Comparative analysis of some immunological parameters depending on the tumor location on the right and left sides of colon

Background: Colorectal cancer is now an urgent problem in oncology. Recently, specialists have been interested in a comparative analysis of differences in the clinical course of malignant tumors in the proximal and distal colon. The sections differ not only in their embryogenesis and sources of blood supply, but also in the clinical course and population and epidemiological characteristics. The issue of distinctive immunological characteristics of tumors of the colon depending on the location remains open.Objective: A comparative analysis of local subpopulations of immunocompetent cells and an assessment of number of cells with the CD45+/- phenotype expressing toll-like receptors (TLRs) depending on the tumor location on the right or left sides of the colon.Material and methods: The study included 50 patients with verified colon cancer. The majority of patients were females – 26 (52%), aged 67 ± 0.4 years, and 50% of patients with stage II disease. Depending on the tumor location (the right or left sides of the colon), the patients were divided into 2 groups of 25 people each. All patients underwent standard surgery at the initial stage. The obtained material was used for subsequent studies: a cell suspension was obtained from a tumor tissue fragment, the perifocal zone (1–3 cm from the tumor) which was processed using an antibody panel (Becton Dickinson, USA) to identify the main subpopulations of leukocytes and lymphocytes. Expression of TLRs (2, 3, 4, 8, 9) on CD45+, CD45- cell populations was also determined using the BD FACSCanto flow cytometer (Becton Dickinson, USA). Statistical processing of the results was performed using the STATISTICA 13.3 package (StatSoft Inc., USA).Results: A comparative analysis of immunological parameters, depending on the tumor location on the right or left sides of the colon, showed:Tissues of the right-sided tumors had a higher T-lymphocytic infiltration, compared to the left-sided tumors, while the latter showed a higher B-lymphocytic infiltration (p = 0.025).Peritumoral zone tissues of left-sided tumors demonstrated a decrease of lymphocytes levels (p = 0.027), NKT – (p = 0.035), NK – (p = 0.041) and В lymphocytes (p = 0.038), and a significant increase in CD8+- (p = 0.02) and DP cells (p = 0.0018).Left-sided tumors showed a percentage decrease of CD45- cells expressing TLR4 and TLR8, compared to right-sided tumors, by 38% (p = 0.038) and 25% (p = 0.043).There was a decrease in the number of CD45+ cells expressing TLR2 and TLR4 in left-sided tumors by 54% (p = 0.035) and 33% (p = 0.04) respectively, than in right-sided tumors.The percent of CD45- cells expressing TLR4 in the perifocal tissues of left-sided tumors decreased by 61% (p = 0.031) in comparison to the corresponding tissues in right-sided tumors.The numbers of CD45+ cells expressing TLR2 and TLR4 were 81% (p = 0.02) and 87% (p = 0.018) lower respectively in the peritumoral tissues of left-sided tumors, compared to the corresponding tissues in right-sided tumors.Conclusion: The revealed characteristics of the local subpopulations of immunocompetent cells and the numbers of CD45+/- cells expressing TLRs depending on the tumor location on the right or left sides of the colon can serve as a prognosis of the disease clinical course and the choice of further treatment tactics

Маркеры рака мочевого пузыря: их роль и прогностическая значимость (обзор литературы)

This review article is devoted to the main problems of early diagnostic and prognosis of non-muscle-invasive bladder cancer, which accounts for 75 % of all newly detected cases of bladder cancer according to statistics. Chromosomal disorders that have been detected in urothelial cells can lead to the development of non-muscle-invasive bladder cancer. The review highlights the main problems of existing diagnostic systems for bladder cancer, their disadvantage and limitations of use in practice. Special attention is given to tumor stem cells, which are actively involved in the development of relapses of malignant neoplasms, and, also play an important role in the development of chemo - and radioresistance of tumor cells. Their significance in the diagnosis, detection of disease recurrence and the possibility of using the data obtained to adjustment therapeutic methods of treatment in oncology is one of the main tasks in cancer pathology.Обзорная статья посвящена основным проблемам диагностики и раннего прогнозирования немышечно-инвазивного рака мочевого пузыря, на долю которого, по данным статистики, приходится 75 % всех впервые выявленных случаев рака мочевого пузыря. В клетках уротелия, как показывают результаты многих исследований, выявлены хромосомные нарушения, обусловливающие развитие немышечно-инвазивного рака мочевого пузыря. В обзоре обозначены основные проблемы существующих диагностических систем при немышечно-инвазивном раке мочевого пузыря, их недостатки и ограничения использования в повседневной работе. Отдельное внимание уделяется опухолевым стволовым клеткам, которые принимают активное участие в развитии рецидивов злокачественных новообразований, а также играют важную роль в развитии химио- и радиорезистентности опухолевых клеток. Определение их значимости в диагностике, выявлении рецидива заболевания и возможности использования полученных данных для корректировки терапевтических методов лечения в онкологии является одной из основных задач

