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Заключение. Несмотря на частое применение такого метода хирургического вмешательства, как резекция, гарантия полного выздоровления отсутствует. Данный метод хирургического лечения направлен на борьбу с осложнениями, но воспаление может распространиться на другие отделы желудочно-кишечного тракта. По этой причине при всех видах оперативных вмешательств в послеоперационном периоде необходима противорецидиви-рующая терапия, а так же профилактика возникновения инфекций и кровотечений, так как могут развиться осложнения, что может привести к необходимости в повторном оперативном вмешательстве и госпитализации.
Список используемой литературы.
1. Воробьева Г.И., Халифа И.Л. Неспецифические воспалительные заболевания кишечника, М.: Миклош, 2008. - С. 400.
2. Ивашкин В. Т., Лапина Т. Л. Гастроэнтерология: национальное руководство. М.:
ГЭОТАР Медиа, 2008. 704 с. (Серия «Национальные руководства».) С. 460-490.
3. Кондаренко П.Г., Губергриц Н.Б., Элин Ф.Э., Смирнов Н.Л. Клиническая колопроктология / Руководство для врачей. - Донецк, 2006.- С. 406.
4. Шелыгина Ю.А., Благодарного Л.А. Справочник по колопроктологии , М.: Литтерра, 2012. — C. 460-522.
5. Якубчик, Т.Н. Клиническая гастроэнтерология: пособие для студентов лечебного, педиатрического, медико-психологического факультетов, врачей-интернов, клинических ординаторов, врачей-гастроэнтерологов и терапевтов - Гродно: ГрГМУ, 2014. - С. 324.
6. Gorgun E., Remzi F. H., Goldberg J. M., et al. Fertility is reduced aft er restorative proctocolec-tomy with ileal pouch anal anastomosis: a study of 300 patients // Surgery. 2004. Vol. 136, N 4. P. 795803.
Рис. 2.Виды оперативных вмешательств при болезни Крона
UDC:615.028-614.03.46-8_
THE ROLE OF MOLECULAR BIOLOGICAL MARKERS IN THE SELECTION OF CONDUCTING IMMUNOTHERAPY AT CERVICAL CANCER AND _OVARIAN CANCER_
Kamishov Sergey Viktorovich
MD, PhD, senior researcher, chemotherapeutist of chemotherapy Department
Akhmedov Odil Mukhammadjanovich MD,PhD, head of oncogynecology Department Nishanov Danier Anorbaevich
MD,PhD, senior researcher,head of pathomorfology 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 экспрессии молекулярно-биологических опухолевых маркеров у пациенток с раком шейки матки и раком яичников и их влияние на курс сопутствующей терапии. Метод исследования: молекулярные биологические опухолевые маркеры были изучены у пациенток с стадиями рака шейки матки (РШМ) и рака яичников (РЯ) T2-3N0-1M0 (II-III клинические стадии), которые были гос-
питализированы в отделения онкогинекологии и химиотерапии в 2009-2014 годах, Иммуногистохимиче-ские методы исследования проводились на гистологических препаратах оперативно-биопсийного материала первичной опухоли пациенток с раком шейки матки, полученных до начала терапии. Результаты исследования: анализ показал, что самые высокие показатели выживаемости в течение 5 лет наблюдались в группе пациентов с раком шейки матки, к которым применялся ЭИФТ с плазмаферезом (ПФ). Вывод: при положительном уровне изученных маркеров наряду с высокой пролиферативной активностью опухоли можно рекомендовать проведение сопутствующей иммунотерапии с помощью ЭИФТ с плазмаферезом.
Ключевые слова: рак шейки матки, рак яичников, адаптивный клеточный иммунитет, молекулярно-биологические маркеры, иммунотерапия
ABSTRACT
The aim of the study was to study the expression of molecular-biological tumor markers in patients with cervical cancer and ovarian cancer, and their effect on the course of accompanying therapy. The Method of research: Molecular biological tumor markers were studied in patients with cervical cancer (CC) and ovarian cancer (OC) T2-3N0-1M0 stages (II-III clinical stages) who were hospitalized in oncogynecology and chemotherapy departments in 2009-2014. Immunohistochemical methods of investigation were carried out on histological preparations of the operational-biopsy material of the primary tumor of patients with cervical cancer, obtained before the initiation of therapy. Results of the research: The analysis showed that the highest rates of 5-year survival were observed in the group of patients with cervical cancer who had EIPHT with plasmapheresis (PPh). Conclusion: At a positive level of these markers, along with high proliferative activity of the tumor, it is possible to recommend carrying out accompanying immunotherapy with EIPHT with plasmapheresis.
