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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">fcmedicine</journal-id><journal-title-group><journal-title xml:lang="ru">Фундаментальная и клиническая медицина</journal-title><trans-title-group xml:lang="en"><trans-title>Fundamental and Clinical Medicine</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2500-0764</issn><issn pub-type="epub">2542-0941</issn><publisher><publisher-name>КемГМУ</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.23946/2500-0764-2024-9-2-72-85</article-id><article-id custom-type="elpub" pub-id-type="custom">fcmedicine-865</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОБЗОРНЫЕ СТАТЬИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>REVIEW ARTICLES</subject></subj-group></article-categories><title-group><article-title>Возможности иммуногистохимических методов для оценки токсичности и механизма действия соединений с предполагаемым противоопухолевым эффектом в ходе доклинического исследования. Часть II. Гибель клетки, васкулогенез и ангиогенез</article-title><trans-title-group xml:lang="en"><trans-title>Immunohistochemistry for Assessing Toxicity and Mechanism of Action of Anticancer Drugs During Preclinical Trials. Part II. Cell Death, Vasculogenesis and Angiogenesis</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8792-6911</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Акименко</surname><given-names>М. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Akimenko</surname><given-names>M. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Акименко Марина Анатольевна, кандидат медицинских наук, ассистент кафедры медицинской биологии и генетики, биолог высшей категории патологоанатомического отделения</p><p>344022, г. Ростов-на-Дону, пер. Нахичеванский, д. 29 </p><p>344011, г. Ростов-на-Дону, ул. Варфоломеева, д. 92а </p></bio><bio xml:lang="en"><p>Dr. Marina A. Akimenko, MD, PhD, Assistant Professor, Department of Medical Biology and Genetics, Biologist, Department of Pathology</p><p>29, Nakhichevansky Prospekt, Rostov-on-Don, 344022</p><p>92a, Varfolomeeva Street, Rostov-on-Don, 344011  </p></bio><email xlink:type="simple">akimenkoma@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2976-0794</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Воронова</surname><given-names>О. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Voronova</surname><given-names>O. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Воронова Ольга Владимировна, кандидат медицинских наук, ассистент кафедры судебной медицины, заведующая патологоанатомическим отделением, главный врач </p><p>344022, г. Ростов-на-Дону, пер. Нахичеванский, д. 29 </p><p>344011, г. Ростов-на-Дону, ул. Варфоломеева, д. 92а </p><p>344015, Ростов-на-Дону, ул. Благодатная, 170А </p><p> </p></bio><bio xml:lang="en"><p>Dr. Olga V. Voronova, MD, PhD, Assistant Professor, Department of Forensic Medicine, Head of the Department of Pathology, the Сhief physician </p><p>29, Nakhichevansky Prospekt, Rostov-on-Don, 344022 </p><p>92a, Varfolomeeva Street, Rostov-on-Don, 344011 </p><p>170A Blagodatnaya str., Rostov-on-Don, 344015 </p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-5123-5289</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Алхусейн-Кулягинова</surname><given-names>М. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Alkhusein-Kulyaginova</surname><given-names>M. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Алхусейн-Кулягинова Маргарита Стефановна, ассистент кафедры патологической физиологии</p><p>344022, г. Ростов-на-Дону, пер. Нахичеванский, д. 29 </p></bio><bio xml:lang="en"><p>Dr. Margarita S. Alkhusein-Kulyaginova, MD, Assistant Professor, Department of Pathophysiology</p><p>29, Nakhichevansky Prospekt, Rostov-on-Don, 344022 </p></bio><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-0485-5869</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Корниенко</surname><given-names>Н. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kornienko</surname><given-names>N. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Корниенко Наталья Александровна, кандидат медицинских наук, доцент кафедры нормальной анатомии</p><p>344022, г. Ростов-на-Дону, пер. Нахичеванский, д. 29 </p></bio><bio xml:lang="en"><p>Dr. Natalia A. Kornienko, MD, PhD, Associate Professor, Department of Normal Anatomy </p><p>29, Nakhichevansky Prospekt, Rostov-on-Don, 344022 </p></bio><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6023-8916</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Гулян</surname><given-names>М. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Gulyan</surname><given-names>M. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Гулян Марина Владимировна, кандидат медицинских наук, доцент кафедры патологической физиологии</p><p>344022, г. Ростов-на-Дону, пер. Нахичеванский, д. 29 </p></bio><bio xml:lang="en"><p>Dr. Marina V. Gulyan, MD, PhD, Associate Professor, Department of Pathophysiology </p><p>29, Nakhichevansky Prospekt, Rostov-on-Don, 344022 </p></bio><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3104-827X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Додохова</surname><given-names>М. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Dodokhova</surname><given-names>M. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Додохова Маргарита Авдеевна, доктор медицинских наук, профессор кафедры патологической физиологии, заведующая ЦНИЛ </p><p>344022, г. Ростов-на-Дону, пер. Нахичеванский, д. 29 </p></bio><bio xml:lang="en"><p>Prof. Margarita A. Dodokhova, MD, DSc, Professor, Department of Pathophysiology, Head of the Central Research Laboratory</p><p>29, Nakhichevansky Prospekt, Rostov-on-Don, 344022 </p></bio><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2796-9466</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Котиева</surname><given-names>И. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Kotieva</surname><given-names>I. M.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Котиева Инга Мовлиевна, доктор медицинских наук, доцент, заведующая кафедрой патологической физиологии, проректор по научной работе</p><p>344022, г. Ростов-на-Дону, пер. Нахичеванский, д. 29 </p></bio><bio xml:lang="en"><p>Prof. Inga M. Kotieva, MD, DSc, Head of the Department of Pathophysiology, Chief Scientific Officer</p><p>29, Nakhichevansky Prospekt, Rostov-on-Don, 344022 </p></bio><xref ref-type="aff" rid="aff-3"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБОУ ВО «Ростовский государственный медицинский университет» Министерства здравоохранения Российской Федерации ; ЧУЗ «Клиническая больница «РЖД-Медицина» г. Ростов-на-Дону»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Rostov State Medical University ; Clinical Hospital “Russian Railways Medicine”</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>ФГБОУ ВО «Ростовский государственный медицинский университет» Министерства здравоохранения Российской Федерации ; ЧУЗ «Клиническая больница «РЖД-Медицина» г. Ростов-на-Дону» ; ГБУ РО «Патолого-анатомическое бюро»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Rostov State Medical University ; Clinical Hospital “Russian Railways Medicine” ; Pathologic and Anatomical Bureau</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>ФГБОУ ВО «Ростовский государственный медицинский университет» Министерства здравоохранения Российской Федерации</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Rostov State Medical University</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2024</year></pub-date><pub-date pub-type="epub"><day>21</day><month>06</month><year>2024</year></pub-date><volume>9</volume><issue>2</issue><fpage>72</fpage><lpage>85</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Акименко М.А., Воронова О.В., Алхусейн-Кулягинова М.С., Корниенко Н.А., Гулян М.В., Додохова М.А., Котиева И.М., 2024</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="ru">Акименко М.А., Воронова О.В., Алхусейн-Кулягинова М.С., Корниенко Н.А., Гулян М.В., Додохова М.А., Котиева И.М.</copyright-holder><copyright-holder xml:lang="en">Akimenko M.A., Voronova O.V., Alkhusein-Kulyaginova M.S., Kornienko N.A., Gulyan M.V., Dodokhova M.A., Kotieva I.M.