Local cytokine levels as prognostic factors for early relapse of non-muscle-invasive bladder carcinoma

The aim of our study is to assess the local cytokine levels as prognostic factors for early relapse in NMIBC patients. 75 patients with NMIBC were enrolled in the study: 51 with primary NMIBC and 24 with initially recurrent NMIBC, LG and HG tumors were diagnosed in each group. Patients with primary NMIBC were monitored during 9 months after treatment: TURB and chemotherapy (No. 6). During TURB samples of tumors were taken, supernatants were obtained and tissue cytokine levels were measured (IL-1β, IL-6, IL-10, IL-18, TNFα, IFNγ, IL-8) by ELISA test. The results showed that in patients with primary NMIBC early relapses were diagnosed in 15 (46.8%) of LG tumors and in 11 (45%) of HG tumors matching that there was no difference depending upon tumor grade. In initially recurrent tumors of both LG and HG NMIBC the amounts of cytokines were maximal: in LG tumors they exceeded the primary ones from 7.1 (IFNγ) to 300 (IL-6) while in HG - from 2.0 (IL-10) to 9.7 (IL-6). The amounts of IL-1β, IL-6, IL-10, IFNγ, IL-8 were higher in those LG primary tumors which relapsed in 6-9 months compared to the ones which didn't, though their levels were much lower than in initially manifested relapse (from 2.6 times for IFNy to 150 times for IL-6). A similar trend, though not for all the same cytokines, was observed in HG tumors: tissue levels of IL-6, IL-10, IL-18 and TNFα were higher in tumors which relapsed in 6-9 months after treatment. The increase of 2 cytokines' levels were common for both LG and HG tumors (IL-6 and IL-10). This finding might be considered as a new prognostic factor of the early relapse. We conclude that relapse of LG and HG NMIBC is related to some immune mechanisms, namely to local hyperproduction of cytokines, especially IL-6 and IL-10, though IL-1β, IL-8, IFNγ could have an impact on LG and IL-18, TNFα — on HG tumors. Taking into account common signaling pathways of IL-6 and IL-10 like JAK/STAT, these transcription factors might be potential targets for new effective approaches to treatment

Метаболизм триптофана при различном эффекте иммунотерапии немелкоклеточного рака легкого ингибиторами PD-1 / PD-L1

