{"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\/tr\/glycolysis-cml\/","title":{"rendered":"Seramid taraf\u0131ndan kronik miyeloid l\u00f6semi h\u00fccrelerinin \u00e7o\u011falmas\u0131n\u0131n inhibisyonunun d\u00fczenlenmesinde glikolizin kat\u0131l\u0131m\u0131 \u00fczerine \u00e7al\u0131\u015fma"},"content":{"rendered":"<p>Seramid taraf\u0131ndan kronik miyeloid l\u00f6semi h\u00fccrelerinin \u00e7o\u011falmas\u0131n\u0131n inhibisyonunun d\u00fczenlenmesinde glikolizin kat\u0131l\u0131m\u0131 \u00fczerine \u00e7al\u0131\u015fma<br \/>\nKronik miyelojen\u00f6z l\u00f6semi (KML) kemik ili\u011fi h\u00fccrelerinin klonal proliferatif bir l\u00f6semisidir ve yeti\u015fkin l\u00f6semi vakalar\u0131n\u0131n yakla\u015f\u0131k 15%'sini olu\u015fturur. Y\u0131ll\u0131k g\u00f6r\u00fclme oran\u0131 2\/100000 olup, 50~55 ya\u015flar\u0131ndaki ki\u015filerde y\u00fcksektir. Kronik miyeloid l\u00f6semi, Philadelphia kromozom translokasyonu yoluyla BCR-ABL1 f\u00fczyon proteini olu\u015fumu ile ili\u015fkili bir t\u00fcm\u00f6rd\u00fcr. \u015eu anda, tirozin kinaz inhibit\u00f6r\u00fc (TKI) hedefli ila\u00e7lar esas olarak tedavi i\u00e7in kullan\u0131lmaktad\u0131r ve bu da KML hastalar\u0131n\u0131n prognozunu \u00f6nemli \u00f6l\u00e7\u00fcde iyile\u015ftirebilir. Bununla birlikte, BCR-ABL1 onkogeninin tirozin kinaz geninin instabilitesinin neden oldu\u011fu TKI direncinin n\u00fcks sorunu hala mevcuttur. Geleneksel \u00c7in t\u0131bb\u0131n\u0131n KML \u00fczerinde kemoterapi etkinli\u011fini artt\u0131rmak ve v\u00fccudun ba\u011f\u0131\u015f\u0131kl\u0131k fonksiyonunu iyile\u015ftirmek gibi terap\u00f6tik etkileri vard\u0131r. Geleneksel \u00c7in t\u0131bb\u0131nda anti KML \u00f6nc\u00fc bile\u015fiklerinin ke\u015ffedilmesi ve etki mekanizmalar\u0131n\u0131n analiz edilmesi, KML tedavisi i\u00e7in yeni fikirler ve deneysel temeller sa\u011flayabilir.<\/p>\n<p>Geleneksel \u00c7in t\u0131bb\u0131 bitkisi Spartina alterniflora'n\u0131n dal ve yapraklar\u0131ndan elde edilen Rocaglamide (RocA), siklopentan benzofuran iskeleti i\u00e7eren do\u011fal bir \u00fcr\u00fcnd\u00fcr. \u00d6ks\u00fcr\u00fck ve ast\u0131m gibi solunum yolu hastal\u0131klar\u0131n\u0131 \u00f6nleme ve tedavi etme, iltihapl\u0131 cilt hastal\u0131klar\u0131, anti-enflamatuar etkiler, ila\u00e7 hasar\u0131n\u0131 azaltma, n\u00f6roproteksiyon ve anti-t\u00fcm\u00f6r etkileri gibi i\u015flevlere sahiptir. \u00d6nceki \u00e7al\u0131\u015fmalar seramidin nanomolar konsantrasyonlarda t\u00fcm\u00f6r h\u00fccrelerinin b\u00fcy\u00fcmesini ve \u00e7o\u011falmas\u0131n\u0131 engelledi\u011fini bulmu\u015ftur. Anti-t\u00fcm\u00f6r mekanizmas\u0131 temel olarak t\u00fcm\u00f6r h\u00fccrelerinin translasyon ba\u015flatma fakt\u00f6rleri eIF4E ve eIF4A'y\u0131 inhibe etmeyi, ATM\/ATR-Chk1\/CHK2 kontrol noktas\u0131 yolunu aktive ederek h\u00fccre d\u00f6ng\u00fcs\u00fcn\u00fc bloke etmeyi ve normal h\u00fccrelerin MAPK p38 ve JNK yollar\u0131n\u0131 etkilemeden t\u00fcm\u00f6r