{"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\/hu\/bioinformatics-screening\/","title":{"rendered":"C\u00e9lzott hagyom\u00e1nyos k\u00ednai gy\u00f3gyszerek el\u0151rejelz\u00e9se a hasny\u00e1lmirigyr\u00e1k differenci\u00e1lis g\u00e9njei \u00e9s immuninv\u00e1zi\u00f3s mechanizmusa alapj\u00e1n bioinformatikai sz\u0171r\u00e9s alapj\u00e1n"},"content":{"rendered":"<p>C\u00e9lzott hagyom\u00e1nyos k\u00ednai gy\u00f3gyszerek el\u0151rejelz\u00e9se a hasny\u00e1lmirigyr\u00e1k differenci\u00e1lis g\u00e9njei \u00e9s immuninv\u00e1zi\u00f3s mechanizmusa alapj\u00e1n bioinformatikai sz\u0171r\u00e9s alapj\u00e1n<br \/>\nA hasny\u00e1lmirigyduktus adenokarcin\u00f3ma (PDAC) glob\u00e1lis terhe az elm\u00falt 25 \u00e9vben t\u00f6bb mint k\u00e9tszeres\u00e9re n\u0151tt, \u00e9s 2030-ra v\u00e1rhat\u00f3an a r\u00e1k okozta hal\u00e1loz\u00e1sok m\u00e1sodik vezet\u0151 ok\u00e1v\u00e1 v\u00e1lik. A PDAC-betegek \u00e1tlagos \u00f6t\u00e9ves t\u00fal\u00e9l\u00e9si ar\u00e1nya mind\u00f6ssze 8%, \u00e9s a betegek 71%-\u00e9nek m\u00e9g a teljes seb\u00e9szi elt\u00e1vol\u00edt\u00e1s ut\u00e1n is fenn\u00e1ll a ki\u00fajul\u00e1s kock\u00e1zata. A magas letalit\u00e1si \u00e9s magas ki\u00fajul\u00e1si ar\u00e1ny tumorjellemz\u0151j\u00e9t a PDAC szoros m\u00e1trixkomponense (fizikai g\u00e1t) hat\u00e1rozza meg, amely megakad\u00e1lyozza az immunhat\u00e1s\u00fa sejtek besziv\u00e1rg\u00e1s\u00e1t a tumorba, \u00e9s lehet\u0151v\u00e9 teszi a hasny\u00e1lmirigyr\u00e1kos sejtek sz\u00e1m\u00e1ra, hogy elker\u00fclj\u00e9k az immunfel\u00fcgyeletet. Jelenleg sz\u00e1mos klinikai vizsg\u00e1lat pr\u00f3b\u00e1lja jav\u00edtani a PDAC betegek \u00e1ltal\u00e1nos hat\u00e9konys\u00e1g\u00e1t immunter\u00e1pi\u00e1val, bele\u00e9rtve az immunellen\u0151rz\u00e9si pont g\u00e1tl\u00f3kat, a r\u00e1k elleni vakcin\u00e1kat, az adopt\u00edv sejtmetaszt\u00e1zisokat stb. A monoklon\u00e1lis antitestter\u00e1pia klinikai hat\u00e9konys\u00e1ga gyenge, \u00e9s nem siker\u00fclt \u00e1tt\u00f6r\u00e9st el\u00e9rni.<\/p>\n<p>A nagy \u00e1tereszt\u0151k\u00e9pess\u00e9g\u0171 genetikai elemz\u00e9sek megjelen\u00e9s\u00e9vel a g\u00e9nexpresszi\u00f3s profilok hat\u00e9kony m\u00f3dszerr\u00e9 v\u00e1ltak a k\u00fcl\u00f6nb\u00f6z\u0151 betegs\u00e9gekben differenci\u00e1lisan kifejez\u0151d\u0151 g\u00e9nek azonos\u00edt\u00e1s\u00e1ra. A CIBERSORT egy olyan analitikai eszk\u00f6z, amely a microarray-adatok vagy az RNS-szekven\u00e1l\u00e1si adatok felhaszn\u00e1l\u00e1s\u00e1val \u00e9rt\u00e9keli az immunsejtek expresszi\u00f3j\u00e1t egy mint\u00e1ban, \u00e9s k\u00fcl\u00f6nb\u00f6z\u0151 immunsejt-ar\u00e1nyokat kap. B\u00e1r t\u00f6bb bioinformatikai