CC BY
9
3. Asschert J.G., Vellenga Е., Hollema H. et al. Expression of macrophage colony-stimulating factor (M-CSF), interleukin-6, (IL-6), interleukin-1 beta (IL-1 beta), interleukin-11 (IL-11) and tumour necrosis factor-alpha (TNF-alpha) in p53-characterised human ovarian carcinomas // Eur. J. Cancer. 1997. Vol. 33(13). P. 2246-2251.
4. Chang E., Rosenberg S.A. Patients with melanoma metastases at cutaneous and subcutaneous sites are highly susceptible to interleukin-2-based therapy. Journal of immunotherapy (Hagerstown, Md : 1997) 2001;24:88-90.
5. Daud A.I., DeConti R.C., Andrews S., Urbas P., Riker A.I., Sondak V.K., et al. Phase I trial of inter-leukin-12 plasmid electroporation in patients with met-astatic melanoma. Journal of Clinical Oncology. 2008;26:5896-5903.
6. Duraiswamy J., Kaluza K.M., Freeman GJ, Coukos G. Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors. Cancer Res. 2013;73:3591-3603.
7. Edwards R.P., Gooding W., Lembersky B.C., Colonello K., Hammond R., Paradise C, et al. Comparison of toxicity and survival following intraperitoneal recombinant interleukin-2 for persistent ovarian cancer after platinum: twenty-four-hour versus 7-day infusion. Journal of Clinical Oncology. 1997;15:3399-3407.
8. Fujita K., Ikarashi H., Takakuwa K., Kodama S., Tokunaga A., Takahashi T., et al. Prolonged disease-free period in patients with advanced
epithelial ovarian cancer after adoptive transfer of tumor-infiltrating lymphocytes. Clinical cancer research: an official journal of the American Association for Cancer Research. 1995;1:501-507.
9. Fyfe G.A., Fisher R.I., Rosenberg S.A., Sznol M., Parkinson D.R., Louie A.C. Long-term response data for 255 patients with metastatic renal cell carcinoma treated with high-dose recombinant interleu-kin-2 therapy. Journal of Clinical Oncology. 1996;14:2410-2411.
10. Kamishov S.V., Pulatov D.A. Supportive immunotherapy in complex treatment of patients with oncogynecologycal diseases // The Scientific Heritage (Budapest, Hungary) 18 (18) 2017 P.1,p. 23-27
Information about the main author:
17. Kamishov Sergey Viktorovich
18. MD, PhD, chemotherapeutist of chemotherapy department
19. Senior researcher
20. ID: ORCID 0000-0002-1581-6032
21. Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology of the Ministry of Health of the Republic of Uzbekistan, Tashkent, Uzbekistan
22. 100174, Uzbekistan, Tashkent, 383 Farabiy
st.
23. +998 90 978 65 38
24. E-mail: sergei_kamyshov@mail.ru
EVALUATION OF THE ROLE OF MOLECULAR BIOLOGICAL TUMOR MARKERS IN CHOOSING IMMUNOTHERAPY METHOD AS SUPPLEMENTARY TREATMENT OF
_OVARIAN AND CERVICAL CANCER_
Kamishov Sergey Viktorovich,
MD,PhD, Senior researcher, chemotherapeutist of Department of chemotherapy Nishanov Danier Anorbaevich MD,PhD, senior researcher,head of pathomorfology Department Akhmedov Odil Mukhammadjanovich MD,PhD, head of oncogynecology Department republican specialized scientific and practical medical center of oncology and radiology of the ministry of health
of the republic of uzbekistan, tashkent.