h\u00fccrelerini aktive etmeyi i\u00e7erir. Son \u00e7al\u0131\u015fmalar, s\u00fclfonamidin kemoterapi etkinli\u011fini art\u0131rabilece\u011fini ve l\u00f6semi h\u00fccrelerinin duyarl\u0131l\u0131\u011f\u0131n\u0131 art\u0131rabilece\u011fini bulmu\u015ftur. \u00c7ok say\u0131da \u00e7al\u0131\u015fma, s\u00fclfonamidin anti-t\u00fcm\u00f6r ila\u00e7lar\u0131n\u0131n geli\u015ftirilmesi i\u00e7in aday k\u00fc\u00e7\u00fck molek\u00fcll\u00fc bir bile\u015fik olarak b\u00fcy\u00fck bir potansiyele sahip oldu\u011funu g\u00f6stermi\u015ftir.<\/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\" \/>Baz\u0131 t\u00fcm\u00f6r h\u00fccreleri, hayatta kalmak ve h\u0131zl\u0131 \u00e7o\u011falmak i\u00e7in enerji ve biyosentetik ihtiya\u00e7lar\u0131n\u0131 kar\u015f\u0131lamak \u00fczere metabolik de\u011fi\u015fikliklere u\u011frar ve aerobik glikoliz seviyelerindeki art\u0131\u015f (yani Wolberg etkisi) t\u00fcm\u00f6r h\u00fccrelerinin metabolik belirte\u00e7lerinden biridir. Aerobik glikoliz, l\u00f6semide se\u00e7ici m\u00fcdahale i\u00e7in \u00f6nemli bir hedef haline gelmi\u015ftir. S\u00fclfonamidin KML glikolizini d\u00fczenleyerek KML proliferasyonunu inhibe edip etmedi\u011fi a\u00e7\u0131k de\u011fildir. Bu makale, seramidin KML h\u00fccre proliferasyonu ve glikoliz \u00fczerindeki etkilerini ara\u015ft\u0131rmak ve seramid ile KML h\u00fccre proliferasyonunun inhibisyonunda aerobik glikolizin d\u00fczenleyici rol\u00fcn\u00fc ke\u015ffetmek i\u00e7in bir h\u00fccre modeli olarak KML h\u00fccre hatt\u0131 K562'yi kullanmaktad\u0131r.<br \/>\nMelitamid, pirin\u00e7 orkidesinden elde edilen ve anti-t\u00fcm\u00f6r etkileri olan aktif bir maddedir. Bu makale, s\u00fclfonamidin aerobik glikoliz yoluyla K562 h\u00fccrelerinin \u00e7o\u011falmas\u0131n\u0131 inhibe edip etmedi\u011fini ara\u015ft\u0131rmaktad\u0131r. MTT testinin sonu\u00e7lar\u0131, K562 h\u00fccrelerinin b\u00fcy\u00fcmesinin ve \u00e7o\u011falmas\u0131n\u0131n Melitamid taraf\u0131ndan zamana ve konsantrasyona ba\u011fl\u0131 bir \u015fekilde \u00f6nemli \u00f6l\u00e7\u00fcde inhibe edildi\u011fini ve K562 h\u00fccrelerinin \u00e7o\u011falmas\u0131n\u0131 inhibe etmek i\u00e7in IC50'nin nanomolar seviyeye ula\u015ft\u0131\u011f\u0131n\u0131 g\u00f6stermi\u015ftir. Ak\u0131\u015f sitometrisi teknolojisinin kullan\u0131m\u0131, azepam\u0131n h\u00fccre d\u00f6ng\u00fcs\u00fcn\u00fcn G2\/M faz\u0131n\u0131 bloke ederek K562 h\u00fccrelerinin \u00e7o\u011falmas\u0131n\u0131 engelledi\u011fini ve apoptozu ind\u00fckledi\u011fini g\u00f6stermi\u015ftir.