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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">10.21294/1814-4861-2017-16-6-41-46</article-id><article-id custom-type="elpub" pub-id-type="custom">oncotomsk-640</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 КЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>LABORATORY AND CLINICAL STUDIES</subject></subj-group></article-categories><title-group><article-title>СРАВНИТЕЛЬНЫЙ АНАЛИЗ БИОЛОГИЧЕСКИХ ЭФФЕКТОВ СЕЛЕКТИВНОГО АГОНИСТА ГЛЮКОКОРТИКОИДНОГО РЕЦЕПТОРА CPDA НА КЛЕТОЧНЫЕ ЛИНИИ РАКА МОЛОЧНОЙ ЖЕЛЕЗЫ РАЗЛИЧНЫХ МОЛЕКУЛЯРНЫХ ПОДТИПОВ</article-title><trans-title-group xml:lang="en"><trans-title>COMPARATIVE ANALYSIS OF BIOLOGICAL EFFECTS OF SELECTIVE ACTIVATOR OF THE GLUCOCORTICOID RECEPTOR CPDA ON DIFFERENT SUBTYPES OF BREAST CANCER CELL LINES</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>Жидкова</surname><given-names>Е. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Zhidkova</surname><given-names>E. M.</given-names></name></name-alternatives><bio xml:lang="ru"><p>лаборант-исследователь отдела химического канцерогенеза</p></bio><bio xml:lang="en"><p>Laboratory Research Assistant, Department of Chemical Carcinogenesis</p></bio><email xlink:type="simple">Zhidkova_EM@mail.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>Кузин</surname><given-names>К. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kuzin</surname><given-names>K. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>младший научный сотрудник отдела химического канцерогенеза</p></bio><bio xml:lang="en"><p>Junior Researcher, Department of Chemical Carcinogenesis</p></bio><email xlink:type="simple">alenka.savinkova@mail.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>Тилова</surname><given-names>Л. Р.</given-names></name><name name-style="western" xml:lang="en"><surname>Tilova</surname><given-names>L. R.</given-names></name></name-alternatives><bio xml:lang="ru"><p>аспирант отдела химического канцерогенеза</p></bio><bio xml:lang="en"><p>Postgraduate, Department of Chemical Carcinogenesis</p></bio><email xlink:type="simple">uhtishkachik@mail.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>Савинкова</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Savinkova</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>младший научный сотрудник отдела химического канцерогенеза</p></bio><bio xml:lang="en"><p>Junior Researcher, Department of Chemical Carcinogenesis</p></bio><email xlink:type="simple">alenka.savinkova@mail.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>Борисова</surname><given-names>О. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Borisova</surname><given-names>O. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>лаборант-исследователь отдела химического канцерогенеза</p></bio><bio xml:lang="en"><p>Laboratory Research Assistant, Department of Chemical Carcinogenesis</p></bio><email xlink:type="simple">deadsilentium@mail.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>Лаврова</surname><given-names>М. Д.</given-names></name><name name-style="western" xml:lang="en"><surname>Lavrova</surname><given-names>M. D.</given-names></name></name-alternatives><bio xml:lang="ru"><p>студент</p></bio><bio xml:lang="en"><p>3-rd-year student</p></bio><email xlink:type="simple">mahoony@mail.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Максимова</surname><given-names>В. П.</given-names></name><name name-style="western" xml:lang="en"><surname>Maximova</surname><given-names>V. P.</given-names></name></name-alternatives><bio xml:lang="ru"><p>лаборант-исследователь отдела химического канцерогенеза</p></bio><bio xml:lang="en"><p>Laboratory Research Assistant, Department of Chemical Carcinogenesis</p></bio><email xlink:type="simple">lavarvar@gmail.com</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>Кирсанов</surname><given-names>К. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Kirsanov</surname><given-names>K. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>кандидат биологических наук, заведующий лабораторией канцерогенных веществ отдела химического канцерогенеза</p><p>SPIN-код: 7329-7263.</p></bio><bio xml:lang="en"><p>PhD, Head of Laboratory of Chemical Carcinogens</p><p>SPIN-code: 7329-7163.</p></bio><email xlink:type="simple">kkirsanov85@yandex.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>Якубовская</surname><given-names>М. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Yakubovskaya</surname><given-names>M. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>доктор медицинских наук, заведующая отделом химического канцерогенеза</p><p>SPIN-код: 6858-3880</p></bio><bio xml:lang="en"><p>MD, PhD, DSc, Head of Department of Chemical Carcinogenesis</p><p>SPIN-code: 6858-3880</p></bio><email xlink:type="simple">mgyakubovskaya@mail.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>Лесовая</surname><given-names>Е. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Lesovaya</surname><given-names>E. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>кандидат биологических наук, старший научный сотрудник отдела химического канцерогенеза</p><p>SPIN-код: 7593-2167.</p></bio><bio xml:lang="en"><p>PhD, Senior Researcher, Department of Chemical Carcinogenesis</p><p>SPIN-code: 7593-2167.</p></bio><email xlink:type="simple">lesovenok@yandex.ru</email><xref ref-type="aff" rid="aff-3"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБУ «Национальный медицинский исследовательский центр онкологии имени Н.Н. Блохина» Минздрава России, г. Москва</institution><country>Россия</country></aff><aff xml:lang="en"><institution>N.N. Blokhin National Medical Research Center of Oncology, Moscow</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>ФГБОУ ВО «Российский химико-технологический университет им. Д.И. Менделеева», г. Москва</institution><country>Россия</country></aff><aff xml:lang="en"><institution>D. Mendeleev University of Chemical Technology of Russia, Moscow</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>ФГБУ «Национальный медицинский исследовательский центр онкологии имени Н.Н. Блохина» Минздрава России, г. Москва;&#13;