АННОТАЦИЯ
Цель исследования состояла в том, чтобы исследовать молекулярные биологические маркеры опухолей как метод выбора схемы лечения для пациенток с раком яичников и раком шейки матки при комбинированной терапии. Материалы и методы: В исследование было включено 136 пациенток с раком яичников и 163 больных раком шейки матки с II-III клиническими стадиями заболевания. Все пациенты проходили клинико-лабораторные анализы крови, которые включали изучение общего анализа крови и мочи, биохимических параметров и свертывания крови. Результаты исследования: эти исследования установили важность изучения молекулярной биологии опухолевых маркеров для выбора наиболее оптимальной схемы лечения. Вывод: предварительная оценка уровня экспрессии молекулярных биологических маркеров р53, HER-2 / neu и EGFR позволяет выбрать более эффективный метод иммунотерапии при сопутствующем лечении рака яичников. У пациентов с предварительной оценкой рака шейки матки показана важность уровня экспрессии маркеров р53 и Bcl-2 для выбора метода иммунотерапии при сопровождающем лечении.
Ключевые слова: рак яичников (РЯ), рак шейки матки (РШМ), экстракорпоральная иммунофармако-терапия, молекулярно-биологические опухолевые маркеры: p53, HER-2 / neu, Bcl-2, EGFR.
ABSTRACT
The aim of research was to investigate molecular biological tumor markers as selection criteria methods in
patients with ovarian cancer and cervical cancer in combined therapy. Materials and methods: in this study were included 136 patients with ovarian cancer and 163 cervical cancer patients with II-III clinical stages of the disease. All patients underwent clinic-laboratorial blood tests, which included the study of a general analysis of blood and urine, biochemical parameters, and blood coagulation. The results of the study: these researches have established the importance of studying the molecular biology of tumor markers to select the most optimal scheme of treatment. Conclusion: Preliminary assessment of the level of expression of molecular biological markers p53, HER-2/neu and EGFR permit to choose more effective method of immunotherapy in the accompanying treatment of ovarian cancer. In patients with cervical cancer preliminary evaluation shows the importance of level of expression of markers p53 and Bcl-2 to select a method of immunotherapy in the accompanying treatment.
Key words: ovarian cancer (OC), cervical cancer (CC), extracorporal immunopharmacotherapy , molecular biological tumor markers: p53, HER-2/neu, Bcl-2, EGFR.
The high level of morbidity and mortality of women from ovarian cancer (OC) and cervical cancer (CC), attracts the attention of the world and makes the scientists to treat these diseases as the most important problems of modern oncology.
Chemotherapy with the operating guidebook and the radiation exposure is a major component of the treatment gynecological cancer diseases. Nevertheless among the most general adverse effects of chemotherapy drugs are myelotoxicity, mucositis, alopecia, nausea and vomiting. Therefore, in order to reduce the toxicity of the treatment and increase effectiveness, usage of immunotherapy is a hopeful method in the accompanying treatment of gynecological cancer.
In recent years, progress in the research of immunology and immunotherapy of cancer has been made, including cancers of the female reproductive system. However, the criteria for the selection of immunological methods have not yet been worked out, as well as lack of awareness of their efficiency in patients with ovarian and cervical cancer [1, -P. 241; 2,-P. 747]. Modern methods of extracorporeal immunopharmacotherapy are an effective method of expansion therapeutic plasmapheresis. In , there is an additional selection of leukocyte fraction, which is subjected to a certain processing vitro drug aimed to modify the functional activity of cells participating in inflammation and immune reactions. The result is an additional immunocorrecting effect. One of the predictive methods in current gynecological
cancer diseases and production treatment strategy is learning molecular biological markers in tumor tissue. It is necessary to find understanding clinical situation, when tumor compared with the same prevalence and histological verification has difference on the flow of aggressiveness. Special attention is concerned about intelligence in abuse proliferation mechanisms, apoptosis, angiogenesis in tumor cells [2,-P. 747].
Applying modern methods of immunotherapy in the treatment of gynecological cancer diseases, using new opportunities of learning molecular biological markers, may possibly provide information about prognosis of the disease, contribute rational and effective treatment and present the point of this research [3, -P. 1130;4, -P. 6752].