Key words: cervical cancer, ovarian cancer, adaptive cellular immunity, molecular-biological markers, immunotherapy
Topicality. To date, modern methods of treating and predicting the course of oncogynecologic diseases are the study of molecular-biological markers in tumor tissue and the mechanisms of their influence on the course of the oncological process [1,-P. 1293;2,-P.4385;3-P.1130;9-P.8878;10-P.707]. The use of modern methods of immunotherapy in the treatment of oncogynecological diseases, using new opportunities for studying microcopter-biological markers, can provide information on the prognosis of the course of the disease, contribute to the designation of rational and effective treatment, which determines the relevance of this study [4, -P.1419;6, -P.677].
Analysis of current literature data allows us to conclude that the immune system is at the center of all attempts currently being undertaken to improve the efficacy of antitumor therapy, and the task of activating the antitumor potential of the immune system is the most important in modern oncology. Immunotherapy with time can be the most promising method of treating tumors, as it is a physiologically adequate method that restores the natural strength of the patient's body to combat the neoplastic process and the infectious complications that often arise during treatment. The acquisition of new unique immunomodulating drugs has created a qualitatively new basis for correcting immunity disorders, it has become possible to influence more selectively the individual components and links of this system [1, -P.1293;5, -P.3999]. On the other hand, the prospects open for methods that have a positive effect on immunity in general - the use of adaptogens, methods of plasmapheresis, perfusion of blood through sorbents, treatment with various activators, etc. Numerous studies have shown that modern immunotherapy methods in the treatment of malignant tumors can have a normalizing effect on the immune status of cancer patients, provide an objective antitumor effect, and also contribute to the regression of tumor pleurisy and ascites in chemo-resistant forms
of cancer. A promising trend in the treatment of malignant neoplasms at the present stage of development of immunotherapy is a combination of methods of activation of specific and nonspecific immunity. In contrast to the usual methods of immunotherapy, when immunomodulating drugs are taken in the form of tablets, or are administered intramuscularly or intravenously, the use of extracorporeal immunopharmacotherapy (EIPHT) methods makes it possible to selectively select from the blood directly the cells of the immune system - the leukocytes. The isolated leukocytes are processed by special technologies with immunomodulating drugs and then, already activated, return back to the vascular channel, after which they are able to synthesize the activation factors of the immune system and activate other cells of the immune system. This direction of immunotherapy has great prospects in oncological practice in connection with the possibility of removing the consequences of cancer and chemoradiation intoxication, and also activate its own system of antitumor protection of the organism [3, -P.1130;9, -P.8878]. However, in the literature there is very little information on the use of the EIPHT method in the treatment of cancer. Today, one of the most promising areas in the diagnosis of malignant tumors is the detection of tumor markers, which can provide additional information about the biological features of the tumor. Much attention is paid to the study of markers that characterize apoptosis, cell proliferation, such as p53, Bcl-2, Ki-67 and EGFR, EGF [5, -P.3999;8, -P.357]. In addition to it, many immunotherapy methods in oncology are still used empirically, no clear criteria indications and contraindications in the treatment of malignant tumors of different localizations. Determining the optimal doses of drugs, the sequence of various effects on the immune system, their duration, and the influence of immunotherapy methods on the immediate and long-
term results of antitumor therapy, require the efforts of many researchers.
Based on the foregoing, the aim of the study was to study the expression of molecular-biological tumor markers in patients with cervical cancer and ovarian cancer, and their effect on the course of accompanying therapy.
Material and methods of investigation.
