ОБЗОРЫ

МикроРНК: малые молекулы с большим значением

ОБЗОРЫ , ,

В.Н. Аушев

ФГБНУ «Российский онкологический научный центр им. Н.Н. Блохина», Каширское ш., д. 24, Москва, Российская Федерация, 115478

Для цитирования: Аушев В.Н. МикроРНК: малые молекулы с большим значением. Клиническая онкогематология. 2015;8(1):1–12.

Для переписки: Василий Николаевич Аушев, канд. биол. наук, Каширское ш., д. 24, Москва, Российская Федерация, 115478; тел.: +7(499)324-17-64; e-mail: vaushev@gmail.com

РЕФЕРАТ

Обоснование. МикроРНК были впервые обнаружены как антисмысловые транскрипты у нематоды Caenorhabditis elegans, где они подавляли экспрессию генов, содержащих в мРНК комплементарные последовательности. Таким образом, данные молекулы наряду с короткими интерферирующими микроРНК являются основными медиаторами РНК-интерференции — универсального механизма регуляции экспрессии.

Результаты. МикроРНК представляют собой небольшие молекулы, транскрибируемые с геномной ДНК и подвергающиеся дальнейшему процессингу и экспорту в цитоплазму. Они могут входить в состав транскриптов, кодирующих белки, либо транскрибироваться с белок-некодирующих участков. Первичный процессинг может осуществляться с участием специализированного ферментного комплекса либо в ходе стандартного сплайсинга мРНК. После экспорта в цитоплазму промежуточный продукт подвергается окончательному процессингу с образованием активного РНК-белкового комплекса, способного связываться с комплементарными участками мРНК-«мишеней». Результатом такого связывания является подавление трансляции с данной мРНК. Сама мРНК во многих случаях может быть расщеплена за счет РНКазной активности комплекса.

Выводы. В геноме человека закодировано несколько тысяч микроРНК, образующих обширную регуляторную сеть, которая задействована в самых разных сигнальных путях и клеточных процессах. Нарушения микроРНК-регуляции вовлечены в развитие широкого спектра заболеваний, включая все типы неоплазий. МикроРНК имеют большое значение в онкологии, в частности в онкогематологии, как перспективные маркеры и потенциальные терапевтические агенты. К настоящему времени показано участие отдельных микроРНК в патогенезе большинства заболеваний системы крови. В ряде случаев предлагается использовать данные молекулы в качестве средств молекулярной диагностики и для определения прогноза заболевания.

Ключевые слова: микроРНК, регуляция экспрессии, онкомаркеры.

Получено: 16 июля 2014 г.

Принято в печать: 7 октября 2014 г.

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Лечение распространенных стадий лимфомы Ходжкина: обзор литературы

ОБЗОРЫ , , , ,

А.А. Леонтьева, Е.А. Демина

ФГБНУ «Российский онкологический научный центр им. Н.Н. Блохина», Каширское ш., д. 24, Москва, Российская Федерация, 115478

Для переписки: Анна Александровна Леонтьева, аспирант, Каширское ш., д. 24, Москва, Российская Федерация, 115478; тел.: +7(499)324-90-89; e-mail: aurevoir-nut@yandex.ru

Для цитирования: Леонтьева А.А., Демина Е.А. Лечение распространенных стадий лимфомы Ходжкина: обзор литературы. Клиническая онкогематология. 2015;8(3):255–66.

РЕФЕРАТ

В последнее десятилетие крупные исследовательские центры в Европе и США, имеющие большие базы данных, провели комплексный анализ эффективности лечебных программ, поздних осложнений терапии и показателей длительной выживаемости больных с распространенными стадиями лимфомы Ходжкина. Этот анализ позволил разработать и предложить практической медицине новые программы, отличающиеся большей эффективностью, и начать поиск менее токсичных вариантов лечения. Однако в отечественной литературе такой комплексный анализ не представлен. Имеющиеся публикации и научные исследования освещают лишь отдельные аспекты диагностики и лечения лимфомы Ходжкина, или в них выборочно обсуждаются проблемы осложнений. Предлагаемый обзор позволяет читателю проследить путь, пройденный в лечении распространенных стадий лимфомы Ходжкина за 75 лет — от абсолютно пессимистического прогноза до современных высоких результатов с дальнейшим совершенствованием терапии этой злокачественной опухоли.

Ключевые слова: лимфома Ходжкина, распространенные стадии, лечение, эффективность, токсичность.

Получено: 20 февраля 2015 г.

Принято в печать: 28 мая 2015 г.

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ЛИТЕРАТУРА

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Ферментные препараты в онкогематологии: актуальные направления экспериментальных исследований и перспективы клинического применения

ОБЗОРЫ , , , , , ,

В.С. Покровский, Е.М. Трещалина

ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» РАМН, Москва, Российская Федерация

РЕФЕРАТ

Последние годы в области разработки новых противоопухолевых препаратов на основе ферментов продемонстрированы существенные достижения. Помимо L-аспарагиназы, которая применяется в онкогематологии уже более 30 лет, два фермента — L-аргининдезиминаза и ранпирназа — прошли несколько этапов клинических исследований. Для целого ряда ферментов показана противоопухолевая активность на доклиническом этапе в экспериментах in vivo: L-метионин-гамма-лиаза, L-лизин-альфа-оксидаза, биназа. В настоящем обзоре представлены ферменты, продемонстрировавшие на различных этапах исследований противоопухолевую активность, и перспективы их использования в онкогематологии.

Ключевые слова: противоопухолевые ферменты, L-аспарагиназа, L-метионин-гамма-лиаза, L-лизин-альфа-оксидаза, L-аргининдезиминаза, L-фенилаланин-аммиак-лиаза, ранпирназа.

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Роль селективности ингибиторов тирозинкиназ в развитии побочных эффектов при терапии хронического миелолейкоза

ОБЗОРЫ , , , , , , , , , , , , , ,

А.А. Зейфман1,2, Е.Ю. Челышева3, А.Г. Туркина3, Г.Г. Чилов1,2

1 ФГБУ «Институт органической химии им. Н.Д. Зелинского РАН», Москва, Российская Федерация

2 ООО «Фьюжн Фарма», Москва, Российская Федерация

3 ФГБУ «Гематологический научный центр» МЗ РФ, Москва, Российская Федерация

РЕФЕРАТ

В обзоре рассмотрен вопрос о связи селективности ингибиторов Bcr-Abl-киназ со спектром нежелательных побочных эффектов у больных хроническим миелолейкозом при проведении терапии. Суммированы данные по структуре и естественным биохимическим функциям наиболее хорошо изученных побочных мишеней ингибиторов Bcr-Abl-киназ: BRAF, FMS, EGFR, PDGFR, PYK2, TIE2, VEGFR1/2/3, а также оценена возможная связь их нецелевого ингибирования и нежелательных побочных эффектов ингибиторов тирозинкиназ.

Ключевые слова: хронический миелолейкоз, ингибиторы тирозинкиназ, селективность, иматиниб, нилотиниб, дазатиниб, понатиниб, PF-114, BRAF, FMS, EGFR, PDGFR, PYK2, TIE2, VEGFR1/2/3.

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