Background: Purpose of research was to investigate molecular biological tumor markers as selection criteria methods in patients with ovarian cancer and cervical cancer in combined therapy.
Materials and methods: The object of the study
were 136 patients with ovarian cancer and 163 cervical cancer patients with II-III clinical stages of the disease who were treated in gynecological cancer department of National Cancer Institute of Uzbekistan from 2006 to 2014 and treated with standard combination therapy. All the patients with ovarian cancer received combined neoadjuvant therapy mode involving chemotherapy CP -cisplatin 75 mg / m2 cyclophosphamide +1000 mg/m2 for four days 2-4 courses every 3 weeks and surgery in the radical or cytoreductive size. Subsequently we conducted 6 courses of adjuvant chemotherapy for 6 cycles once every 3 weeks.
All patients with cervical cancer received combined and complex treatment, including chemotherapy (CT), surgery and radiation therapy (RT). In the first stage patients with cervical cancer, received systemic or intraarterial chemotherapy of cisplatin 50 mg/m2 + 5-FU 1000 mg/m2 for four days 4-6 courses 1 every 3 weeks. PC spent as in adjuvant and neoadjuvant mode. The second stage was operation in a radical size or combined RT in radical program. The third phase was carried out radiotherapy, which included remote telegam-maherapy (RTGT) and intracavitary brachytherapy. RTGT performed on "Theratron" or "AGAT-R" split rate at 2 Gr to 50 Gr, 5 times a week. Brachytherapy was performed using the "Gammamed" Nature SD 5 Gr to TD 45-55 Gr, day every other day. In group 1 (control) patients with one of the following immunomodulators: neovir a total dose of 750 mg (3 procedures); cycloferon -750 mg (Procedure 3) or polioxidoniy- 36 mg (immunotherapy was not performed (Table 1).
In group 2 patients with cervical and ovarian cancer conducted EIPT: 200-250 ml of autologous blood were taken in sterile containers "Hemacon" or "Terumo", were incubated Procedure3) at 37C for 60100 minutes followed by reinfusion to the patient conjugate resulting.
In the third group of patients we used the method, which is to expand the possibilities of plasmapheresis. Carried exfusion 500-1000 ml of autologous blood in sterile containers "Hemacon" or "Terumo", and then it was centrifuged at 3000 rev/ min for 30 min. 50-80 ml supernatant plasma was removed containing antibodies circulating immune complexes, cytokines, products of cell metabolism. Then, the resulting leucoplatelets and packed red blood cells were incubated with one of the following immunomodulators: neovir a total dose of 750 mg (3treatments); cycloferon -750 mg (Procedure 3) or polyoxidoniy- 36 mg (Procedure 3) at 37° C for 60-100min, followed by reinfusion of the conjugate into the circulatory system of patients.
Age of surveyed patients with ovarian cancer Staging of the disease was performed according to
ranged from23 to 75 years, average age - 42,6 ± 6,5 the International TNM clinical classification (7th edi-
years. Age of cervical cancer patients was from 21 to 74 tion, 2006). years, averageage - 45,7 ± 7,07 years.
Tablel. Groups of patients with ovarian cancer and cervical cancer
Immunotherapy methods OC, n=136 CC, n=163
Abs % Abs %
1. Control (no IT) 72 52,9 86 52,8
2. EIPHT 36 26,5 42 25,7
3. EIPHT +plasmapheresis 28 20,6 35 21,5
The study of history data showed that the majority of patients with gynecological cancer diseases, history ranged from 1 to 3 months (from 43.8% of patients with ovarian cancer and in 47.3% of cases of cervical cancer).