ФГБОУ ВО «Рязанский государственный медицинский университет» Минздрава России, г. Рязань</institution><country>Россия</country></aff><aff xml:lang="en"><institution>N.N. Blokhin National Medical Research Center of Oncology, Moscow;&#13;
Ryazan State Medical University named after academician I.P. Pavlov</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2017</year></pub-date><pub-date pub-type="epub"><day>23</day><month>12</month><year>2017</year></pub-date><volume>16</volume><issue>6</issue><fpage>41</fpage><lpage>46</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Жидкова Е.М., Кузин К.А., Тилова Л.Р., Савинкова А.В., Борисова О.И., Лаврова М.Д., Максимова В.П., Кирсанов К.И., Якубовская М.Г., Лесовая Е.А., 2017</copyright-statement><copyright-year>2017</copyright-year><copyright-holder xml:lang="ru">Жидкова Е.М., Кузин К.А., Тилова Л.Р., Савинкова А.В., Борисова О.И., Лаврова М.Д., Максимова В.П., Кирсанов К.И., Якубовская М.Г., Лесовая Е.А.</copyright-holder><copyright-holder xml:lang="en">Zhidkova E.M., Kuzin K.A., Tilova L.R., Savinkova A.V., Borisova O.I., Lavrova M.D., Maximova V.P., Kirsanov K.I., Yakubovskaya M.G., Lesovaya E.A.</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/640">https://www.siboncoj.ru/jour/article/view/640</self-uri><abstract><p>Глюкокортикоиды (GC) широко применяются в терапии рака молочной железы (РМЖ) в качестве средств сопроводительной терапии для снижения побочных эффектов цитостатических препаратов. При этом GС могут проявлять собственное про- или антипролиферативное действие на клетки РМЖ, в зависимости от их молекулярно-биологического подтипа, что, в свою очередь, может улучшать или ухудшать прогноз терапии. Кроме того, применение GC ведет к развитию побочных эффектов. Реализация биологического действия GC осуществляется путем активации глюкокортикоидного рецептора (GR) по двум механизмам: транс-репрессии, обусловливающей терапевтических эффект GC, и транс- активации, с которой связаны побочные эффекты, резистентность к цитотоксическим препаратам, а также прогрессия и метастазирование РМЖ. Ранее в нашей лаборатории было показано, что соединение класса селективных агонистов глюкокортикоидного рецептора (SEGRA) Compound A (CpdA) проявляет GR-зависимый противоопухолевый эффект на моделях гемобластозов in vitro, не запуская при этом механизм транс-активации GR. Цель исследования – изучение биологической активности CpdA в отношении РМЖ с различными молекулярными характеристиками на клеточных моделях in vitro. В ходе работы было показано антипролиферативное действие CpdA на клетки РМЖ различных молекулярно-биологических подтипов и его способность вызывать трансрепрессию GR-зависимых генов, не вызывая транс-активации. Сравнительный анализ эффектов CpdA и дексаметазона показал, что SEGRA потенциально являются более безопасными и эффективными препаратами как для использования в качестве средств поддерживающей терапии, так и для возможного адъюванта при проведении химиотерапии.</p></abstract><trans-abstract xml:lang="en"><p>Glucocorticoids (GCs) are often used as an adjuvant therapy to reduce the adverse effects of chemotherapy in breast cancer patients. Moreover, GCs can display pro-proliferative or anti-proliferative effects on BC cells depending on their molecular subtype. In addition, long-term use of GCs can induce drug resistance and tumor progression. The biological activity of GCs is mediated by glucocorticoid receptor (GR) via either transrepression or transactivation. The anti-inflammatory effects of GCs are thought to be due to transrepression, while side effects, drug resistance and tumor progression/metastasis are associated with transactivation. We have previously demonstrated that Compound A, a selective GR agonist (SEGRA), has a GR-dependent antitumor effect on blood cancer cells in vitro, not triggering the GR transactivation. This study was focused on the analysis of the CpdA activity in BC models in vitro. We demonstrated the antiproliferative effect of CpdA on BC cells and its ability to induce transrepression of GR-depended genes such as CCND1-3, COX-2, iNOS without the induction of transactivation. A comparative analysis showed that CpdA was an effective and safe alternative to dexamethasone in adjuvant chemotherapy for breast cancer.</p><p> </p></trans-abstract><kwd-group xml:lang="ru"><kwd>молекулярные подтипы рака молочной железы</kwd><kwd>глюкокортикоиды</kwd><kwd>селективные агонисты глюкокортикоидного рецептора</kwd><kwd>Compound A</kwd><kwd>CpdA</kwd></kwd-group><kwd-group xml:lang="en"><kwd>molecular subtypes of breast cancer</kwd><kwd>glucocorticoids</kwd><kwd>selective activators of glucocorticoid receptor</kwd><kwd>Compound A</kwd><kwd>CpdA</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">Lippman M., Bolan G., Huff K. The effects of glucocorticoids and progesterone on hormone-responsive human breast cancer in long-term tissue culture. Cancer Res. 1976 Dec; 36 (12): 4602–9.</mixed-citation><mixed-citation xml:lang="en">Lippman M., Bolan G., Huff K. 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