{"id":3717,"date":"2024-08-03T07:33:30","date_gmt":"2024-08-03T07:33:30","guid":{"rendered":"https:\/\/longchangextracts.com\/?p=3717"},"modified":"2024-08-03T07:33:30","modified_gmt":"2024-08-03T07:33:30","slug":"glycolysis-cml","status":"publish","type":"post","link":"https:\/\/longchangextracts.com\/hu\/glycolysis-cml\/","title":{"rendered":"A glikol\u00edzis r\u00e9szv\u00e9tel\u00e9nek vizsg\u00e1lata a kr\u00f3nikus myeloid leuk\u00e9mi\u00e1s sejtek prolifer\u00e1ci\u00f3j\u00e1nak ceramid \u00e1ltali g\u00e1tl\u00e1s\u00e1nak szab\u00e1lyoz\u00e1s\u00e1ban"},"content":{"rendered":"<p>A glikol\u00edzis r\u00e9szv\u00e9tel\u00e9nek vizsg\u00e1lata a kr\u00f3nikus myeloid leuk\u00e9mi\u00e1s sejtek prolifer\u00e1ci\u00f3j\u00e1nak ceramid \u00e1ltali g\u00e1tl\u00e1s\u00e1nak szab\u00e1lyoz\u00e1s\u00e1ban<br \/>\nA kr\u00f3nikus myelog\u00e9n leuk\u00e9mia (CML) a csontvel\u0151sejtek klon\u00e1lis proliferat\u00edv leuk\u00e9mi\u00e1ja, amely a feln\u0151ttkori leuk\u00e9mi\u00e1s esetek k\u00f6r\u00fclbel\u00fcl 15%-j\u00e9t teszi ki. \u00c9ves el\u0151fordul\u00e1si ar\u00e1nya 2\/100000, magas az 50~55 \u00e9vesek k\u00f6r\u00e9ben. A kr\u00f3nikus myeloid leuk\u00e9mia a BCR-ABL1 f\u00fazi\u00f3s feh\u00e9rje Philadelphia kromosz\u00f3ma transzlok\u00e1ci\u00f3n kereszt\u00fcl t\u00f6rt\u00e9n\u0151 kialakul\u00e1s\u00e1val j\u00e1r\u00f3 daganat. Jelenleg f\u0151k\u00e9nt tirozinkin\u00e1z-g\u00e1tl\u00f3 (TKI) c\u00e9lzott gy\u00f3gyszereket haszn\u00e1lnak a kezel\u00e9sre, amelyek jelent\u0151sen jav\u00edthatj\u00e1k a CML betegek progn\u00f3zis\u00e1t. Tov\u00e1bbra is fenn\u00e1ll azonban a TKI-rezisztencia visszat\u00e9r\u0151 probl\u00e9m\u00e1ja, amelyet a BCR-ABL1 onkog\u00e9n tirozinkin\u00e1z g\u00e9nj\u00e9nek instabilit\u00e1sa okoz. A hagyom\u00e1nyos k\u00ednai gy\u00f3gy\u00e1szat ter\u00e1pi\u00e1s hat\u00e1ssal van a CML-re, p\u00e9ld\u00e1ul fokozza a kemoter\u00e1pia hat\u00e9konys\u00e1g\u00e1t \u00e9s jav\u00edtja a szervezet immunfunkci\u00f3j\u00e1t. A hagyom\u00e1nyos k\u00ednai orvosl\u00e1sban tal\u00e1lhat\u00f3 CML-ellenes vezet\u0151 vegy\u00fcletek felfedez\u00e9se \u00e9s hat\u00e1smechanizmusuk elemz\u00e9se \u00faj \u00f6tleteket \u00e9s k\u00eds\u00e9rleti alapokat ny\u00fajthat a CML kezel\u00e9s\u00e9hez.<\/p>\n<p>A rokaglamid (RocA), amely a Spartina alterniflora hagyom\u00e1nyos k\u00ednai gy\u00f3gyn\u00f6v\u00e9ny \u00e1gaib\u00f3l \u00e9s leveleib\u0151l sz\u00e1rmazik, egy ciklopent\u00e1n benzofur\u00e1n v\u00e1zat tartalmaz\u00f3 term\u00e9szetes term\u00e9k. Olyan funkci\u00f3kkal rendelkezik, mint a l\u00e9gz\u0151szervi betegs\u00e9gek, p\u00e9ld\u00e1ul a k\u00f6h\u00f6g\u00e9s \u00e9s az asztma megel\u0151z\u00e9se \u00e9s kezel\u00e9se, gyullad\u00e1sos b\u0151rbetegs\u00e9gek, gyullad\u00e1scs\u00f6kkent\u0151 hat\u00e1sok, a gy\u00f3gyszerk\u00e1rosod\u00e1s cs\u00f6kkent\u00e9se, neuroprotekt\u00edv \u00e9s daganatellenes hat\u00e1sok. Kor\u00e1bbi tanulm\u00e1nyok meg\u00e1llap\u00edtott\u00e1k, hogy a ceramid nanomol\u00e1ris