The operation-tumor biopsy tissue specimens of patients with ovarian cancer investigated in immuno-histochemical method. This method studied the expression level of p53, HER-2/neu, and epidermal growth factor (EGFR), and patients with cervical cancer- the expression level of p53, Bcl-2 and EGFR. [7;8, p. 763;10, -P. 105]
Immunohistochemical method. Samples of tumor tissue were fixed in neutral buffered formalin with a standard wiring and pouring paraffin. The histological preparations were stained by conventional methods. Paraffin sections were rehydrated and dewaxed according to standard procedures. The expression of mt p53 immunohistochemical evaluation using mouse monoclonal antibody p53, DO-7 clone, Ig G2b (M7001 Dako Cytomation) diluted 1: 100 in 60 minutes exposure time. Bcl-2 was detected using monoclonal antibodies to Bcl-2, Bcl-2 clone/ 00/D5, IgGi (NCL-Bcl-2 Novocastra) at a dilution of 1:80 at 60 min incubation. Detection of HER2 /neo was performed using polyclonal antibodies Dako Teckmate 500 Instrument: DakoHercepTest to p185 (HER - 2/neu) (code № K 5206) at 1: 500 dilution according to the manufacturer's instructions. To detect EGFR also used the polyclonal antibodies of the company Dako. To visualize the immunohistochemical reaction DAB+ system (Dako) was used. The reaction was conducted in the dark for 5-10 minutes. Sections were stained with Meyer's hematoxylin and embedded in
Canada balsam. Assessment of staining results was performed using a light microscope. For all markers assessed localization of staining in the cell. Numbers of positive cells were evaluated in the zones containing a maximum quantity. A tumor was considered negative if there was no nuclear reactivity with antibodies, or the number of stained cells was less than 25% in the tumor tissue; and positive if more than 25% tumor nuclei were stained cells [5, -P. 299; 6, -P. 71; 9,-P. 44].
Results and discussion: In appointing patients extracorporeal immunotherapy methods, we tried to take into account in the largest amount all studies.
The best results since immunotherapeutic methods observed in the third group of patients, which was reflected in the improvement of blood count, reducing leukopenia and lymphopenia, as well as normalization of B- lymphocytes, CD4 +, CD8 + and NK. Less prominent results were observed in the 2nd group of patients.
The degree of toxicity of chemotherapy in patients with ovarian and cervical cancer was evaluated by the scale CTC-NCIC. In the control group of patients with chemotherapy led to severe manifestations of toxicity. Severity of such adverse events of chemotherapy, anemia, leukopenia, poor appetite, nausea and alopecia, in some patients was the third degree of toxicity.
Study depending 5-year survival of patients with ovarian cancer tumor marker levels showed that reducing the level of p53 decreased the duration of their life, while the increase in the expression of this marker resulted in increased survival (Table 2). At the same time, reducing HER2 / neu EGFR contributed increasing the duration life of patients.
Table 2. The survival of patients with ovarian cancer, depending on immunotherapy method and the expression of molecular biology tumor markers._
Markers Number of patients, n=136 5-year survival
Abs. % 1 group Without immunotherapy 2 group without plasmapheresis, n=36 3 group without plasmapheresis, n=28
p53 - 98 72,1 56,6=73,9 68,6±5,6** 74,4±5,8*
+ 38 27,9 67,4±4,7 76,1±6,4** 79,2±6,5*
HER-2/neu - 53 39,0 63,8±4,1 72,3±6,0* 80,5±6,2**
+ 83 61,0 50,1±4,4 64,2±5,5* 69,8±6,7*
EGFR - 92 67,6 68,3±3,8 77,4±6,9** 77,2±7,0*
+ 44 32,4 54,0±4,0 60,7±5,6* 67,4±6,8**
* - reliability of differences from the control group, P <0,05;**
- reliability of differences with the control group P <0,01
Herewith decrease p53 in tumor tissue was observed in 98 (72.1%) patients with ovarian cancer. Of these 83 patients overexpression of HER-2/neu it has been observed simultaneously and 44 - increasing the expression of EGFR. Average total 5-year survival rate for these patients accounted for 63,1 ± 5,3% (p=0.031), while in group 1 - 55,2 ± 4,9%, in group 2 - 63, 4 ± 5,4% (p= 0.037) and in the 3rd - 70,5 ± 6,4% (p=0.042) (De-pictionl). The remaining 51 (31.3%) patients who had
observed increased expression of p53 with simultaneous reduction of HER-2 / neu marker and EGFR in the tumor, the average overall 5-year survival rates were higher and amounted to 72,7 ± 5,5% (P=0.030). Of these, in the 1st group, the figures were 65,2 ± 4,2%, in the 2nd - 75,2 ± 6,8% (p= 0.035) and in the third group - 78,1 ± 6, 7% (P= 0.038).
