<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<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">10.21294/1814-4861-2020-19-6-141-147</article-id><article-id custom-type="elpub" pub-id-type="custom">oncotomsk-1653</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>ОБЗОРЫ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>REVIEWS</subject></subj-group></article-categories><title-group><article-title>СОВРЕМЕННЫЕ ПРЕДСТАВЛЕНИЯ О РОЛИ ГИПОКСИИ В РАЗВИТИИ РАДИОРЕЗИСТЕНТНОСТИ ЗЛОКАЧЕСТВЕННЫХ ОПУХОЛЕЙ</article-title><trans-title-group xml:lang="en"><trans-title>MODERN CONCEPTS ON THE ROLE OF HYPOXIA IN THE DEVELOPMENT OF TUMOR RADIORESISTANCE</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8371-740X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Сеньчукова</surname><given-names>М. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Senchukova</surname><given-names>M. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Россия, 460000, г. Оренбург, ул. Советская, 6</p><p>Россия, 460021, г. Оренбург, пр. Гагарина, 11</p></bio><bio xml:lang="en"><p>MD, DSc, Professor of the Radiation Diagnostics, Radiation Therapy, Oncology Department; Oncologist, Surgical Thoracic Department</p><p>6, Sovetskaya Street, 460000, Orenburg, Russia</p><p>11, Gagarina Street, 460021, Orenburg, Russia</p></bio><email xlink:type="simple">malena2419@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/0000-0002-5796-3719</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Макарова</surname><given-names>Е. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Makarova</surname><given-names>E. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Россия, 460000, г. Оренбург, ул. Советская, 6</p><p>Россия, 460021, г. Оренбург, пр. Гагарина, 11</p></bio><bio xml:lang="en"><p>MD, Postgraduate, Radiation Diagnostics, Radiation Therapy, Oncology Department; Oncologist</p><p>6, Sovetskaya Street, 460000, Orenburg, Russia</p><p>11, Gagarina Street, 460021, Orenburg, Russia</p></bio><email xlink:type="simple">malena2419@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/0000-0001-5329-3589</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Калинин</surname><given-names>Е. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kalinin</surname><given-names>E. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Россия, 460021, г. Оренбург, пр. Гагарина, 11</p></bio><bio xml:lang="en"><p>11, Gagarina Street, 460021, Orenburg, Russia</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/0000-0002-8733-2205</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ткачев</surname><given-names>В. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Tkachev</surname><given-names>V. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Россия, 460021, г. Оренбург, пр. Гагарина, 11</p></bio><bio xml:lang="en"><p>11, Gagarina Street, 460021, Orenburg, Russia</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/0000-0001-7025-0206</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Зубарева</surname><given-names>Е. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Zubareva</surname><given-names>E. Y.</given-names></name></name-alternatives><bio xml:lang="ru"><p>аспирант кафедры лучевой диагностики, лучевой терапии, онкологии; врач-онколог</p><p>Россия, 460000, г. Оренбург, ул. Советская, 6</p><p>Россия, 460021, г. Оренбург, пр. Гагарина, 11</p><p> </p></bio><bio xml:lang="en"><p>MD, Postgraduate, Radiation Diagnostics, Radiation Therapy, Oncology Department; Oncologist</p><p>6, Sovetskaya Street, 460000, Orenburg, Russia</p><p>11, Gagarina Street, 460021, Orenburg, Russia</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru">ФГБОУ ВО «Оренбургский государственный медицинский университет»;&#13;
ГБУЗ «Оренбургский областной клинический онкологический диспансер»<country>Россия</country></aff><aff xml:lang="en">Orenburg State Medical University;&#13;
Orenburg Regional Oncology Clinic<country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru">ГБУЗ «Оренбургский областной клинический онкологический диспансер»<country>Россия</country></aff><aff xml:lang="en">Orenburg Regional Oncology Clinic<country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2020</year></pub-date><pub-date pub-type="epub"><day>30</day><month>12</month><year>2020</year></pub-date><volume>19</volume><issue>6</issue><fpage>141</fpage><lpage>147</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Сеньчукова М.А., Макарова Е.В., Калинин Е.А., Ткачев В.В., Зубарева Е.Ю., 2020</copyright-statement><copyright-year>2020</copyright-year><copyright-holder xml:lang="ru">Сеньчукова М.А., Макарова Е.В., Калинин Е.А., Ткачев В.В., Зубарева Е.Ю.</copyright-holder><copyright-holder xml:lang="en">Senchukova M.A., Makarova E.V., Kalinin E.A., Tkachev V.V., Zubareva E.Y.