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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">oncotomsk</journal-id><journal-title-group><journal-title xml:lang="ru">Сибирский онкологический журнал</journal-title><trans-title-group xml:lang="en"><trans-title>Siberian journal of oncology</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1814-4861</issn><issn pub-type="epub">2312-3168</issn><publisher><publisher-name>Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.21294/1814-4861-2022-21-6-81-90</article-id><article-id custom-type="elpub" pub-id-type="custom">oncotomsk-2377</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>ЛАБОРАТОРНЫЕ И ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>LABORATORY AND EXPERIMENTAL STUDIES</subject></subj-group></article-categories><title-group><article-title>Морфологическая гетерогенность внутриопухолевых макрофагов в опухоли предстательной железы</article-title><trans-title-group xml:lang="en"><trans-title>Morphological heterogeneity of intratumoral macrophages in prostate tumors</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4374-2923</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Данилко</surname><given-names>К. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Danilko</surname><given-names>K. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Данилко Ксения Владимировна, кандидат биологических наук, старший научный сотрудник ЦНИЛ, </p><p>450008, г. Уфа, ул. Ленина, 3</p></bio><bio xml:lang="en"><p>Ksenia V. Danilko, PhD, Senior Researcher, Central Research Laboratory,</p><p>3, Lenin St., 450008, Ufa</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5995-2124</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Еникеева</surname><given-names>К. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Enikeeva</surname><given-names>K. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Еникеева Кадрия Ильдаровна, ассистент кафедры фармакологии с курсом клинической фармакологии, </p><p>450008, г. Уфа, ул. Ленина, 3</p></bio><bio xml:lang="en"><p>Assistant of the Department of Pharmacology with a Course of Clinical Pharmacology, </p><p>3, Lenin St., 450008, Ufa</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9581-8918</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кабиров</surname><given-names>И. Р.</given-names></name><name name-style="western" xml:lang="en"><surname>Kabirov</surname><given-names>I. R.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кабиров Ильдар Раифович, кандидат медицинских наук, доцент кафедры урологии с курсом ИДПО, </p><p>450008, г. Уфа, ул. Ленина, 3</p></bio><bio xml:lang="en"><p>Ildar R. Kabirov, MD, PhD, Associate Professor, Department of Urology,</p><p>3, Lenin St., 450008, Ufa</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4169-9124</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Максимова</surname><given-names>С. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Maksimova</surname><given-names>S. Y.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Максимова Серафима Юрьевна, ассистент кафедры урологии с курсом ИДПО, </p><p>450008, г. Уфа, ул. Ленина, 3</p></bio><bio xml:lang="en"><p>Serafima Yu. Maksimova, Assistant of the Department of Urology, </p><p>3, Lenin St., 450008, Ufa</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7339-0589</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Вишняков</surname><given-names>Д. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Vishnyakov</surname><given-names>D. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Вишняков Дмитрий Сергеевич, младший научный сотрудник ЦНИЛ, </p><p>450008, г. Уфа, ул. Ленина, 3</p></bio><bio xml:lang="en"><p>Dmitry S. Vishnyakov, Junior Researcher of Central Research Laboratory, </p><p>3, Lenin St., 450008, Ufa</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-0898-3075</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кжышковска</surname><given-names>Ю. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Kzhyshkowska</surname><given-names>J. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кжышковска Юлия Георгиевна, доктор биологических наук, профессор, заведующая отделом врожденного иммунитета и иммунологической толерантности, медицинский факультет Маннгейма, 68167, г. Маннгейм, Theodor-Kutzer-Ufer, 1-322;</p><p>68167, г. Маннгейм, Friedrich-Ebert, 1073;</p><p>заведующая лабораторией трансляционной клеточной и молекулярной биомедицины, 634050, г. Томск, ул. Ленина, 364;</p><p>заведующая лабораторией, 634050, г. Томск, Московский тракт, 2</p></bio><bio xml:lang="en"><p>Julia G. Kzhyshkowska, MD, PhD, Professor, Head of Department of Innate Immunity and Immunological Tolerance, 1-3, Theodor-Kutzer-Ufer, 68167-Mannheim;</p><p>107, Friedrich-Ebert St., 68167-Mannheim</p><p>Head of Laboratory of Translational Cellular and Molecular Biomedicine, 36, Lenina St., 634050, Tomsk;</p><p>Head of Laboratory, 2, Moskovsky tract, 634050, Tomsk</p></bio><email xlink:type="simple">julia.kzhyshkowska@gmail.com</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2125-4897</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Павлов</surname><given-names>В. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Pavlov</surname><given-names>V. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Павлов Валентин Николаевич, доктор медицинских наук, академик РАН, заведующий кафедрой урологии с курсом ИДПО,</p><p>450008, г. Уфа, ул. Ленина, 3</p></bio><bio xml:lang="en"><p>Valentin N. Pavlov, MD, Professor, RAS academician, Head of the Department of Urology,</p><p>3, Lenin St., 450008, Ufa</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБОУ ВО «Башкирский государственный медицинский университет» Минздрава России</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Bashkir State Medical University of the Ministry of Health of Russia</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Институт трансфузионной медицины и иммунологии, Университет Гейдельберга;&#13;
Служба крови Немецкого Красного Креста Баден-Вюртемберг-Гессен;&#13;
ФГАОУ ВО «Национальный исследовательский Томский государственный университет»;&#13;
ФГБОУ ВО «Сибирский государственный медицинский университет» Минздрава России</institution><country>Германия</country></aff><aff xml:lang="en"><institution>Institute for Transfusion Medicine and Immunology, University of Heidelberg;&#13;
German Red Cross Blood Service Baden-Württemberg – Hessen;&#13;
National Research Tomsk State University;&#13;
Siberian State Medical University of the Ministry of Health of Russia</institution><country>Germany</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2022</year></pub-date><pub-date pub-type="epub"><day>31</day><month>12</month><year>2022</year></pub-date><volume>21</volume><issue>6</issue><fpage>81</fpage><lpage>90</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Данилко К.В., Еникеева К.И., Кабиров И.Р., Максимова С.Ю., Вишняков Д.С., Кжышковска Ю.Г., Павлов В.Н., 2023</copyright-statement><copyright-year>2023</copyright-year><copyright-holder xml:lang="ru">Данилко К.В., Еникеева К.И., Кабиров И.Р., Максимова С.Ю., Вишняков Д.С., Кжышковска Ю.Г., Павлов В.Н.</copyright-holder><copyright-holder xml:lang="en">Danilko K.V., Enikeeva K.I., Kabirov I.R., Maksimova S.Y., Vishnyakov D.S., Kzhyshkowska J.G., Pavlov V.N.</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://www.siboncoj.ru/jour/article/view/2377">https://www.siboncoj.ru/jour/article/view/2377</self-uri><abstract><sec><title>Введение</title><p>Введение. Наиболее распространенным среди мужчин во всем мире является рак предстательной железы (РПЖ). В прогрессировании РПЖ общее количество макрофагов в опухолевой ткани ассоциировано с плохим прогнозом и повышенным риском метастазирования. Однако гетерогенность внутриопухолевых макрофагов на различных стадиях развития заболевания и роль опухоль-ассоциированных макрофагов (ОАМ) при раке простаты изучены недостаточно.</p><p>Цель исследования ‒ анализ морфологических особенностей, размера и количества макрофагов в образцах тканей РПЖ и выявление взаимосвязи их субпопуляций с клиническими данными пациентов.