koncentr\u00e1ci\u00f3ban g\u00e1tolja a tumorsejtek n\u00f6veked\u00e9s\u00e9t \u00e9s szaporod\u00e1s\u00e1t. A tumorellenes mechanizmusa els\u0151sorban a tumorsejtek eIF4E \u00e9s eIF4A transzl\u00e1ci\u00f3s inici\u00e1ci\u00f3s faktorainak g\u00e1tl\u00e1s\u00e1ban, a sejtciklus blokkol\u00e1s\u00e1ban az ATM\/ATR-Chk1\/CHK2 ellen\u0151rz\u0151pont \u00fatvonal aktiv\u00e1l\u00e1s\u00e1val, valamint a tumorsejtek aktiv\u00e1l\u00e1s\u00e1ban \u00e1ll, an\u00e9lk\u00fcl, hogy befoly\u00e1soln\u00e1 a norm\u00e1l sejtek MAPK p38 \u00e9s JNK \u00fatvonal\u00e1t. A leg\u00fajabb vizsg\u00e1latok szerint a szulfonamid jav\u00edthatja a kemoter\u00e1pia hat\u00e9konys\u00e1g\u00e1t \u00e9s fokozhatja a leuk\u00e9mi\u00e1s sejtek \u00e9rz\u00e9kenys\u00e9g\u00e9t. T\u00f6bb tanulm\u00e1ny is kimutatta, hogy a szulfonamid nagy potenci\u00e1llal rendelkezik, mint kis molekul\u00e1j\u00fa vegy\u00fcletjel\u00f6lt a daganatellenes gy\u00f3gyszerek fejleszt\u00e9s\u00e9hez.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3718\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/1-2.png\" alt=\"\" width=\"1040\" height=\"402\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/1-2.png 1040w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/1-2-768x297.png 768w\" sizes=\"(max-width: 1040px) 100vw, 1040px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3719\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/2-1.png\" alt=\"\" width=\"1024\" height=\"336\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/2-1.png 1024w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/2-1-768x252.png 768w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3720\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/3-1.png\" alt=\"\" width=\"1002\" height=\"462\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/3-1.png 1002w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/3-1-768x354.png 768w\" sizes=\"(max-width: 1002px) 100vw, 1002px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3721\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/4-2.png\" alt=\"\" width=\"1058\" height=\"444\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/4-2.png 1058w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/4-2-768x322.png 768w\" sizes=\"(max-width: 1058px) 100vw, 1058px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3722\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/5-2.png\" alt=\"\" width=\"554\" height=\"474\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3723\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/6-2.png\" alt=\"\" width=\"982\" height=\"338\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/6-2.png 982w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/6-2-768x264.png 768w\" sizes=\"(max-width: 982px) 100vw, 982px\" \/><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-3724\" src=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/7-1.png\" alt=\"\" width=\"1036\" height=\"746\" srcset=\"https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/7-1.png 