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://fcm.kemsmu.ru/jour/article/view/865">https://fcm.kemsmu.ru/jour/article/view/865</self-uri><abstract><p>Злокачественные новообразования не только в России, но и в мире в целом являются социально значимой проблемой. В качестве противоопухолевых лекарственных средств в России зарегистрировано около 120 химических соединений. Поиск и изучение перспективных кандидатов в противоопухолевые препараты остаются актуальными задачами для специалистов в области патофизиологии, фармакологии и онкологии. На современном этапе развития медицины выделяют несколько механизмов действия, особое внимание следует уделить неоваскуло- и неоангиогенезу и опосредованной активации некроза и /или апоптоза атипичных клеток первичного опухолевого узла и метастатических очагов. На этапе углубленного изучения соединений-лидеров, обладающих доказанным противоопухолевым/антиметастатическим эффектом, целесообразно оценить их влияние на собственно процесс неоангио- и васкулогенеза, на формирование васкулогенных альтернативных сосудов, установление механизма действия соединений при доказанной фармакологической активности на экспериментальных моделях злокачественных новообразований in vitro и in vivo, в том числе активации апоптоза. Такой комплексный подход даст возможность выявить новые мишени для реализации фармакологической активности средств, что в перспективе приблизит медицинское сообщество к более эффективной помощи пациентам со злокачественныминовообразованиями различной стадийности процесса. Цель исследования – выявить интегральные маркеры активности некроза и апоптоза, а также провести сравнительный анализ маркеров активности традиционного и альтернативного неоангиогенеза при развитии опухолевого процесса для более эффективного использования морфологического и иммуногистохимического методов исследования в доклиническом изучении соединений с предполагаемой противоопухолевой активностью для оценки перспектив их применения. В работе представлены актуальные молекулярно-биологические маркеры для исследования основных видов гибели клетки, играющих важную роль в изменении молекулярного патогенеза опухолевого роста под действием соединений - перспективных кандидатов в противоопухолевые средства. При иммуногистохимическом исследовании наиболее целесообразно использовать следующий молекулярно-биологический маркер некротического процесса - TNF-α, а для определения апоптотического компонента – CSE1L, Bcl-2 и APAF1. При изучении процесса образования новых сосудов соответственно рекомендуются к использованию следующие маркеры – VEGF-А, HIF-1α и PDGF. Изучение и анализ механизмов кровоснабжения опухоли и процессов метастазирования, а также способности клеток активировать свою программу апоптоза имеет как теоретическое, так и практическое значение с прямым выходом в фармацевтическую отрасль.</p></abstract><trans-abstract xml:lang="en"><p>About 120 chemical compounds are registered in Russia as anticancer drugs, and screening and investigation of novel therapies remain an urgent task for specialists in pathophysiology, pharmacology and oncology. Among them, treatments targeting neovascularisation and regulated cell death of atypical cells within the malignant tumours are of utmost importance. Hence, development of novel anti-cancer drugs must include testing of their pro-apoptotic and anti-angiogenic activity. Here we review the markers of angiogenesis and regulated cell death during the tumor development and the respective immunohistochemical applications for preclinical trials. Here we discuss relevant molecular markers for studying primary cell death subroutines which can be targeted by anticancer agents. The most sensitive and specific immunohistochemical markers of programmed cell death are tumor necrosis factor alpha (TNF-α) for necrosis and anti-cellular apoptosis susceptibility/CSE1L, Bcl-2, and apoptotic protease activating factor-1 (APAF1) for apoptosis. Primary markers of angiogenesis include vascular endothelial growth factor A (VEGF-A), hypoxia-inducible factor 1-alpha (HIF-1α), and platelet-derived growth factor (PDGF). Analysis of tumour blood supply, metastasis and apoptosis has both theoretical and practical significance with direct implications for the pharmaceutical industry.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>противоопухолевые лекарственные средства</kwd><kwd>иммуногистохимия</kwd><kwd>апоптоз</kwd><kwd>некроз</kwd><kwd>ангиогенез</kwd><kwd>васкулогенная мимикрия</kwd></kwd-group><kwd-group xml:lang="en"><kwd>anticancer drugs</kwd><kwd>immunohistochemistry</kwd><kwd>apoptosis</kwd><kwd>necrosis</kwd><kwd>angiogenesis</kwd><kwd>vasculogenic mimicry</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Каприна А.Д., Старинского В.В., Шахзадовой А.О., ред. 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