elemz\u00e9st v\u00e9geztek a PDAC-ban differenci\u00e1lisan kifejezett g\u00e9nekr\u0151l, hi\u00e1nyzik az immunmechanizmusok \u00e9s a ter\u00e1pi\u00e1s c\u00e9lpontok el\u0151rejelz\u00e9s\u00e9nek tov\u00e1bbi m\u00e9lyrehat\u00f3 kutat\u00e1sa, k\u00fcl\u00f6n\u00f6sen a n\u00f6v\u00e9nyi gy\u00f3gyszerek ter\u00e1pi\u00e1s potenci\u00e1lj\u00e1nak tekintet\u00e9ben. A hagyom\u00e1nyos k\u00ednai orvosl\u00e1s szisztematikus meg\u00e9rt\u00e9st alak\u00edtott ki az olyan gyakori betegs\u00e9gekr\u0151l, mint a PDAC-hez t\u00e1rsul\u00f3 s\u00e1rgas\u00e1g \u00e9s aszcitisz. Ugyanakkor a hagyom\u00e1nyos k\u00ednai orvosl\u00e1s a t\u00f6bbc\u00e9l\u00fas\u00e1g term\u00e9szetes el\u0151ny\u00e9vel hat\u00e9konyan beavatkozhat a komplex immunmikrok\u00f6rnyezetbe, ami tov\u00e1bbi kutat\u00e1st \u00e9rdemel. Ez\u00e9rt ez a tanulm\u00e1ny a Gene Expression Omnibus (GEO) adatb\u00e1zist haszn\u00e1lta fel a PDAC betegek p\u00e1ros\u00edtott sz\u00f6vetmint\u00e1inak kiv\u00e1laszt\u00e1s\u00e1ra a korrel\u00e1ci\u00f3s elemz\u00e9shez. A betegs\u00e9g mechanizmus\u00e1t genetikai szinten vizsg\u00e1ltuk, t\u00fal\u00e9l\u00e9si k\u00fcl\u00f6nbs\u00e9geket \u00e9s immunrendszerrel kapcsolatos elemz\u00e9seket v\u00e9gezt\u00fcnk. A CIBERSORT dekonvol\u00faci\u00f3s algoritmust haszn\u00e1lt\u00e1k az immunsejtek besziv\u00e1rg\u00e1si mint\u00e1zat\u00e1nak \u00e1br\u00e1zol\u00e1s\u00e1ra a PDAC-sz\u00f6vetekben. V\u00e9g\u00fcl a potenci\u00e1lisan hat\u00e9kony hagyom\u00e1nyos k\u00ednai gy\u00f3gyszereket \u00e1tfog\u00f3an megj\u00f3solt\u00e1k \u00e9s \u00e1tvil\u00e1g\u00edtott\u00e1k, ami alapot szolg\u00e1ltatott a klinikai gy\u00f3gyszerkiv\u00e1laszt\u00e1shoz \u00e9s -fejleszt\u00e9shez.<\/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 \/>\nJelenleg a hasny\u00e1lmirigyr\u00e1k immunter\u00e1pi\u00e1ja n\u00e9mi el\u0151rel\u00e9p\u00e9st \u00e9rt el, ami rem\u00e9nyt adott a hasny\u00e1lmirigyr\u00e1k klinikai kezel\u00e9s\u00e9nek. Mivel azonban a hasny\u00e1lmirigyr\u00e1k mikrok\u00f6rnyezete \u00e1ltal\u00e1ban immunszuppressz\u00edv sejtburj\u00e1nz\u00e1st, immunsejt-inaktiv\u00e1ci\u00f3t \u00e9s alacsony tumormut\u00e1ci\u00f3s terhel\u00e9st tartalmaz, az immunter\u00e1pia eredm\u00e9nyei t\u00f6bbnyire nem kiel\u00e9g\u00edt\u0151ek. A nagy \u00e1tereszt\u0151k\u00e9pess\u00e9g\u0171 technol\u00f3gia fejl\u0151d\u00e9s\u00e9vel Lv et al. t\u00f6bb adatk\u00e9szletet haszn\u00e1lt a hasny\u00e1lmirigyr\u00e1k differenci\u00e1lis magg\u00e9njeinek b\u00e1ny\u00e1szat\u00e1hoz, Xiao et al. \"gyullad\u00e1sos r\u00e1k\" differenci\u00e1lis g\u00e9neket haszn\u00e1lt a hagyom\u00e1nyos k\u00ednai orvosl\u00e1s