Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC18210.15690/vramn.v68i5.659ONCOLOGY: CURRENT ISSUESАКТУАЛЬНЫЕ ВОПРОСЫ ОНКОЛОГИИCLINICAL PROSPECTS OF TUMOR-ASSOCIATED PROTEASES AND THEIR TISSUE INHIBITORS INVESTIGATION IN ONCOLOGIC PATIENTSКЛИНИЧЕСКИЕ ПЕРСПЕКТИВЫ ИССЛЕДОВАНИЯ АССОЦИИРОВАННЫХ С ОПУХОЛЬЮ ПРОТЕАЗ И ИХ ТКАНЕВЫХ ИНГИБИТОРОВ У ОНКОЛОГИЧЕСКИХ БОЛЬНЫХGershteinE. S.ГерштейнЕ. С.
Russian Federation

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

esgershtein@gmail.comKushlinskiiN. E.КушлинскийН. Е.
Russian Federation

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

biochimia@mtu-net.ruN.N. Blokhin Russian Cancer Research Center of RAMS, Moscow, Russian FederationРОНЦ им. Н.Н. Блохина РАМН, Москва, Российская Федерация14052013685Vestnik Rossiiskoi akademii medetsinskikh nauk / Annals of the Russian academy of medical sciencesВестник Российской академии медицинских наук162707082015Copyright ©; 1970, "Paediatrician" Publishers LLCCopyright ©; 1970, Издательство "Педиатръ"1970"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/article/view/182

Review of authors’ results and the most representative literature data on the role of tumor-associated proteolitic systems involved in invasion, metastasizing and angiogenic processes in diagnostics and prognosis in various oncologic diseases is presented in this paper. The main attention is paid to the key matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) as well as to the plasminogen activation system components (uPA, PAI-1) study in tumor tissues and peripheral blood. Personal results demonstrated an increase of most MMPs, uPA and PAI-1 expression in the tumors of 70–90% patients with various neoplasms as compared to histologically unchanged adjacent tissues. MMP-7 was shown to be a promising serologic marker of ovarian and colorectal cancer (CRC): its sensitivity at 70% specificity level comprised about 70% in both diseases. The greatest clinical interest should be paid to the implication of tumor-associated proteases as prognostic factors. Thus, results of 5-years monitoring have demonstrated that high preoperative serum MMP-7 and TIMP-1 levels were independent unfavorable prognostic factors for CRC and univariate analysis revealed unfavorable prognostic role of high tumor MMP-7 in patients with disseminated process. Tumor PAI-1 level was shown to be a valuable prognostic factor for stage III CRC. In the final part of the review possibilities and prospects of tumor-associated proteases usage as targets for specific molecular directed therapy are discussed.

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.

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