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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">surgumed</journal-id><journal-title-group><journal-title xml:lang="ru">Вестник СурГУ. Медицина</journal-title><trans-title-group xml:lang="en"><trans-title>Vestnik SurGU. Meditsina</trans-title></trans-title-group></journal-title-group><issn pub-type="epub">2949-3447</issn><publisher><publisher-name>Сургутский государственный университет</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.34822/2304-9448-2021-2-61-70</article-id><article-id custom-type="elpub" pub-id-type="custom">surgumed-424</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>МЕДИКО-БИОЛОГИЧЕСКИЕ НАУКИ. ОБЗОР ЛИТЕРАТУРЫ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>LIFE SCIENCES. REVIEWS</subject></subj-group></article-categories><title-group><article-title>СОВРЕМЕННЫЙ ВЗГЛЯД НА КОНЦЕПЦИЮ ПОЛЕВОЙ КАНЦЕРИЗАЦИИ</article-title><trans-title-group xml:lang="en"><trans-title>A MODERN VIEW ON THE CONCEPT OF FIELD CANCERIZATION</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1145-3710</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Наумова</surname><given-names>Л. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Naumova</surname><given-names>L. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>доктор медицинских наук, профессор кафедры патофизиологии и общей патологии, Медицинский институт</p><p>Е-mail: naumovala@yandex.ru</p><p> </p></bio><bio xml:lang="en"><p>Doctor of Sciences (Medicine), Professor of the Department of Pathophysiology and General Pathology, Medical InstituteЕ-mail: naumovala@yandex.ru</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Сургутский государственный университет, Сургут</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Surgut State University, Surgut</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2021</year></pub-date><pub-date pub-type="epub"><day>06</day><month>07</month><year>2021</year></pub-date><volume>0</volume><issue>2 (48)</issue><fpage>61</fpage><lpage>70</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Наумова Л.А., 2021</copyright-statement><copyright-year>2021</copyright-year><copyright-holder xml:lang="ru">Наумова Л.А.</copyright-holder><copyright-holder xml:lang="en">Naumova L.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.surgumed.ru/jour/article/view/424">https://www.surgumed.ru/jour/article/view/424</self-uri><abstract><p>Цель – анализ современных представлений о феномене полевой канцеризации, механизмах его пато-и морфогенеза, значении для клиники, профилактики, ранней диагностики, а также о перспективных подходах к лечению. Материал и методы. Поиск литературы проводился с использованием следующих электронных информационных ресурсов: СyberLeninka, PubMed, Nature Pathology, MEDLINE, PLOS ONE. Глубина поиска не превышала 10 лет и определялась фундаментальностью работ. Используемые при поиске ключевые слова: опухолевое поле, полевая канцеризация, опухоль-стромальные отношения. Результаты. В работах последних лет опухолевое поле, или полевая канцеризация, рассматривается как ткань с накопленными генетическими и эпигенетическими изменениями, обеспечивающими клеткам клональные различия и пролиферативное превосходство с постепенной эволюцией их фенотипа от нормального к предопухолевому (очаговая гиперплазия, мета- и дисплазия, cancer in situ) и опухолевому, отличающемуся появлением способности эпителиальных клеток к эпителиально-мезенхимальному переходу, инвазии и метастазированию. Среди важнейших детерминантформирования опухолевого поля выделяют старение, действие химических, физических мутагенов и хронического воспаления, а среди