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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">mimmun</journal-id><journal-title-group><journal-title xml:lang="ru">Медицинская иммунология</journal-title><trans-title-group xml:lang="en"><trans-title>Medical Immunology (Russia)</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1563-0625</issn><issn pub-type="epub">2313-741X</issn><publisher><publisher-name>SPb RAACI</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.15789/1563-0625-2017-5-567-576</article-id><article-id custom-type="elpub" pub-id-type="custom">mimmun-1358</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>ОРИГИНАЛЬНЫЕ СТАТЬИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL ARTICLES</subject></subj-group></article-categories><title-group><article-title>CРАВНИТЕЛЬНАЯ ОЦЕНКА ПРОДУКЦИИ ЦИТОКИНОВ ИММУНОКОМПЕТЕНТНЫМИ КЛЕТКАМИ КРОВИ И ОПУХОЛИ В РАЗЛИЧНЫХ ВОЗРАСТНЫХ ГРУППАХ БОЛЬНЫХ ИНВАЗИВНЫМ ПРОТОКОВЫМ РАКОМ МОЛОЧНОЙ ЖЕЛЕЗЫ</article-title><trans-title-group xml:lang="en"><trans-title>COMPARATIVE ANALYSIS OF CYTOKINE PRODUCTION BY BLOOD IMMUNOCOMPETENT CELLS AND TUMOR IN DIFFERENT AGE GROUPS OF PATIENTS WITH INVASIVE DUCTAL CARCINOMA</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кунц</surname><given-names>Т. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kunts</surname><given-names>T. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кунц Т.А. – к.б.н., старший научный сотрудник Центральной научно-исследовательской лаборатории ФГБОУ ВО «Новосибирский государственный медицинский университет» Министерства здравоохранения РФ. </p><p>630091, Россия, г. Новосибирск, Красный пр., 52.</p></bio><bio xml:lang="en"><p>Kunts T.A., PhD (Biology), Senior Research Associate, Сentral Research Laboratory, Novosibirsk State Medical University.</p><p>630091,  Novosibirsk, Krasny ave, 52. </p></bio><email xlink:type="simple">tkunts@ngs.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Михайлова</surname><given-names>Е. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Mikhaylova</surname><given-names>E. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Михайлова Е.С. – научный сотрудник Центральной научно-исследовательской лаборатории ФГБОУ ВО «Новосибирский государственный медицинский университет» Министерства здравоохранения РФ; старший научный сотрудник лаборатории метаболизма лекарств и фармакокинетики ФГБНУ «Научноисследовательский институт молекулярной биологии и биофизики».</p><p>г. Новосибирск.</p></bio><bio xml:lang="en"><p>Mikhaylova E.S., Research Associate, Сentral Research Laboratory, Novosibirsk State Medical University; Senior Research Associate, Laboratory of Drug Metabolism and Pharmacokinetics, Research Institute of Molecular Biology and Biophysics.</p><p>Novosibirsk.</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Маринкин</surname><given-names>И. О.</given-names></name><name name-style="western" xml:lang="en"><surname>Marinkin</surname><given-names>I. O.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Маринкин И.О. – д.м.н., профессор, заведующий кафедрой, ФГБОУ ВО «Новосибирский государственный медицинский университет» Министерства здравоохранения РФ, г.</p><p>Новосибирск.</p></bio><bio xml:lang="en"><p>Marinkin I.O., PhD, MD (Medicine), Professor, Head of Department, Novosibirsk State Medical University.</p><p>Novosibirsk.</p></bio><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Вараксин</surname><given-names>Н. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Varaksin</surname><given-names>N. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Вараксин Н.А. – заведующий лабораторией, АО «Вектор-Бест».</p><p>Новосибирская область.</p></bio><bio xml:lang="en"><p>Varaksin N.A., Head of Laboratory, JSC “Vector-Best”.</p><p>Novosibirsk Region.</p></bio><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Аутеншлюс</surname><given-names>А. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Autenshlyus</surname><given-names>A. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Аутеншлюс А.И. – д.б.