</copyright-holder><license 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/1653">https://www.siboncoj.ru/jour/article/view/1653</self-uri><abstract><p>Цель исследования – систематизировать и обобщить современные представления о роли гипоксии в развитии радиорезистентности злокачественных опухолей. </p><sec><title>Материал и методы</title><p>Материал и методы. Для поиска научных источников использовались базы pubmed, elibrary.Ru и springer. Проведен анализ публикаций с 1953 по 2020 г., 57 из которых были использованы для написания данного обзора. </p></sec><sec><title>Результаты</title><p>Результаты. Лучевая терапия является одним из важнейших методов лечения злокачественных новообразований. Основной причиной неудовлетворительных  результатов лечения пациентов, перенесших лучевую терапию, является развитие рецидива заболевания на фоне радиорезистентности опухолевых клеток. Механизмы  радиорезистентности рака очень сложны и зависят от многих факторов, из которых  гипоксия является наиболее важным. Под влиянием гипоксии происходит активация механизмов ангиогенеза, эпителиально-мезенхимальной трансформации, формируется пул раковых стволовых клеток, отличающихся химио- и радиорезистентностью. В свою  очередь, выраженность гипоксии во многом зависит от особенностей кровоснабжения  опухоли. При этом не только количество, но и качественные характеристики сосудов могут влиять на развитие тканевой гипоксии в опухоли. </p></sec><sec><title>Заключение</title><p>Заключение. Таким образом, комплексная оценка выраженности гипоксии,  особенностей ангиогенеза и эпителиальномезенхимальной трансформации может  способствовать лучшему пониманию механизмов развития радиорезистентности  злокачественных новообразований. </p></sec></abstract><trans-abstract xml:lang="en"><p>The purpose of the study was to systematize and summarize modern ideas about the role of hypoxia in the development of tumor radioresistance.</p><sec><title>Material and Methods</title><p>Material and Methods. PubMed, eLibrary and Springer databases were used to identify reviews published from 1953 to 2020, of which 57 were selected to write our review.</p></sec><sec><title>Results</title><p>Results. Radiation therapy is one of the most important components in cancer treatment. The major drawback of radiation therapy is the development radiation resistance in cancerous cells and secondary malignancies. The mechanisms of cancer radioresistance are very complicated and affected by many factors, of which hypoxia is the most important. Hypoxia is able to activate the mechanisms of angiogenesis, epithelial-mesenchymal transformation and contribute to the formation of the pool of cancer stem cell, which are characterized by chemo- and radioresistance. In turn, the severity of hypoxia largely dependent on tumor blood flow. Moreover, not only the quantitative but also the qualitative characteristics of blood vessels can affect the development of tissue hypoxia in the tumor.</p></sec><sec><title>Conclusion</title><p>Conclusion. A comprehensive assessment of the severity of hypoxia, as well as characteristics of angiogenesis and EMT can contribute to a better understanding of the mechanisms of development of cancer radioresistance.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>злокачественные опухоли</kwd><kwd>лучевая терапия</kwd><kwd>радиорезистентность</kwd><kwd>гипоксия</kwd><kwd>эпителиально-мезенхимальная трансформация</kwd><kwd>ангиогенез</kwd></kwd-group><kwd-group xml:lang="en"><kwd>malignant tumors</kwd><kwd>radiation therapy</kwd><kwd>radioresistance</kwd><kwd>hypoxia</kwd><kwd>epithelial-mesenchymal transformation</kwd><kwd>angiogenesis</kwd></kwd-group><funding-group xml:lang="ru"><funding-statement>Работа выполнена при финансовой поддержке РФФИ и субъекта РФ в рамках научных проектов № 18-415-560005 и 19-415-560004.</funding-statement></funding-group><funding-group xml:lang="en"><funding-statement>The study was funded by Russian Foundation for Basic Research, grant No 18-415-560005 and No.19-415- 560004.</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">Iyer N.G., Tan D.S., Tan V.K., Wang W., Hwang J., Tan N.C., Sivanandan R., Tan H.K., Lim W.T., Ang M.K., Wee J., Soo K.C., Tan E.H. Randomized trial comparing surgery and adjuvant radiotherapy versus concurrent chemoradiotherapy in patients with advanced, nonmetastatic squamous cell carcinoma of the head and neck: 10-year update and subset analysis. Cancer. 2015 May 15; 121(10): 1599–607. doi: 10.1002/cncr.29251.</mixed-citation><mixed-citation xml:lang="en">Iyer N.G., Tan D.S., Tan V.K., Wang W., Hwang J., Tan N.C., Sivanandan R., Tan H.K., Lim W.T., Ang M.K., Wee J., Soo K.C., Tan E.H. Randomized trial comparing surgery and adjuvant radiotherapy versus concurrent chemoradiotherapy in patients with advanced, nonmetastatic squamous cell carcinoma of the head and neck: 10-year update and subset analysis. Cancer. 2015 May 15; 121(10): 1599–607. doi: 10.1002/cncr.29251.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Roxburgh C.S., Weiser M.R. Selective use of radiation for locally advanced rectal cancer: one size does not fit all. Minerva Chir. 2018 Dec; 73(6): 592–600. doi: 10.23736/S0026-4733.18.07791-X.</mixed-citation><mixed-citation xml:lang="en">Roxburgh C.S., Weiser M.R. Selective use of radiation for locally advanced rectal cancer: one size does not fit all. Minerva Chir. 2018 Dec; 73(6): 592–600. doi: 10.23736/S0026-4733.18.07791-X.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Baskar R., Itahana K. Radiation therapy and cancer control in developing countries: Can we save more lives? Int J Med Sci. 2017 Jan 1; 14(1): 13–17. doi: 10.7150/ijms.17288.</mixed-citation><mixed-citation xml:lang="en">Baskar R., Itahana K. Radiation therapy and cancer control in developing countries: Can we save more lives? Int J Med Sci. 2017 Jan 1; 14(1): 13–17. doi: 10.7150/ijms.17288.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Hekim N., Cetin Z., Nikitaki Z., Cort A., Saygili E.I. Radiation triggering immune response and inflammation. Cancer Lett. 2015 Nov 28; 368(2): 156–63. doi: 10.1016/j.canlet.2015.04.016.