механизмов формирования поля большое значение имеют метилирование ДНК и дисрегуляция микроРНК. Изменения в стромальном компартменте ткани (экстрацеллюлярном матриксе, клетках соединительной ткани) могут играть ведущую роль в инициации опухолевого процесса, что определяется появлением особого опухоль-ассоциированного фенотипа фибробластов и макрофагов, а также изменением иммунного статуса ткани. Понимание концепции опухолевого поля имеет большое значение для раннего выявления предопухолевых изменений, профилактики развития рака и его ранней диагностики, а также разработки новой тактики таргетной терапии.</p></abstract><trans-abstract xml:lang="en"><p>The study aims to analyze modern ideas about the phenomenon of field cancerization, the mechanisms of its pathogenesis and morphogenesis, its importance for the clinical findings, preventive care, early diagnosis, and promising approaches to the treatment of tumors. Material and methods. The literature search is carried out using the following databases: CyberLeninka, PubMed, Nature Pathology, MEDLINE, and PLOS ONE. The search depth does not exceed ten years and is determined by the fundamental nature of the work. The keywords used in the search are tumor field, field cancerization, tumor-stroma interaction. Results. In the works of recent years, the tumor field or the field cancerization is considered to be a tissue with accumulated genetic and epigenetic changes. These changes provide cells with clonal differences and proliferative dominance with a gradual evolution of their phenotype from normal to precancerous (focal hyperplasia, metaplasia and dysplasia, cancer in situ) and tumor, characterized by the appearance of the ability to epithelial-mesenchymal transition, invasion, and metastasis. Among the most important determinants of the formation of the tumor field are aging, the action of chemical and physical mutagens, and chronic inflammation. Whereas among the mechanisms of field formation, DNA methylation and microRNA dysregulation are of great importance. Changes in the stromal compartment of the tissue (extracellular matrix, connective tissue cells) can play a leading role in the initiation of the tumor process, which is determined by the appearance of a special tumor-associated phenotype of fibroblasts and macrophages, as well as changes in the immune status of the tissue. Understanding the concept of the tumor field is of high significance for the early detection of precancerous changes, the prevention of cancer development and its early diagnosis, as well as the development of new tactics of targeted therapy.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>опухолевое поле</kwd><kwd>полевая канцеризация</kwd><kwd>опухоль-стромальные отношения.</kwd></kwd-group><kwd-group xml:lang="en"><kwd>tumor field</kwd><kwd>field cancerization</kwd><kwd>tumor-stroma interaction.</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">Dotto G. P. Multifocal Epithelial Tumors and Field Cancerization: Stroma as a Primary Determinant // J Clin Invest. 2014. № 124 (4). P. 1446–1453. DOI 10.1172/JCI72589.</mixed-citation><mixed-citation xml:lang="en">Dotto G. P. Multifocal Epithelial Tumors and Field Cancerization: Stroma as a Primary Determinant // J Clin Invest. 2014. № 124 (4). P. 1446–1453. DOI 10.1172/JCI72589.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Fernández J. P., Méndez-Sánchez S. C., Gonzalez-Correa C. A., Miranda D. A. Could Field Cancerization Be Interpreted as a Biochemical Anomaly Amplification due to Transformed Cells? // Med Hypotheses. 2016. № 97. P. 107–111. DOI 10.1016/j.mehy.2016.10.026.