н., профессор, заведующий Центральной научно-исследовательской лабораторией ФГБОУ ВО «Новосибирский государственный медицинский университет» Министерства здравоохранения РФ; главный научный сотрудник лаборатории метаболизма лекарств и фармакокинетики ФГБНУ «Научноисследовательский институт молекулярной биологии и биофизики».</p><p>г. Новосибирск.</p></bio><bio xml:lang="en"><p>Autenshlyus A.I., PhD, MD (Biology), Professor, Head, Central Research Laboratory, Novosibirsk State Medical University; Chief Research Associate, Laboratory of Drug Metabolism and Pharmacokinetics, Research Institute of Molecular Biology and Biophysics.</p><p>Novosibirsk.</p></bio><xref ref-type="aff" rid="aff-2"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБОУ ВО «Новосибирский государственный медицинский университет» Министерства здравоохранения РФ.</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Novosibirsk State Medical University.</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>ФГБОУ ВО «Новосибирский государственный медицинский университет» Министерства здравоохранения РФ; ФГБНУ «Научно-исследовательский институт молекулярной биологии и биофизики».</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Novosibirsk State Medical University; Research Institute of Molecular Biology and Biophysics.</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>ФГБОУ ВО «Новосибирский государственный медицинский университет» Министерства здравоохранения РФ.</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Novosibirsk State Medical University</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-4"><aff xml:lang="ru"><institution>АО «Вектор-Бест».</institution><country>Россия</country></aff><aff xml:lang="en"><institution>JSC “Vector-Best”.</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2017</year></pub-date><pub-date pub-type="epub"><day>19</day><month>10</month><year>2017</year></pub-date><volume>19</volume><issue>5</issue><fpage>567</fpage><lpage>576</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Кунц Т.А., Михайлова Е.С., Маринкин И.О., Вараксин Н.А., Аутеншлюс А.И., 2017</copyright-statement><copyright-year>2017</copyright-year><copyright-holder xml:lang="ru">Кунц Т.А., Михайлова Е.С., Маринкин И.О., Вараксин Н.А., Аутеншлюс А.И.</copyright-holder><copyright-holder xml:lang="en">Kunts T.A., Mikhaylova E.S., Marinkin I.O., Varaksin N.A., Autenshlyus A.I.</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.mimmun.ru/mimmun/article/view/1358">https://www.mimmun.ru/mimmun/article/view/1358</self-uri><abstract><p>Известно, что существует взаимосвязь между возрастом пациента и патогенезом злокачественных новообразований, который сопряжен со способностью клеток опухоли и ее микроокружения секретировать цитокины, играющие значительную роль в канцерогенезе. Целью исследования явился сравнительный анализ продукции цитокинов клетками периферической крови и опухоли при воздействии на них поликлональных активаторов (ПА) при инвазивном протоковом раке молочной железы в различных возрастных группах больных. Материалом исследования служили образцы периферической крови и опухоли 54 женщин с инвазивным протоковым раком, являющимся по гистологическому типу аденокарциномой. Пациенты были разделены на группы по возрасту: I гр. – 40-60 лет, II гр. – 61 и более. В группе I метастазы в лимфатических узлах на момент исследования были выявлены у 13 пациентов из 31 (42%), в отличие от группы II, где количество пациентов с метастазами составило всего 3 человека из 23 (10%). Определение критерия Фишера показало достоверные различия между встречаемостью на момент исследования лимфоузлов с метастазами в зависимости от возраста пациентов (p = 0,034). В обеих возрастных группах пациентов отмечалось повышение концентрации IL-6, IL-8, IL-10, IL-17, IL-18, IL-1ra, G-CSF, GM-CSF и VEGF в супернатанте клеток опухоли и ее микроокружения по сравнению с продукцией цитокинов клетками крови, что свидетельствовало о высокой функциональной активности новообразования в совокупности с его микроокружением. Добавление ПА в среду культивирования приводило к повышению концентраций IL-2, IL-10, IL-17, IL-1β, IL-1ra, TNFα и IFNγ в супернатанте клеток крови, что свидетельствовало об их высоком потенциале в