif dokusu ile ilgili genler (COL1A2, COL1A1, COL3A1, COL5A1, COL5A2), ADAM metallopeptidaz (ADAMTS2), bazal membran polisakkarit (LUM), integrin alt birimi alfa 2 (ITGA2), fibronektin (FN1) ve matris metalloproteinaz (MMP2) dahil olmak \u00fczere PPI arac\u0131l\u0131\u011f\u0131yla \u00e7ekirdek diferansiyel olarak ifade edilen genler tan\u0131mlanm\u0131\u015ft\u0131r. Yukar\u0131da farkl\u0131 \u015fekilde ifade edilen genlerin t\u00fcm\u00f6r dokular\u0131nda yukar\u0131 do\u011fru d\u00fczenlendi\u011fi, kolajen metabolizmas\u0131yla ili\u015fkili oldu\u011fu ve \u00e7o\u011funlukla COL1, COL3 ve COL5 ailelerine ait oldu\u011fu kan\u0131tlanm\u0131\u015ft\u0131r. Bunlar aras\u0131nda, COL1A2'nin ekspresyonunun qRT PCR ile dokuda en y\u00fcksek oldu\u011fu do\u011frulanm\u0131\u015f ve bu sonucun y\u00fcksek g\u00fcvenilirli\u011fini g\u00f6stermi\u015ftir. Di\u011fer solid t\u00fcm\u00f6rlerin aksine, PDAC t\u00fcm\u00f6r mikro\u00e7evresi pankreatik stellat h\u00fccreleri, kanserle ili\u015fkili fibroblastlar, imm\u00fcn h\u00fccreler ve h\u00fccre d\u0131\u015f\u0131 matriksin a\u015f\u0131r\u0131 fibrozisini i\u00e7eren yo\u011fun bir matriks ortam\u0131d\u0131r. Matristeki yo\u011fun fibrozis yan\u0131t\u0131 ve t\u00fcm\u00f6r\u00fcn ba\u011f\u0131\u015f\u0131kl\u0131k ortam\u0131ndaki de\u011fi\u015fiklikler, PDAC tedavisinin mevcut ba\u015far\u0131s\u0131zl\u0131\u011f\u0131n\u0131n ana nedenleri olarak kabul edilmektedir. Daha ileri sa\u011fkal\u0131m analizi, bu \u00e7ekirdek diferansiyel olarak ifade edilen genlerin PDAC hastalar\u0131nda RFS ile \u00f6nemli \u00f6l\u00e7\u00fcde korele oldu\u011funu ve \u00e7e\u015fitli t\u00fcm\u00f6r h\u00fccrelerinin infiltrasyon derecesi ile pozitif korelasyon g\u00f6sterdi\u011fini ortaya koyarak, bu genlerin t\u00fcm\u00f6r imm\u00fcn mikro\u00e7evresini de\u011fi\u015ftirerek PDAC hastalar\u0131n\u0131n klinik prognozuna arac\u0131l\u0131k edebilece\u011fini d\u00fc\u015f\u00fcnd\u00fcrmektedir. Bu noktan\u0131n klinik sonu\u00e7lar\u0131 de\u011fi\u015ftirmek i\u00e7in nas\u0131l kullan\u0131laca\u011f\u0131 olas\u0131 at\u0131l\u0131mlardan biri haline gelmi\u015ftir.<br \/>\nDiferansiyel olarak ifade edilen genlerin daha ileri GO ve KEGG zenginle\u015ftirme analizi, biyolojik s\u00fcre\u00e7lerinin n\u00f6trofil degran\u00fclasyonu, g\u00f6\u00e7, kemokinler, T yard\u0131mc\u0131 h\u00fccre farkl\u0131la\u015fmas\u0131, humoral imm\u00fcn yan\u0131t ve di\u011fer s\u00fcre\u00e7leri i\u00e7erdi\u011fini g\u00f6stermektedir. PDAC mikro\u00e7evresi esasen enflamatuard\u0131r ve kemokinlerin ve di\u011fer fakt\u00f6rlerin t\u00fcm\u00f6rlerin enflamatuar mikro\u00e7evresini destekledi\u011fi ger\u00e7e\u011fi de kan\u0131tlanm\u0131\u015ft\u0131r. Sitokinler ve kemokinlere ek olarak, n\u00f6trofillerin aktivasyonu genellikle ilk molek\u00fcler olayd\u0131r ve bunu t\u00fcm\u00f6r dokusuna do\u011fru g\u00f6\u00e7 takip eder. PDAC kanser h\u00fccrelerinin polimorfon\u00fckleer n\u00f6trofilleri t\u00fcm\u00f6r \u00e7evresine toplayabildi\u011fi, ancak bunlar\u0131n \u00e7o\u011funun anti-t\u00fcm\u00f6r yan\u0131tlar\u0131 \u00fcretemedi\u011fi a\u00e7\u0131kt\u0131r. Tipik olarak, y\u00fcksek n\u00f6trofil bollu\u011fu PDAC'nin ilerlemesini te\u015fvik eder ve k\u00f6t\u00fc prognozla ili\u015fkilidir; Son in vitro deneyler, pankreas kanseri h\u00fccrelerinin n\u00f6trofillerin h\u00fccre d\u0131\u015f\u0131 tuzaklar\u0131n\u0131n olu\u015fumunu ind\u00fckledi\u011fini ve b\u00f6ylece PDAC'nin karaci\u011fer mikrometastaz\u0131n\u0131n olu\u015fumunu te\u015fvik etti\u011fini g\u00f6stermi\u015ftir; Ayn\u0131 zamanda, y\u00fcksek fibrozisin neden oldu\u011fu lokal hipoksi, ba\u011f\u0131\u015f\u0131kl\u0131k ortam\u0131n\u0131 belirler ve reaktif oksijen t\u00fcrlerinin s\u00fcrekli sal\u0131n\u0131m\u0131 lokal hipoksiye yol a\u00e7ar, b\u00f6ylece n\u00f6trofil infiltrasyonunu artt\u0131r\u0131r. Bu nedenle, n\u00f6trofiller pankreas kanserinin mikro\u00e7evresinde \u00e7ok \u00f6nemlidir. Ayr\u0131ca, bu \u00e7al\u0131\u015fman\u0131n sonu\u00e7lar\u0131, farkl\u0131 \u015fekilde ifade edilen genlerin T h\u00fccre farkl\u0131la\u015fmas\u0131 ve humoral imm\u00fcn d\u00fczenlemede do\u011frudan rol oynad\u0131\u011f\u0131n\u0131 g\u00f6stermektedir.<\/p>\n<p>PDAC patogenezinde imm\u00fcn infiltrasyonun rol\u00fcn\u00fc daha fazla ara\u015ft\u0131rmak i\u00e7in, bu \u00e7al\u0131\u015fmada genel t\u00fcm\u00f6r \u00f6rneklerini analiz etmek i\u00e7in CIBERSORT dekonvol\u00fcsyon y\u00f6ntemi kullan\u0131lm\u0131\u015ft\u0131r. Normal pankreas dokusuyla kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda, M2 makrofajlar\u0131 ve istirahat halindeki bellek CD4+T h\u00fccreleri t\u00fcm\u00f6r dokusunda \u00f6nemli \u00f6l\u00e7\u00fcde artarken, CD8+T h\u00fccreleri \u00f6nemli \u00f6l\u00e7\u00fcde azalm\u0131\u015ft\u0131r. Ayn\u0131 e\u011filim e\u015fle\u015ftirilmi\u015f \u00f6rneklerde de g\u00f6zlenmi\u015ftir. M2 makrofajlar\u0131, pankreas kanserinin k\u00f6t\u00fc prognoz g\u00f6stergelerinden biri oldu\u011fu do\u011frulanan t\u00fcm\u00f6r ilerlemesini destekleyen anti-enflamatuar sinyaller \u00fcretir. 2013 y\u0131l\u0131nda, IHC yoluyla PDAC hastalar\u0131nda imm\u00fcn h\u00fccre infiltrasyonunun derecesini g\u00f6zlemleyen bir \u00e7al\u0131\u015fma, daha y\u00fcksek seviyelerde t\u00fcm\u00f6r infiltre eden pan makrofaj M2, Treg ve CD4+T'nin daha k\u0131sa sa\u011fkal\u0131m ile \u00f6nemli \u00f6l\u00e7\u00fcde ili\u015fkili oldu\u011funu g\u00f6stermi\u015ftir. PDAC fare modelinde, t\u00fcm\u00f6rle ili\u015fkili makrofajlar\u0131n sitokinler, proteazlar ve b\u00fcy\u00fcme fakt\u00f6rleri salg\u0131layarak imm\u00fcn bask\u0131lama ve anjiyogeneze arac\u0131l\u0131k etti\u011fi ve t\u00fcm\u00f6r ilerlemesini te\u015fvik etti\u011fi g\u00f6sterilmi\u015ftir. Ayr\u0131ca, CCR2'nin inhibisyonunun kemoterapi etkinli\u011fini art\u0131rd\u0131\u011f\u0131, metastaz\u0131 engelledi\u011fi, radyoterapi etkinli\u011fini art\u0131rd\u0131\u011f\u0131 ve monositlerin t\u00fcm\u00f6r mikro\u00e7evresine al\u0131nmas\u0131n\u0131 engelleyerek T h\u00fccresi imm\u00fcn infiltrasyonunu art\u0131rd\u0131\u011f\u0131 g\u00f6sterilmi\u015ftir. Bu nedenle, makrofajlar\u0131n insan PDAK'\u0131na