КЛИНИЧЕСКИЕ ПЕРСПЕКТИВЫ ИССЛЕДОВАНИЯ АССОЦИИРОВАННЫХ С ОПУХОЛЬЮ ПРОТЕАЗ И ИХ ТКАНЕВЫХ ИНГИБИТОРОВ У ОНКОЛОГИЧЕСКИХ БОЛЬНЫХ

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Представлен обзор результатов собственных исследований и наиболее репрезентативных данных литературы о роли ассоциированных с опухолями протеолитических систем, участвующих в процессах инвазии, метастазирования и ангиогенеза, в диагностике и прогнозировании результатов лечения различных онкологических заболеваний. Основное внимание уделено ключевым матриксным металлопротеиназам (ММП) и их тканевым ингибиторам (ТИМП), а также компонентам системы активации плазминогена (uPA, PAI-1) в опухолях и периферической крови. В собственных исследованиях продемонстрировано повышение уровня экспрессии большинства ММП, uPA и PAI-1 в опухолях у 70–90% больных различными новообразованиями по сравнению с окружающими гистологически неизмененными тканями. Показано, что ММП-7 является перспективным серологическим маркером рака яичников и рака толстой кишки (РТК): уровень его чувствительности при 70% специфичности составляет около 70% для обеих локализаций. Наибольший интерес с клинической точки зрения представляет использование опухоль-ассоциированных протеаз в качестве прогностических факторов. Так, по результатам 5-летнего наблюдения показано, что высокие предоперационные уровни ММП-7 и ТИМП-1 в плазме крови являются независимыми факторами неблагоприятного прогноза РТК, а при однофакторном анализе обнаружено также неблагоприятное прогностическое значение высокого содержания ММП-7 в опухолевой ткани больных с диссеминированным процессом. Значимым фактором прогноза РТК III стадии является уровень PAI-1 в опухоли. В заключительной части обзора рассмотрены возможности использования опухоль-ассоциированных протеаз в качестве мишеней для молекулярно-направленной терапии.

 

Об авторах

Е. С. Герштейн

РОНЦ им. Н.Н. Блохина РАМН, Москва, Российская Федерация

Автор, ответственный за переписку.
Email: esgershtein@gmail.com
PhD, Professor, Leading Research Worker, the Clinical Biochemistry Laboratory, N. N. Blokhin Russian Cancer Research Center of RAMS Address: 115478, Moscow, Kashirskoye Highway 24; tel.: (499) 324-11-59 Россия

Н. Е. Кушлинский

РОНЦ им. Н.Н. Блохина РАМН, Москва, Российская Федерация

Email: biochimia@mtu-net.ru
PhD, Professor, RAMS cor. member, Head of the Clinical Biochemistry Laboratory, N. N. Blokhin Russian Cancer Research Center of RAMS Address: 115478, Moscow, Kashirskoye Highway 24; tel.: (499) 324-11-59 Россия

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