</mixed-citation><mixed-citation xml:lang="en">Hekim N., Cetin Z., Nikitaki Z., Cort A., Saygili E.I. Radiation triggering immune response and inflammation. Cancer Lett. 2015 Nov 28; 368(2): 156–63. doi: 10.1016/j.canlet.2015.04.016.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Wennerberg E., Lhuillier C., Vanpouille-Box C., Pilones K.A., García-Martínez E., Rudqvist N.P., Formenti S.C., Demaria S. Barriers to Radiation-Induced In Situ Tumor Vaccination. Front Immunol. 2017 Mar 13; 8: 229. doi: 10.3389/fimmu.2017.00229.</mixed-citation><mixed-citation xml:lang="en">Wennerberg E., Lhuillier C., Vanpouille-Box C., Pilones K.A., García-Martínez E., Rudqvist N.P., Formenti S.C., Demaria S. Barriers to Radiation-Induced In Situ Tumor Vaccination. Front Immunol. 2017 Mar 13; 8: 229. doi: 10.3389/fimmu.2017.00229.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Tsoutsou P.G., Zaman K., Martin Lluesma S., Cagnon L., Kandalaft L., Vozenin M.C. Emerging Opportunities of Radiotherapy Combined With Immunotherapy in the Era of Breast Cancer Heterogeneity. Front Oncol. 2018 Dec 12; 8: 609. doi: 10.3389/fonc.2018.00609.</mixed-citation><mixed-citation xml:lang="en">Tsoutsou P.G., Zaman K., Martin Lluesma S., Cagnon L., Kandalaft L., Vozenin M.C. Emerging Opportunities of Radiotherapy Combined With Immunotherapy in the Era of Breast Cancer Heterogeneity. Front Oncol. 2018 Dec 12; 8: 609. doi: 10.3389/fonc.2018.00609.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Rachmadi L., Siregar N.C., Kanoko M., Andrijono A., Bardosono S., Suryandari D.A., Sekarutami S.M., Hernowo B.S. Role of Cancer Stem Cell, Apoptotic Factor, DNA Repair, and Telomerase Toward Radiation Therapy Response in Stage IIIB Cervical Cancer. Oman Med J. 2019; 34(3): 224–30. doi: 10.5001/omj.2019.43.</mixed-citation><mixed-citation xml:lang="en">Rachmadi L., Siregar N.C., Kanoko M., Andrijono A., Bardosono S., Suryandari D.A., Sekarutami S.M., Hernowo B.S. Role of Cancer Stem Cell, Apoptotic Factor, DNA Repair, and Telomerase Toward Radiation Therapy Response in Stage IIIB Cervical Cancer. Oman Med J. 2019; 34(3): 224–30. doi: 10.5001/omj.2019.43.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Tang L., Wei F., Wu Y., He Y., Shi L., Xiong F., Gong Z., Guo C., Li X., Deng H., Cao K., Zhou M., Xiang B., Li X., Li Y., Li G., Xiong W., Zeng Z. Role of metabolism in cancer cell radioresistance and radiosensitization methods. J Exp Clin Cancer Res. 2018 Apr 23; 37(1): 87. doi: 10.1186/s13046-018-0758-7.</mixed-citation><mixed-citation xml:lang="en">Tang L., Wei F., Wu Y., He Y., Shi L., Xiong F., Gong Z., Guo C., Li X., Deng H., Cao K., Zhou M., Xiang B., Li X., Li Y., Li G., Xiong W., Zeng Z. Role of metabolism in cancer cell radioresistance and radiosensitization methods. J Exp Clin Cancer Res. 2018 Apr 23; 37(1): 87. doi: 10.1186/s13046-018-0758-7.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Васильченко Н.Г., Кутилин Д.С., Тимошкина Н.Н., Потемкин Д.С., Полуэктов С.И., Гусарева М.А., Кошелева Н.Г., Солдатова К.И., Максимов А.Ю., Кит О.И., Сидоренко Ю.С. Современные схемы лучевой терапии и биомаркеры радиорезистентности опухолевых клеток прямой кишки. Сибирский онкологический журнал. 2019; 18(6): 105–113. doi: 10.21294/1814-4861-2019-18-6-105-113.</mixed-citation><mixed-citation xml:lang="en">Vasilchenko N.G., Kutilin D.S., Timoshkina N.N., Potyomkin D.S., Poluektov S.I., Gusareva M.A., Kosheleva N.G., Soldatova K.I., Maksimov A.Y., Kit O.I., Sidorenko Yu.S. Modern radiotherapy regimens and biomarkers of radioresistant rectal tumor cells. Siberian Journal of Oncology. 2019; 18(6): 105–113. (in Russian). doi: 10.21294/1814-4861-2019-18-6-105-113.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Akiyama A., Minaguchi T., Fujieda K., Hosokawa Y., Nishida K., Shikama A., Tasaka N., Sakurai M., Ochi H., Satoh T. Abnormal accumulation of p53 predicts radioresistance leading to poor survival in patients with endometrial carcinoma. Oncol Lett. 2019; 18(6): 5952–58. doi: 10.3892/ol.2019.10940.</mixed-citation><mixed-citation xml:lang="en">Akiyama A., Minaguchi T., Fujieda K., Hosokawa Y., Nishida K., Shikama A., Tasaka N., Sakurai M., Ochi H., Satoh T. Abnormal accumulation of p53 predicts radioresistance leading to poor survival in patients with endometrial carcinoma. Oncol Lett. 2019; 18(6): 5952–58. doi: 10.3892/ol.2019.10940.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Chou S.Y., Yen S.L., Huang C.C., Huang E.Y. Galectin-1 is a poor prognostic factor in patients with glioblastoma multiforme after radiotherapy. BMC Cancer. 2018 Jan 30; 18(1): 105. doi: 10.1186/s12885-018-4025-2.</mixed-citation><mixed-citation xml:lang="en">Chou S.Y., Yen S.L., Huang C.C., Huang E.Y. Galectin-1 is a poor prognostic factor in patients with glioblastoma multiforme after radiotherapy. BMC Cancer. 2018 Jan 30; 18(1): 105. doi: 10.1186/s12885-018-4025-2.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Duregon E., Senetta R., Pittaro A., Verdun di Cantogno L., Stella G., De Blasi P., Zorzetto M., Mantovani C., Papotti M., Cassoni P. CAVEOLIN-1 expression in brain metastasis from lung cancer predicts worse outcome and radioresistance, irrespective of tumor histotype. Oncotarget. 2015 Oct 6; 6(30): 29626–36. doi: 10.18632/oncotarget.4988.</mixed-citation><mixed-citation xml:lang="en">Duregon E., Senetta R., Pittaro A., Verdun di Cantogno L., Stella G., De Blasi P., Zorzetto M., Mantovani C., Papotti M., Cassoni P. CAVEOLIN-1 expression in brain metastasis from lung cancer predicts worse outcome and radioresistance, irrespective of tumor histotype. Oncotarget. 