Molecular biological tumor markers were studied in patients with cervical cancer (CC) and ovarian cancer (OC) T2-3N0-1M0 stages (II-III clinical stages) who were hospitalized in oncogynecology and chemotherapy departments in 2009-2014. Immunohistochemical methods of investigation were carried out on histological preparations of the operational-biopsy material of the primary tumor of patients with cervical cancer, obtained before the initiation of therapy. Samples of tumor tissue were fixed in neutral buffered formalin with conventional standard wiring and paraffin waxing. Histological preparations were stained by conventional methods and immunohistochemical studies were performed. Paraffin sections were dewaxed and rehydrated using a standard procedure. To visualize the immunohistochemical reaction, a DAB + system was used [DakoCytomation, Denmark]. The staining results were evaluated using a light microscope "Leica" (Germany) under magnification x10; x20; x40. For the marker, the localization of staining in the cell (nucleus, cytoplasm, membrane) was evaluated. The number of positive cells was evaluated in the zones containing their maximum number. In patients with cervical cancer, monoclonal mouse antibodies to p53 (clone DO-7), Bc1-2 (clone 124), EGFR (clone E30), VEGF (clone VG1), Ki-67 (clone M1B-1) were used in immunohistochemical evaluation of p53 expression. (DakoCytomation, Denmark). The following criteria for the evaluation of markers were used in the study: 1. The tumor was considered negative for p53 if there was no nuclear reactivity with antibodies in the tumor tissue or the number of stained cells was less than 25%; and positive for p53, if more than 25% of the nuclei of tumor cells were stained; 2. The tumor was considered negative for Bc1-2, EGFR, and VEGF if there was no cytoplasmic reactivity with antibodies in the tumor tissue or the number of stained cells was less than 25%; and positive if more than 25% of tumor cells were colored; 3. To estimate the proliferative activity (PA) of the tumor, the number of Ki-67 positive tumor cells per 300 tumor cells was counted. The Ki-67 index was determined by the formula: PA = number of Ki-67-positive cells x 100 / total number of cells. The proliferative activity of the tumor was estimated as the percentage of Ki-67 positive cells from the total number of tumor cells. High proliferative activity corresponded to the Ki-67 index> 40%, low proliferative activity of the tumor corresponded to the Ki-67 index <40%. Immunotherapy in the complex of standard polychemotherapy was carried out on three groups of patients: The 1 group - 22 patients with cervical cancer and OC without immunotherapy (control group); The 2 group - 19 patients with cervical cancer and OC in combination with extracorporeal immunopharmacotherapy (EIPHT); The 3 group - 24
patients with cervical cancer and ovarian cancer in combination with EIPHT + plasmapheresis (EIPHT + PPh).
The results obtained and their discussion. The
analysis showed that the highest rates of 5-year survival were observed in the group of patients with cervical cancer who had EIPHT with plasmapheresis (PPh). Thus, in the control group of patients, the survival rate with negative p53 level was 64.4 ± 6.7%, while in the groups with EIPHT and EIPHT + PPh these values were 73.2 ± 7.7 (p> 0.05) and 77 , 4 ± 8.4% (p> 0.05), respectively. With a positive value of this oncomarker, the 5-year survival was 46.1 ± 5.1% for the control group without immunotherapy and 55.6 ± 4.9 (p <0.05) and 60.5 ± 6.4% (p <0.05) for groups using immunotherapy methods, respectively. The p53 gene suppressor encodes a nuclear protein that modulates gene expression, responsible for DNA repair, cell division and apoptosis. To date, there is no consensus in the literature about the dynamics of p53 expression in the progression of cervical cancer. According to several authors, it can both increase and decrease with this disease. The accumulation rate of mut-p53 increases with the growth of malignancy of tumors, whereas mutant p53 does not occur in benign tumors, and in malignant tumors the accumulation rate increases to 46% [6,9]. Protein Bcl-2 has an important role in the regulation of apoptosis. It was shown that a high degree of expression of the tumor cell Bid (protein from the Bcl family, which plays an important role in the regulation of apoptosis and integrating signals for mitochondria) correlates with the unfavorable cervical prognosis. Bcl-2 can completely delay apoptosis caused by p53 and other stimulants, including cytostatic drugs, but does not stop apoptosis caused by cytotoxic T-lymphocytes. In various studies, a sharp and significant enhancement of Bcl-2 expression was observed in localized forms of cervical cancer compared with the initial stages and a subsequent decrease in expression in a locally advanced process. The 