100
80
60
40
20
0
p53(-) HER(-) p53(+) HER-2neu(-)
2neu(+) EGFR(+) EGFR(-)
5-year survival ofpatients with ovarian cancer, depending on the level of a tumor marker and a method of
immunotherapy.
When we studied the dependence of the 5-year survival rate of cervical cancer patients by molecular biological level in tumor tissue it has been shown that the decreased expression of p53 leads to a decrease in lifespan, while its expression as amplification corresponded higher rates of survival (Table 3). The inverse
relationship was observed against Bcl-2. Increased EGFR levels in patients with cervical cancer was rare, while there was no evidence that the impact on the survival of the marker.
Table 3. The survival of patients with cervical cancer, depending on the method of immunotherapy and the expression of molecular biologic tumor markers
Markers Numbe tie r of pants 5-year survival
Abs. % 1 group Without immunotherapy, n=86 2 group without plasmapheresis, n=42 3 group with plasmapheresis, n=35
p53 112 68,7 56,1±5,1 65,6±4,9* 70,5±6,4*
+ 51 31,3 62,6±4,8 74,1±6,7* 78,1±7,7**
Bcl-2 67 41,1 57,2±5,0 73,7±7,2** 76,4±7,0*
+ 96 58,9 53,5±5,6 57,5±5,4* 66,2±6,4*
EGFR 148 90,8 55,4±5,3 66,8±6,3** 69,5±6,3**
+ 15 9,2 54,8±5,8 64,3±6,9** 67,4±6,8*
* - reliability of differences from the control group, P <0,05;**- Reliability of differences with the control group P <0.01
In 112 (68.7%) of patients with cervical cancer decreased expression of p53 in tumor tissue was observed. Of these 96 patients simultaneously overexpression of Bcl-2 has been observed. Mean total 5-year survival rate for these patients accounted for 59,7 ± 5,1% (p=0.027), while in group 1 - 51,7 ± 5,4%, in group 2 - 60, 3 ± 5,2% (p=036) and in the 3rd - 67,4 ± 7,2% (p= 0.040) (Figure 2). The remaining 51 (31.3%) patients who had observed increased expression of p53 with simultaneous
reduction of Bcl-2 levels in the tumor tissue, the average overall 5-year survival rates were higher and amounted to 70,2 ± 5,4% (p=0.028). Of these, the figures were 60,1 ± 4,7%, in the 2nd to the 1st group - 72,4 ± 7,0% (p=0.034) and in the third group - 77,5 ± 7, 3% (p=0.039).
100
50
67,4
60,3
77,4
72,4
60,1
!
p53(-), Bcl-2(+) p53(+), Bcl-2(-)
■ control group EIPT no PP EIPT+PP
0
Fig.2. 5-year survival ofpatients with cervical cancer, depending on the level of a tumor marker and a method
of immunotherapy.
These researches have established the importance of studying the molecular biology of tumor markers to select the most optimal scheme . Preliminary assessment of the level of expression of molecular biological markers p53, HER-2/neu and EGFR permit to choose more effective method of immunotherapy in the accompanying treatment of ovarian cancer. In patients with cervical cancer preliminary evaluation shows the importance of level of expression of markers p53 and Bcl-2 to select a method of immunotherapy in the accompanying treatment.