2015 Oct 6; 6(30): 29626–36. doi: 10.18632/oncotarget.4988.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Fiedler M., Weber F., Hautmann M.G., Haubner F., Reichert T.E., Klingelhöffer C., Schreml S., Meier J.K., Hartmann A., Ettl T. Biological predictors of radiosensitivity in head and neck squamous cell carcinoma. Clin Oral Investig. 2018 Jan; 22(1): 189–200. doi: 10.1007/s00784-017-2099-x.</mixed-citation><mixed-citation xml:lang="en">Fiedler M., Weber F., Hautmann M.G., Haubner F., Reichert T.E., Klingelhöffer C., Schreml S., Meier J.K., Hartmann A., Ettl T. Biological predictors of radiosensitivity in head and neck squamous cell carcinoma. Clin Oral Investig. 2018 Jan; 22(1): 189–200. doi: 10.1007/s00784-017-2099-x.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Чернышова А.Л., Старцева Ж.А., Затолокина А.А. Оптимизация выбора адъювантной лучевой терапии у больных раком тела матки I cтадии. Сибирский онкологический журнал. 2014; (6): 54–59.</mixed-citation><mixed-citation xml:lang="en">Chernyshova А.L., Startseva Z.А., Zatolokina А.А. Optimization of the choice of adjuvant therapy in patients with uterine corpus cancer. Siberian Journal of Oncology. 2014; (6): 54–59. (in Russian).</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Horsman M.R., Overgaard J. The impact of hypoxia and its modification of the outcome of radiotherapy. J Radiat Res. 2016 Aug; 57 Suppl 1(Suppl 1): i90i98. doi: 10.1093/jrr/rrw007.</mixed-citation><mixed-citation xml:lang="en">Horsman M.R., Overgaard J. The impact of hypoxia and its modification of the outcome of radiotherapy. J Radiat Res. 2016 Aug; 57 Suppl 1(Suppl 1): i90i98. doi: 10.1093/jrr/rrw007.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Span P.N., Bussink J. The Role of Hypoxia and the Immune System in Tumor Radioresistance. Cancers (Basel). 2019 Oct 14; 11(10): 1555. doi: 10.3390/cancers11101555.</mixed-citation><mixed-citation xml:lang="en">Span P.N., Bussink J. The Role of Hypoxia and the Immune System in Tumor Radioresistance. Cancers (Basel). 2019 Oct 14; 11(10): 1555. doi: 10.3390/cancers11101555.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Brown J.M., Wilson W.R. Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer. 2004 Jun; 4(6): 437–47. doi: 10.1038/nrc1367.</mixed-citation><mixed-citation xml:lang="en">Brown J.M., Wilson W.R. Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer. 2004 Jun; 4(6): 437–47. doi: 10.1038/nrc1367.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Eales K.L., Hollinshead K.E., Tennant D.A. Hypoxia and metabolic adaptation of cancer cells. Oncogenesis. 2016; 5(1): e190. doi: 10.1038/oncsis.2015.50.</mixed-citation><mixed-citation xml:lang="en">Eales K.L., Hollinshead K.E., Tennant D.A. Hypoxia and metabolic adaptation of cancer cells. Oncogenesis. 2016; 5(1): e190. doi: 10.1038/oncsis.2015.50.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Wang H., Jiang H., Van De Gucht M., De Ridder M. Hypoxic Radioresistance: Can ROS Be the Key to Overcome It? Cancers (Basel). 2019 Jan 18; 11(1): 112. doi: 10.3390/cancers11010112.</mixed-citation><mixed-citation xml:lang="en">Wang H., Jiang H., Van De Gucht M., De Ridder M. Hypoxic Radioresistance: Can ROS Be the Key to Overcome It? Cancers (Basel). 2019 Jan 18; 11(1): 112. doi: 10.3390/cancers11010112.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Muz B., de la Puente P., Azab F., Azab A.K. The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy. Hypoxia (Auckl). 2015 Dec 11; 3: 83–92. doi: 10.2147/HP.S93413.</mixed-citation><mixed-citation xml:lang="en">Muz B., de la Puente P., Azab F., Azab A.K. The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy. Hypoxia (Auckl). 2015 Dec 11; 3: 83–92. doi: 10.2147/HP.S93413.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Rohwer N., Cramer T. Hypoxia-mediated drug resistance: novel insights on the functional interaction of HIFs and cell death pathways. Drug Resist Updat. 2011 Jun; 14(3): 191–201. doi: 10.1016/j.drup.2011.03.001.</mixed-citation><mixed-citation xml:lang="en">Rohwer N., Cramer T. Hypoxia-mediated drug resistance: novel insights on the functional interaction of HIFs and cell death pathways. Drug Resist Updat. 2011 Jun; 14(3): 191–201. doi: 10.1016/j.drup.2011.03.001.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Fu Z., Chen D., Cheng H., Wang F. Hypoxia-inducible factor-1α protects cervical carcinoma cells from apoptosis induced by radiation via modulation of vascular endothelial growth factor and p53 under hypoxia. Med Sci Monit. 2015 Jan 27; 21: 318–25. doi: 10.12659/MSM.893265.</mixed-citation><mixed-citation xml:lang="en">Fu Z., Chen D., Cheng H., Wang F. Hypoxia-inducible factor-1α protects cervical carcinoma cells from apoptosis induced by radiation via modulation of vascular endothelial growth factor and p53 under hypoxia. Med Sci Monit. 2015 Jan 27; 21: 318–25. doi: 10.12659/MSM.893265.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Ebner D.K., Tinganelli W., Helm A., Bisio A., Yamada S., Kamada T., Shimokawa T., Durante M. The Immunoregulatory Potential of Particle Radiation in Cancer Therapy. Front Immunol. 2017 Feb 6; 8: 99. doi: 10.3389/fimmu.2017.00099.</mixed-citation><mixed-citation xml:lang="en">Ebner D.K., Tinganelli W., Helm A., Bisio A., Yamada S., Kamada T., Shimokawa T., Durante M. The Immunoregulatory Potential of Particle Radiation in Cancer Therapy. Front Immunol. 