akusherstvoObstetrics, Gynecology and ReproductionАкушерство, Гинекология и Репродукция2313-73472500-3194IRBIS LLC10.17749/2313-7347/ob.gyn.rep.2023.432akusherstvo-1762Research ArticleОRIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИNeutrophil extracellular traps-associated markers in malignant neoplasms of the female reproductive system after surgical treatment and adjuvant chemotherapyМаркеры внеклеточных ловушек нейтрофилов у женщин со злокачественными новообразованиями репродуктивной системы, получавших хирургическое лечение и адъювантную терапиюhttps://orcid.org/0000-0001-7441-2778СлуханчукЕ. В.SlukhanchukE. V.

Слуханчук Екатерина Викторовна – к.м.н., доцент кафедры акушерства, гинекологии и перинатальной медицины Клинического института детского здоровья имени Н.Ф. Филатова 

Ekaterina V. Slukhanchuk – MD, PhD, Associate Professor, Department of Obstetrics, Gynecology and Perinatal Medicine, Filatov Clinical Institute of Children’s Healt2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991

ekaterina@ginekologhirurg.ruhttps://orcid.org/0000-0001-8404-1042БицадзеВ. О.BitsadzeV. O.

Бицадзе Виктория Омаровна – д.м.н., профессор РАН, профессор кафедры акушерства, гинекологии и перинатальной медицины Клинического института детского здоровья имени Н.Ф. Филатова 

Scopus Author ID: 6506003478.Researcher ID: F-8409-2017.

Victoria O. Bitsadze – MD, Dr Sci Med, Professor of RAS, Professor, Department of Obstetrics, Gynecology and Perinatal Medicine, Filatov Clinical Institute of Children’s Health

Scopus Author ID: 6506003478.Researcher ID: F-84092017

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991

https://orcid.org/0000-0002-7456-2386СолоповаА. Г.SolopovaA. G.

Солопова Антонина Григорьевна – д.м.н., профессор кафедры акушерства, гинекологии и перинатальной медицины Клинического института детского здоровья имени Н.Ф. Филатова 

Scopus Author ID: 6505479504.Researcher ID: Q-1385-2015

Antonina G. Solopova – MD, Dr Sci Med, Professor, Department of Obstetrics, Gynecology and Perinatal Medicine, Filatov Clinical Institute of Children's HealthScopus Author ID: 6505479504.Researcher ID: Q-1385-20152 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991

 

https://orcid.org/0000-0002-0725-9686ХизроеваД. Х.KhizroevaJ. Kh.

Хизроева Джамиля Хизриевна – д.м.н., профессор кафедры акушерства, гинекологии и перинатальной медицины Клинического института детского здоровья имени Н.Ф. Филатова 

Scopus Author ID: 57194547147.Researcher ID: F-8384-2017

Jamilya Kh. Khizroeva – MD, Dr Sci Med, Professor, Department of Obstetrics, Gynecology and Perinatal Medicine, Filatov Clinical Institute of Children’s HealthScopus Author ID: 57194547147.Researcher ID: F-8384-20172 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991

https://orcid.org/0000-0002-9899-9910ГриЖ.-К.GrisJ.-K.

Гри Жан-Кристоф – д.м.н., профессор кафедры акушерства, гинекологии и перинатальной медицины Клинического института детского здоровья имени Н.Ф. Филатова Ф Сеченовского университета; профессор гематологии, зав. лабораторией гематологии факультета биологических и фармацевтических наук Университета Монпелье и Университетской больницы Нима, Франция; иностранный член РАН

Scopus Author ID: 7005114260.Researcher ID: AAA-2923-2019

Jean-Christophe Gris – MD, Dr Sci Med, Professor, Department of Obstetrics, Gynecology and Perinatal Medicine, Filatov Clinical Institute of Children’s Health, Sechenov University; Professor of Haematology, Head of the Laboratory of Haematology, Faculty of Biological and Pharmaceutical Sciences, Montpellier University and University Hospital of Nîmes, France; Foreign Member of RAS

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991, Russia; 163 Rue Auguste Broussonnet, Montpellier 34090, France

https://orcid.org/0000-0002-9576-1368ЭлаламиИ.ElalamyI.