b\u00e1ny\u00e1szat\u00e1hoz stb., amelyek mind elm\u00e9ly\u00edtett\u00e9k a hasny\u00e1lmirigyr\u00e1k molekul\u00e1ris mechanizmus\u00e1nak meg\u00e9rt\u00e9s\u00e9t. A betegs\u00e9g immunrendszerrel kapcsolatos mechanizmusaival kapcsolatos munka azonban el\u00e9gtelen, ami nem seg\u00edti el\u0151 a betegek hossz\u00fa t\u00e1v\u00fa t\u00fal\u00e9l\u00e9si progn\u00f3zis\u00e1nak jav\u00edt\u00e1s\u00e1t. Ez\u00e9rt ez a tanulm\u00e1ny az els\u0151, amely tov\u00e1bb vizsg\u00e1lja a relev\u00e1ns immunsz\u0171r\u0151 mechanizmusokat \u00e9s a potenci\u00e1lisan hat\u00e9kony hagyom\u00e1nyos k\u00ednai orvosl\u00e1st a differenci\u00e1lis g\u00e9nek alapj\u00e1n, azzal a c\u00e9llal, hogy jav\u00edtsa a mechanizmusokat \u00e9s el\u0151seg\u00edtse a gy\u00f3gyszerfejleszt\u00e9st. El\u0151sz\u00f6r is, ez a tanulm\u00e1ny a GEO-adatb\u00e1zison kereszt\u00fcl sz\u0171rte a megfelel\u0151 g\u00e9nchipeket, \u00e9s \u00f6sszehasonl\u00edtotta a hasny\u00e1lmirigy-tumor \u00e9s az azonos egy\u00e9ni betegb\u0151l sz\u00e1rmaz\u00f3 norm\u00e1l sz\u00f6vetmint\u00e1k g\u00e9nexpresszi\u00f3s profiljait, 2653 differenci\u00e1lisan kifejezett g\u00e9nt kapva. A legfontosabb differenci\u00e1lisan expressz\u00e1lt g\u00e9neket PPI seg\u00edts\u00e9g\u00e9vel azonos\u00edtott\u00e1k, bele\u00e9rtve az extracellul\u00e1ris m\u00e1trixsz\u00f6vethez \u00e9s a kollag\u00e9nsz\u00e1lakhoz kapcsol\u00f3d\u00f3 sz\u00f6veti g\u00e9neket (COL1A2, COL1A1, COL3A1, COL5A1, COL5A2), ADAM metallopeptid\u00e1zt (ADAMTS2), baz\u00e1lmembr\u00e1n poliszacharidot (LUM), integrin alegys\u00e9g alfa 2 (ITGA2), fibronektint (FN1) \u00e9s m\u00e1trix metalloprotein\u00e1zt (MMP2). A fenti differenci\u00e1lisan expressz\u00e1l\u00f3d\u00f3 g\u00e9nekr\u0151l bebizonyosodott, hogy a tumorsz\u00f6vetekben felfel\u00e9 szab\u00e1lyozottak, a kollag\u00e9n anyagcser\u00e9vel kapcsolatosak, \u00e9s t\u00f6bbnyire a COL1, COL3 \u00e9s COL5 csal\u00e1dokba tartoznak. K\u00f6z\u00fcl\u00fck qRT PCR seg\u00edts\u00e9g\u00e9vel a COL1A2 expresszi\u00f3ja bizonyult a legmagasabbnak a sz\u00f6vetben, ami az eredm\u00e9ny nagyfok\u00fa megb\u00edzhat\u00f3s\u00e1g\u00e1t jelzi. M\u00e1s szolid tumorokt\u00f3l elt\u00e9r\u0151en a PDAC tumor mikrok\u00f6rnyezete s\u0171r\u0171 m\u00e1trixk\u00f6rnyezet, amely hasny\u00e1lmirigy-csillagsejteket, r\u00e1khoz kapcsol\u00f3d\u00f3 fibroblasztokat, immunsejteket \u00e9s az extracellul\u00e1ris m\u00e1trix t\u00falzott m\u00e9rt\u00e9k\u0171 fibr\u00f3zis\u00e1t tartalmazza. A m\u00e1trix s\u0171r\u0171 fibr\u00f3zisv\u00e1lasz\u00e1t \u00e9s a tumor immunk\u00f6rnyezet\u00e9nek v\u00e1ltoz\u00e1sait tartj\u00e1k a PDAC kezel\u00e9s jelenlegi