2017 Feb 6; 8: 99. doi: 10.3389/fimmu.2017.00099.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Menon H., Ramapriyan R., Cushman T.R., Verma V., Kim H.H., Schoenhals J.E., Atalar C., Selek U., Chun S.G., Chang J.Y., Barsoumian H.B., Nguyen Q.N., Altan M., Cortez M.A., Hahn S.M., Welsh J.W. Role of Radiation Therapy in Modulation of the Tumor Stroma and Microenvironment. Front Immunol. 2019 Feb 15; 10: 193. doi: 10.3389/fimmu.2019.00193.</mixed-citation><mixed-citation xml:lang="en">Menon H., Ramapriyan R., Cushman T.R., Verma V., Kim H.H., Schoenhals J.E., Atalar C., Selek U., Chun S.G., Chang J.Y., Barsoumian H.B., Nguyen Q.N., Altan M., Cortez M.A., Hahn S.M., Welsh J.W. Role of Radiation Therapy in Modulation of the Tumor Stroma and Microenvironment. Front Immunol. 2019 Feb 15; 10: 193. doi: 10.3389/fimmu.2019.00193.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Shevtsov M., Sato H., Multhoff G., Shibata A. Novel Approaches to Improve the Efficacy of Immuno-Radiotherapy. Front Oncol. 2019 Mar 19; 9: 156. doi: 10.3389/fonc.2019.00156.</mixed-citation><mixed-citation xml:lang="en">Shevtsov M., Sato H., Multhoff G., Shibata A. Novel Approaches to Improve the Efficacy of Immuno-Radiotherapy. Front Oncol. 2019 Mar 19; 9: 156. doi: 10.3389/fonc.2019.00156.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Sethumadhavan S., Silva M., Philbrook P., Nguyen T., Hatfield S.M., Ohta A., Sitkovsky M.V. Hypoxia and hypoxia-inducible factor (HIF) downregulate antigen-presenting MHC class I molecules limiting tumor cell recognition by T cells. PLoS One. 2017; 12(11): e0187314. doi: 10.1371/journal.pone.0187314.</mixed-citation><mixed-citation xml:lang="en">Sethumadhavan S., Silva M., Philbrook P., Nguyen T., Hatfield S.M., Ohta A., Sitkovsky M.V. Hypoxia and hypoxia-inducible factor (HIF) downregulate antigen-presenting MHC class I molecules limiting tumor cell recognition by T cells. PLoS One. 2017; 12(11): e0187314. doi: 10.1371/journal.pone.0187314.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Noman M.Z., Hasmim M., Lequeux A., Xiao M., Duhem C., Chouaib S., Berchem G., Janji B. Improving Cancer Immunotherapy by Targeting the Hypoxic Tumor Microenvironment: New Opportunities and Challenges. Cells. 2019 Sep 14; 8(9): 1083. doi: 10.3390/cells8091083.</mixed-citation><mixed-citation xml:lang="en">Noman M.Z., Hasmim M., Lequeux A., Xiao M., Duhem C., Chouaib S., Berchem G., Janji B. Improving Cancer Immunotherapy by Targeting the Hypoxic Tumor Microenvironment: New Opportunities and Challenges. Cells. 2019 Sep 14; 8(9): 1083. doi: 10.3390/cells8091083.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Smolarczyk R., Cichoń T., Pilny E., Jarosz-Biej M., Poczkaj A., Kułach N., Szala S. Combination of anti-vascular agent DMXAA and HIF-1α inhibitor digoxin inhibits the growth of melanoma tumors. Sci Rep. 2018 May 9; 8(1): 7355. doi: 10.1038/s41598-018-25688-y.</mixed-citation><mixed-citation xml:lang="en">Smolarczyk R., Cichoń T., Pilny E., Jarosz-Biej M., Poczkaj A., Kułach N., Szala S. Combination of anti-vascular agent DMXAA and HIF-1α inhibitor digoxin inhibits the growth of melanoma tumors. Sci Rep. 2018 May 9; 8(1): 7355. doi: 10.1038/s41598-018-25688-y.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Vanpouille-Box C., Diamond J.M., Pilones K.A., Zavadil J., Babb J.S., Formenti S.C., Barcellos-Hoff M.H., Demaria S. TGFβ Is a Master Regulator of Radiation Therapy-Induced Antitumor Immunity. Cancer Res. 2015 Jun 1; 75(11): 2232–42. doi: 10.1158/0008-5472.CAN-14-3511.</mixed-citation><mixed-citation xml:lang="en">Vanpouille-Box C., Diamond J.M., Pilones K.A., Zavadil J., Babb J.S., Formenti S.C., Barcellos-Hoff M.H., Demaria S. TGFβ Is a Master Regulator of Radiation Therapy-Induced Antitumor Immunity. Cancer Res. 2015 Jun 1; 75(11): 2232–42. doi: 10.1158/0008-5472.CAN-14-3511.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Horsman M.R. Measurement of Tumor Oxygenation. Int J Radiat Oncol Biol Phys. 1998 Nov 1; 42 (4): 701–4. doi: 10.1016/s0360-3016(98)00332-0.</mixed-citation><mixed-citation xml:lang="en">Horsman M.R. Measurement of Tumor Oxygenation. Int J Radiat Oncol Biol Phys. 1998 Nov 1; 42 (4): 701–4. doi: 10.1016/s0360-3016(98)00332-0.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Cao X., Rao Allu S., Jiang S., Jia M., Gunn J.R., Yao C., LaRochelle E.P., Shell J.R., Bruza P., Gladstone D.J., Jarvis L.A., Tian J., Vinogradov S.A., Pogue B.W. Tissue pO2 distributions in xenograft tumors dynamically imaged by Cherenkov-excited phosphorescence during fractionated radiation therapy. Nat Commun. 2020 Jan 29; 11(1): 573. doi: 10.1038/s41467-020-14415-9.</mixed-citation><mixed-citation xml:lang="en">Cao X., Rao Allu S., Jiang S., Jia M., Gunn J.R., Yao C., LaRochelle E.P., Shell J.R., Bruza P., Gladstone D.J., Jarvis L.A., Tian J., Vinogradov S.A., Pogue B.W. Tissue pO2 distributions in xenograft tumors dynamically imaged by Cherenkov-excited phosphorescence during fractionated radiation therapy. Nat Commun. 2020 Jan 29; 11(1): 573. doi: 10.1038/s41467-020-14415-9.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Peerlings J., Van De Voorde L., Mitea C., Larue R., Yaromina A., Sandeleanu S., Spiegelberg L., Dubois L., Lambin P., Mottaghy F.M. Hypoxia and hypoxia response-associated molecular markers in esophageal cancer: A systematic review. Methods. 