</mixed-citation><mixed-citation xml:lang="en">Fernández J. P., Méndez-Sánchez S. C., Gonzalez-Correa C. A., Miranda D. A. Could Field Cancerization Be Interpreted as a Biochemical Anomaly Amplification due to Transformed Cells? // Med Hypotheses. 2016. № 97. P. 107–111. DOI 10.1016/j.mehy.2016.10.026.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Curtius K., Wright N. A., Graham T. A. An Evolutionary Perspective on Field Cancerization // Nat Rev Cancer. 2017. № 18 (1). P. 19–32. DOI 10.1038/nrc.2017.102.</mixed-citation><mixed-citation xml:lang="en">Curtius K., Wright N. A., Graham T. A. An Evolutionary Perspective on Field Cancerization // Nat Rev Cancer. 2017. № 18 (1). P. 19–32. DOI 10.1038/nrc.2017.102.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Pereira A. L., Magalhães L., Moreira F. C. et al. Epigenetic Field Cancerization in Gastric Cancer: Micrornas as Promising Biomarkers // Journal of Cancer. 2019. № 10 (6). P. 1560–1569. DOI 10.7150/jca.27457.</mixed-citation><mixed-citation xml:lang="en">Pereira A. L., Magalhães L., Moreira F. C. et al. Epigenetic Field Cancerization in Gastric Cancer: Micrornas as Promising Biomarkers // Journal of Cancer. 2019. № 10 (6). P. 1560–1569. DOI 10.7150/jca.27457.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Takeshima H., Ushijima T. Accumulation of Genetic and Epigenetic Alterations in Normal Cells and Cancer Risk // NPJ Precision Oncology. 2019. № 3. DOI 10.1038/s41698- 019-0079-0.</mixed-citation><mixed-citation xml:lang="en">Takeshima H., Ushijima T. Accumulation of Genetic and Epigenetic Alterations in Normal Cells and Cancer Risk // NPJ Precision Oncology. 2019. № 3. DOI 10.1038/s41698- 019-0079-0.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Бабаян А. Ю., Залетаев Д. В., Немцова М. В. Подтверждение значения полей канцеризации в генезе поверхностного рака мочевого пузыря // Молекуляр. медицина, 2013. № 1. С. 24–28.</mixed-citation><mixed-citation xml:lang="en">Бабаян А. Ю., Залетаев Д. В., Немцова М. В. Подтверждение значения полей канцеризации в генезе поверхностного рака мочевого пузыря // Молекуляр. медицина, 2013. № 1. С. 24–28.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Christensen S. R. Recent Advances in Field Cancerization and Management of Multiple Cutaneous Squamous Cell Carcinomas // F1000Research. 2018.№ 7. DOI 10.12688/f1000research.12837.1.</mixed-citation><mixed-citation xml:lang="en">Christensen S. R. Recent Advances in Field Cancerization and Management of Multiple Cutaneous Squamous Cell Carcinomas // F1000Research. 2018.№ 7. DOI 10.12688/f1000research.12837.1.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Hande A. H., Mohite D. P., Chaudhary M. S. et al. Evidence Based Demonstration of the Concept of Field Cancerization’ by p53 Expression in Mirror Image Biopsies of Patients with Oral Squamous Cell Carcinoma – an Immunohistochemical Study // Rom J Morphol Em-bryol. 2015.№ 56 (3). P. 1027–1033.</mixed-citation><mixed-citation xml:lang="en">Hande A. H., Mohite D. P., Chaudhary M. S. et al. Evidence Based Demonstration of the Concept of Field Cancerization’ by p53 Expression in Mirror Image Biopsies of Patients with Oral Squamous Cell Carcinoma – an Immunohistochemical Study // Rom J Morphol Em-bryol. 2015.№ 56 (3). P. 1027–1033.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Stearman R., Dwyer-Nield L., Grady M. C., Malkinson A. M., Yeraci M. W. A Macrophage Gene Expression Signature Defines a field Effect in the Lung Tumor Microenvironment // Cancer res. 2008. № 68 (1). P. 34–43. DOI 10.1158/0008-5472.CAN-07-0988.