</p></sec><sec><title>Материал и методы</title><p>Материал и методы. Иммуногистохимический анализ парафиновых блоков опухолевой ткани 36 пациентов с РПЖ стадии pT2a–3bN0–1M0 проводили с использованием антител к скавенджер-рецептору CD68. Результаты. В опухолевой ткани обнаружены «пенистые» CD68-позитивные макрофаги. Анализ показателя «количество макрофагов на общее количество полей зрения с макрофагами» продемонстрировал рост значений по мере прогрессирования опухолевого процесса. Он оказался самым низким у пациентов с суммой баллов по шкале Глисона 6 – 5,8 и самым высоким – 11,0, у пациентов с баллом по шкале Глисона ≥ 8. Макрофаги образовывали более крупные скопления у пациентов с тяжелой формой РПЖ. Мелкие (менее 100 мкм2), но не крупные (более 100 мкм2) макрофаги встречались значительно чаще у пациентов с метастазами в лимфоузлы – 48 против 24 в группе N0 (р=0,14). Количество мелких макрофагов возрастало в ряду пациентов с суммой баллов по шкале Глисона 6, 7 и ≥ 8 – 24; 47,5; 72 соответственно (р=0,052).</p></sec><sec><title>Заключение</title><p>Заключение. По мере прогрессирования опухолевого процесса и повышения риска биохимического рецидива демонстрировались тенденция к увеличению общей площади крупных, пенистых ОАМ, вероятно, богатых липидами, а также большее распространение мелких, секретирующих макрофагов и склонность к образованию кластеров. Вероятно, пенистые макрофаги принимают участие в дальнейшем привлечении мелких, что в дальнейшем ведет к метастазированию и опухолевой прогрессии. </p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Background</title><p>Background. Prostate cancer (PCa) is the most common human cancer worldwide. In the progression of prostate cancer, the total number of macrophages in the tumor tissue is associated with poor prognosis and increased risk of metastasis. However, the heterogeneity of intratumoral macrophages at various stages of PCa development, and the role of tumor-associated macrophages (TAMs) have been insuffciently investigated.</p><p>The aim of the study was to analyze the morphological features, size and number of TAMs in PCa tissue samples, and to reveal their correlation with clinical data of patients.</p></sec><sec><title>Material and Methods</title><p>Material and Methods. Immunohistochemical analysis of 36 paraffn blocks of patients with PCa (pT2a–3bN0–1M0) was performed using antibodies to the scavenger receptor CD68.</p></sec><sec><title>Results</title><p>Results. Foamy CD68+ macrophages were found in the tumor tissue. The indicator “number of macrophages per total number of felds of view with macrophages” was the lowest in patients with a Gleason score of 6 (5.8) (11.0 – in patients with a Gleason score ≥ 8). Macrophages formed larger clusters in patients with severe PCa. Small but not large macrophages were signifcantly more common in patients with lymph node metastases (48 vs 24 in the N0 group; p=0.14). The number of small macrophages (smaller than 100 µm2) increased in a series of patients with Gleason scores of 6, 7 and ≥ 8 (24, 47.5, 72, respectively, p=0.052).</p></sec><sec><title>Conclusion</title><p>Conclusion. As the tumor process progressed and the risk of biochemical recurrence increased, there was a trend towards an increase in the total area of large, foamy TAMs, presumably rich in lipids, as well as wider distribution of small macrophages with a tendency to form clusters. We hypothesize that foamy macrophages are involved in the further recruitment of small TAMs, subsequently leading to metastasis and tumor progression. </p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>рак предстательной железы</kwd><kwd>опухоль-ассоциированные макрофаги</kwd><kwd>гигантские макрофаги</kwd><kwd>опухолевая прогрессия</kwd></kwd-group><kwd-group xml:lang="en"><kwd>prostate cancer</kwd><kwd>tumor-associated macrophages</kwd><kwd>giant macrophages</kwd><kwd>tumor progression</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Исследование выполнено за счет гранта Министерства науки и высшего образования Российской Федерации «Генетическое и эпигенетическое редактирование опухолевых клеток и микроокружения с целью блокирования метастазирования» № 075-15-2021-1073 (эксперименты) и программы «Приоритет 2030» (клинические данные).</funding-statement><funding-statement xml:lang="en">The study was funded by the state grant of the Ministry of Science and Higher Education of the Russian Federation “Genetic and epigenetic editing of tumor cells and the microenvironment to block metastasis” No. 075-15-2021-1073 (experiments) and BSMU Strategic Academic Leadership Program PRIORITY-2030 (clinical data analysis).</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Torre L.A., Bray F., Siegel R.L., Ferlay J., Lortet-Tieulent J., Jemal A. 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