sikertelens\u00e9g\u00e9nek f\u0151 ok\u00e1nak. A tov\u00e1bbi t\u00fal\u00e9l\u00e9si elemz\u00e9s kimutatta, hogy ezek a k\u00f6zponti differenci\u00e1lisan expressz\u00e1l\u00f3d\u00f3 g\u00e9nek szignifik\u00e1nsan korrel\u00e1lnak a PDAC betegek RFS-\u00e9vel, \u00e9s pozit\u00edvan korrel\u00e1lnak a k\u00fcl\u00f6nb\u00f6z\u0151 tumorsejtek infiltr\u00e1ci\u00f3j\u00e1nak m\u00e9rt\u00e9k\u00e9vel, ami arra utal, hogy ezek a g\u00e9nek k\u00f6zvet\u00edthetik a PDAC betegek klinikai progn\u00f3zis\u00e1t a tumor immunmikrok\u00f6rnyezet\u00e9nek megv\u00e1ltoztat\u00e1s\u00e1val. Az egyik lehets\u00e9ges \u00e1tt\u00f6r\u00e9ss\u00e9 v\u00e1lt, hogyan lehet ezt a pontot a klinikai eredm\u00e9nyek megv\u00e1ltoztat\u00e1s\u00e1ra felhaszn\u00e1lni.<br \/>\nA differenci\u00e1lisan expressz\u00e1lt g\u00e9nek tov\u00e1bbi GO \u00e9s KEGG gazdagod\u00e1si elemz\u00e9se arra utal, hogy biol\u00f3giai folyamataik neutrofil degranul\u00e1ci\u00f3val, migr\u00e1ci\u00f3val, kemokinekkel, T-helper sejtek differenci\u00e1l\u00f3d\u00e1s\u00e1val, humor\u00e1lis immunv\u00e1laszokkal \u00e9s m\u00e1s folyamatokkal kapcsolatosak. A PDAC mikrok\u00f6rnyezete alapvet\u0151en gyullad\u00e1sos, \u00e9s az is bizony\u00edtott t\u00e9ny, hogy a kemokinek \u00e9s m\u00e1s t\u00e9nyez\u0151k el\u0151seg\u00edtik a daganatok gyullad\u00e1sos mikrok\u00f6rnyezet\u00e9t. A citokinek \u00e9s kemokinek mellett gyakran a neutrofilek aktiv\u00e1ci\u00f3ja az els\u0151 molekul\u00e1ris esem\u00e9ny, amelyet a tumorsz\u00f6vet fel\u00e9 t\u00f6rt\u00e9n\u0151 migr\u00e1ci\u00f3 k\u00f6vet. Egy\u00e9rtelm\u0171, hogy a PDAC r\u00e1kos sejtek k\u00e9pesek polimorfonukle\u00e1ris neutrofileket toborozni a tumor k\u00f6zel\u00e9be, de t\u00f6bbs\u00e9g\u00fck nem k\u00e9pes tumorellenes v\u00e1laszt produk\u00e1lni. Jellemz\u0151en a neutrofilek nagysz\u00e1m\u00fa el\u0151fordul\u00e1sa el\u0151seg\u00edti a PDAC progresszi\u00f3j\u00e1t, \u00e9s rossz progn\u00f3zissal j\u00e1r egy\u00fctt; A leg\u00fajabb in vitro k\u00eds\u00e9rletek kimutatt\u00e1k, hogy a hasny\u00e1lmirigyr\u00e1kos sejtek a neutrofilek extracellul\u00e1ris csapd\u00e1inak kialakul\u00e1s\u00e1t induk\u00e1lj\u00e1k, ez\u00e1ltal el\u0151seg\u00edtik a PDAC m\u00e1j-mikrometaszt\u00e1zis\u00e1nak el\u0151fordul\u00e1s\u00e1t; Ugyanakkor a magas fibr\u00f3zis okozta helyi hipoxia meghat\u00e1rozza az immunk\u00f6rnyezetet, \u00e9s a reakt\u00edv oxig\u00e9nfajok folyamatos felszabadul\u00e1sa helyi hipoxi\u00e1hoz vezet, \u00edgy fokozza a neutrofil infiltr\u00e1ci\u00f3t. Ez\u00e9rt a neutrofilek kulcsfontoss\u00e1g\u00faak a hasny\u00e1lmirigyr\u00e1k mikrok\u00f6rnyezet\u00e9ben. Ezen t\u00falmen\u0151en, e tanulm\u00e1ny eredm\u00e9nyei arra utalnak, hogy a differenci\u00e1lisan expressz\u00e1l\u00f3d\u00f3 g\u00e9nek k\u00f6zvetlen\u00fcl r\u00e9szt vesznek a T-sejtek differenci\u00e1l\u00f3d\u00e1s\u00e1ban \u00e9s a humor\u00e1lis immunrendszer szab\u00e1lyoz\u00e1s\u00e1ban.