1036w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/7-1-768x553.png 768w, https:\/\/longchangextracts.com\/wp-content\/uploads\/2024\/08\/7-1-1000x720.png 1000w\" sizes=\"(max-width: 1036px) 100vw, 1036px\" \/>Egyes tumorsejtek metabolikus v\u00e1ltoz\u00e1sokon mennek kereszt\u00fcl, hogy kiel\u00e9g\u00edts\u00e9k a t\u00fal\u00e9l\u00e9shez \u00e9s a gyors prolifer\u00e1ci\u00f3hoz sz\u00fcks\u00e9ges energia- \u00e9s bioszintetikus sz\u00fcks\u00e9gleteiket, \u00e9s az aerob glikol\u00edzis megn\u00f6vekedett szintje (azaz a Wolberg-effektus) a tumorsejtek egyik metabolikus markere. Az aerob glikol\u00edzis a leuk\u00e9mia szelekt\u00edv beavatkoz\u00e1s\u00e1nak fontos c\u00e9lpontj\u00e1v\u00e1 v\u00e1lt. Nem vil\u00e1gos, hogy a szulfonamid g\u00e1tolja-e a CML prolifer\u00e1ci\u00f3j\u00e1t a CML glikol\u00edzis\u00e9nek szab\u00e1lyoz\u00e1s\u00e1val. Ez a tanulm\u00e1ny a K562-es CML-sejtvonalat haszn\u00e1lja sejtmodellk\u00e9nt a ceramid CML-sejtek prolifer\u00e1ci\u00f3j\u00e1ra \u00e9s glikol\u00edzis\u00e9re gyakorolt hat\u00e1s\u00e1nak vizsg\u00e1lat\u00e1ra, \u00e9s felt\u00e1rja az aerob glikol\u00edzis szab\u00e1lyoz\u00f3 szerep\u00e9t a CML-sejtek prolifer\u00e1ci\u00f3j\u00e1nak ceramid \u00e1ltali g\u00e1tl\u00e1s\u00e1ban.<br \/>\nA melitamid a rizs orchide\u00e1b\u00f3l kivont hat\u00f3anyag, amely daganatellenes hat\u00e1ssal rendelkezik. Ez a cikk azt vizsg\u00e1lja, hogy a szulfonamid g\u00e1tolja-e a K562 sejtek prolifer\u00e1ci\u00f3j\u00e1t az aerob glikol\u00edzisen kereszt\u00fcl. Az MTT-vizsg\u00e1lat eredm\u00e9nyei azt mutatt\u00e1k, hogy a K562 sejtek n\u00f6veked\u00e9s\u00e9t \u00e9s prolifer\u00e1ci\u00f3j\u00e1t a Melitamid id\u0151- \u00e9s koncentr\u00e1ci\u00f3f\u00fcgg\u0151 m\u00f3don jelent\u0151sen g\u00e1tolta, \u00e9s a K562 sejtek prolifer\u00e1ci\u00f3j\u00e1nak g\u00e1tl\u00e1s\u00e1ra szolg\u00e1l\u00f3 IC50 \u00e9rt\u00e9ke el\u00e9rte a nanomol\u00e1ris szintet. Az \u00e1raml\u00e1si citometri\u00e1s technol\u00f3gia alkalmaz\u00e1sa kimutatta, hogy az azepam g\u00e1tolja a K562 sejtek prolifer\u00e1ci\u00f3j\u00e1t \u00e9s apopt\u00f3zist induk\u00e1l, blokkolva a sejtciklus G2\/M f\u00e1zis\u00e1t.<br \/>\nA tumorsejtek aerob k\u00f6r\u00fclm\u00e9nyek k\u00f6z\u00f6tt is magas gl\u00fck\u00f3zfelv\u00e9telt, glikol\u00edzist \u00e9s lakt\u00e1tszintet mutatnak, ami a Warburg-effektus n\u00e9ven ismert. A c-Myc transzkripci\u00f3s faktor sz\u00e9les k\u00f6rben r\u00e9szt vesz az olyan sejtfunkci\u00f3k szab\u00e1lyoz\u00e1s\u00e1ban, mint a sejtprolifer\u00e1ci\u00f3, a sejtek t\u00fal\u00e9l\u00e9se, a sz\u00f6veti remodelling \u00e9s az angiogenezis, valamint a tumorsejtek metabolikus \u00e1tprogramoz\u00e1s\u00e1t is elind\u00edtja. A c-Myc felszab\u00e1lyozza a gl\u00fck\u00f3z transzportereket \u00e9s szinte az \u00f6sszes glikolitikus enzimet, ez\u00e1ltal el\u0151seg\u00edti a tumorsejtek gl\u00fck\u00f3z-anyagcser\u00e9j\u00e9t. A 13C-jel\u00f6lt gl\u00fck\u00f3z kimutatta, hogy a c-Myc el\u0151seg\u00edti a