y\u00f6nelik yeni terap\u00f6tik stratejiler i\u00e7in potansiyel hedefler haline gelme olas\u0131l\u0131\u011f\u0131 y\u00fcksektir. Daha \u00f6nce fibroblastlar ve fibroblastlardan olu\u015fan PDAC imm\u00fcnosupresif mikro\u00e7evresinin T h\u00fccrelerinin infiltrasyonunu s\u0131n\u0131rlayaca\u011f\u0131na inan\u0131l\u0131yordu, ancak son ara\u015ft\u0131rmalar T h\u00fccrelerinin spesifik uzaysal da\u011f\u0131l\u0131m\u0131n\u0131 ortaya \u00e7\u0131karm\u0131\u015ft\u0131r, \u00e7\u00fcnk\u00fc korelasyon \u0131s\u0131 haritas\u0131 pankreas kanseri dokusunda istirahat haf\u0131zas\u0131 CD4+T h\u00fccreleri ile CD8+T h\u00fccreleri aras\u0131nda \u00f6nemli bir negatif korelasyon oldu\u011funu g\u00f6stermektedir (r=-0,64) ve bunun \u00f6zellikle PDAC olmak \u00fczere k\u00f6t\u00fc prognoz g\u00f6stergelerinden biri oldu\u011fu kan\u0131tlanm\u0131\u015ft\u0131r. T\u00fcm\u00f6r dokusunda CD8+T h\u00fccrelerinin infiltrasyonu, t\u00fcm\u00f6r h\u00fccreleri ve hasta sa\u011fkal\u0131m oran\u0131 ile yak\u0131ndan ili\u015fkilidir. Son zamanlarda akademisyenler, uzun s\u00fcreli sa\u011fkalanlarda ba\u015far\u0131l\u0131 bir ba\u011f\u0131\u015f\u0131kl\u0131k olu\u015fturman\u0131n t\u00fcm\u00f6r i\u00e7inde y\u00fcksek miktarda CD8+T h\u00fccresi gerektirdi\u011fini vurgulam\u0131\u015flard\u0131r. CD8+T h\u00fccrelerinin itici fakt\u00f6rlerinin ve CD8+T h\u00fccrelerinin infiltrasyon mekanizmas\u0131n\u0131n anla\u015f\u0131lmas\u0131, PDAC tedavi planlar\u0131n\u0131n daha da geli\u015ftirilmesi i\u00e7in \u00e7ok \u00f6nemlidir. \u015eu anda, PDAC imm\u00fcn infiltrasyon h\u00fccreleri aras\u0131ndaki ili\u015fkinin geni\u015f \u00f6l\u00e7ekli do\u011frulamas\u0131 eksiktir ve bu tahminin belirli bir referans \u00f6nemi vard\u0131r.<br \/>\nGeleneksel \u00c7in t\u0131bb\u0131nda PDAC, \"dalak birikimi\", \"hedeflenen qi\", \"birikim\", \"qi durgunlu\u011fu\" ve \"fu liang\" kategorilerine aittir. Vaka serisi literat\u00fcr ara\u015ft\u0131rmas\u0131 ve meta-analiz sonu\u00e7lar\u0131, PDAC i\u00e7in kombine geleneksel \u00c7in t\u0131bb\u0131 tedavisinin hasta mortalitesini etkili bir \u015fekilde azaltabilece\u011fini ve uzun vadeli prognozu iyile\u015ftirebilece\u011fini g\u00f6stermektedir. Son temel ara\u015ft\u0131rmalar, PDAC tedavisinde geleneksel \u00c7in t\u0131bb\u0131 mekanizmas\u0131n\u0131n esas olarak t\u00fcm\u00f6r mikro\u00e7evresini iyile\u015ftirerek dolayl\u0131 olarak t\u0131bbi sonu\u00e7lar\u0131 iyile\u015ftirdi\u011fini ortaya koymu\u015ftur. Bu nedenle, t\u00fcm\u00f6r imm\u00fcn mikro\u00e7evresinin ara\u015ft\u0131r\u0131lmas\u0131, etkili geleneksel \u00c7in t\u0131bb\u0131 bulmak i\u00e7in \u00e7ok \u00f6nemlidir. \u015eu anda, geleneksel \u00c7in t\u0131bb\u0131nda PDAC patogenezinin \u00e7o\u011funlukla nemli \u0131s\u0131 ve toksin birikimine odaklanan \"k\u00f6ken eksikli\u011fi ama \u00f6z fazlal\u0131\u011f\u0131\" oldu\u011funa inan\u0131lmaktad\u0131r. Ancak bu \u00e7al\u0131\u015fma, geleneksel \u00c7in t\u0131bb\u0131n\u0131n etkinli\u011finin esas olarak \u0131s\u0131 temizleme (Scutellaria baicalensis, Sagittaria