<\/p>\n<p>Az immuninfiltr\u00e1ci\u00f3nak a PDAC patogenezis\u00e9ben j\u00e1tszott szerep\u00e9nek tov\u00e1bbi felt\u00e1r\u00e1sa \u00e9rdek\u00e9ben ez a tanulm\u00e1ny a CIBERSORT dekonvol\u00faci\u00f3s m\u00f3dszert alkalmazta a teljes tumormint\u00e1k elemz\u00e9s\u00e9hez. A norm\u00e1l hasny\u00e1lmirigysz\u00f6vethez k\u00e9pest az M2 makrof\u00e1gok \u00e9s a nyugalmi mem\u00f3ria CD4+T sejtek szignifik\u00e1nsan megn\u00f6vekedtek a tumorsz\u00f6vetben, m\u00edg a CD8+T sejtek szignifik\u00e1nsan cs\u00f6kkentek. Ugyanez a tendencia volt megfigyelhet\u0151 a p\u00e1ros\u00edtott mint\u00e1kban is. Az M2 makrof\u00e1gok gyullad\u00e1scs\u00f6kkent\u0151 jeleket termelnek, amelyek el\u0151seg\u00edtik a tumor progresszi\u00f3j\u00e1t, ami meger\u0151s\u00edt\u00e9st nyert, hogy a hasny\u00e1lmirigyr\u00e1k rossz progn\u00f3zis\u00e1nak egyik indik\u00e1tora. 2013-ban egy tanulm\u00e1ny, amely az immunsejtek besz\u0171r\u0151d\u00e9s\u00e9nek m\u00e9rt\u00e9k\u00e9t figyelte meg PDAC betegekn\u00e9l IHC seg\u00edts\u00e9g\u00e9vel, kimutatta, hogy a tumorba besz\u0171r\u0151d\u0151 M2 p\u00e1n makrof\u00e1gok, Tregek \u00e9s CD4+T magasabb szintje szignifik\u00e1nsan \u00f6sszef\u00fcgg\u00f6tt a r\u00f6videbb t\u00fal\u00e9l\u00e9ssel. PDAC eg\u00e9rmodellben kimutatt\u00e1k, hogy a tumorhoz t\u00e1rsul\u00f3 makrof\u00e1gok citokinek, prote\u00e1zok \u00e9s n\u00f6veked\u00e9si faktorok felszabad\u00edt\u00e1s\u00e1val immunszupresszi\u00f3t \u00e9s angiogenezist k\u00f6zvet\u00edtenek, \u00e9s el\u0151seg\u00edtik a tumor progresszi\u00f3j\u00e1t. Tov\u00e1bb\u00e1 a CCR2 g\u00e1tl\u00e1sa bizony\u00edtottan fokozza a kemoter\u00e1pia hat\u00e9konys\u00e1g\u00e1t, g\u00e1tolja az \u00e1tt\u00e9tk\u00e9pz\u0151d\u00e9st, fokozza a sug\u00e1rter\u00e1pia hat\u00e9konys\u00e1g\u00e1t, \u00e9s n\u00f6veli a T-sejtes immuninfiltr\u00e1ci\u00f3t az\u00e1ltal, hogy g\u00e1tolja a monocit\u00e1k toborz\u00e1s\u00e1t a tumor mikrok\u00f6rnyezet\u00e9be. Ez\u00e9rt a makrof\u00e1gok nagy val\u00f3sz\u00edn\u0171s\u00e9ggel a hum\u00e1n PDAC \u00faj ter\u00e1pi\u00e1s strat\u00e9gi\u00e1inak potenci\u00e1lis c\u00e9lpontjai lesznek. Kor\u00e1bban \u00fagy v\u00e9lt\u00e9k, hogy a PDAC fibroblasztokb\u00f3l \u00e9s fibroblasztokb\u00f3l \u00e1ll\u00f3 immunszuppressz\u00edv mikrok\u00f6rnyezete korl\u00e1tozza a T-sejtek besziv\u00e1rg\u00e1s\u00e1t, de a leg\u00fajabb