Изучение механизмов спонтанных реверсий злокачественных клеток к неопухолеродному фенотипу
Диссертация
Актуальность исследования. Одной из наиболее серьезных проблем клинической онкологии является метастазирование опухолей и, особенно, молчащее метастазирование. Молчащие (дремлющие) метастазы практически не поддаются ранней диагностике, а клетки таких метастазов отличаются повышенной резистентностью к различным типам противоопухолевой терапии. Указанные проблемы являются следствием того, что… Читать ещё >
Содержание
- СПИСОК ПРИНЯТЫХ СОКРАЩЕНИЙ
- ГЛАВА 1. ОБЗОР ЛИТЕРАТУРЫ
- 1. 1. Трансформация клеток и приобретение ими опухолевого фенотипа
- 1. 1. 1. Молекулярные аспекты иммортализации
- 1. 1. 2. Контактное торможение
- 1. 1. 3. Рост в неприкрепленном состоянии, анойкис
- 1. 2. Реверсия опухолеродных клеток к неопухолеродному фенотипу
- 1. 2. 1. Индуцированные реверсии
- 1. 2. 2. Спонтанные реверсии .'
- 1. 2. 3. Спонтанные реверсии как источник дремлющих метастазов
- 1. 1. Трансформация клеток и приобретение ими опухолевого фенотипа
- 2. 1. Клеточные линии и культуры
- 2. 1. 1. Оценка роста клеток в сингенных животных
- 2. 1. 2. Оценка контактного торможения клеток по включению 3Н-тимидина
- 2. 1. 3. Оценка способности клеток к росту в неприкрепленном состоянии
- 2. 2. Выделение суммарной РНК из клеток
- 2. 3. ДНКазная обработка и анализ выделенной РНК
- 2. 4. Обратная транскрипция
- 2. 5. Определение относительных концентраций полученной кДНК методом полуколичественного ПЦР
- 2. 6. Сравнение уровней экспрессии исследованных генов в различных клетках методом полуколичественного ПЦР
- 2. 7. Математическая обработка полученных данных
- 2. 8. Проточная цитофлюорометрия
- 3. 1. Сравнение ростовых характеристик злокачественных и ревертантных линий и клонов in vitro и in vivo
- 3. 1. 1. Оценка опухолеродности клеток по росту опухолей в сингенных животных
- 3. 1. 2. Оценка опухолеродности клеток по основным параметрам роста in vitro
- 3. 2. Сравнение уровней мРНК различных ростовых факторов и их рецепторов в злокачественных и ревертантных линиях и клонах in vitro и in vivo
- 3. 2. 1. Оценка уровней синтеза мРНК основных ростовых факторов клетками in vitro
- 3. 2. 2. Оценка уровней синтеза мРНК рецепторов ростовых факторов клетками in vitro и in vivo
- 3. 2. 3. Оценка уровней синтеза мРНК Гепатоцитарного Ростового Фактора (HGF) опухолевыми и псевдонормальными клетками in vitro и in vivo
- 3. 3. Сравнение злокачественных и псевдонормальных клеток по содержанию белковых продуктов исследованных генов
- 3. 3. 1. Сравнение опухолевых и псевдонормальных клеток, находящихся в логарифмической фазе роста, по содержанию белковых продуктов HGF, HGFR и EGFR
- 3. 3. 2. Сравнение количества белкового продукта HGF в псевдонормальных клетках, находящихся в логарифмической фазе роста и в GO, обусловленной контактным торможением (конфлюэнтные клетки)
- 3. 4. Реакция клеток на HGF, EGF и PDGF АА
- 3. 4. 1. Эффективность спасения клеток от алоптоза в присутствии HGF, EGF и PDGF АА
- 3. 4. 2. Влияние антител против рецептора HGF на пролиферацию и апоптоз клеток
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