</mixed-citation><mixed-citation xml:lang="en">Stearman R., Dwyer-Nield L., Grady M. C., Malkinson A. M., Yeraci M. W. A Macrophage Gene Expression Signature Defines a field Effect in the Lung Tumor Microenvironment // Cancer res. 2008. № 68 (1). P. 34–43. DOI 10.1158/0008-5472.CAN-07-0988.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Braakhuis B. J. M., Brakenhoff R. H., Leemans C. R. Second Field Tumor: A New Opportunity for Cancer Preventing?// The Oncologist. 2005. № 10 (7). P. 493–500. DOI 10.1634/theoncologist.10-7-493theoncologist.alphamedpress.org/content/10/7/493.</mixed-citation><mixed-citation xml:lang="en">Braakhuis B. J. M., Brakenhoff R. H., Leemans C. R. Second Field Tumor: A New Opportunity for Cancer Preventing?// The Oncologist. 2005. № 10 (7). P. 493–500. DOI 10.1634/theoncologist.10-7-493theoncologist.alphamedpress.org/content/10/7/493.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Redente E. F., Orlicky D. J., Bouchard R. J. Tumour Signaling to the Bone Marrow Changes to the Phenotype of Monocytes and Pulmonary Macrophages During Urethane-Induced Primary Lung Tumourogenesis in A/J Mice // Am J Pathol. 2007. № 170 (2). P. 693–708. DOI 10.2353/ajpath.2007.060566.</mixed-citation><mixed-citation xml:lang="en">Redente E. F., Orlicky D. J., Bouchard R. J. Tumour Signaling to the Bone Marrow Changes to the Phenotype of Monocytes and Pulmonary Macrophages During Urethane-Induced Primary Lung Tumourogenesis in A/J Mice // Am J Pathol. 2007. № 170 (2). P. 693–708. DOI 10.2353/ajpath.2007.060566.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Кит О. И., Франциянц Е. М., Геворкян Ю. А., Комарова Е. Ф., Сальникова М. М., Малейко М. Л. Состояние стероидного гомеостаза опухолевой ткани различных морфологических форм рака желудка // Паллиатив. медицина и реабилитация. 2011. № 4. C. 35–38.</mixed-citation><mixed-citation xml:lang="en">Кит О. И., Франциянц Е. М., Геворкян Ю. А., Комарова Е. Ф., Сальникова М. М., Малейко М. Л. Состояние стероидного гомеостаза опухолевой ткани различных морфологических форм рака желудка // Паллиатив. медицина и реабилитация. 2011. № 4. C. 35–38.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Tan M. P., Tot T. The Sick Lobe Hypothesis, Field Cancerisation and the New Era of Preci-sion Breast Surgery // Gland Surg. 2018. № 7 (6). P. 611–618. DOI 10.21037/gs.2018.09.08.</mixed-citation><mixed-citation xml:lang="en">Tan M. P., Tot T. The Sick Lobe Hypothesis, Field Cancerisation and the New Era of Preci-sion Breast Surgery // Gland Surg. 2018. № 7 (6). P. 611–618. DOI 10.21037/gs.2018.09.08.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Lee S. S., Cheah Y. K. The Interplay between MicroRNAs and Cellular Components of Tumour Microenvironment (TME) on Non-Small-Cell Lung Cancer (NSCLC) Progression // Journal of Immunology Research. 2019. DOI 10.1155/2019/3046379.</mixed-citation><mixed-citation xml:lang="en">Lee S. S., Cheah Y. K. The Interplay between MicroRNAs and Cellular Components of Tumour Microenvironment (TME) on Non-Small-Cell Lung Cancer (NSCLC) Progression // Journal of Immunology Research. 2019. DOI 10.1155/2019/3046379.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Förster S., Gretschel S., Jöns T., Yashiro M., Kemmner W. THBS4, a Novel Stromal Mole-cule of Diffuse-Type Gastric Adenocarcinomas, Identified by Transcriptome-Wide Expres-sion Profiling // Mod Pathol. 2011. № 24 (10). P. 1390–1403. DOI 10.1038/modpathol.2011.99.</mixed-citation><mixed-citation xml:lang="en">Förster S., Gretschel S., Jöns T., Yashiro M., Kemmner W. THBS4, a Novel Stromal Mole-cule of Diffuse-Type Gastric Adenocarcinomas, Identified by Transcriptome-Wide Expres-sion Profiling // Mod Pathol. 2011. № 24 (10). P. 1390–1403. DOI 10.1038/modpathol.2011.99.