angustifolia, \u015fakay\u0131k kabu\u011fu, mor ot vb.) kategorisine ait oldu\u011funu ve bunu geleneksel \u00c7in t\u0131bb\u0131n\u0131n patogenezine uygun tonik ila\u00e7lar\u0131n (ginseng, eucommia ulmoides, limon otu, kaplumba\u011fa kabu\u011fu, e\u015fek derisi tutkal\u0131 vb. Hastal\u0131\u011f\u0131n yeri a\u00e7\u0131s\u0131ndan bak\u0131ld\u0131\u011f\u0131nda, eski \u00c7in t\u0131bb\u0131 kitaplar\u0131ndaki anatomik yer ve fizyolojik i\u015flev tan\u0131mlar\u0131yla kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda, \u00e7o\u011fu bilim adam\u0131 pankreas\u0131n be\u015f organ aras\u0131nda dala\u011fa atfedilmesini desteklemektedir. Ancak bu \u00e7al\u0131\u015fma, geleneksel \u00c7in t\u0131bb\u0131n\u0131n etkili tahminlerinin b\u00fcy\u00fck \u00e7o\u011funlu\u011funun karaci\u011fer meridyenine ait oldu\u011funu, bunu akci\u011fer ve b\u00f6brek meridyenlerinin izledi\u011fini g\u00f6stermekte ve belki de karaci\u011fer teorisinden gelen nemli \u0131s\u0131n\u0131n dalak eksikli\u011fine yard\u0131mc\u0131 olmakla birlikte tedavi edilmesinin tedavi etkinli\u011fini daha da art\u0131rabilece\u011fini d\u00fc\u015f\u00fcnd\u00fcrmektedir. Ara\u015ft\u0131rman\u0131n ard\u0131ndan, bu teorinin da\u011f\u0131n\u0131k deneyimlere ve inceleme raporlar\u0131na sahip oldu\u011fu ve sistematik bir anlay\u0131\u015f olu\u015fturmak i\u00e7in daha fazla ara\u015ft\u0131rmaya de\u011fer oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. Buna ek olarak, bu \u00e7al\u0131\u015fmada birka\u00e7 geleneksel \u00c7in ilac\u0131 elde etmek i\u00e7in ters tahmin kullan\u0131lm\u0131\u015ft\u0131r. Y\u00fcksek korelasyona sahip \u00c7in t\u0131bb\u0131 s\u0131ralar\u0131 aras\u0131nda, ginsenosidlerin MMP2 ve di\u011fer fakt\u00f6rlerin ekspresyonunu a\u015fa\u011f\u0131 \u00e7ekerek anjiyogenezi ve t\u00fcm\u00f6r h\u00fccresi beslenme kayna\u011f\u0131n\u0131 azaltabilece\u011fi bulunmu\u015ftur; Curcumin, Wnt\/\u03b2 - Catenin sinyal yolunun aktivitesi yoluyla PDAC k\u00f6k h\u00fccrelerinin kendini yenilemesini inhibe eder ve PDAC subkutan transplant t\u00fcm\u00f6r modeli dokusunda lokal mikrosirk\u00fclasyonu iyile\u015ftirebilir, t\u00fcm\u00f6r mikro\u00e7evresinde kan ve oksijen tedarikini art\u0131rabilir ve t\u00fcm\u00f6r h\u00fccrelerinin ve stromal h\u00fccrelerin hipoksik stres yan\u0131t\u0131n\u0131 inhibe edebilir; Yukar\u0131daki literat\u00fcr, bu \u00e7al\u0131\u015fman\u0131n \u00f6ng\u00f6r\u00fclen sonu\u00e7lar\u0131ndan baz\u0131lar\u0131n\u0131 desteklemektedir, ancak PDAC'nin geleneksel \u00c7in t\u0131bb\u0131 tedavisi ile ilgili ba\u011f\u0131\u015f\u0131kl\u0131k mekanizmalar\u0131 konusunda hala ara\u015ft\u0131rma eksikli\u011fi vard\u0131r.