5-year survival in the control group of cervical cancer patients in the control group Bcl-2 was 57.2 ± 5.0% with a negative level and 49.5 ± 5.6% with a positive value. Accordingly, in groups with immunotherapy, this indicator was 73.7 ± 7.2% (p <0.05) and 76.4 ± 7.0% (p> 0.05) at a negative level and 57.5 ± 5, 4% (p> 0.05) and 66.2 ± 7.4% (p> 0.05) - with its positive value. The epidermal growth factor receptor EGFR is a transmembrane glycoprotein localized on chromosome 7p12. The EGFR functions through dimerization, activating tyrosine kinase, by participating in the regulation of normal and neoplastic cell proliferation. During the transformation of cells, the synthesis of these proteins is enhanced and the overexpression of receptors on the cell surface. EGFR is present in many normal tissues and pronounced expression is observed in solid tumors, including cervical cancer. According to literature data, expression of EGFR is observed in approximately 40% of malignant tumors of the digestive tract, lung, ovary, uterus. In this case, the role of EGFR as a prognostic marker in cervical cancer is not definitively determined. When examining the EGFR marker, it was
shown that, with its negative value, the 5-year survival in patients with cervical cancer in the group without immunotherapy was 55.4 ± 5.3, and at positive - 54.8 ± 5.8%. In the EIPHT group, the corresponding indices were 66.8 ± 7.0 (p <0.05) and 64.3 ± 6.9% (p> 0.05), and in the EIPHT + PPh group 69.5 ± 6.3 (p> 0.05) and 67.4 ± 6.8% (p> 0.05). The main activator of angiogenesis is the vascular endothelial growth factor (VEGF), responsible for the proliferation and migration of endothelial cells, and is also directly related to tumor invasion and metastasis. The data supporting the participation of VEGF and EGFR in the construction of the vascular bed, the growth and progression of malignant neoplasms have been accumulated. Moreover, the interaction of these ligands with transmembrane tyrosine kinase receptors is considered as the most important autocrine pathway of tumor promotion. At the negative VEGF level in the control group, the 5-year survival rate of the patients was 64.3 ± 7.2 and, if positive, 53.0 ± 6.0%. In the groups of patients in whom the accompanying immunotherapy was used, the corresponding values for a negative VEGF were 73.4 ± 6.8 (p> 0.05) and 75.2 ± 7.4% (p> 0.05), with a positive the level of this oncomarker is 60.7 ± 5.6 (p <0.05) and 67.4 ± 6.8% (p <0.05).
The Ki-67 antigen is a nuclear protein, the expression of which is noted in the active phase of the cell cycle, including mitosis. According to literature data, the expression of Ki-67 increases with cervical lesions. The proliferative index of Ki-67 is considered as an independent prognostic indicator of the occurrence of relapse, general and disease-free survival, a predictive factor for determining sensitivity to chemotherapy (CT) and radiation therapy (RT). The Ki-67 index allows to assess the degree of malignancy of the tumor and to predict the course of the disease in conjunction with other factors. It is shown that a high level of the Ki-67 index is associated with an unfavorable forecast. In particular, with a high level of Ki-67, there is a deterioration in the indices of disease-free and overall survival of patients with breast, ovarian, colon, bladder, soft tissue sarcomas, etc. The Ki-67 tumor marker was not detected in tumors of 7 patients with cervical cancer who had a 5-year survival rate of 65.2 ± 5.8% in the control group. At its positive level in the group without immunotherapy, this indicator was 44.2 ± 6.1%. In the groups with EIPH and EIFT + PPh at negative Ki-67, the survival rates were
76.4 ± 7.9 (p> 0.05) and 77.8 ± 6.7% (p> 0.05), respectively, and at positive - 57,8 ± 5,9 (p <0,05) and 63,3 ± 7,4% (p <0,05). At a low level of the PA index, which was calculated from Ki-67, the 5-year survival rate in patients with cervical cancer in the group without immunotherapy was 62.6 ± 5.8, with a high level of 44.8 ± 5.1%. In groups with immunotherapy, 5-year survival at a low PA index was 73.7 ± 8.2 (p> 0.05) and 78.1 ± 7.7% (p> 0.05), with a high index -
54.5 ± 5.4 (p> 0.05) and 62.2 ± 6.4% (p <0.05). When studying the expression of molecular-biological tumor markers in patients with ovarian cancer, it was shown that a negative level of p53 was noted in 5 (16.6%) patients, positive in 25 (83.3%). Corresponding indices in the study of HER-2 / neu were found in 24 (80.0%)
and 6 (20.0%) patients, in the study of EGFR - in 21 (70.0%) and 9 (30.0%), VEGF - in 4 (13.3%) and 26 (86.7%) and in studying Ki-67 - in 6 (20.0%) and 24 (80.0%) patients. Thus, in the majority of patients with OC, the level of oncomarkers studied was positive, with the exception of HER-2 / neu and EGFR, which were negative in 80.0 and 70.0% of patients, respectively.