Элалами Исмаил – д.м.н., профессор кафедры акушерства, гинекологии и перинатальной медицины Клинического института детского здоровья имени Н.Ф. Филатова Сеченовского Университета,; профессор медицинского Университета Сорбонны; директор гематологии Центра Тромбозов, Госпиталь Тенон

Scopus Author ID: 7003652413.Researcher ID: AAC-9695-2019

Sechenov University; Medicine Sorbonne University; Hospital TenonRussian Federation

Ismail Elalamy – MD, Dr Sci Med, Professor, Department of Obstetrics, Gynecology and Perinatal Medicine, Filatov Clinical Institute of Children’s Health, Sechenov University; Professor, Medicine Sorbonne University, Paris, France; Director of Hematology, Department of Thrombosis Center, Hospital Tenon

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991, Russia; 12 Rue de l’École de Médecine, Paris 75006, France; 4 Rue de la Chine, Paris 75020, France

https://orcid.org/0000-0002-8100-0189ДегтяреваН. Д.DegtyarevaN. D.

Дегтярева Наталья Дмитриевна – студент 5-го курса Клинического института детского здоровья имени Н.Ф. Филатова

Natalia D. Degtyareva – 5th year Student, Filatov Clinical Institute of Children’s Health

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991

https://orcid.org/0009-0005-1689-7240ГилеваМ. А.GilevaM. A.

Гилева Мария Алексеевна – клинический ординатор кафедры акушерства, гинекологии и перинатальной медицины Клинического института детского здоровья имени Н.Ф. Филатова 

Maria A. Gileva – MD, Clinical Resident, Department of Obstetrics, Gynecology and Perinatal Medicine, Filatov Clinical Institute of Children's Health

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991

https://orcid.org/0000-0002-4564-8439СамбуроваН. В.SamburovaN. V.

Самбурова Наталья Викторовна – к.м.н., доцент кафедры патофизиологии Института биодизайна и моделирования сложных систем 

Scopus Author ID: 57208129705

Natalia V. Samburova – MD, PhD, Associate Professor, Department of Pathophysiology, Institute of Biodesign and Modeling of Complex Systems

Scopus Author ID: 57208129705

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991

https://orcid.org/0000-0003-0226-9276ЩербаковД. В.ShcherbakovD. V.

Щербаков Денис Викторович – к.м.н., доцент кафедры общей гигиены института общественного здоровья имени Ф.Ф. Эрисмана 

Denis V. Shcherbakov – MD, PhD, Associate Professor, Department of General Hygiene, Erisman Institute of Public Health

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991

https://orcid.org/0000-0002-8882-1588ЯкубоваФ. Э.YakubovaF. E.

Якубова Фидан Эльчин кызы – клинический ординатор кафедры акушерства, гинекологии и перинатальной медицины Клинического института детского здоровья имени Н.Ф. Филатова 

Fidan E. Yakubova – MD, Clinical Resident, Department of Obstetrics, Gynecology and Perinatal Medicine, Filatov Clinical Institute of Children's Health

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991

https://orcid.org/0000-0002-3058-900XЗелепухинаМ. Е.ZelepukhinaM. E.

Зелепухина Мария Евгеньевна – студент 5-го курса Клинического института детского здоровья имени Н.Ф. Филатова 

119991 Москва, ул. Большая Пироговская, д. 2, стр. 4

Maria E. Zelepukhina – 5th year Student, Filatov Clinical Institute of Children’s Health

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991

https://orcid.org/0000-0002-3367-9844БлиновД. В.BlinovD. V.