Introduction. In the structure of cancer incidence, lung cancer ranks first among men. In order to study the molecular mechanisms of the initiation and progression of lung cancer, it is necessary to study not only the tumor cells themselves, but also the features of the systemic tryptophan metabolism. Tryptophan catabolites, being to a large extent product of the metabolic activity of the intestinal microbiota, can affect the effectiveness of immunotherapy with checkpoint inhibitors. The kynurenine pathway of tryptophan metabolism is intensified in the body of cancer patients; its products have a pro-oncogenic and immunosuppressive effect, which may hinder the effectiveness of immunotherapy.Objective – to study the dynamics of changes in various metabolites of tryptophan metabolism in the blood serum and feces of patients with non-small cell lung cancer with various effects of immunotherapy with inhibitors of PD-1 (programmed cell death receptor 1) / PD-L1 (programmed cell death receptor 1 ligand).Materials and methods. The study included blood serum and stool samples obtained from 20 patients with non-small cell lung cancer treated with PD-1 / PD-L1 inhibitors. Using high-performance liquid chromatography with mass spectrometric analysis, the levels of 13 tryptophan metabolites were assessed in patients with various effects of immunotherapy. The significance of differences between the samples was assessed using a nonparametric method according to the Mann – Whitney test. They were considered statistically significant at p <0.05.Results. In fecal analyzes of patients in whom a positive effect of immunotherapy was observed, baseline levels of 5-hydroxyindole acetate and quinolinic acid were lower than in patients with tumor progression. Positive clinical dynamics was accompanied by a decrease in the content of indole-3-lactate, kynurenine and indole-3-carboxaldehyde in the feces of patients. In the serum of patients with a positive response, the initial content of 5-hydroxyindole acetate, indole-3-acetate, indole-3-butyrate and quinoline acid was lower than in patients with progression of non-small cell lung cancer. A positive response to immunotherapy was characterized by an increase in the levels of indole-3-butyrate and indole-3-propionate, and a negative response was not accompanied by statistically significant changes in the studied tryptophan metabolites.Conclusion. Profiling tryptophan metabolites in feces and serum of patients with non-small cell lung cancer can be used to predict the effectiveness of immunotherapy with PD-1 / PD-L1 inhibitors.Введение. В структуре онкологической заболеваемости рак легкого занимает 1-е место среди мужчин. С целью изучения молекулярных механизмов инициации и прогрессирования рака легких необходимо исследовать не только сами опухолевые клетки, но и особенности системного метаболизма триптофана. Катаболиты триптофана, будучи в большой степени продуктами метаболической активности микробиоты кишечника, могут влиять на эффективность проведения иммунотерапии ингибиторами контрольных точек. Кинурениновый путь метаболизма триптофана интенсифицируется в организме онкологических пациентов, его продукты имеют проонкогенное и иммуносупрессивное действие, что может препятствовать эффективности иммунотерапии.Цель исследования – изучение динамики изменений различных метаболитов триптофанового обмена в сыворотке крови и кале больных немелкоклеточным раком легкого при различных эффектах иммунотерапии ингибиторами PD-1 (рецептора программируемой клеточной гибели 1) / PD-L1 (лиганда рецептора программируемой клеточной гибели 1).Материалы и методы. В исследование были включены образцы сыворотки крови и кала, полученные от 20 больных немелкоклеточным раком легкого, получавших ингибиторы PD-1 / PD-L1. С помощью высокоэффективной жидкостной хроматографии с масс-спектрометрическим анализом проведена оценка уровней 13 метаболитов триптофана у больных с различными эффектами иммунотерапии. Достоверность различий между выборками оценивали с помощью непараметрического метода по критерию Манна–Уитни. Они считались статистически значимыми при р <0,05.Результаты. В анализах кала пациентов, у которых наблюдали положительный эффект от иммунотерапии, исходные уровни 5-гидроксииндолацетата и хинолиновой кислоты были ниже, чем у больных с прогрессированием опухоли. Положительная клиническая динамика сопровождалась снижением содержания индол-3-лактата, кинуренина и индол-3-карбоксальдегида в анализах кала больных. В сыворотке пациентов с положительным ответом исходное содержание 5-гидроксииндолацетата, индол-3-ацетата, индол-3-бутирата и хинолиновой кислоты оказалось ниже, чем у пациентов с прогрессированием немелкоклеточного рака легкого. Положительный ответ на иммунотерапию характеризовался повышением уровней индол-3-бутирата и индол-3-пропионата, а отрицательный – не сопровождался статистически значимыми изменениями исследованных триптофановых метаболитов.Заключение. Профилирование метаболитов триптофана в кале и сыворотке больных немелкоклеточным раком легкого может быть использовано для прогнозирования эффективности иммунотерапии ингибиторами PD-1 / PD-L1

Взаимосвязь хинолоновых регуляторов Pseudomonas aeruginosa и уровня иммуноглобулинов в крови больных раком легких

