akusherstvoObstetrics, Gynecology and ReproductionАкушерство, Гинекология и Репродукция2313-73472500-3194IRBIS LLC10.17749/2313-7347/ob.gyn.rep.2022.335akusherstvo-1421Research ArticleОRIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИNeutrophil extracellular traps as markers of thromboinflammation in the pathogenesis of female genital tract and breast malignant neoplasmsВнеклеточные ловушки нейтрофилов как маркеры тромбовоспаления в патогенезе злокачественных новообразований женских половых органов и молочной железыhttps://orcid.org/0000-0001-7441-2778СлуханчукЕ. В.SlukhanchukE. V.

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

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

Ekaterina V. Slukhanchuk – MD, PhD, Associate Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health

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

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

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

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

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

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

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

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

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

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

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

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

Antonina G. Solopova – MD, Dr Sci Med, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children's Health

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

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

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

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

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

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

Jamilya Kh. Khizroeva – MD, Dr Sci Med, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health

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

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

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

Гри Жан-Кристоф – д.м.н., профессор кафедры акушерства и гинекологии Клинического института детского здоровья имени Н.Ф. Филатова; профессор гематологии, зав. лабораторией гематологии факультета биологических и фармацевтических наук; иностранный член РАН

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

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

Франция, 34090 Монпелье, ул. Огюста Бруссоне, д. 163

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

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

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 и гинекологии Клинического института детского здоровья имени Н.Ф. Филатова; профессор; директор гематологии Центра Тромбозов

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

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

Франция, 75006 Париж, Улица медицинского факультета, д. 12

Франция, 75020 Париж, Китайская улица, д. 4

Ismail Elalamy – MD, Dr Sci Med, Professor, Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health

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

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/0000-0001-7415-4633МакацарияА. Д.MakatsariyaA. D.

Макацария Александр Давидович – д.м.н., профессор, академик РАН, зав. кафедрой акушерства и гинекологии Клинического института детского здоровья имени Н.Ф. Филатова

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

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

Alexander D. Makatsariya – MD, Dr Sci Med, Academician of RAS, Professor, Head of the Department of Obstetrics and Gynecology, Filatov Clinical Institute of Children’s Health

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

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

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 Federation202215092022164426437Copyright © Slukhanchuk E.V., Bitsadze V.O., Solopova A.G., Khizroeva J.K., Gris J., Elalamy I., Makatsariya A.D., 20222022Слуханчук Е.В., Бицадзе В.О., Солопова А.Г., Хизроева Д.Х., Гри Ж., Элалами И., Макацария А.Д.Slukhanchuk E.V., Bitsadze V.O., Solopova A.G., Khizroeva J.K., Gris J., Elalamy I., 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/1421Introduction

Introduction. Thrombosis is a formidable complication of the oncological process that still profoundly contributes to overall mortality despite the anticoagulant use. According to the recent data, thrombosis in cancer represents a special type of prothrombotic state, wherein thromboinflammationis one of its constituents. In addition, thromboinflammation contributes both to the disease progression and intensity of metastasis processes. Recently, a large number of studies worldwide have been devoted to investigating thromboinflammation in cancer patients.

Aim

Aim: to assess NETosis activity (the process of neutrophils extracellular traps synthesis), namely, the concentration of citrullinated histone H3 (citH3) as a blood plasma NETosis marker in women with malignant genital organs and breast neoplasms.

Materials and Мethods

Materials and Мethods. The prospective observational controlled non-randomized study included 45 patients (main group) with malignant neoplasms of uterus body, ovaries, cervix (adenocarcinoma of the cervical canal) and mammary glands admitted to the hospital for planned surgical treatment (13, 15, 5 and 13 patients, respectively) and 33 women with benign neoplasms of the genital organs and mammary gland (control group). The plasma citН3 concentration was determined using an enzyme immunoassay.

Results

Results. It was found that cancer patients had citН3 concentration significantly increased (1.434–2.058 ng/ml) compared with the control group (0.281–0.371 ng/ml). The concentration of citH3 in patients with tumors of the uterine body and cervix ranged from 2.271 to 2.992 ng/ml, patients with ovarian tumors – from 1.357 to 2.123 ng/ml, patients with breast tumors – from 0.331 to 0.859 ng/ml. The study revealed no significant differences in the citH3 concentration in patients with breast tumors compared to the control group. Upon elevating citН3 concentration, such parameters as C-reactive protein, D-dimer, neutrophils and platelets count, as well as neutrophils/lymphocytes ratio were significantly increased. Significant differences were revealed in platelet count in the main group (236,68–273,77×109/L) vs. control group (178,14–202,35×109/L).

Conclusion

Conclusion. The study demonstrated the activation of NETosis in patients with tumors of the uterine body as well as cervix (adenocarcinoma) and ovaries that might be combined with hemostasis activation and systemic inflammatory response.

Введение

Введение. Тромбоз является грозным осложнением онкологического процесса, вклад которого в общую летальность остается высоким, несмотря на использование антикоагулянтов. По последним данным, тромбоз при раке представляет собой особый вид протромботического состояния, одной из составных частей которого, как оказалось, является тромбовоспаление. Кроме этого, тромбовоспаление вносит свой вклад и в прогрессию заболевания и в интенсивность процессов метастазирования. Вопросам изучения тромбовоспаления у онкологических пациентов в последнее время посвящено большое количество исследований в мире.

Цель

Цель: оценка активности нетоза (процесса синтеза внеклеточных ловушек нейтрофилов), а именно, концентрации цитруллинированного гистона Н3 (citН3) как маркера нетоза в плазме крови пациенток со злокачественными новообразованиями половых органов и молочной железы.

Материалы и методы

Материалы и методы. В проспективное наблюдательное контролируемое нерандомизированное исследование вошли 45 пациенток (основная группа) со злокачественными новообразованиями тела матки, яичников, шейки матки (аденокарцинома цервикального канала) и молочных желез, поступивших в стационар для проведения планового оперативного лечения (13, 15, 5 и 13 пациенток, соответственно), и 33 женщины с доброкачественными новообразованиями половых органов и молочной железы (контрольная группа). Концентрацию citН3 определяли в плазме c помощью иммуноферментного анализа.

Результаты

Результаты. У пациенток основной группы уровень citН3 оказался достоверно повышен (1,434–2,058 нг/мл) по сравнению с контрольной группой (0,281–0,371 нг/мл). Содержание citН3 у больных с опухолями тела и шейки матки составляло от 2,271 до 2,992 нг/мл, у больных с опухолями яичников – от 1,357 до 2,123 нг/мл, у больных с опухолями молочной железы – от 0,331 до 0,859 нг/мл. Не выявлено статистически значимых различий в концентрации citН3 у больных с опухолями молочной железы по сравнению с контрольной группой. При повышении концентрации citH3 были достоверно повышены значения таких показателей, как С-реактивный белок и D-димер, количество нейтрофилов и тромбоцитов и соотношение нейтрофилы/лимфоциты. Выявлены значимые различия в количестве тромбоцитов в основной группе (236,68–273,77×109/л) по сравнению с контрольной группой (178,14–202,35×109/л).

Заключение

Заключение. Продемонстрирована активация процессов нетоза у пациенток с опухолями тела и шейки (аденокациномы) матки и яичников, а также сочетание этой активации с активацией системы гемостаза и системным воспалительным ответом.

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