O‘SMALAR MIKRO-MUHITIDA LEYKOTSIT DISFUNKTSIYASI, ANORMAL ANGIOGENEZ, TOMIR MORFOLOGIYASINING BUZILISHI VA METASTAZNING ANATOMIK YO‘LLARI
Keywords:
O‘smalar mikro-muhiti, Leykotsit disfunktsiyasi, Mieloid kelib chiqishli supressiv hujayralar (MDSC), Anormal angiogenez, Tomir anormalligi, Metastaz anatomiyasi, Pre-metastatik mikro-muhit, Immunoterapiya, Antiangiogen terapiya, Gemato-ensefalik to‘siq.Abstract
Xavfli o‘smalar rivojlanishida o‘smalar mikro-muhiti (tumor microenvironment – TME) hal qiluvchi rol o‘ynaydi. Ushbu sharhli maqola so‘nggi o‘n yil (2015-2025) davomida o‘rganilgan TME ning asosiy komponentlari – immun tizim, qon tomirlari va ekstrasellyular matritsa o‘rtasidagi o‘zaro ta’sirga, xususan, leykotsitlarning funktsional buzilishiga, anormal angiogenez jarayonlariga va shu asosda shakllanadigan tugun ichi tomir tizimining (intratumoral vasculature) morfologik va funktsional “anormallik”lariga e’tibor qaratadi. Maqolada immunitetning immunosupressiv holatga aylanishi, uning sabablari (masalan, mieloid kelib chiqishli supressiv hujayralar – MDSC, regulator T limfotsitlar – Treg, M2 makrofaglar) hamda bu holatning o‘sma rivojlanishi va davolashga chidamliligiga ta’siri muhokama qilinadi. Bundan tashqari, tangis-hipoksiya-indutse qilingan omillar (HIF-1α) tomonidan rag‘batlantiriladigan noto‘g‘ri tuzilgan, kavernoz va o‘tkazuvchanligi oshgan tomirlarning shakllanishi (abnormal angiogenesis), ularning perfuziya va bosim darajasidagi nuqsonlari, shuningdek, gemato-ensefalik to‘siq kabi fiziolojik to‘siqlarni buzishdagi roli chuqur tahlii qilinadi. Metastazlanishning anatomik yo‘llari – limfogen, gematogen va implantatsion yo‘llar, shu jumladan “seed and soil” nazariyasi doirasida metastatik uchrash joylarining spesifikligi, pre-metastatik mikro-muhitning shakllanishi va jarayonga TME komponentlarining hissasi, ayniqsa, ekstrasellyular vezikulalar va tomirlarning o‘tkazuvchanligi orqali saraton hujayralarining tarqalishi tahlil qilinadi. Yakun qismida, ushbu tushunchalar asosida ishlab chiqilgan yangi terapevtik strategiyalar – immunoterapiya, antiangiogen terapiya va ularning kombinatsiyalari, shuningdek, bo‘g‘in nuqtali davolash (targeted therapy) istiqbollari haqida xulosa kelitirilgan. Bu maqola ushbu sohada so‘nggi o‘n yil ichida to‘plangan bilimlarni umumlashtirib, saraton biologiyasi va onkologik klinik amaliyot o‘rtasidagi uzilgan bog‘lanishni mustahkamlashga qaratilgan. [1,2,3,4,5]
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