As in the groups of cervical cancer, the highest 5-year survival rates were observed in patients with EPL with plasmapheresis. Thus, in the control group of patients, the survival rate with negative p53 level was 62.6 ± 6.8%, while in the groups with EIPHT and EIHT + PPh these indices were 74.1 ± 6.7 (p> 0.05) and 78 , 1 ± 7.7% (p> 0.05), respectively. With a positive value of this oncomarker, the 5-year survival was 43.8 ± 5.8% for the control group without immunotherapy and 58.6 ± 6.7 (p <0.05) and 60.4 ± 6.3% (p > 0.05) for groups with the use of immunotherapy, respectively. The p53 protein, being the product of the TP53 tumor suppressor gene, is expressed in all cells of the body. In the absence of damage to the genetic apparatus, the p53 protein is in an inactive state, and when DNA damage occurs, the DNA is activated. The result of p53 activation is the stopping of the cell cycle and DNA replication; with a strong stress signal - the initiation of apoptosis. Violations of the mechanism of apoptosis development can occur when the key gene of this process p53 loses its function. This can occur as a result of mutation of the p53 gene with the formation of a mutant oncoprotein - mut-p53, which is observed in conditions of pathology or as a result of blockade of p53 by other proteins, to which Bcl-2 primarily applies. Increasing the expression of mutated p53 in a tumor is accompanied by its greater aggressiveness, as the number of tumor cells undergoing apoptosis decreases. At OC, according to different researchers, mutant p53 is detected in more than half of patients already in the early stages of the disease. In some works devoted to ovarian cancer, it has been shown that the amplification of HER-2 / neu, occurring in 10-50%, indicates an unfavorable prognosis of the course of the disease. However, there are also conflicting data, so the practical significance of HER-2 / neu testing remains controversial today [7, -P.1885]. Recently, it was found that some mucinous ovarian carcinomas have amplification of the HER2 / neu gene and overexpression of its protein. In recently published results of a genomic analysis of 50 samples of light-cell ovarian cancer, the presence of HER2 / neu amplification in 14% of cases was shown [8, -P.357]. It turns out that with a rare frequency of HER2 / neu overexpression and amplification of its gene in the general ovarian carcinoma group in a subgroup of mucinous and clear cell carcinomas, this receptor is much more common. The 5-year survival in the control group of patients when the HER-2 / neu marker was examined in the control group was 62.7 ± 4.6% with a negative level and 55.2 ± 6.4% with a positive value. Accordingly, in groups with immunotherapy, this indicator was 68.2 ± 7.2 (p <0.05) and 74.3 ± 6.7% (p <0.05) at a negative level and 69.8 ± 6.5 (p> 0.05) and 77.1 ± 6.7% (p> 0.05) - with its positive value. The epidermal growth factor receptor EGFR is a
transmembrane glycoprotein localized on chromosome 7p12. EGFR functions through dimerization, activating tyrosine kinase, by participating in the regulation of normal and neoplastic cell proliferation. The EGFR receptor family consists of 4 members: EGFR / ErB1 / HER1, ErbB2 / Neu / HER2, ErB3 / HER3 and ErB4 / HER4. Under normal physiological conditions, activation of HER receptors is controlled by temporary low expression of their ligands. When cells are transformed, overexpression of these proteins and an increase in the number of receptors on the cell surface are observed. EGFR is present in many normal tissues and expressed expression is observed in solid tumors. According to literature data, expression of EGFR is observed in approximately 40% of malignant tumors of the digestive tract, lung, ovary, uterus [6, -P.677;9, -P.8878]. When considering the EGFR marker, it was shown that, with its negative value in the group without immunotherapy, the 5-year survival was 64.4 ± 5.8%, and at a positive - 57.2 ± 6.0%. In the EIPHT group, the corresponding indices were 72.4 ± 6.9 (p>0.05) and
65.7 ± 5.6% (p>0.05), and in the group with EIPHT + PPh - 74.8 ± 7.4 (p<0.05) and 68.0 ± 6.8% (p>0.05).
