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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">cardio</journal-id><journal-title-group><journal-title xml:lang="ru">Кардиология</journal-title><trans-title-group xml:lang="en"><trans-title>Kardiologiia</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">0022-9040</issn><issn pub-type="epub">2412-5660</issn><publisher><publisher-name>Kardiomag</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.18087/cardio.2020.5.n1069</article-id><article-id custom-type="elpub" pub-id-type="custom">cardio-1069</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>RESEARCH ARTICLES</subject></subj-group></article-categories><title-group><article-title>Васкулотоксичность полихимиотерапии: оценка динамики уровня биомаркеров дисфункции эндотелия у больных раком желудка</article-title><trans-title-group xml:lang="en"><trans-title>Vasculotoxicity of Chemotherapy: Assessment оf Endothelial Dysfunction Biomarkers’ Levels in Gastric Cancer Patients</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8271-7704</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кириченко</surname><given-names>Ю. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Kirichenko</surname><given-names>Yu. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>врач-терапевт терапевтического отделения УКБ №1 Сеченовского Университета. аспирант кафедры Госпитальной терапии №1 ИКМ им. Н.В. Склифосовского Сеченовского Университета</p></bio><bio xml:lang="en"><p>MD, postgraduated student of Hospital Therapy №1, Sechenov University</p></bio><email xlink:type="simple">Kataraza@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/0000-0002-3014-6129</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Беленков</surname><given-names>Ю. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Belenkov</surname><given-names>Yu. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>академик РАН, д.м.н., проф., зав. кафедрой Госпитальной терапии №1 ИКМ им. Н.В. Склифосовского Сеченовского Университета</p></bio><bio xml:lang="en"><p>Academician of the Russian Academy of Sciences, MD, PhD, Professor, Head of Chair of Hospital Therapy №1, Sechenov University</p></bio><email xlink:type="simple">ynbelenkov@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9908-9476</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Привалова</surname><given-names>Е. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Privalova</surname><given-names>E. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>д.м.н., проф. кафедры Госпитальной терапии №1 ИКМ им. Н.В. Склифосовского Сеченовского Университета</p></bio><bio xml:lang="en"><p>MD, PhD, Professor, Chair of Hospital Therapy №1, Sechenov University</p></bio><email xlink:type="simple">ev_privalova@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>Найманн</surname><given-names>Ю. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Naymann</surname><given-names>Yu. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>к.м.н., асс. кафедры Госпитальной терапии №1 ИКМ им. Н.В. Склифосовского Сеченовского Университета. Зав.кардиологическим отделением №1 УКБ №1 Cеченовского Университета</p></bio><bio xml:lang="en"><p>MD, PhD, Assistant, Chair of Hospital Therapy №1, Sechenov University</p></bio><email xlink:type="simple">Kataraza@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>Гитель</surname><given-names>Е. П.</given-names></name><name name-style="western" xml:lang="en"><surname>Gitel</surname><given-names>E. P.</given-names></name></name-alternatives><bio xml:lang="ru"><p>руководитель централизованной лабораторно-диагностической службы Cеченовского Университета</p></bio><bio xml:lang="en"><p>Head of clinical laboratory, Sechenov University</p></bio><email xlink:type="simple">Kataraza@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>Новикова</surname><given-names>О. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Novikova</surname><given-names>O. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>врач клинико-лабораторной диагностики межклинической биохимической лаборатории централизованной лабораторно-диагностической службы Cеченовского Университета</p></bio><bio xml:lang="en"><p>MD, clinical laboratory, Sechenov University</p></bio><email xlink:type="simple">Kataraza@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/0000-0001-6817-6270</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ильгисонис</surname><given-names>И. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Ilgisonis</surname><given-names>I. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>к.м.н., доцент кафедры Госпитальной терапии №1 ИКМ им. Н.В. Склифосовского Сеченовского Университета</p></bio><bio xml:lang="en"><p>MD, PhD, Associate Professor, Chair of Hospital Therapy №1, Sechenov University</p></bio><email xlink:type="simple">Kataraza@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГАОУ ВО Первый Московский государственный медицинский университет им. И. М. Сеченова Минздрава России (Сеченовский Университет), Москва, Россия</institution><country>Россия</country></aff><aff xml:lang="en"><institution>M. Sechenov First Moscow State Medical University, Moscow, Russia</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2020</year></pub-date><pub-date pub-type="epub"><day>02</day><month>06</month><year>2020</year></pub-date><volume>60</volume><issue>5</issue><elocation-id>35–40</elocation-id><permissions><copyright-statement>Copyright &amp;#x00A9; Kardiomag, 2020</copyright-statement><copyright-year>2020</copyright-year><copyright-holder xml:lang="ru">Kardiomag</copyright-holder><copyright-holder xml:lang="en">Kardiomag</copyright-holder><license xlink:href="https://cardio.elpub.ru/jour/about/submissions#copyrightNotice" xlink:type="simple"><license-p>https://cardio.elpub.ru/jour/about/submissions#copyrightNotice</license-p></license></permissions><self-uri xlink:href="https://cardio.elpub.ru/jour/article/view/1069">https://cardio.elpub.ru/jour/article/view/1069</self-uri><abstract><p>Цель Оценка динамики биомаркеров дисфункции эндотелия (ДЭ): эндотелин-1 (ЕТ-1), фактора Виллебранда (VWF) у больных раком желудка (аденокарцинома) до и после полихимиотерапии (ПХТ); сравнение указанных данных с результатами обследования здоровых добровольцев и больных с сердечно-сосудистыми заболеваниями (ССЗ); корреляционный анализ уровня изучаемых биомаркеров ДЭ и параметров инструментальной оценки нарушений функции эндотелия.