Introduction. Researchers in the field of oncology have a significant interest in the role of microorganisms in development of malignant neoplasms.Aim. To study the levels of 2-heptyl-3-hydroxy-4-quinolone (PQS) and 2-heptyl-4-quinolone (HHQ) produced by Pseudomonas aeruginosa in the blood of patients with lung cancer and to analyze the relation between their changes and changes in the level of immunoglobulins and vascular endothelial growth factor (VEGF) in the blood of patients with lung cancer.Materials and methods.  PQS and HHQ were quantified in the blood of patients using high performance liquid chromatography. The levels of immunoglobulins G (IgG),  secretory immunoglobulin A (s-IgA),  and VEGF in the blood were determined using ELISA.Results. Analysis have shown that the level of PQS in the blood of patients with lung cancer is 2-fold higher than in the control group. This change is accompanied by a decrease in the level of immunoglobulins IgG, as well as an increase in the content of s-IgA and growth factor VEGF in the blood.Conclusion. PQS level in the blood of patients with lung cancer is elevated creating conditions aggravating the course of the main disease and worsening its prognosis.Введение. Большой интерес у исследователей в области онкологии вызывает вопрос о роли микроорганизмов в развитии злокачественных новообразований.Цель исследования – изучить содержание 2-гептил-3-гидрокси-4-хинолона  (PQS) и 2-гептил-4-хинолона (HHQ), продуцируемых Pseudomonas aeruginosa, в крови больных раком легких и проанализировать взаимосвязь этого показателя с изменением уровня иммуноглобулинов и фактора роста эндотелия сосудов (vascular endothelial growth factor, VEGF) в крови.Материалы и методы. Выполнены количественное определение PQS и HHQ в крови больных с помощью высокоэффективной жидкостной хроматографии, а также анализ иммуноглобулинов класса G (IgG), секреторного иммуноглобулина а (s-IgA) и VEGF с помощью твердофазного иммуноферментного анализа.Результаты. Исследования показали, что уровень PQS в крови больных раком легких в 2 раза выше, чем у обследованных контрольной группы. На фоне данного сдвига наблюдаются снижение уровня иммуноглобулинов IgG, а также повышение содержания s-IgA и VEGF в крови.Заключение. У больных раком легких происходит повышение уровня PQS в крови, что формирует предпосылки для отягощения течения основного заболевания и ухудшения его прогноза

ОСОБЕННОСТИ ЭКСПРЕССИИ CD133 И CD44 МАРКЕРОВ ОПУХОЛЕВЫХ СТВОЛОВЫХ КЛЕТОК ПРИ МЕТАСТАТИЧЕСКОМ И НЕМЕТАСТАТИЧЕСКОМ РАКЕ ЖЕЛУДКА

Background. Gastric cancer is the second leading cause of cancer-related death due to advanced disease. A special role in the pathogenesis and metastasis of the tumor is assigned to tumor stem cells (TSC ),  responsible for resistance to chemotherapy and radiotherapy and causing tumor progression.Objective: to determine the CD 44 and CD 133 markers of TSC in tumor tissues of non-metastatic and metastatic gastric cancer using the immunohistochemical method.Material and Methods. A prospective study of tumors in patients with gastric cancer was conducted: Group 1 – 20 people with T3–4aN0–3M0G2 tumor, average age 58.9 ± 9.7; Group 2 – 20 people with T3–4aN0–3M1G2 tumor, with metastases in the peritoneum, average age 53.4 ± 11.9. The expression of CD 44 and CD 133 in the tumor tissue was determined by immunohistochemistry.Results. Differences were found in the number of tumor cells expressing the CD 44 marker in the presence and absence of metastases in patients with gastric cancer – their number was 10.0 ± 3.08 and 6.0 ± 2.3, respectively. The CD 133 molecule was detected in 100 % of cases having metastases, while in cases having no metastases, the marker was detected only in 80 % of cases. The average percentage of CD 133 + cells was 21.3 ± 11.6 % in patients with metastatic gastric cancer and 10.0 ± 2.4 % in patients having no metastases.Conclusion. The degree of expression of the CD 44 and CD 133 markers had characteristic differences in patients with gastric cancer, which can be used further to explain the results of the treatment and the prognosis of the disease.Введение. В структуре смертности рак желудка (РЖ) занимает второе место, что обусловлено поздней диагностикой в сочетании с агрессивным течением заболевания. Особую роль в патогенезе и метастазировании опухоли отводят опухолевым стволовым клеткам, ответственным за устойчивость к химио- и радиотерапии и обусловливающим прогрессию опухоли. Цель исследования – определение cd44 и cd133 маркеров опухолевых стволовых клеток в ткани опухоли при неметастатическом и метастатическом раке желудка с  использованием иммуногистохимического метода. Материал и методы. Проведено проспективное исследование опухолевой ткани у больных раком желудка: 1-я группа – 20 больных РЖ t3–4аN0–3m0, степень дифференцировки опухоли – g2, средний возраст – 58,9 ± 9,7 года; 2-я группа – 20 больных РЖ t3–4аN0–3m1 с метастатическим поражением брюшины, степень  дифференцировки опухоли – g2, средний возраст – 53,4 ± 11,9 года. Экспрессию cd44 и cd133 в ткани опухолей осуществляли иммуногистохимическим методом. Результаты. Выявлены отличия в количестве опухолевых клеток, экспрессирующих cd44 маркер при наличии и отсутствии метастазов у больных раком желудка – их количество составило 10,0 ± 3,08 % и 6,0 ± 2,3 % соответственно. При этом cd133 молекула при наличии метастазов выявлялась в 95 %, при их отсутствии – в 80 % случаев. Средний уровень cd133+-клеток при метастатическом раке желудка составил 21,3 ± 11,6 %, при локализованном – 10,0 ± 2,4 %. Заключение. Степень экспрессии выбранных молекул имела характерные отличия у больных различными формами рака желудка, что может быть использовано в дальнейшем для понимания результатов лечения и прогноза течения заболевания