2017 Nov; 130: 51–62. doi: 10.1016/j.ymeth.2017.07.002.</mixed-citation><mixed-citation xml:lang="en">Peerlings J., Van De Voorde L., Mitea C., Larue R., Yaromina A., Sandeleanu S., Spiegelberg L., Dubois L., Lambin P., Mottaghy F.M. Hypoxia and hypoxia response-associated molecular markers in esophageal cancer: A systematic review. Methods. 2017 Nov; 130: 51–62. doi: 10.1016/j.ymeth.2017.07.002.</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Harada H. Hypoxia-inducible factor 1-mediated characteristic features of cancer cells for tumor radioresistance. J Radiat Res. 2016 Aug; 57 Suppl 1(Suppl 1): 99–105. doi: 10.1093/jrr/rrw012.</mixed-citation><mixed-citation xml:lang="en">Harada H. Hypoxia-inducible factor 1-mediated characteristic features of cancer cells for tumor radioresistance. J Radiat Res. 2016 Aug; 57 Suppl 1(Suppl 1): 99–105. doi: 10.1093/jrr/rrw012.</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Zeng L., Morinibu A., Kobayashi M., Zhu Y., Wang X., Goto Y., Yeom C.J., Zhao T., Hirota K., Shinomiya K., Itasaka S., Yoshimura M., Guo G., Hammond E.M., Hiraoka M., Harada H. Aberrant IDH3α Expression Promotes Malignant Tumor Growth by Inducing HIF-1-mediated Metabolic Reprogramming and Angiogenesis. Oncogene. 2015; 34(36): 4758–66. doi: 10.1038/onc.2014.411.</mixed-citation><mixed-citation xml:lang="en">Zeng L., Morinibu A., Kobayashi M., Zhu Y., Wang X., Goto Y., Yeom C.J., Zhao T., Hirota K., Shinomiya K., Itasaka S., Yoshimura M., Guo G., Hammond E.M., Hiraoka M., Harada H. Aberrant IDH3α Expression Promotes Malignant Tumor Growth by Inducing HIF-1-mediated Metabolic Reprogramming and Angiogenesis. Oncogene. 2015; 34(36): 4758–66. doi: 10.1038/onc.2014.411.</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Yeo C.D., Kang N., Choi S.Y., Kim B.N., Park C.K., Kim J.W., Kim Y.K., Kim S.J. The role of hypoxia on the acquisition of epithelialmesenchymal transition and cancer stemness: a possible link to epigenetic regulation. Korean J Intern Med. 2017 Jul; 32(4): 589–599. doi: 10.3904/kjim.2016.302.</mixed-citation><mixed-citation xml:lang="en">Yeo C.D., Kang N., Choi S.Y., Kim B.N., Park C.K., Kim J.W., Kim Y.K., Kim S.J. The role of hypoxia on the acquisition of epithelialmesenchymal transition and cancer stemness: a possible link to epigenetic regulation. Korean J Intern Med. 2017 Jul; 32(4): 589–599. doi: 10.3904/kjim.2016.302.</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Kakurina G.V., Kondakova I.V., Spirina L.V., Kolegova E.S., Shashova E.E., Cheremisina O.V., Novikov V.A., Choinzonov E.L. Expression of genes encoding cell motility proteins during progression of head and neck squamous cell carcinoma. Bull Exp Biol Med. 2018; 166(2): 250–252. doi: 10.1007/S10517-018-4325-1.</mixed-citation><mixed-citation xml:lang="en">Kakurina G.V., Kondakova I.V., Spirina L.V., Kolegova E.S., Shashova E.E., Cheremisina O.V., Novikov V.A., Choinzonov E.L. Expression of genes encoding cell motility proteins during progression of head and neck squamous cell carcinoma. Bull Exp Biol Med. 2018; 166(2): 250–252. doi: 10.1007/S10517-018-4325-1.</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Liu Z.J., Semenza G.L., Zhang H.F. Hypoxia-inducible factor 1 and breast cancer metastasis. J Zhejiang Univ Sci B. 2015 Jan; 16(1): 32–43. doi: 10.1631/jzus.B1400221.</mixed-citation><mixed-citation xml:lang="en">Liu Z.J., Semenza G.L., Zhang H.F. Hypoxia-inducible factor 1 and breast cancer metastasis. J Zhejiang Univ Sci B. 2015 Jan; 16(1): 32–43. doi: 10.1631/jzus.B1400221.</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Luo Y., Li M., Zuo X., Basourakos S.P., Zhang J., Zhao J., Han Y., Lin Y., Wang Y., Jiang Y., Lan L. βcatenin nuclear translocation induced by HIF1α overexpression leads to the radioresistance of prostate cancer. Int J Oncol. 2018 Jun; 52(6): 1827–1840. doi: 10.3892/ijo.2018.4368.</mixed-citation><mixed-citation xml:lang="en">Luo Y., Li M., Zuo X., Basourakos S.P., Zhang J., Zhao J., Han Y., Lin Y., Wang Y., Jiang Y., Lan L. βcatenin nuclear translocation induced by HIF1α overexpression leads to the radioresistance of prostate cancer. Int J Oncol. 2018 Jun; 52(6): 1827–1840. doi: 10.3892/ijo.2018.4368.</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Koukourakis M., Kakouratos C., Kalamida D., Bampali Z., Mavropoulou S., Sivridis E., Giatromanolaki A. Hypoxia-inducible proteins HIF1α and lactate dehydrogenase LDH5, key markers of anaerobic metabolism, relate with stem cell markers and poor post-radiotherapy outcome in bladder cancer. Int J Radiat Biol. 2016 Jul; 92(7): 353–63. doi: 10.3109/09553002.2016.1162921.</mixed-citation><mixed-citation xml:lang="en">Koukourakis M., Kakouratos C., Kalamida D., Bampali Z., Mavropoulou S., Sivridis E., Giatromanolaki A. Hypoxia-inducible proteins HIF1α and lactate dehydrogenase LDH5, key markers of anaerobic metabolism, relate with stem cell markers and poor post-radiotherapy outcome in bladder cancer. Int J Radiat Biol. 2016 Jul; 92(7): 353–63. doi: 10.3109/09553002.2016.1162921.</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Lee S.Y., Jeong E.K., Ju M.K., Jeon H.M., Kim M.Y., Kim C.H., Park H.G., Han S.I., Kang H.S. Induction of metastasis, cancer stem cell phenotype, and oncogenic metabolism in cancer cells by ionizing radiation. Mol Cancer. 2017 Jan 30; 16(1): 10. doi: 10.1186/s12943-016-0577-4.