Материал и методы В исследовании приняли участие 75 человек: 25 здоровых добровольцев (группа контроля); 25 пациентов с доказанными ССЗ (артериальная гипертония + ишемическая болезнь сердца); 25 пациентов основной группы с гистологически подтвержденным раком желудка (аденокарцинома) II–IV стадии, которые получали различные курсы ПХТ с использованием препаратов платины (оксалиплатин, цисплатин) и фторпиримидинов (5 фторурацил, капецитабин). Всем пациентам основной группы до ПХТ и в течение 1 мес после окончания последнего курса проводили лабораторную оценку уровней биомаркеров ДЭ, компьютерную видеокапилляроскопию околоногтевого ложа (КВК) и лазерную пальцевую фотоплетизмографию – ФПГ (методы неинвазивной оценки состояния сосудистой стенки и ДЭ), электрокардиографию, суточное мониторирование электрокардиограммы по Холтеру, эхокардиографию (ЭхоКГ). Здоровым добровольцам и пациентам группы ССЗ указанные исследования были проведены однократно во время включения в исследование.Результаты В основной группе уровни ЕТ-1 были недостоверно ниже нормы и не изменились во время курсов противоопухолевого лечения: 0,95 [0,6; 1,4] и 0,94 [0,7; 1,4] пг / мл (р&lt;0,9) до и после ПХТ соответственно. При этом выявлены статистически значимые различия между группой контроля и онкологическими больными после лечения (р&lt;0,04). Уровень VWF оставался в пределах нормы у всех обследуемых и статистически значимо не различался между исследуемыми группами, включая онкологических больных до и после специфического лечения (р&gt;0,05 для всех сравнений). В ходе корреляционного анализа выявлены достоверные взаимосвязи между уровнем ЕТ-1 и функциональными нарушениями микроциркуляторного русла: ET-1 и индекс окклюзии (rs=0,56; p=0,005), ЕТ-1 и ПКВ (процент капиллярного восстановления, rs= –0,72; p=0,018); а также с частотой возникновения наджелудочковой экстрасистолии (rs=0,48; p=0,032).Заключение В ходе данного исследования впервые изучена динамика биомаркеров ДЭ у больных раком желудка на фоне специфической противоопухолевой терапии. Несмотря на то что достоверных изменений уровней ЕТ-1 и VWF во время ПХТ не выявлено (вследствие возможного истощения эндотелиальной системы, малой выборки пациентов), указанные параметры могут быть рассмотрены в качестве ранних маркеров развития васкулотоксичности ввиду наличия значимых корреляций с показателями ухудшения функции эндотелия по данным инструментальных методов.</p></abstract><trans-abstract xml:lang="en"><p>Aim To evaluate dynamics of biomarkers for endothelial dysfunction (ED), including endothelin-1 (ET-1) and von Willebrand factor (VWF) in patients with stomach cancer (adenocarcinoma) before and after polychemotherapy (PCT); to compare these results with respective values in healthy volunteers and patients with cardiovascular diseases (CVD); to study correlations of the ED biomarkers with indexes of instrumental evaluation of endothelial dysfunction.Material and methods The study included 75 participants, including 25 healthy volunteers (control group), 25 patients with documented CVDs (arterial hypertension + ischemic heart disease), and 25 patients of the main group with histologically documented stage II-IV stomach cancer (adenocarcinoma) who received different courses of PCT with platinum-based agents (oxaliplatin, cisplatin) and fluoropyrimidines (5 fluorouracil, capecitabin). Laboratory measurement of ED biomarkers, computerized nailfold video capillaroscopy (CNVC), and finger laser photoplethysmography (PPG) (methods for noninvasive evaluation of vascular wall and ED), electrocardiography, 24-h ECG Holter monitoring, and echocardiography (EchoCG) were performed for all patients of the main group prior to PCT and within one months after the last course completion. This evaluation was performed once for healthy volunteers and patients of the CVD group upon inclusion into the study.Results In the main group, ET-1 levels were non-significantly lower than normal and did not change during the courses of antitumor treatment (0.95 [0.6; 1.4] and 0.94 [0.7; 1.4] pg /ml (р&lt;0.9) before and after PCT, respectively). Statistically significant differences were found between the control group and oncological patients after the treatment (р&lt;0.04). Levels of VWF remained within the normal range in all examined participants and did not significantly differ between study groups, including oncological patients before and after the specific treatment (р&gt;0.05 for all comparisons). The correlation analysis detected significant correlations of ET-1 levels with functional disorders of microcirculation, ET-1 with the occlusion index (rs=0.56; p=0.005), ЕТ-1 with percentage of capillary restoration (PCR, rs= –0.72; p=0.018) and with the incidence rate of supraventricular extrasystole (rs=0.48; p=0.032).Conclusion The dynamics of ED biomarkers was studied for the first time in patients with stomach cancer receiving a specific antitumor therapy. Although no significant changes in ЕТ-1 and VWF were observed during the PCT (probably due to exhaustion of the endothelial system and a small patient sample), these indexes can be considered as early vasculotoxicity markers due to the presence of significant correlations with indexes of impaired endothelial function according to the results of instrumental evaluation.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>Дисфункция эндотелия</kwd><kwd>биомаркеры</kwd><kwd>эндотелин-1</kwd><kwd>фактор Виллебранда</kwd><kwd>рак желудка</kwd><kwd>полихимио­терапия</kwd></kwd-group><kwd-group xml:lang="en"><kwd>Endothelial dysfunction</kwd><kwd>biomarkers</kwd><kwd>endothelin-1</kwd><kwd>von Willebrand factor</kwd><kwd>stomach cancer</kwd><kwd>polychemotherapy</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Исследование выполнено при финансовой поддержке РФФИ  в рамках научного проекта № 19‑315‑90034. 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