One of the most studied indicators of the aggressiveness of tumor growth is cell proliferation, which can be estimated with the help of the mitotic index and the Ki-67 index. The Ki-67 antigen is a nuclear protein, the expression of which is noted in the active phase of the cell cycle, including mitosis. According to literature data, the expression of Ki-67 increases with cervical lesions. The proliferative index of Ki-67 is considered as an independent prognostic indicator of the occurrence of relapse, general and disease-free survival, a predictive factor for determining sensitivity to chemotherapy (CT) and radiation therapy (RT). The Ki-67 index allows to assess the degree of malignancy of the tumor and to predict the course of the disease in conjunction with other factors. It is shown that a high level of the Ki-67 index is associated with an unfavorable forecast. In particular, with a high level of Ki-67, there is a worsening of the disease-free and overall survival rates of patients with breast, ovarian, colon, bladder, soft tissue sarcomas, etc. In most cases, a high level of Ki-67 expression is detected in malignant ovarian tumors [ 2,6,]. The Ki-67 tumor marker was not detected in tumors of 6 patients who had a 5-year survival rate of 68.4 ± 6.9% in the control group. At its positive level in the group without immunotherapy, this indicator was
41.8 ± 3.8%. In the groups with EIPHT and EIPHT + PPh at negative Ki-67, survival rates were 78.1 ± 6.5 (p> 0.05) and 76.8 ± 7.9% (p> 0.05), respectively, and at positive - 58,6 ± 6,3 (p <0,05) and 60,4 ± 6,5% (p <0,05). With a low level of PA index, which was calculated from Ki-67, the 5-year survival rate in the group without immunotherapy was 68.3 ± 7.7, with a high level of 49.4 ± 5.4%. In groups with immunotherapy, 5-year survival at a low PA index was 76.1 ± 7.8 (p> 0.05) and 79.2 ± 8.0% (p> 0.05), with a high index - 64.2 ± 6.8 (p <0.05) and 69.8 ± 6.7% (p> 0.05). Thus, in most patients with cervical cancer (73.3, 80.0 and 76.7%, respectively), molecular-biological markers p53 and Ki-67 were present. At the same time,
the Bcl-2 and EGFR markers were detected in 36.7 and 30.0% of the patients, respectively. A comparative assessment of the level of tumor markers and 5-year survival of cervical cancer patients showed that molecular biology markers p53, VEGF and Ki-67, as well as the level of proliferative activity (PA) of the tumor have the greatest prognostic significance with respect to treatment effectiveness. Molecular biological markers p53, VEGF and Ki-67 were present in most patients with OC (83.3, 86.7 and 80.0%, respectively). In this case, the HER-2 / neu and EGFR markers were detected in 20.0 and 30.0% of the patients, respectively. It was shown that the positive level of p53, VEGF and Ki-67 markers had a noticeable negative effect on the 5-year survival of patients with OC, in the case of HER-2 / neu and EGFR, this effect was not so pronounced, indicating a smaller prognostic significance in this disease. The greatest effect in increasing the 5-year survival of patients with cervical cancer, as well as OC, was provided by a scheme of accompanying immunotherapy, including EIPHT with plasmapheresis: this effect of this method was manifested both in positive and negative levels of cancer markers. The analysis of the correlation of the tumor markers level and the 5-year survival rate of patients allows us to conclude that the positive level of p53, VEGF and Ki-67 in patients with cervical cancer and OC, along with high proliferative activity of the tumor, may serve as a basis for carrying out this category of patients accompanying immunotherapy with EIPHT, which can significantly increase the effectiveness of standard antitumor treatment regimens. At a positive level of these markers, along with high proliferative activity of the tumor, it is possible to recommend carrying out accompanying immunotherapy with EIPHT with plasmapheresis.