<br \/>\nT\u00fcm\u00f6r h\u00fccreleri, Warburg etkisi olarak bilinen aerobik ko\u015fullar alt\u0131nda hala y\u00fcksek d\u00fczeyde glikoz al\u0131m\u0131, glikoliz ve laktat seviyeleri sergilemektedir. Transkripsiyon fakt\u00f6r\u00fc c-Myc, h\u00fccre \u00e7o\u011falmas\u0131, h\u00fccre sa\u011fkal\u0131m\u0131, doku yeniden \u015fekillenmesi ve anjiyogenez gibi h\u00fccresel i\u015flevlerin d\u00fczenlenmesinde yayg\u0131n olarak yer al\u0131r ve ayr\u0131ca t\u00fcm\u00f6r h\u00fccrelerinin metabolik yeniden programlanmas\u0131n\u0131 ba\u015flat\u0131r. c-Myc, glikoz ta\u015f\u0131y\u0131c\u0131lar\u0131n\u0131 ve neredeyse t\u00fcm glikolitik enzimleri yukar\u0131 do\u011fru d\u00fczenler, b\u00f6ylece t\u00fcm\u00f6r h\u00fccresi glikoz metabolizmas\u0131n\u0131 te\u015fvik eder. 13C etiketli glukoz, c-Myc'nin Burkitt lenfoma ve c-Myc'ye ba\u011fl\u0131 karaci\u011fer kanserinde glukoz t\u00fcketimini te\u015fvik etti\u011fini g\u00f6stermi\u015ftir. Ara\u015ft\u0131rmalar, c-Myc'nin sadece glikolizde yer alan bir metabolik madde de\u011fil, ayn\u0131 zamanda anjiyogenez, ba\u011f\u0131\u015f\u0131kl\u0131ktan ka\u00e7\u0131\u015f, h\u00fccre g\u00f6\u00e7\u00fc, metabolik talep ve di\u011fer kanserojen etkilerin desteklenmesine de kat\u0131lan laktat salg\u0131lanmas\u0131n\u0131 te\u015fvik etti\u011fini bulmu\u015ftur. K562 h\u00fccrelerinin glukoz a\u00e7l\u0131\u011f\u0131 tedavisi ile glukozun \u00e7\u0131kar\u0131lmas\u0131n\u0131n laktat \u00fcretim seviyesini ve c-Myc'nin protein ekspresyon seviyesini azaltt\u0131\u011f\u0131n\u0131 ve K562 h\u00fccrelerinin \u00e7o\u011falmas\u0131na elveri\u015fli olmad\u0131\u011f\u0131n\u0131 bulduk. Bu, K562 h\u00fccrelerinin b\u00fcy\u00fcmesinin ve \u00e7o\u011falmas\u0131n\u0131n glikoz tedarikine ba\u011fl\u0131 oldu\u011funu do\u011frulamakta ve K562 h\u00fccrelerindeki c-Myc seviyeleri ile glikoz seviyeleri aras\u0131ndaki korelasyonu yans\u0131tmaktad\u0131r. A\u00e7l\u0131k ko\u015fullar\u0131 alt\u0131nda, glukozun \u00e7\u0131kar\u0131lmas\u0131ndan sonra formamidin K562 h\u00fccreleri \u00fczerindeki g\u00f6receli inhibisyon oran\u0131n\u0131n glukoz eklenen gruptan daha d\u00fc\u015f\u00fck oldu\u011fu bulunmu\u015ftur. Bu nedenle, formamidin K562 h\u00fccre b\u00fcy\u00fcmesini inhibe etmesinin k\u0131smen glikoza ba\u011fl\u0131 oldu\u011fu, yani formamidin glikoz kayna\u011f\u0131 olmadan K562 h\u00fccrelerinde b\u00fcy\u00fcme inhibisyonunu daha fazla ind\u00fckleyemeyece\u011fi tahmin edilmektedir. Melitamid ayr\u0131ca K562 h\u00fccrelerinin s\u00fcpernatant\u0131ndaki glukoz t\u00fcketimini ve laktat \u00fcretim seviyelerini \u00f6nemli \u00f6l\u00e7\u00fcde azaltm\u0131\u015ft\u0131r, bu da Melitamid'in K562 h\u00fccrelerinde aerobik glikolizi inhibe etti\u011fini g\u00f6stermektedir.<br \/>\nHekzokinaz 2 (HK2), t\u00fcm\u00f6r h\u00fccrelerinin y\u00fcksek h\u0131zl\u0131 aerobik glikolizini s\u00fcrd\u00fcrmek ve t\u00fcm\u00f6r h\u00fccrelerinin h\u0131zl\u0131 \u00e7o\u011falmas\u0131 i\u00e7in enerji sa\u011flamak \u00fczere d\u0131\u015f mitokondriyal membrana ba\u011flanabilen t\u00fcm\u00f6r h\u00fccresi glikolizinde spesifik bir anahtar enzimdir. Ara\u015ft\u0131rmac\u0131lar, fare modellerini kullanarak HK2'nin meme kanseri, akci\u011fer kanseri ve di\u011fer t\u00fcm\u00f6rlerin olu\u015fumunda ve geli\u015fiminde \u00f6nemli bir rol