Conclusions:
1. Studies have shown that when selecting the optimal scheme in the accompanying EIPT treatment of patients with ovarian cancer are the most significant on-comarkers p53, HER-2/neu and EGFR and in the treatment of patients with cervical cancer - p53 and Bcl-2. At the same time it did not reveal the effect of EGFR on the overall survival of patients with cervical cancer.
2. By reducing the expression of p53 and increase the level of expression of HER-2/neu and EGFR in patients with ovarian cancer, the average overall 5-year survival rates were 63,1 ± 5,3% (p= 0.031). In the control group without immunotherapy they reached 55,2 ± 4,9%, in the group without using plasmapheresis EIPT - 63,4 ± 5,4% (p=0.037) in the group with a plasmapheresis EIPT - 70,5 ± 6.4% (P= 0.042).
3. Increased expression of p53 and decrease the level of expression of HER-2 / neu and EGFR in patients with ovarian cancer, leads to an increase in overall 5-
year survival rate - 72,7 ± 5,5% (p = 0.030). In the group without immunotherapy they reached 65,2 ± 4,2%, in the group without EIPT plasmapheresis - 75,2 ± 6,8% (p = 0.035) in the group with a plasmapheresis EIPT -
78.1 ± 6,7% (P= 0.038).
4. By reducing the expression of p53 and increase Bcl- expression level in patients with cervical cancer, the average overall 5-year survival rates were 59,7 ± 5,1% (p=0.027). In the control group without immunotherapy they reached 51,7 ± 5,4%, in the group without using plasmapheresis EIPT - 60,3 ± 5,2% (p = 0.036) in the group with a plasmapheresis EIPT - 67,4 ± 7 2% (P = 0.040).
5. Increased p53 expression and decreased expression of Bcl-2 levels in patients with cervical cancer, leads to an increase in overall 5-year vyzhivaemosti-
70.2 ± 5,4% (p = 028). In the group without immunotherapy they reached 60,1 ± 4,7%, in the group without EIPT plasmapheresis - 72,4 ± 7,0% (p=0.034) in the group with a plasmapheresis - 77,5 ± 7,3%(P=0.039).
References:
1. Keith B., Simon M. (2008) Tumor angiogene-sis. The Molecular Basis of Cancer [eds. J. Mendelsohn], Amsterdam: Elseiver, pp. 241-251.
2. Parkin D.M., Bray F., Ferlay J., Pissini P. (2005) Global Cancer Statistics, 2002. A Cancer Journal for Clinicians, vol. 55, pp. 74-108.
3. Bhardwaj N. (2007) Harnessing the immune system to treat cancer. Journal of Clinical Investigation, vol. 117, pp. 1130-1136.
4. Schindlbeck C., Janni W., Schaffer P. (2002) Tumor biology of primary breast cancer and minimal residual disease. Acta Medica Austria, vol. 29, pp. 27-31. Curtsinger J.M., Geurer M.Y., Lins D.C., Mescher M.F. (2007) Signal 3 Availability Limits the CD8 T Cell Response to a Solid Tumor. Journal of Immunology, vol. 178, pp. 6752-6760.
5. Rosenberg S., Restifo N., Yang J., Morgan R., Dudley M. (2008) Adoptive cell transfer a clinical path to effective cancer immunotherapy. Nature Reviews Cancer, no 8, pp.299- 308.
6. Gushhin I.S., Leskov V.P., Prozorovskij N.S., Pisarev V.M. (1987) [Experimental study of extracorporeal immunopharmacotherapy]. [Topical issues im-munopharmacotherapy], Moscow: Medicine, pp. 71-76.
7. Kostyuchenko A.L. (2000) [Therapy efferent], SPb: Foliatt (in Russian).
8. Han C.P., Hsu J.D., Yao C.C., Lee M.Y., Ruan A., Tyan Y.S., Yang S.F., Chiang H. (2010) HER2 gene amplification in primary mucinous ovarian cancer: a potential therapeutic target. Histopathology, vol. 57, no 5, pp. 763-764.
