Молекулярные эффекты ингибирования конститутивной активности рецептора c-KIT в саркомах мягких тканей: изменение передачи сигнала и профиля экспрессии генов
Диссертация
Анализ экспрессии генов, определяющих эффективность ответа на Гливек, позволил найти прогностические маркеры результативности лечения Гливеком, которые можно определять даже в тонкоигольных биоптатах СОЖКТ. Выявленные маркеры являются высоконадежнымидействительно, предсказание совпадало с клинической картиной в 100% случаев. Разработанная модель СОЖКТ in vitro имеет большую практическую ценность… Читать ещё >
Список литературы
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- Трансмембранный домен Юкстамембранный домен
- Киназный домен АТФ-связывающая область Киназная вставка
- Киназный домен Фосфотрансферазная область1. Цитоплазматический регионсоон
- Рис. 1. Схема доменной организации рецептора KIT.
- Цитозольные/цитоскелетные мишени: Фосфолипаза Аг1. Транскрипционные факторы1. Транскрипция генов
- Прогрессия клеточного цикла/ Апоптоз
- Рис. 2. Сеть каскадов трансдукции сигнала внутрь клетки от рецептора KIT.1. KITэцд17,3%тмд1. ЮМДкд
- Соматические дупликации Ala-502 иТуг-503 в спорадических СОЖКТ
- Различные соматические мутации между Lys-550 и Asp-579 в соматических СОЖКТ
- Различные терминальные мутации между Lys-550 и Asp-579 в наследственых и множественных СОЖКТ
- Соматическая точечная мутация Lys-642 в спорадических СОЖКТ
- Герминальная точечная мутация Lys-642 в наследственых и множественных СОЖКТ
- Соматическая точечная мутация Asp-816 в новообразованиях тучных клеток
- Рис 3. Частота встречаемости и характеристика мутаций KIT при спорадических и наследственных формах СОЖК. ЭЦД, экстрацеллюлярный домен- ТМД, трансмембранный домен- ЮМД, юкстамембранный домен- КД, киназный домен- KB, киназная вставка1. Иматиниба мезилат
- Молекулярный вес 589.7 Формула C30H36N7SO4
- Рис. 4. Структурная формула и непатентованное название препарата Гливек.
- ДНКюриоаыхттм «ДНК н нормальныхтестер) (яра йир) с"шфоааииым Адаптером 1 ваятая, а избыта1. ДНК и ра"о"ы> 1ЛГГО"тестер) с пишроиниьш Адаптером 2b, c, d +Iвторой цикл гибридизации с добавлением свежей порции драйверазаполнение концевых брешей
- Добавление праймеров М w ПЦР амплификацияa. d отсутствие амплификации
- Ь-*Ь' отсутствие амплификациис линейная амплификация, «экспоненциальная амплификация
- Энзиматическое фрагментирование якорной эндонуклеазой (ЯЭ) и связывание со стрптавидиновыми бусами1. GATC GATC QATC
- Разделение реакции пополам и лигирование линкеров, А и В1. ПСТАв GATC1. CTAG GATC
- Рестрикция «тэг'-эндонуклеаздй (ТЭ)
- ТЭ ЯЭ Тэг (микрофрагмент) ТЭ ЯЭ Тэг (микрофрагмент)
- GATGCTAGXXXXXXXXX | | CTAGYYYYYYYYY
- СТAGGAT СХХХХХХХХХ II GAT CYYYYYYYYY
- Лигирование и амплификация
- Лигирование и амплификация /с использованием якорных праймеров, А и ъ /
- Двойной микрофрагмент IGGATG CTAGXXXXXXXXXYYYYYYYYYCTAG ICCTAGGATCXXXXXXXXXYYYYYYYYYGATC
- Рестрикция якорной эндонуклеазой, Выделение и объединение двойных микрофрагментов, Клонирование
- CTAGXXXXXXXXXYYYYYYYYYCTACXXXXXXXXXYYYYYYYYYCTACXXXXXXXXXYYYYYYYYYCTAC GATCXXXXXXXXXYYYYYYYYYGATCXXXXXXXXXYYYYYYYYYGATCXXXXXXXXXYYYYYYYYYGATG
- Двойной микрофрагмент Двойной микрофрагмент Двойной микрофрагмент
- Рис. 6. Схематическое изображение метода серийного анализа экспрессии генов (SAGE).1. Выбор клонова*