gl\u00fck\u00f3zfogyaszt\u00e1st Burkitt-limf\u00f3m\u00e1ban \u00e9s c-Myc \u00e1ltal vez\u00e9relt m\u00e1jr\u00e1kban. A kutat\u00e1sok meg\u00e1llap\u00edtott\u00e1k, hogy a c-Myc el\u0151seg\u00edti a lakt\u00e1t kiv\u00e1laszt\u00e1s\u00e1t, amely nemcsak a glikol\u00edzisben r\u00e9szt vev\u0151 anyagcsere-anyag, hanem r\u00e9szt vesz az angiogenezis, az immunmenek\u00fcl\u00e9s, a sejtmigr\u00e1ci\u00f3, a metabolikus ig\u00e9nybev\u00e9tel \u00e9s m\u00e1s r\u00e1kkelt\u0151 hat\u00e1sok el\u0151seg\u00edt\u00e9s\u00e9ben is. A K562 sejtek gl\u00fck\u00f3z-\u00e9heztet\u00e9ses kezel\u00e9s\u00e9vel meg\u00e1llap\u00edtottuk, hogy a gl\u00fck\u00f3z elt\u00e1vol\u00edt\u00e1sa cs\u00f6kkentette a lakt\u00e1ttermel\u00e9s szintj\u00e9t \u00e9s a c-Myc feh\u00e9rje expresszi\u00f3s szintj\u00e9t, \u00e9s nem volt kedvez\u0151 a K562 sejtek prolifer\u00e1ci\u00f3j\u00e1ra. Ez meger\u0151s\u00edti, hogy a K562 sejtek n\u00f6veked\u00e9se \u00e9s prolifer\u00e1ci\u00f3ja a gl\u00fck\u00f3zell\u00e1t\u00e1st\u00f3l f\u00fcgg, ami t\u00fckr\u00f6zi a K562 sejtek c-Myc szintje \u00e9s gl\u00fck\u00f3zszintje k\u00f6z\u00f6tti \u00f6sszef\u00fcgg\u00e9st. \u00c9hez\u00e9si k\u00f6r\u00fclm\u00e9nyek k\u00f6z\u00f6tt azt tal\u00e1ltuk, hogy a formamid relat\u00edv g\u00e1tl\u00e1si ar\u00e1nya a K562 sejteken a gl\u00fck\u00f3z elt\u00e1vol\u00edt\u00e1sa ut\u00e1n alacsonyabb volt, mint a gl\u00fck\u00f3z hozz\u00e1ad\u00e1s\u00e1val kezelt csoportban. Ez\u00e9rt felt\u00e9telezhet\u0151, hogy a formamid K562-sejtek n\u00f6veked\u00e9s\u00e9nek g\u00e1tl\u00e1sa r\u00e9szben gl\u00fck\u00f3zf\u00fcgg\u0151, ami azt jelenti, hogy a formamid gl\u00fck\u00f3zell\u00e1t\u00e1s n\u00e9lk\u00fcl nem k\u00e9pes tov\u00e1bbi n\u00f6veked\u00e9si g\u00e1tl\u00e1st el\u0151id\u00e9zni a K562-sejtekben. A melitamid a K562 sejtek fel\u00fcl\u00fasz\u00f3j\u00e1ban a gl\u00fck\u00f3zfogyaszt\u00e1s \u00e9s a lakt\u00e1ttermel\u00e9s szintj\u00e9t is jelent\u0151sen cs\u00f6kkentette, ami arra utal, hogy a melitamid g\u00e1tolta az aerob glikol\u00edzist a K562 sejtekben.<br \/>\nA hexokin\u00e1z 2 (HK2) a tumorsejtek glikol\u00edzis\u00e9nek specifikus kulcsenzime, amely a k\u00fcls\u0151 mitokondri\u00e1lis membr\u00e1nhoz k\u00f6t\u0151dve k\u00e9pes fenntartani a tumorsejtek nagy sebess\u00e9g\u0171 aerob glikol\u00edzis\u00e9t, \u00e9s energi\u00e1t szolg\u00e1ltat a tumorsejtek gyors prolifer\u00e1ci\u00f3j\u00e1hoz. A kutat\u00f3k eg\u00e9rmodellek seg\u00edts\u00e9g\u00e9vel igazolt\u00e1k, hogy a HK2 fontos szerepet j\u00e1tszik az eml\u0151r\u00e1k, a t\u00fcd\u0151r\u00e1k \u00e9s m\u00e1s daganatok kialakul\u00e1s\u00e1ban \u00e9s fejl\u0151d\u00e9s\u00e9ben; A hexokin\u00e1z 1 (HK1) sz\u00e9les k\u00f6rben kifejez\u0151dik a feln\u0151tt sz\u00f6vetekben, \u00e9s a hexokin\u00e1z h\u00e1ztart\u00e1si alt\u00edpus\u00e1nak tekinthet\u0151; A foszfofruktokin\u00e1z P (PFKP) d\u00f6nt\u0151 szerepet j\u00e1tszik a r\u00e1k kialakul\u00e1s\u00e1ban \u00e9s \u00e1tt\u00e9tk\u00e9pz\u0151d\u00e9s\u00e9ben. Egyes