kutat\u00e1sok felt\u00e1rt\u00e1k a T-sejtek specifikus t\u00e9rbeli eloszl\u00e1s\u00e1t, mivel a korrel\u00e1ci\u00f3s h\u0151t\u00e9rk\u00e9p azt mutatja, hogy a hasny\u00e1lmirigyr\u00e1k sz\u00f6vet\u00e9ben a nyugalmi mem\u00f3ria CD4 + T-sejtek \u00e9s a CD8 + T-sejtek k\u00f6z\u00f6tt szignifik\u00e1ns negat\u00edv korrel\u00e1ci\u00f3 van (r = - 0,64), ami bizony\u00edtottan a rossz progn\u00f3zis, k\u00fcl\u00f6n\u00f6sen a PDAC egyik mutat\u00f3ja. A CD8+T sejtek besziv\u00e1rg\u00e1sa a tumorsz\u00f6vetbe szoros kapcsolatban \u00e1ll a tumorsejtekkel \u00e9s a betegek t\u00fal\u00e9l\u00e9si ar\u00e1ny\u00e1val. A k\u00f6zelm\u00faltban a tud\u00f3sok hangs\u00falyozt\u00e1k, hogy a hossz\u00fa t\u00e1v\u00fa t\u00fal\u00e9l\u0151kben a sikeres immunit\u00e1s kialak\u00edt\u00e1s\u00e1hoz a CD8+T-sejtek nagysz\u00e1m\u00fa el\u0151fordul\u00e1sa sz\u00fcks\u00e9ges a tumoron bel\u00fcl. A CD8+T sejtek hajt\u00f3 t\u00e9nyez\u0151inek \u00e9s a CD8+T sejtek besziv\u00e1rg\u00e1si mechanizmus\u00e1nak meg\u00e9rt\u00e9se kulcsfontoss\u00e1g\u00fa a PDAC kezel\u00e9si tervek tov\u00e1bbfejleszt\u00e9s\u00e9hez. Jelenleg hi\u00e1nyzik a PDAC immunrendszerbe besziv\u00e1rg\u00f3 sejtek k\u00f6z\u00f6tti \u00f6sszef\u00fcgg\u00e9s nagyszab\u00e1s\u00fa valid\u00e1l\u00e1sa, \u00e9s ennek az el\u0151rejelz\u00e9snek van bizonyos referenci\u00e1lis jelent\u0151s\u00e9ge.<br \/>\nA PDAC a hagyom\u00e1nyos k\u00ednai orvosl\u00e1sban a \"l\u00e9p felhalmoz\u00f3d\u00e1sa\", a \"c\u00e9lzott qi\", a \"felhalmoz\u00f3d\u00e1s\", a \"qi stagn\u00e1l\u00e1sa\" \u00e9s a \"fu liang\" kateg\u00f3ri\u00e1j\u00e1ba tartozik. Az esetsorozatos irodalomkutat\u00e1s \u00e9s a metaanal\u00edzis eredm\u00e9nyei arra utalnak, hogy a PDAC kombin\u00e1lt hagyom\u00e1nyos k\u00ednai gy\u00f3gy\u00e1szati kezel\u00e9se hat\u00e9konyan cs\u00f6kkentheti a betegek hal\u00e1loz\u00e1s\u00e1t \u00e9s jav\u00edthatja a hossz\u00fa t\u00e1v\u00fa progn\u00f3zist. A leg\u00fajabb alapkutat\u00e1sok felt\u00e1rt\u00e1k, hogy a hagyom\u00e1nyos k\u00ednai orvosl\u00e1s mechanizmusa a PDAC kezel\u00e9s\u00e9ben els\u0151sorban a tumor mikrok\u00f6rnyezet\u00e9nek jav\u00edt\u00e1s\u00e1n kereszt\u00fcl, k\u00f6zvetve jav\u00edtva az orvosi eredm\u00e9nyeket. Ez\u00e9rt a tumor immunmikrok\u00f6rnyezet\u00e9nek felt\u00e1r\u00e1sa kulcsfontoss\u00e1g\u00fa a hat\u00e9kony hagyom\u00e1nyos k\u00ednai orvosl\u00e1s megtal\u00e1l\u00e1s\u00e1hoz. Jelenleg a PDAC patogenezis\u00e9t a hagyom\u00e1nyos k\u00ednai orvosl\u00e1sban t\u00f6bbnyire \u00fagy v\u00e9lik, hogy az \"eredet hi\u00e1nya, de a l\u00e9nyeg feleslege\", a nedves h\u0151 \u00e9s a toxin felhalmoz\u00f3d\u00e1s\u00e1ra \u00f6sszpontos\u00edtva. Ez a tanulm\u00e1ny azonban azt j\u00f3solja, hogy a hagyom\u00e1nyos k\u00ednai orvosl\u00e1s hat\u00e9konys\u00e1ga els\u0151sorban a h\u0151tiszt\u00edt\u00f3 gy\u00f3gyszerek (Scutellaria baicalensis, Sagittaria angustifolia, bazsar\u00f3zsa k\u00e9reg, lila f\u0171 stb.) kateg\u00f3ri\u00e1j\u00e1ba tartozik, amelyet a toniz\u00e1l\u00f3 gy\u00f3gyszerek (ginzeng, eucommia ulmoides, citromf\u0171, tekn\u0151sb\u00e9kap\u00e1nc\u00e9l, szam\u00e1rb\u0151r ragaszt\u00f3 stb.) k\u00f6vetnek, ami megfelel a hagyom\u00e1nyos k\u00ednai orvosl\u00e1s patogenezis\u00e9nek. A betegs\u00e9g elhelyezked\u00e9se szempontj\u00e1b\u00f3l, \u00f6sszehasonl\u00edtva az anat\u00f3miai elhelyezked\u00e9s \u00e9s a fiziol\u00f3giai funkci\u00f3 le\u00edr\u00e1s\u00e1val az \u0151si k\u00ednai orvosl\u00e1s k\u00f6nyveiben, a legt\u00f6bb tud\u00f3s t\u00e1mogatja a hasny\u00e1lmirigynek az \u00f6t szerv k\u00f6z\u00fcl a l\u00e9phez val\u00f3 hozz\u00e1rendel\u00e9s\u00e9t. Ez a tanulm\u00e1ny azonban azt mutatja, hogy a hagyom\u00e1nyos k\u00ednai orvosl\u00e1s hat\u00e9kony el\u0151rejelz\u00e9seinek t\u00falnyom\u00f3 t\u00f6bbs\u00e9ge a m\u00e1j meridi\u00e1nhoz tartozik, amelyet a t\u00fcd\u0151 \u00e9s a vese meridi\u00e1nok k\u00f6vetnek, ami arra utal, hogy tal\u00e1n a m\u00e1jelm\u00e9letb\u0151l sz\u00e1rmaz\u00f3 nedves h\u0151 kezel\u00e9se a l\u00e9p hi\u00e1ny\u00e1nak seg\u00edt\u00e9s\u00e9vel kombin\u00e1lva tov\u00e1bb jav\u00edthatja a kezel\u00e9s hat\u00e9konys\u00e1g\u00e1t. A keres\u00e9s ut\u00e1n kider\u00fclt, hogy ez az elm\u00e9let elsz\u00f3rt tapasztalatokkal \u00e9s fel\u00fclvizsg\u00e1lati jelent\u00e9sekkel rendelkezik, \u00e9s \u00e9rdemes tov\u00e1bb vizsg\u00e1lni a szisztematikus meg\u00e9rt\u00e9s kialak\u00edt\u00e1sa \u00e9rdek\u00e9ben. Ezenk\u00edv\u00fcl ez a tanulm\u00e1ny ford\u00edtott el\u0151rejelz\u00e9st haszn\u00e1lt sz\u00e1mos hagyom\u00e1nyos k\u00ednai gy\u00f3gyszer megszerz\u00e9s\u00e9hez. A magas korrel\u00e1ci\u00f3val rendelkez\u0151 k\u00ednai gy\u00f3gyszerk\u00e9sz\u00edtm\u00e9nyek sorai k\u00f6z\u00fcl kider\u00fclt, hogy a ginsenozidok cs\u00f6kkenthetik az angiogenezist \u00e9s a tumorsejtek t\u00e1pl\u00e1l\u00e9kell\u00e1t\u00e1s\u00e1t az MMP2 \u00e9s m\u00e1s t\u00e9nyez\u0151k expresszi\u00f3j\u00e1nak visszaszor\u00edt\u00e1s\u00e1val; A kurkumin g\u00e1tolja a PDAC \u0151ssejtek \u00f6nmeg\u00fajul\u00e1s\u00e1t a Wnt \/ \u03b2 - Catenin jel\u00e1tviteli \u00fatvonal aktivit\u00e1s\u00e1n kereszt\u00fcl, \u00e9s jav\u00edthatja a helyi mikrocirkul\u00e1ci\u00f3t a PDAC szubkut\u00e1n transzplant\u00e1ci\u00f3s tumormodell sz\u00f6vet\u00e9ben, n\u00f6velheti