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Information about the main author:
1. Kamishov Sergey Viktorovich
2. MD, PhD, chemotherapeutist of chemotherapy department
3. Senior researcher
4. ID: ORCID 0000-0002-1581-6032
5. Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology of the Ministry of Health of the Republic of Uzbekistan, Tashkent, Uzbekistan
6. 100174, Uzbekistan, Tashkent, 383 Farabiy
st.
7. +998 90 978 65 38
8. E-mail: sergei_kamyshov@mail.ru
UDC:615.028-614.03.46-8_
THE EVALUATION OF THE STATE OF CELL FACTORS OF IMMUNITY IN PATIENTS WITH OVARIAN CANCER DEPENDING ON THE EXPRESSION OF _HER-2 / NEU_
Kamishov Sergey Viktorovich
MD, PhD, senior researcher, chemotherapeutist of chemotherapy Department
Nishanov Danier Anorbaevich
MD,PhD, senior researcher,head of pathomorfology 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 основных факторов клеточного иммунитета у пациентов с раком яичников в зависимости от экспрессии молекулярно-биологических маркеров. Метод исследования: семьдесят пациенток с РЯ на стадиях T2-3N0-1M0 были исследованы в отделениях онкогинекологии и химиотерапии РСНПМЦОР МЗ РУз с 2009 по 2013 год. Все пациенты прошли клинические и лабораторные, инструментальные исследования. Результаты исследования: На основе нашего материала гиперэкспрессия Her-2 / neu коррелировала с прогностически важными неблагоприятными чертами, такими как молодой возраст, рост инфильтративной опухоли, высокая злокачественность процесса с сопутствующим участием метастатических лимфатических узлов. В этом отношении, мы поставили цель исследовать иммунологические параметры женщин с РЯ в зависимости от наличия избыточной экспрессии Her-2 / neu по сравнению со значениями женщин без гиперэкспрессии Her-2 / neu. Вывод: выявленные нами иммунологические изменения показали наличие глубоких иммунологических изменений, с учетом которых необходимо провести адекватную интерпретацию и коррекцию иммунологических показателей. Оценка иммунологических параметров женщин с РЯ как функция избыточной экспрессии Her-2 / neu может быть использована в качестве прогностического критерия для развития заболевания. Полученные нами результаты также показывают, что избыточная экспрессия Her-2 / neu коррелирует с прогностически неблагоприятными признаками клинического течения РЯ. Ключевые слова: рак яичников, адаптивный клеточный иммунитет, Т- и В-лимфоциты, молекулярно-биологические маркеры
ABSTRACT
The aim of the study was to study the basic cellular immunity factors in patients with ovarian cancer depending on the expression of molecular-biological markers. The method of research: seventy patients with OC at the stages T2-3N0-1M0 were examined in the oncogynecology and chemotherapy departments of the RSCPMCOR MOH RUz from 2009 to 2013. All patients underwent clinical and laboratory, instrumental studies. Results of the research: on the base of our material, the Her-2 / neu overexpression correlated with prognostically important adverse traits, such as young age, infiltrative tumor growth, high malignancy of the process with concomitant metastatic lymph node involvement. In this regard, we set the goal to investigate the immunological parameters of women with OC depending on the presence of overexpression of Her-2 / neu in comparison with the values of women without hyperexpression of Her-2 / neu. Conclusion: the immunological changes revealed by us have shown the presence of deep immunological changes, taking into account which it is necessary to carry out an adequate interpretation and correction of immunological indices. The evaluation of the immunological parameters of women with OC as a function of the overexpression of Her-2/neu can be used as a prognostic criterion for the course of the disease. The results obtained by us also show that the overexpression of Her-2/neu correlates with the prognostically unfavorable signs of the clinical course of the OC.