tanulm\u00e1nyok kimutatt\u00e1k, hogy a PFKP potenci\u00e1lisan diagnosztikai marker vagy gy\u00f3gyszerc\u00e9lpont lehet az eml\u0151r\u00e1k \u00e9s a t\u00fcd\u0151r\u00e1k eset\u00e9ben; a piruv\u00e1t-kin\u00e1z 2 (PKM2) minden olyan sejtben expressz\u00e1l\u00f3dik, ahol magas a nukleinsavszint\u00e9zis sebess\u00e9ge, p\u00e9ld\u00e1ul a norm\u00e1l prolifer\u00e1l\u00f3 sejtekben, az embrion\u00e1lis sejtekben \u00e9s k\u00fcl\u00f6n\u00f6sen a tumorsejtekben; a lakt\u00e1t-dehidrogen\u00e1z A (LDHA) kataliz\u00e1lja a piruv\u00e1t \u00e9s az L-tejsav k\u00f6lcs\u00f6n\u00f6s \u00e1talakul\u00e1s\u00e1t. Sz\u00e1mos hum\u00e1n tumorsejt LDHA-szintje magasabb, mint a norm\u00e1l sejtek\u00e9. Az LDHA g\u00e1tl\u00e1sa cs\u00f6kkentheti a daganatos sejtek, p\u00e9ld\u00e1ul a fej- \u00e9s nyaki r\u00e1k, a hasny\u00e1lmirigyr\u00e1k, a m\u00e9hnyakr\u00e1k \u00e9s a prosztatar\u00e1k prolifer\u00e1ci\u00f3j\u00e1t. Elemezt\u00fck a ceramid hat\u00e1s\u00e1t a HK2, HK1, PFKP, PKM2, LDHA \u00e9s az onkog\u00e9n transzkripci\u00f3s faktor c-Myc feh\u00e9rje expresszi\u00f3s szintj\u00e9re K562 sejtekben, \u00e9s azt tal\u00e1ltuk, hogy a ceramid alig szab\u00e1lyozta a HK1, PFKP, PKM2 \u00e9s LDHA feh\u00e9rje expresszi\u00f3s szintj\u00e9t, de jelent\u0151sen lefel\u00e9 szab\u00e1lyozta a c-Myc \u00e9s HK2 feh\u00e9rje expresszi\u00f3s szintj\u00e9t. Felt\u00e9telezz\u00fck, hogy a melinamid a c-Myc \u00e9s a HK2 downregul\u00e1l\u00e1s\u00e1val \u00e9s az aerob glikol\u00edzis \u00fatvonalainak g\u00e1tl\u00e1s\u00e1val fejti ki K562 sejtek elleni hat\u00e1s\u00e1t. A c-Myc \u00e9s a HK2 k\u00f6z\u00f6tti szab\u00e1lyoz\u00e1si kapcsolat tov\u00e1bbi felt\u00e1r\u00e1st ig\u00e9nyel.<\/p>\n<p>&nbsp;<\/p>","protected":false},"excerpt":{"rendered":"<p>Study on the involvement of glycolysis in regulating the inhibition of proliferation of chronic myeloid leukemia cells by ceramide Chronic myelogenous leukemia (CML) is a clonal proliferative leukemia of bone marrow cells, accounting for about 15% of adult leukemia cases. Its annual incidence rate is 2\/100000, high in people aged 50~55 years. Chronic myeloid leukemia [&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>Study on the involvement of glycolysis in regulating the inhibition of proliferation of chronic myeloid leukemia cells by ceramide - 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\/glycolysis-cml\/\" \/>\n<meta property=\"og:locale\" content=\"hu_HU\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Study on the involvement of glycolysis in regulating the inhibition of proliferation of chronic myeloid leukemia cells by ceramide - China Chemical Manufacturer\" \/>\n<meta property=\"og:description\" content=\"Study on the involvement of glycolysis in regulating the inhibition of proliferation of chronic myeloid leukemia cells by ceramide Chronic myelogenous leukemia (CML) is a clonal proliferative leukemia of bone marrow cells, accounting for about 15% of adult leukemia cases. 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