a v\u00e9r- \u00e9s oxig\u00e9nell\u00e1t\u00e1st a tumor mikrok\u00f6rnyezet\u00e9ben, \u00e9s g\u00e1tolja a tumorsejtek \u00e9s a strom\u00e1lis sejtek hipoxikus stresszv\u00e1lasz\u00e1t; A fenti irodalom t\u00e1mogatja e tanulm\u00e1ny n\u00e9h\u00e1ny el\u0151re jelzett eredm\u00e9ny\u00e9t, de m\u00e9g mindig hi\u00e1nyzik a PDAC hagyom\u00e1nyos k\u00ednai gy\u00f3gy\u00e1szati kezel\u00e9s\u00e9vel kapcsolatos immunmechanizmusok kutat\u00e1sa.<br \/>\nEz a tanulm\u00e1ny a g\u00e9nchipek sz\u0171r\u00e9sekor figyelembe vette az immunmechanizmusok elemz\u00e9s\u00e9nek egy\u00e9ni k\u00fcl\u00f6nbs\u00e9geit, \u00e9s a PDAC k\u00eds\u00e9rleti adatait p\u00e1ros\u00edtott mintaelemz\u00e9ssel szigor\u00faan \u00e1tvil\u00e1g\u00edtotta. Ugyanakkor, figyelembe v\u00e9ve, hogy ez a tanulm\u00e1ny l\u00e9nyeg\u00e9ben a kor\u00e1bbi egyedi GSE-adatok m\u00e1sodlagos b\u00e1ny\u00e1szata, k\u00fcl\u00f6nb\u00f6z\u0151 szinteket haszn\u00e1ltak a k\u00f6zponti differenci\u00e1lisan expressz\u00e1lt g\u00e9nek expresszi\u00f3j\u00e1nak ellen\u0151rz\u00e9s\u00e9re, cs\u00f6kkentve a kock\u00e1zatot. Ennek a tanulm\u00e1nynak azonban m\u00e9g mindig megvannak a k\u00f6vetkez\u0151 hi\u00e1nyoss\u00e1gai: (1) A kis mintam\u00e9ret miatt az adatelemz\u00e9snek van bizonyos torz\u00edt\u00e1sa, \u00e9s a k\u00e9s\u0151bbi szakaszban t\u00f6bb, a k\u00f6vetelm\u00e9nyeknek megfelel\u0151 adatk\u00e9szletet vonnak be az elemz\u00e9sbe; (2) A CIBERSORT dekonvol\u00faci\u00f3s algoritmus elemz\u00e9se korl\u00e1tozott genetikai adatokon alapul, amelyek elt\u00e9rhetnek a sejtes heterot\u00edpusos k\u00f6lcs\u00f6nhat\u00e1sokt\u00f3l, a betegs\u00e9get kiv\u00e1lt\u00f3 t\u00e9nyez\u0151kt\u0151l \u00e9s a betegs\u00e9g fenot\u00edpusainak plaszticit\u00e1s\u00e1t\u00f3l. A klinikai \u00e9s alapkutat\u00e1sok \u00e1tfog\u00f3bban \u00e9s objekt\u00edvebben t\u00fckr\u00f6zhetik az egy\u00e9ni immunst\u00e1tuszt. \u00d6sszefoglalva, ez a tanulm\u00e1ny az els\u0151, amely bioinformatikai technik\u00e1kat haszn\u00e1l a CIBERSORT dekonvol\u00faci\u00f3s algoritmussal kombin\u00e1lva a PDAC immunsz\u0171r\u0151 mechanizmus\u00e1nak felt\u00e1r\u00e1s\u00e1ra \u00e9s a potenci\u00e1lisan hat\u00e9kony hagyom\u00e1nyos k\u00ednai gy\u00f3gyszerek el\u0151rejelz\u00e9s\u00e9re, ami bizonyos \u00e9rt\u00e9kkel b\u00edr az e ter\u00fcleten v\u00e9gzett j\u00f6v\u0151beli kutat\u00e1sok sz\u00e1m\u00e1ra.<\/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\/hu\/bioinformatics-screening\/\" \/>\n<meta property=\"og:locale\" content=\"hu_HU\" \/>\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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