oynad\u0131\u011f\u0131n\u0131; Hekzokinaz 1'in (HK1) yeti\u015fkin dokularda yayg\u0131n olarak ifade edildi\u011fini ve hekzokinaz\u0131n bir housekeeping alt tipi olarak kabul edildi\u011fini; Fosfofruktokinaz P'nin (PFKP) kanserin ba\u015flamas\u0131nda ve metastaz\u0131nda \u00e7ok \u00f6nemli bir rol oynad\u0131\u011f\u0131n\u0131 do\u011frulad\u0131lar. Baz\u0131 \u00e7al\u0131\u015fmalar, PFKP'nin meme kanseri ve akci\u011fer kanseri i\u00e7in tan\u0131sal bir belirte\u00e7 veya ila\u00e7 hedefi olma potansiyeline sahip oldu\u011funu g\u00f6stermi\u015ftir; Piruvat kinaz 2 (PKM2), normal \u00e7o\u011falan h\u00fccreler, embriyonik h\u00fccreler ve \u00f6zellikle t\u00fcm\u00f6r h\u00fccreleri gibi y\u00fcksek n\u00fckleik asit sentez oranlar\u0131na sahip t\u00fcm h\u00fccrelerde eksprese edilir; Laktat dehidrojenaz A (LDHA), piruvat ve L-laktik asidin kar\u015f\u0131l\u0131kl\u0131 d\u00f6n\u00fc\u015f\u00fcm\u00fcn\u00fc katalize eder. Bir\u00e7ok insan t\u00fcm\u00f6r h\u00fccresinin LDHA seviyesi normal h\u00fccrelerden daha y\u00fcksektir. LDHA'n\u0131n inhibe edilmesi ba\u015f ve boyun kanseri, pankreas kanseri, rahim a\u011fz\u0131 kanseri ve prostat kanseri gibi t\u00fcm\u00f6r h\u00fccrelerinin \u00e7o\u011falmas\u0131n\u0131 azaltabilir. Seramidin K562 h\u00fccrelerinde HK2, HK1, PFKP, PKM2, LDHA ve onkojenik transkripsiyon fakt\u00f6r\u00fc c-Myc'nin protein ifade d\u00fczeyleri \u00fczerindeki etkilerini analiz ettik ve seramidin HK1, PFKP, PKM2 ve LDHA'n\u0131n protein ifade d\u00fczeylerini neredeyse hi\u00e7 d\u00fczenlemedi\u011fini, ancak c-Myc ve HK2'nin protein ifade d\u00fczeylerini \u00f6nemli \u00f6l\u00e7\u00fcde d\u00fc\u015f\u00fcrd\u00fc\u011f\u00fcn\u00fc bulduk. Melinamidin anti-K562 h\u00fccre aktivitesini c-Myc ve HK2'yi a\u015fa\u011f\u0131 reg\u00fcle ederek ve aerobik glikoliz yolaklar\u0131n\u0131 inhibe ederek ger\u00e7ekle\u015ftirdi\u011fini d\u00fc\u015f\u00fcn\u00fcyoruz. c-Myc ve HK2 aras\u0131ndaki d\u00fczenleyici ili\u015fkinin daha fazla ara\u015ft\u0131r\u0131lmas\u0131 gerekmektedir.<\/p>\n<p>&nbsp;<\/p>","protected":false},"excerpt":{"rendered":"<p>Seramid ile kronik miyeloid l\u00f6semi h\u00fccrelerinin proliferasyonunun inhibisyonunun d\u00fczenlenmesinde glikolizin kat\u0131l\u0131m\u0131 \u00fczerine \u00e7al\u0131\u015fma Kronik miyelojen\u00f6z l\u00f6semi (KML), kemik ili\u011fi h\u00fccrelerinin klonal proliferatif bir l\u00f6semisidir ve yeti\u015fkin l\u00f6semi vakalar\u0131n\u0131n yakla\u015f\u0131k 15%'sini olu\u015fturur. Y\u0131ll\u0131k g\u00f6r\u00fclme oran\u0131 2\/100000 olup, 50~55 ya\u015flar\u0131ndaki ki\u015filerde y\u00fcksektir. Kronik miyeloid l\u00f6semi [...]<\/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\/tr\/glycolysis-cml\/\" \/>\n<meta property=\"og:locale\" content=\"tr_TR\" \/>\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. Its annual incidence rate is 2\/100000, high in people aged 50~55 years. 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