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">West J., Bianconi G., Severini S., Teschendorff A. E. Differential Network Entropy Reveals Cancer System Hallmarks // Scientific Reports. 2012. № 802. DOI 10.1038/ srep00802.</mixed-citation><mixed-citation xml:lang="en">West J., Bianconi G., Severini S., Teschendorff A. E. Differential Network Entropy Reveals Cancer System Hallmarks // Scientific Reports. 2012. № 802. DOI 10.1038/ srep00802.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">DeFilippis R. A., Fordyce C., Patten K. et al. Stress Signaling from Human Mammary Epithelial Cells Contributes to Phenotypes of Mammographic Density // Cancer Res. 2014. № 74 (18). P. 5032–5044. DOI 10.1158/0008-5472.CAN-13-3390.</mixed-citation><mixed-citation xml:lang="en">DeFilippis R. A., Fordyce C., Patten K. et al. Stress Signaling from Human Mammary Epithelial Cells Contributes to Phenotypes of Mammographic Density // Cancer Res. 2014. № 74 (18). P. 5032–5044. DOI 10.1158/0008-5472.CAN-13-3390.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Gonzalez D. M., Medici D. Signaling Mechanisms of the Epithelial-Mesenchymal Transition // Science Signaling. 2014. № 7 (344). DOI 10.1126/scisignal.2005189.</mixed-citation><mixed-citation xml:lang="en">Gonzalez D. M., Medici D. Signaling Mechanisms of the Epithelial-Mesenchymal Transition // Science Signaling. 2014. № 7 (344). DOI 10.1126/scisignal.2005189.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Spinelli F. M., Vitale D. L., Demarchi G., Cristina C., Alaniz L. The Immunological Effect of Hyaluronan in Tumor Angiogenesis // Clin Transl Immunology. 2015. № 4 (12). P. 1–9. DOI 10.1038/cti.2015.35.</mixed-citation><mixed-citation xml:lang="en">Spinelli F. M., Vitale D. L., Demarchi G., Cristina C., Alaniz L. The Immunological Effect of Hyaluronan in Tumor Angiogenesis // Clin Transl Immunology. 2015. № 4 (12). P. 1–9. DOI 10.1038/cti.2015.35.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Afik R., Zigmond E., Vugman M. et al. Tumor Macrophages</mixed-citation><mixed-citation xml:lang="en">Afik R., Zigmond E., Vugman M. et al. Tumor Macrophages</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">are Pivotal Constructors of Tumor Collagenous Matrix // J Exp Med. 2016. № 213 (11). P. 2315–2331. DOI 10.1084/ jem.20151193.</mixed-citation><mixed-citation xml:lang="en">are Pivotal Constructors of Tumor Collagenous Matrix // J Exp Med. 2016. № 213 (11). P. 2315–2331. DOI 10.1084/ jem.20151193.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Gascard Ph., Tlsty Th. D. Carcinoma-Associated Fibroblasts:</mixed-citation><mixed-citation xml:lang="en">Gascard Ph., Tlsty Th. D. Carcinoma-Associated Fibroblasts:</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Orchestrating the Composition of Malignancy // Genes Dev. 2016. № 30 (9). P. 1002–1019. DOI 10.1101/ gad.279737.116.</mixed-citation><mixed-citation xml:lang="en">Orchestrating the Composition of Malignancy // Genes Dev. 2016. № 30 (9). P. 1002–1019. DOI 10.1101/ gad.279737.116.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Walker C., Mojares E., Del Río Hernández A. Role of Extracellular Matrix in Development and Cancer Progression // Int J Mol Sci. 2018. № 19 (10). DOI 10.3390/ijms19103028.</mixed-citation><mixed-citation xml:lang="en">Walker C., Mojares E., Del Río Hernández A. Role of Extracellular Matrix in Development and Cancer Progression // Int J Mol Sci. 2018. № 19 (10). DOI 10.3390/ijms19103028.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Kim B., Jang J., Heo Y. J. et al. Dysregulated miRNA in a Cancer-Prone Environment: A Study of Gastric Non-Neoplastic Mucosa // Sci Rep. 2020. № 10 (1). DOI 10.1038/ s41598-020-63230-1.