rpmjResearch'n Practical Medicine JournalResearch and Practical Medicine Journal2410-1893"QUASAR", LLC10.17709/2409-2231-2019-6-3-2rpmj-418Research ArticleОригинальные статьи. Онкология, лучевая терапияOriginal Articles. ОncologyИЗУЧЕНИЕ СОДЕРЖАНИЯ VEGF-A И TGF-Β В БИОПТАТАХ ПЛОСКОКЛЕТОЧНОГО РАКА ЯЗЫКА И СЛИЗИСТОЙ ОБОЛОЧКИ ДНА ПОЛОСТИ РТА ПРИ ПОЛИХИМИОТЕРАПИИ С МОНОКЛОНАЛЬНЫМИ АНТИТЕЛАМИ – ЦЕТУКСИМАБОМSTUDY OF VEGF-A AND TGF-Β LEVELS IN BIOPTATES OF SQUAMOUS CELL CARCINOMA OF THE TONGUE AND MOUTH FLOOR MUCOSA IN POLYCHEMOTHERAPY WITH MONOCLONAL ANTIBODIES – CETUXIMABhttps://orcid.org/0000-0003-3061-6108КитО. И.KitO. I.

член-корреспондент РАН, д. м.н., профессор, генеральный директор

Member Russian Academy of Sciences, MD, PhD, DSc, professor, general director

https://orcid.org/0000-0003-3618-6890ФранциянцЕ. М.FrantsiyantsE. M.

д. б.н., профессор, заместитель генерального директора по науке, руководитель лаборатории изучения патогенеза злокачественных опухолей

PhD, DSc (Biology), professor, deputy director general for science, head of laboratory for the study of the pathogenesis of malignant tumors

https://orcid.org/0000-0002-7395-3086НескубинаИ. В.NeskubinaI. V.

к. б.н., старший научный сотрудник лаборатории изучения патогенеза злокачественных опухолей

PhD (Biology), senior researcher, laboratory for the study of the pathogenesis of malignant tumors

neskubina.irina@mail.ruhttps://orcid.org/0000-0003-4236-6476ВладимироваЛ. Ю.VladimirovaL. Yu.

д. м.н., профессор, руководитель отдела лекарственного лечения опухолей, руководитель отделения противоопухолевой лекарственной терапии № 1

MD, PhD, DSc, professor, head of the department of drug treatment of tumors, head of the department of anticancer drug therapy No. 1

https://orcid.org/0000-0001-8723-5897ЛьяноваА. А.LyanovaA. A.

врач-онколог отделения противоопухолевой лекарственной терапии № 1

oncologist, department of anticancer drug therapy No. 1

https://orcid.org/0000-0002-2674-9832ПогореловаЮ. А.PogorelovaYu. A.

к. б.н., старший научный сотрудник лаборатории изучения патогенеза злокачественных опухолей

PhD (Biology), senior researcher, laboratory for the study of the pathogenesis of malignant tumors

https://orcid.org/0000-0001-7742-4918ШалашнаяЕ. В.ShalashnayaE. V.

к. б.н., старший научный сотрудник лаборатории изучения патогенеза злокачественных опухолей

PhD (Biology), senior researcher, laboratory for the study of the pathogenesis of malignant tumors

https://orcid.org/0000-0001-7293-2358ЕнгибарянМ. А.ЕngibaryanM. A.

к. м.н., заведующая отделением опухолей головы и шеи

MD, PhD, head of the head and neck tumors department

https://orcid.org/0000-0001-8511-7280СидоренкоЮ. С.SidorenkoYu. S.

академик РАН, д. м.н., профессор, руководитель отдела опухолей репродуктивной системы

Аcademician Russian Academy of Sciences, MD, PhD, DSc, professor, head of the department of reproductive system tumors

ФГБУ «Ростовский научно-исследовательский онкологический институт» Министерства здравоохранения Российской ФедерацииРоссияRostov Research Institute of Oncology (RRIO)Russian Federation201904092019632028Copyright © Кит О.И., Франциянц Е.М., Нескубина И.В., Владимирова Л.Ю., Льянова А.А., Погорелова Ю.А., Шалашная Е.В., Енгибарян М.А., Сидоренко Ю.С., 20192019Кит О.И., Франциянц Е.М., Нескубина И.В., Владимирова Л.Ю., Льянова А.А., Погорелова Ю.А., Шалашная Е.В., Енгибарян М.А., Сидоренко Ю.С.Kit O.I., Frantsiyants E.M., Neskubina I.V., Vladimirova L.Y., Lyanova A.A., Pogorelova Y.A., Shalashnaya E.V., Еngibaryan M.A., Sidorenko Y.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.rpmj.ru/rpmj/article/view/418Цель исследования

Цель исследования. Изучение факторов роста VEGF-A и TGF-β в биоптатах опухолевой ткани у больных плоскоклеточным раком языка и слизистой оболочки дна полости рта в зависимости от эффективности лечения полихимиотерапии с таргетным препаратом — цетуксимабом.