9. Konrdikov N.I., Shamarakova M.V., Gorba-
chevaYu.V. (2010)[The value of immunohisto-chemical determination of biomarkers squamous intraepithelial lesions of the cervix]. [Obstetrics and Gynecology], no 6, pp. 44-48.
10. Soussi T., Dehouche K., Beroud C. (2000) p53 website and analysis of p53 gene mutations in human cancer: forging a link between epidemiology and carcinogenesis. Human Mutation Impact Factor, vol. 15, pp. 105-113.
Information about the main author:
25. Kamishov Sergey Viktorovich
26. MD, PhD, chemotherapeutist of chemotherapy department
27. Senior researcher
28. ID: ORCID 0000-0002-1581-6032
29. Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology of the Ministry of Health of the Republic of Uzbekistan, Tashkent, Uzbekistan
30. 100174, Uzbekistan, Tashkent, 383 Farabiy st.
31. +998 90 978 65 38
32. E-mail: sergei_kamyshov@mail.ru
THE DEGREE OF IMMUNOLOGICAL DISORDERS AND THEIR DYNAMICS ON THE BACKGROUND OF IMMUNOTHERAPY IN PATIENTS WITH _OVARIAN CANCER_
Kamishov Sergey Viktorovich
MD, PhD, senior researcher, chemotherapy Department
Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology of the Ministry
of Health of the Republic of Uzbekistan, Tashkent, Uzbekistan
АННОТАЦИЯ
Цель исследования: изучение степени иммунологических нарушений у больных РЯ, в частности, основных параметров врожденного и адаптивного иммунитета, а также определенного спектра цитокинов до применения различных видов иммунотерапии и на фоне применения ЭИФТ и ПФ. Методы: В обследование были включены 176 больных РЯ Т2-3Нс-1М0 стадий (II-III клинические стадии). В соответствии с поставленными задачами исследования, больные РЯ были разделены на группы с целью проведения сравнительной характеристики иммунологических результатов в зависимости от используемого метода иммунотерапии, вошедшего в состав комплексного лечения. Результаты: Выявлена активация CD95+ на Т-лимфоцитах, что подтверждает наличие Т-клеточного иммунодефицита за счет апоптоза Т-лимфоцитов. Включение в комплекс сопроводительного лечения ЭИФТ и ЭИФТ+ПФ, является одним из путей уменьшения эндогенной интоксикации при проведении противоопухолевой лекарственной терапии. Разработанная методика ЭИФТ имеет большие перспективы в онкологической практике в связи с возможностью снимать последствия раковой и химиолучевой интоксикации, а также активировать систему противоопухолевой защиты организма. Выводы: применение ЭИФТ и ЭИФТ+ПФ с последующей неоадъювантной ПХТ у больных РЯ с клинико-лабораторными признаками эндогенной интоксикации является оправданным и эффективным методом, так как приводит к нормализации показателей основных сывороточных ци-токинов иммунной системы, позволяет улучшить непосредственные результаты лечения, приводит к уменьшению клинических проявлений заболевания, улучшает качество жизни больных, позволяет переводить больных из неоперабельного состояния в операбельное.
Ключевые слова: рак яичников, иммунотерапия, экстракорпоральная иммунофармакотерапия, иммунитет, интерлейкины, полихимиотерапия
ABSTRACT
The aim of the study was to study the degree of immunological disorders in patients with ovarian cancer, in particular, the basic parameters of congenital and adaptive immunity, as well as a certain spectrum of cytokines before the application of various types of immunotherapy and against the background of the use of EIPHT and PPh. Methods: 176 patients with T2-3N0-1M0 stages (II-III clinical stages) were included in the survey. In accordance with the objectives of the study, patients with OC were divided into groups in order to perform a comparative analysis of the immunological results, depending on the immunotherapy method used, which was included in the complex treatment. Results: activation of CD95 + on T-lymphocytes was confirmed, which confirms the presence