</mixed-citation><mixed-citation xml:lang="en">Lee S.Y., Jeong E.K., Ju M.K., Jeon H.M., Kim M.Y., Kim C.H., Park H.G., Han S.I., Kang H.S. Induction of metastasis, cancer stem cell phenotype, and oncogenic metabolism in cancer cells by ionizing radiation. Mol Cancer. 2017 Jan 30; 16(1): 10. doi: 10.1186/s12943-016-0577-4.</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Rycaj K., Tang D.G. Cancer stem cells and radioresistance. International journal of radiation biology. 2014; 90: 615–21. doi: 10.3109/09553002.2014.892227.</mixed-citation><mixed-citation xml:lang="en">Rycaj K., Tang D.G. Cancer stem cells and radioresistance. International journal of radiation biology. 2014; 90: 615–21. doi: 10.3109/09553002.2014.892227.</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Gomez-Casal R., Bhattacharya C., Ganesh N., Bailey L., Basse P., Gibson M., Epperly M., Levina V. Non-small cell lung cancer cells survived ionizing radiation treatment display cancer stem cell and epithelialmesenchymal transition phenotypes. Mol Cancer. 2013; 12(1): 94. doi: 10.1186/1476-4598-12-94.</mixed-citation><mixed-citation xml:lang="en">Gomez-Casal R., Bhattacharya C., Ganesh N., Bailey L., Basse P., Gibson M., Epperly M., Levina V. Non-small cell lung cancer cells survived ionizing radiation treatment display cancer stem cell and epithelialmesenchymal transition phenotypes. Mol Cancer. 2013; 12(1): 94. doi: 1186/1476-4598-12-94.</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Barker H.E., Paget J.T., Khan A.A., Harrington K.J. The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence. Nat Rev Cancer. 2015 Jul; 15(7): 409–25. doi: 10.1038/nrc3958.</mixed-citation><mixed-citation xml:lang="en">Barker H.E., Paget J.T., Khan A.A., Harrington K.J. The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence. Nat Rev Cancer. 2015 Jul; 15(7): 409–25. doi: 10.1038/nrc3958.</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Hellevik T., Pettersen I., Berg V., Winberg J.O., Moe B.T., Bartnes K., Paulssen R.H., Busund L.T., Bremnes R., Chalmers A., Martinez-Zubiaurre I. Cancer-associated fibroblasts from human NSCLC survive ablative doses of radiation but their invasive capacity is reduced. Radiat Oncol. 2012 Apr 13; 7: 59. doi: 10.1186/1748-717X-7-59.</mixed-citation><mixed-citation xml:lang="en">Hellevik T., Pettersen I., Berg V., Winberg J.O., Moe B.T., Bartnes K., Paulssen R.H., Busund L.T., Bremnes R., Chalmers A., Martinez-Zubiaurre I. Cancer-associated fibroblasts from human NSCLC survive ablative doses of radiation but their invasive capacity is reduced. Radiat Oncol. 2012 Apr 13; 7: 59. doi: 10.1186/1748-717X-7-59.</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Lindblom E.K., Dasu A., Toma-Dasu I. Hypoxia Induced by Vascular Damage at High Doses Could Compromise the Outcome of Radiotherapy. Anticancer Res. 2019 May; 39(5): 2337–2340. doi: 10.21873/anticanres.13350.</mixed-citation><mixed-citation xml:lang="en">Lindblom E.K., Dasu A., Toma-Dasu I. Hypoxia Induced by Vascular Damage at High Doses Could Compromise the Outcome of Radiotherapy. Anticancer Res. 2019 May; 39(5): 2337–2340. doi: 10.21873/anticanres.13350.</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Lindblom E., Toma-Dasu I., Dasu A.Accounting for Two Forms of Hypoxia for Predicting Tumour Control Probability in Radiotherapy: An In Silico Study. Adv Exp Med Biol. 2018; 1072: 183–87. doi: 10.1007/978-3-319-91287-5_29.</mixed-citation><mixed-citation xml:lang="en">Lindblom E., Toma-Dasu I., Dasu A.Accounting for Two Forms of Hypoxia for Predicting Tumour Control Probability in Radiotherapy: An In Silico Study. Adv Exp Med Biol. 2018; 1072: 183–87. doi: 10.1007/978-3-319-91287-5_29.</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Vaupel P., Mayer A. Hypoxia in Tumors: Pathogenesis-Related Classification, Characterization of Hypoxia Subtypes, and Associated Biological and Clinical Implications. Adv Exp Med Biol 2014; 812: 19–24. doi: 10.1007/978-1-4939-0620-8_3.</mixed-citation><mixed-citation xml:lang="en">Vaupel P., Mayer A. Hypoxia in Tumors: Pathogenesis-Related Classification, Characterization of Hypoxia Subtypes, and Associated Biological and Clinical Implications. Adv Exp Med Biol 2014; 812: 19–24. doi: 10.1007/978-1-4939-0620-8_3.</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Orel V.B., Zabolotny M.A., Orel V.E. Heterogeneity of hypoxia in solid tumours and mechanochemical reactions with oxygen nanobubbles. Med Hypotheses. 2017 May; 102: 82–86. doi: 10.1016/j.mehy.2017.03.006.</mixed-citation><mixed-citation xml:lang="en">Orel V.B., Zabolotny M.A., Orel V.E. Heterogeneity of hypoxia in solid tumours and mechanochemical reactions with oxygen nanobubbles. Med Hypotheses. 2017 May; 102: 82–86. doi: 10.1016/j.mehy.2017.03.006.</mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Birau A., Ceausu R.A., Cimpean A.M., Gaje P., Raica M., Olariu T. Assessement of angiogenesis reveals blood vessel heterogeneity in lung carcinoma. Oncol Lett. 2012 Dec; 4(6): 1183–86. doi: 10.3892/ol.2012.893.</mixed-citation><mixed-citation xml:lang="en">Birau A., Ceausu R.A., Cimpean A.M., Gaje P., Raica M., Olariu T. Assessement of angiogenesis reveals blood vessel heterogeneity in lung carcinoma. Oncol Lett. 2012 Dec; 4(6): 1183–86. doi: 10.3892/ol.2012.893.</mixed-citation></citation-alternatives></ref><ref id="cit50"><label>50</label><citation-alternatives><mixed-citation xml:lang="ru">Nagy J.A., Dvorak H.F. Heterogeneity of the tumor vasculature: the need for new tumor blood vessel type-specific targets. Clin Exp Metastasis. 