Блинов Дмитрий Владиславович – к.м.н., ассистент кафедры спортивной медицины и медицинской реабилитации Института клинической медицины имени Н.В. Склифосовского  Сеченовского Университета; руководитель по медицинским и научным вопросам, Институт Превентивной и Социальной Медицины; доцент кафедры спортивной, физической и реабилитационной медицины АНО ДПО «Московский медико-социальный институт имени Ф.П. Гааза»

Scopus Author ID: 6701744871.Researcher ID: E-8906-2017

Dmitry V. Blinov – MD, PhD, MBA, Assistant, Department of Sports Medicine and Medical Rehabilitation, Sklifosovsky Institute of Clinical Medicine, Sechenov University; Head of Medical and Scientific Affairs, Institute for Preventive and Social Medicine; Associate Professor, Department of Sports, Physical and Rehabilitation Medicine, Moscow Haass Medical – Social Institute

2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991;4–10 Sadovaya-Triumfalnaya Str., Moscow 127006; 2/44 Salyama Adilya Str., Moscow 123423

https://orcid.org/0000-0001-7415-4633МакацарияА. Д.MakatsariyaA. D.

Макацария Александр Давидович – д.м.н., профессор, академик РАН, зав. кафедрой акушерства, гинекологии и перинатальной медицины Клинического института детского здоровья имени Н.Ф. Филатова  Сеченовского Университета; вице-президент Российского общества акушеров-гинекологов (РОАГ); Заслуженный врач Российской Федерации; Почетный профессор Венского Университета

Scopus Author ID: 57222220144.Researcher ID: M-5660-2016

Alexander D. Makatsariya – MD, Dr Sci Med, Academician of RAS, Professor, Head of the Department of Obstetrics, Gynecology and Perinatal Medicine, Filatov Clinical Institute of Children’s Health, Sechenov University; Vice-President of the Russian Society of Obstetricians and Gynecologists (RSOG); Honorary Doctor of the Russian Federation; Emeritus Professor of the University of Vienna2 bldg. 4, Bolshaya Pirogovskaya Str., Moscow 119991

 

ФГАОУ ВО Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский университет)РоссияSechenov UniversityRussian FederationФГАОУ ВО Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский университет); Университет МонпельеРоссияSechenov University; University of MontpellierRussian FederationФГАОУ ВО Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский университет); Медицинский Университет Сорбонны; Госпиталь ТенонРоссияSechenov University; Medicine Sorbonne University; Hospital TenonRussian FederationФГАОУ ВО Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский университет); Институт Превентивной и Социальной Медицины; АНО ДПО «Московский медико-социальный институт имени Ф.П. Гааза»;РоссияSechenov University; Institute for Preventive and Social Medicine; Moscow Haass Medical – Social InstituteRussian Federation202305092023174420432Copyright © Slukhanchuk E.V., Bitsadze V.O., Solopova A.G., Khizroeva J.K., Gris J., Elalamy I., Degtyareva N.D., Gileva M.A., Samburova N.V., Shcherbakov D.V., Yakubova F.E., Zelepukhina M.E., Blinov D.V., Makatsariya A.D., 20232023Слуханчук Е.В., Бицадзе В.О., Солопова А.Г., Хизроева Д.Х., Гри Ж., Элалами И., Дегтярева Н.Д., Гилева М.А., Самбурова Н.В., Щербаков Д.В., Якубова Ф.Э., Зелепухина М.Е., Блинов Д.В., Макацария А.Д.Slukhanchuk E.V., Bitsadze V.O., Solopova A.G., Khizroeva J.K., Gris J., Elalamy I., Degtyareva N.D., Gileva M.A., Samburova N.V., Shcherbakov D.V., Yakubova F.E., Zelepukhina M.E., Blinov D.V., Makatsariya A.D.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.gynecology.su/jour/article/view/1762Introduction

Introduction. Studies evidence about a relation between increased circulating free DNA (cfDNA) concentrations and chemotherapy, the majority of which have been focused on considering a tumor as a source of cfDNA. It has been suggested that neutrophils also contribute to this process, as cancer-related cfDNA characteristics resemble those of neutrophil extracellular traps (NETs). Therefore, the elevated concentration of cfDNA observed in chemotherapy patients may be associated with NETosis.

Aim

Aim: assessment of NETosis markers in surgical treatment and adjuvant chemotherapy of patients with malignant neoplasms of the female reproductive system.