<br \/>\nBu \u00e7al\u0131\u015fma, gen \u00e7iplerini tararken ba\u011f\u0131\u015f\u0131kl\u0131k mekanizmas\u0131 analizindeki bireysel farkl\u0131l\u0131klar\u0131 dikkate alm\u0131\u015f ve e\u015fle\u015ftirilmi\u015f \u00f6rnek analizi kullanarak PDAC deneysel verilerini titizlikle taram\u0131\u015ft\u0131r. Ayn\u0131 zamanda, bu \u00e7al\u0131\u015fman\u0131n esasen \u00f6nceki tek GSE verilerinin ikincil bir madencili\u011fi oldu\u011fu d\u00fc\u015f\u00fcn\u00fcld\u00fc\u011f\u00fcnde, \u00e7ekirdek diferansiyel olarak ifade edilen genlerin ifadesini do\u011frulamak i\u00e7in farkl\u0131 seviyeler kullan\u0131lm\u0131\u015f ve risk azalt\u0131lm\u0131\u015ft\u0131r. Bununla birlikte, bu \u00e7al\u0131\u015fma hala a\u015fa\u011f\u0131daki eksikliklere sahiptir: (1) K\u00fc\u00e7\u00fck \u00f6rneklem boyutu nedeniyle, veri analizinin belirli \u00f6nyarg\u0131lar\u0131 vard\u0131r ve sonraki a\u015famada analiz i\u00e7in gereksinimleri kar\u015f\u0131layan daha fazla veri seti dahil edilecektir; (2) CIBERSORT dekonvol\u00fcsyon algoritmas\u0131 analizi, h\u00fccresel heterotipik etkile\u015fimlerden, hastal\u0131\u011f\u0131 tetikleyen fakt\u00f6rlerden ve hastal\u0131k fenotiplerinin plastisitesinden sapabilen s\u0131n\u0131rl\u0131 genetik verilere dayanmaktad\u0131r. Klinik ve temel \u00e7al\u0131\u015fmalar bireysel ba\u011f\u0131\u015f\u0131kl\u0131k durumunu daha kapsaml\u0131 ve objektif bir \u015fekilde yans\u0131tabilir. \u00d6zetle, bu \u00e7al\u0131\u015fma PDAC'nin imm\u00fcn infiltrasyon mekanizmas\u0131n\u0131 ke\u015ffetmek ve bu alanda gelecekteki ara\u015ft\u0131rmalar i\u00e7in belirli bir de\u011fere sahip olan potansiyel etkili geleneksel \u00c7in ila\u00e7lar\u0131n\u0131 tahmin etmek i\u00e7in CIBERSORT dekonvol\u00fcsyon algoritmas\u0131 ile birlikte biyoinformatik tekniklerini kullanan ilk \u00e7al\u0131\u015fmad\u0131r.<\/p>","protected":false},"excerpt":{"rendered":"<p>Predicting Targeted Traditional Chinese Medicine by Differential Genes and Immune Invasion Mechanism of pancreatic cancer Based on Bioinformatics Screening The global burden of pancreatic ductal adenocarcinoma (PDAC) has more than doubled in the past 25 years, and it is expected to become the second leading cause of cancer-related deaths by 2030. The average five-year survival [&hellip;]<\/p>","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[20],"tags":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v23.0 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Predicting Targeted Traditional Chinese Medicine by Differential Genes and Immune Invasion Mechanism of pancreatic cancer Based on Bioinformatics Screening - China Chemical Manufacturer<\/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:\/\/longchangextracts.com\/tr\/bioinformatics-screening\/\" \/>\n<meta property=\"og:locale\" content=\"tr_TR\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Predicting Targeted Traditional Chinese Medicine by Differential Genes and Immune Invasion Mechanism of pancreatic cancer Based on Bioinformatics Screening - China Chemical Manufacturer\" \/>\n<meta property=\"og:description\" content=\"Predicting Targeted Traditional Chinese Medicine by Differential Genes and Immune Invasion Mechanism of pancreatic cancer Based on Bioinformatics Screening The global burden of pancreatic ductal adenocarcinoma (PDAC) has more than doubled in the past 25 years, and it is expected to become the second leading cause of cancer-related deaths by 2030. 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