Пациенты и методы

Пациенты и методы. В исследование были включены данные от 30 больных плоскоклеточным раком языка и слизистой дна полости рта сT3–4N0–1M0, St III–IV. Всем пациентам проводили 2 курса лечения: цисплатин 100мг/м2 , внутривенно, 1‑й день, 5‑фторурацил 1000мг/м2 /сут, внутривенно, 96‑часовой непрерывной инфузией в сочетании с таргетной терапией (цетуксимаб 400 мг/м2 в 1‑й день в нагрузочной дозе, затем по 250 мг/м2 в 8‑й и 15‑й дни). Были сформированы две подгруппы: с чувствительностью пациентов к полихимиотерапии с цетуксимабом (частичная регрессия и стабилизация) (n = 17) и резистентностью соответственно (прогрессирование) (n = 13). В биоптатах ткани опухоли больных методом иммуноферментного анализа (ИФА) с использованием стандартных тест-систем определяли уровень ростовых факторов VEGF-A и TGF-β (Bender Med System, Австрия). Статистический анализ результатов проводили с помощью пакета программ Statistica 6.0 (Stat-Soft, 2001).

Результаты

Результаты. Проведение полихимиотерапии с цетуксимабом у части больных (n = 13) не привело к статистически значимым изменениям уровней VEGF-A, TGF-β и значений коэффициента VEGF-A/TGF-β относительно исходных величин. У другой группы больных (n = 17) исследуемые маркеры в биоптатах опухолевой ткани статистически значимо отличались от исходных значений: VEGF-A был снижен в 1,46 раза, TGF-β — в 2,96 раза, а коэффициент VEGF-A/TGF-β, напротив, повышен в 2 раза.

Заключение

Заключение. Полученные результаты по содержанию факторов роста VEGF-A и TGF-β, а также коэффициента VEGF-A/TGF-β имеют определенную прогностическую ценность и могут быть использованы в качестве критериев для оценки эффективности противоопухолевой терапии у больных плоскоклеточным раком языка и слизистой оболочки дна полости рта.

Aim

Aim. Study of VEGF-A and TGF-β growth factors in tumor tissue bioptates in patients with squamous cell carcinoma of the tongue and floor of the oral cavity depending on the effectiveness of polychemotherapy targeted therapy with cetuximab.

Patients and methods

Patients and methods. The study included 30 patients with squamous cell carcinoma of the tongue and mouth floor mucosa (T3-4N0-1M0). All patients received 2 cycles of therapy: cisplatin 100 mg/m2 , intravenously, day 1, 5-fluorouracil 1000 mg/m2 /day, intravenously, 96-hour continuous infusion in combination with targeted therapy (cetuximab 400 mg/ m2 on day 1 in a loading dose, then 250 mg/m2 on days 8 and 15). Patients were divided into two subgroups: target sensitivity of patients (partial regression and stabilization) n = 17 and target resistance (progression) n = 13. Levels of growth factors VEGF-A and TGF-β were determined in tumor tissue bioptates by ELISA using standard test systems (Bender Med System, Austria). Statistical processing of results was performed using the Statistica 6.0 program (Stat-Soft, 2001).

Results

Results. Polychemotherapy with cetuximab in some patients (n = 13), antitumor therapy with cetuximab did not result in statistically significant changes in levels of VEGF-A, TGF-β and the VEGF-A/TGF-β ratio compared to the initial values. In other patients (n = 17), the studied markers in tumor tissue bioptates were statistically significantly different from the initial values: VEGF-A was decreased by 1.46 times, TGF-β by 2.96 times, while the VEGF-A/TGF-β ratio was twice elevated.

Conclusions

Conclusions. The results on levels of growth factors VEGF-A and TGF-β, as well as the VEGF-A/TGF-β ratio, are of a certain prognostic value and can be used as criteria for evaluating the efficacy of antitumor therapy in patients with squamous cell carcinoma of the tongue and mouth floor mucosa.

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Method of prognosing the efficacy of targeted cetuximab therapy in patients with squamous cell carcinoma of the tongue and mouth floor mucosa. Ruspatent. Patent application № 2019108624 from 25.03.2019, acknowledgements of receipt has been received. (In Russian).Kit OI, Frantsiyants EM, Neskubina IV, Vladimirova LYu, L’yanova AA, Engibaryan MA, Shalashnaya EV, Volkova VL. «A method of predicting the effectiveness of targeted therapy with cetuximab in patients with squamous cell carcinoma of the tongue and oral mucosa». Priority information is obtained, the application № 2019108624 от 25.03.2019. (In Russian).

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