2012 Oct; 29(7): 657–62. doi: 10.1007/s10585-012-9500-6.</mixed-citation><mixed-citation xml:lang="en">Nagy J.A., Dvorak H.F. Heterogeneity of the tumor vasculature: the need for new tumor blood vessel type-specific targets. Clin Exp Metastasis. 2012 Oct; 29(7): 657–62. doi: 10.1007/s10585-012-9500-6.</mixed-citation></citation-alternatives></ref><ref id="cit51"><label>51</label><citation-alternatives><mixed-citation xml:lang="ru">Senchukova M.A., Nikitenko N.V., Tomchuk O.N., Zaitsev N.V., Stadnikov A.A. Different types of tumor vessels in breast cancer: morphology and clinical value. Springerplus. 2015 Sep 17; 4: 512. doi: 10.1186/s40064-015-1293-z.</mixed-citation><mixed-citation xml:lang="en">Senchukova M.A., Nikitenko N.V., Tomchuk O.N., Zaitsev N.V., Stadnikov A.A. Different types of tumor vessels in breast cancer: morphology and clinical value. Springerplus. 2015 Sep 17; 4: 512. doi: 10.1186/s40064-015-1293-z.</mixed-citation></citation-alternatives></ref><ref id="cit52"><label>52</label><citation-alternatives><mixed-citation xml:lang="ru">Zhou X., Liu H., Zheng Y., Han Y., Wang T., Zhang H., Sun Q., Li Z. Overcoming Radioresistance in Tumor Therapy by Alleviating Hypoxia and Using the HIF-1 Inhibitor. ACS Appl Mater Interfaces. 2020 Jan 29; 12(4): 4231–4240. doi: 10.1021/acsami.9b18633.</mixed-citation><mixed-citation xml:lang="en">Zhou X., Liu H., Zheng Y., Han Y., Wang T., Zhang H., Sun Q., Li Z. Overcoming Radioresistance in Tumor Therapy by Alleviating Hypoxia and Using the HIF-1 Inhibitor. ACS Appl Mater Interfaces. 2020 Jan 29; 12(4): 4231–4240. doi: 10.1021/acsami.9b18633.</mixed-citation></citation-alternatives></ref><ref id="cit53"><label>53</label><citation-alternatives><mixed-citation xml:lang="ru">Siemann D.W., Horsman M.R. Modulation of the tumor vasculature and oxygenation to improve therapy. Pharmacol Ther. 2015 Sep; 153: 107–24. doi: 10.1016/j.pharmthera.2015.06.006.</mixed-citation><mixed-citation xml:lang="en">Siemann D.W., Horsman M.R. Modulation of the tumor vasculature and oxygenation to improve therapy. Pharmacol Ther. 2015 Sep; 153: 107–24. doi: 10.1016/j.pharmthera.2015.06.006.</mixed-citation></citation-alternatives></ref><ref id="cit54"><label>54</label><citation-alternatives><mixed-citation xml:lang="ru">Liu S., Wu F., Zhang Y., Qin R., Zhu N., Li Y., Wang M., Zeng Q., Xie D., Li Y., Fan J., Han Y. Apatinib Combined With Radiotherapy Enhances Antitumor Effects in an In Vivo Nasopharyngeal Carcinoma Model. Cancer Control. 2020 Jan-Dec; 27(1): 1073274820922553. doi: 10.1177/1073274820922553.</mixed-citation><mixed-citation xml:lang="en">Liu S., Wu F., Zhang Y., Qin R., Zhu N., Li Y., Wang M., Zeng Q., Xie D., Li Y., Fan J., Han Y. Apatinib Combined With Radiotherapy Enhances Antitumor Effects in an In Vivo Nasopharyngeal Carcinoma Model. Cancer Control. 2020 Jan-Dec; 27(1): 1073274820922553. doi: 10.1177/1073274820922553.</mixed-citation></citation-alternatives></ref><ref id="cit55"><label>55</label><citation-alternatives><mixed-citation xml:lang="ru">Janssens G.O., Rademakers S.E., Terhaard C.H., Doornaert P.A., Bijl H.P., van den Ende E., Chin A., Takes R.P., de Bree R., Hoogsteen I.J., Bussink J., Span P.N., Kaanders J.H. Improved RecurrenceFree Survival with ARCON for Anemic Patients with Laryngeal Cancer. Clinical Cancer Research. 2014; 20(5): 1345–54. doi: 10.1158/1078-0432.CCR-13-1730.</mixed-citation><mixed-citation xml:lang="en">Janssens G.O., Rademakers S.E., Terhaard C.H., Doornaert P.A., Bijl H.P., van den Ende E., Chin A., Takes R.P., de Bree R., Hoogsteen I.J., Bussink J., Span P.N., Kaanders J.H. Improved RecurrenceFree Survival with ARCON for Anemic Patients with Laryngeal Cancer. Clinical Cancer Research. 2014; 20(5): 1345–54. doi: 10.1158/1078-0432.CCR-13-1730.</mixed-citation></citation-alternatives></ref><ref id="cit56"><label>56</label><citation-alternatives><mixed-citation xml:lang="ru">Akanji M.A., Rotimi D., Adeyemi O.S. Hypoxia-Inducible Factors as an Alternative Source of Treatment Strategy for Cancer. Oxid Med Cell Longev. 2019 Aug 14; 2019: 8547846. doi: 10.1155/2019/8547846.</mixed-citation><mixed-citation xml:lang="en">Akanji M.A., Rotimi D., Adeyemi O.S. Hypoxia-Inducible Factors as an Alternative Source of Treatment Strategy for Cancer. Oxid Med Cell Longev. 2019 Aug 14; 2019: 8547846. doi: 10.1155/2019/8547846.</mixed-citation></citation-alternatives></ref><ref id="cit57"><label>57</label><citation-alternatives><mixed-citation xml:lang="ru">Nabors L.B., Mikkelsen T., Hegi M.E., Ye X., Batchelor T., Lesser G., Peereboom D., Rosenfeld M.R., Olsen J., Brem S., Fisher J.D., Grossman S.A.; New Approaches to Brain Tumor Therapy (NABTT) Central Nervous System Consortium. A safety run-in and randomized phase 2 study of cilengitide combined with chemoradiation for newly diagnosed glioblastoma (NABTT 0306). Cancer. 2012 Nov 15; 118(22): 5601–7. doi: 10.1002/cncr.27585.</mixed-citation><mixed-citation xml:lang="en">Nabors L.B., Mikkelsen T., Hegi M.E., Ye X., Batchelor T., Lesser G., Peereboom D., Rosenfeld M.R., Olsen J., Brem S., Fisher J.D., Grossman S.A.; New Approaches to Brain Tumor Therapy (NABTT) Central Nervous System Consortium. A safety run-in and randomized phase 2 study of cilengitide combined with chemoradiation for newly diagnosed glioblastoma (NABTT 0306). Cancer. 2012 Nov 15; 118(22): 5601–7. doi: 10.1002/cncr.27585.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