</mixed-citation><mixed-citation xml:lang="en">Kim B., Jang J., Heo Y. J. et al. Dysregulated miRNA in a Cancer-Prone Environment: A Study of Gastric Non-Neoplastic Mucosa // Sci Rep. 2020. № 10 (1). DOI 10.1038/ s41598-020-63230-1.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Grigolato R., Bizzoca M. E., Calabrese L., Leuci S.,Mignogna M. D., Muzio L. L. Leukoplakia and Immunology: New Chemoprevention Landscapes? // Int J Mol Sci. 2020. № 21 (18). DOI 10.3390/ijms21186874.</mixed-citation><mixed-citation xml:lang="en">Grigolato R., Bizzoca M. E., Calabrese L., Leuci S.,Mignogna M. D., Muzio L. L. Leukoplakia and Immunology: New Chemoprevention Landscapes? // Int J Mol Sci. 2020. № 21 (18). DOI 10.3390/ijms21186874.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Chaves A. L. F., Silva A. G., Maia F. M. et al. Reduced CD8 + T Cells Infiltration Can Be Associated to a Malignant Transformation in Potentially Malignant Oral Epithelial Lesions // Clin Oral Investig. 2019. № 23 (4). P. 1913–1919. DOI 10.1007/s00784-018-2622-8.</mixed-citation><mixed-citation xml:lang="en">Chaves A. L. F., Silva A. G., Maia F. M. et al. Reduced CD8 + T Cells Infiltration Can Be Associated to a Malignant Transformation in Potentially Malignant Oral Epithelial Lesions // Clin Oral Investig. 2019. № 23 (4). P. 1913–1919. DOI 10.1007/s00784-018-2622-8.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Pirlog R., Cismaru A., Nutu A., Berindan-Neagoe I. Field Cancerization in NSCLC: A New Perspective on MicroRNAs in Macrophage Polarization // Int J Mol Sci. 2021. № 22 (2). P. 746. DOI 10.3390/ijms22020746.</mixed-citation><mixed-citation xml:lang="en">Pirlog R., Cismaru A., Nutu A., Berindan-Neagoe I. Field Cancerization in NSCLC: A New Perspective on MicroRNAs in Macrophage Polarization // Int J Mol Sci. 2021. № 22 (2). P. 746. DOI 10.3390/ijms22020746.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Кулигина Е. Ш. Эпидемиологические и молекулярные аспекты рака молочной железы // Практич. онкология. 2010. Т. 11, № 4. C. 203–216.</mixed-citation><mixed-citation xml:lang="en">Кулигина Е. Ш. Эпидемиологические и молекулярные аспекты рака молочной железы // Практич. онкология. 2010. Т. 11, № 4. C. 203–216.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Augsten M., Cancer-Associated Fibroblasts as Another Polarized Cell Type of the Tumor Microenvironment // Front Oncol. 2014. № 4 (62). DOI 10.3389/fonc.2014.00062.</mixed-citation><mixed-citation xml:lang="en">Augsten M., Cancer-Associated Fibroblasts as Another Polarized Cell Type of the Tumor Microenvironment // Front Oncol. 2014. № 4 (62). DOI 10.3389/fonc.2014.00062.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Kasashima H., Yashiro M., Nakamae H. et al. Bone Marrow-Derived Stromal Cells are Associated with Gastric Cancer Progression // Br J Cancer. 2015. № 113 (3). P. 443–452. DOI 10.1038/bjc.2015.236.</mixed-citation><mixed-citation xml:lang="en">Kasashima H., Yashiro M., Nakamae H. et al. Bone Marrow-Derived Stromal Cells are Associated with Gastric Cancer Progression // Br J Cancer. 2015. № 113 (3). P. 443–452. DOI 10.1038/bjc.2015.236.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Наумова Л. А. Общепатологические аспекты рака желудка, ассоциированного с системной недифференцированной дисплазией соединительной ткани. Новосибирск, 2019. 160 с.</mixed-citation><mixed-citation xml:lang="en">Наумова Л. А. Общепатологические аспекты рака желудка, ассоциированного с системной недифференцированной дисплазией соединительной ткани. Новосибирск, 2019. 160 с.</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>