Materials and Methods

Materials and Methods. A prospective non-randomized interventional controlled study was carried out by enrolling 111 patients with malignant breast diseases and female genital organs of various localizations and stages hospitalized for elective surgical treatment or chemotherapy course. The control group included 33 healthy women. 69 patients underwent surgical treatment. Adjuvant chemotherapy with paclitaxel and carboplatin was performed in 25 patients with ovarian cancer and 17 patients with breast cancer. In cancer patients, citrullinated histone H3 (citH3) and myeloperoxidase (MPO) were chosen as NETosis biomarkers allowing to distinguish NETs from other tumor-derived cfDNA thereby improving quality of research study. The concentration of NETosis markers was assessed before surgery or onset of chemotherapy upon admission to hospital and 14 days after surgery or 14 days after the second course of chemotherapy.

Results

Results. In all patients, the concentrations of NETosis markers before the start of therapy were significantly increased compared to the control group as well as 14 days after surgical treatment and 14 days after the second course of chemotherapy. However, in surgical patients, no significantly increased concentration of NETosis markers postvs. pre-surgery magnitude was observed. Upon that, patients underwent 2 courses of chemotherapy vs. baseline level were found to have significantly elevated magnitude of NETosis markers.

Conclusion

Conclusion. The study revealed the relationship between administration of paclitaxel-containing chemotherapy in patients with ovarian cancer and breast cancer and a rise in NETs level. Chemotherapy is an essential component for management of patients with malignant neoplasms of the female reproductive system, therefore, development of new strategies to lower a risk of thrombosis and resistance to it is of crucial importance.

 

 

Введение

Введение. Исследования свидетельствуют о связи между повышением концентрации внеклеточной ДНК (вкДНК) и химиотерапией, при этом большинство из них сосредоточены на опухоли как источнике вкДНК. Повышенная концентрация вкДНК, наблюдаемая у пациентов на фоне химиотерапии, может быть связана с нетозом, так как вкДНК при раке по своим характеристикам сходна с внеклеточными ловушками нейтрофилов (англ. neutrophil extracellular traps, NETs).

Цель

Цель: оценка маркеров нетоза при хирургическом лечении и адьювантной химиотерапии пациенток со злокачественными новообразованиями женской репродуктивной системы.

Материалы и методы

Материалы и методы. В проспективном нерандомизированном интервенционном контролируемом исследовании приняли участие 111 пациенток со злокачественными заболеваниями молочных желез и женских половых органов различных локализаций и стадий, госпитализированных с целью проведения планового оперативного лечения или курса химиотерапии. В контрольную группу вошли 33 здоровые женщины. Оперативному лечению подверглись 69 пациенток. Адъювантная химиотерапия с паклитакселом и карбоплатином проведена 25 пациенткам подгруппы «рак яичников» и 17 пациенткам подгруппы «рак молочной железы». В качестве биомаркеров нетоза были выбраны цитруллинированный гистон H3 (англ. citrullinated histone H3, citH3) и миелопероксидаза (англ. myeloperoxidase, MPO). Эти маркеры отличают NETs от другой вкДНК, полученной из опухоли, что повышает информативность исследования. Концентрацию маркеров нетоза оценивали дважды – до операции или начала курса химиотерапии при поступлении пациенток в отделение и через 14 дней после операции или через 14 дней после второго курса химиотерапии.

Результаты

Результаты. У всех пациенток концентрации маркеров нетоза до начала терапии были достоверно повышены по сравнению с контрольной группой (р = 0,0001), также как и через 14 дней после оперативного лечения (р = 0,0001) или после второго курса химиотерапии (р = 0,0001). Однако у прооперированных пациенток не было выявлено значимого повышения концентрации маркеров нетоза после операции по сравнению с дооперационными значениями. При этом у пациенток, прошедших 2 курса химиотерапии, было установлено достоверное повышение маркеров нетоза по сравнению с исходными значениями.

Заключение

Заключение. Проведенное исследование выявило взаимосвязь между использованием паклитаксел-содержащей химиотерапии и ростом концентрации NETs у пациенток подгрупп «рак яичников» и «рак молочной железы». Химиотерапия является важнейшими компонентом ведения пациентов со злокачественными новообразованиями женской репродуктивной системы, поэтому разработка новых стратегий для снижения риска тромбоза и резистентности к ней имеет жизненно важное значение.

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The authors declare that there are no conflicts of interest present.