отношении их секреции. В группе пациентов в возрасте 40-60 лет индекс влияния ПА на продукцию IFNγ в несколько раз превышал аналогичный показатель у больных в возрасте 61 и более лет. Повышение ИВПА на продукцию практически всех цитокинов в супернатанте крови по сравнению с показателями супернатанта опухоли можно объяснить изначально высокими уровнями спонтанной продукции цитокинов опухолью и ее микроокружением, обеспечивающими злокачественную прогрессию, поэтому действие ПА на опухоль не приводило к такому же эффекту, как при действии на иммунокомпетентные клетки крови. Единственным цитокином, к продукции которого клетки опухоли и микроокружения сохраняли высокий потенциал, был IL-18, что подтверждает его важную роль в канцерогенезе. На основании полученных данных о влиянии поликлональных активаторов на цитокинпродуцирующую функцию клеток опухоли и крови можно прийти к выводу о том, что постоянно циркулирующие иммунокомпетентные клетки, обладая высокой способностью к секреции цитокинов, являются тем резервом, который обеспечивает опухолевую прогрессию.</p></abstract><trans-abstract xml:lang="en"><p>It is known that a relationship exists between patient’s age and pathogenesis of malignant tumors associated with ability of tumor and its microenvironment to secrete cytokines that may play an important role in carcinogenesis. The aim of present study was a comparative analysis of cytokine production by peripheral blood cells and tumor samples when exposed to polyclonal activators (PA) in patients of different age groups with invasive ductal carcinoma. Peripheral blood samples of 54 women with invasive ductal carcinoma were under study. The patients were divided into the following groups: I, 40-60 years old; II, 61 year and older. Metastases into lymph nodes were revealed at the moment of study in 13 patients (42%) from group I. By contrast, only 3 of 23 (10%) patients with metastases were revealed in group II. Fisher’s ratio test showed significant differences between occurrence of metastases in lymph nodes, and patient age (p = 0.034). In both groups of patients, there was an increase of IL-6, IL-8, IL-10, IL-17, IL-18, IL-1ra, G-CSF, GM-CSF and VEGF concentrations in tumor supernates and its microenvironment, when compared with the production of cytokines by blood cells, thus indicating to high functional activity of tumor together with its microenvironment. Effect of PA led to increase of IL-2, IL-10, IL-17, IL-1β, IL-1ra, TNFα and IFNγ concentrations in blood cells supernatant which suggested their high ability to produce cytokines. In the group of patients who were 40-60 years old, the stimulatory index of PA (SIPA) for IFNγ production was several times higher than similar index in patients aged 61 years or more. Increase of SIPA for all cytokines in blood cells supernates, in comparison to SIPA of tumor supernates, could be explained by initially high levels of spontaneous cytokine production by the tumor and its microenvironment that are able to promote tumor growth. Therefore, effect of PA upon tumor tissue was not so expressed as its effect upon immunocompetent blood cells. Both tumor and microenvironment maintained high ability of IL-18 production, thus confirming its important role in carcinogenesis. In summary, these findings suggest that circulating immunocompetent cells may serve as an additional factor providing tumor progression, due to their high ability to secrete cytokines.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>цитокины</kwd><kwd>супернатант</kwd><kwd>поликлональные активаторы</kwd><kwd>рак молочной железы</kwd></kwd-group><kwd-group xml:lang="en"><kwd>cytokines</kwd><kwd>supernatant</kwd><kwd>polyclonal activators</kwd><kwd>breast cancer</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">Аутеншлюс А.И., Соснина А.В., Великая Н.В., Фурсов С.А., Михайлова Е.С., Исакова Н.Б., Морозов Д.В., Лыков А.П., Вараксин Н.А. Оценка цитокинпродуцирующей функции клеток крови и пролиферативной активности опухолевых клеток при раке толстой кишки // Российский аллергологический журнал, 2011. № 4. С. 34-35. 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