КЛИНИЧЕСКИЙ СЛУЧАЙ УСПЕШНОГО ЛЕЧЕНИЯ ПОДРОСТКА С САРКОМОЙ ЮИНГА IV СТАДИИ

Background. Ewing’s sarcoma is one of the most common musculoskeletal cancers in children and adolescents. Extremely aggressive clinical course of Ewing’s sarcoma makes a successful treatment of this tumor difficult. Despite a comprehensive multidisciplinary approach to the treatment of this cancer, including chemotherapy, surgery and radiation therapy, rapid tumor progression, recurrence and resistance to chemotherapy are still common.Our purpose was to present the results of a personalized approach to multidisciplinary combination treatment for musculoskeletal cancer involving polychemotherapy, 3D conformal radiation therapy and modern surgical technologies.Description of the clinical case. A female patient presented to Rostov Research Institute of Oncology complaining of a tumor and moderate pain in soft tissues of the left iliac region, left lower extremity, and lameness when walking. After complete examination, the patient was diagnosed with Ewing’s sarcoma of the left ilium with lung metastases (Т3N0M1). The patient received 6 cycles of neoadjuvant chemotherapy according to EURO EWING 2008 protocol; tumor progression and lung metastasis were registered. Two cycles of second-line chemotherapy were performed; by the decision of the doctors’ council, the first stage of surgical treatment was performed: resection of the left ilium and the defect replacement with a temporary cement spacer. In the postoperative period, the patient underwent 8 cycles of adjuvant chemotherapy, external beam radiation therapy to the lungs (12 Gy total dose) and the primary tumor (46 iGy total dose), and 12 cycles of supporting therapy. A delayed second reconstructive stage of surgical treatment involved removal of a temporary cement spacer and implantation of an individual pelvic stability system. The patient was followed-up for 25 months after the combination treatment, had no complaints, and was able to ambulate without assistance; the motor function of the left hip joint was fully preserved. Conclusion. The use of non-standard high-technology approaches to surgical treatment of unfavorably localized Ewing’s Sarcoma in combination with chemo-radiation therapy allows patients with advanced tumors to achieve satisfactory results and good quality of life. Актуальность. Саркома Юинга занимает одно из лидирующих мест в онкологической патологии опорно-двигательной системы у детей и подростков. Успешное лечение затрудняет крайне агрессивное течение опухолевого процесса. Несмотря на мультидисциплинарный подход в лечении, включающий наряду с химиотерапевтическим и хирургическим методами лечения лучевую терапию, быстрая генерализация опухолевого процесса, рецидивы и резистентные к химиотерапии формы опухоли попрежнему часты.Целью работы явилось представление результатов персонифицированного подхода в комплексном мультидисциплинарном лечении злокачественной патологии опорно-двигательной системы с использованием многокомпонентной полихимиотерапии, 3D-конформной лучевой терапии и высоких хирургических технологий.Описание клинического случая. Больная обратилась в ФГБУ «РНИОИ» МЗ РФ в апреле 2016 г. с жалобами на наличие опухолевого образования и умеренных болей в мягких тканях левой подвздошной области, левой нижней конечности, хромоту при ходьбе. По данным обследования установлен диагноз: саркома Юинга левой подвздошной кости с метастазами в легкие, IV стадия (Т3N0M1). После 6 курсов неоадъювантной полихимиотерапии, согласно протоколу EWING 2008, отмечено прогрессирование опухоли с метастазами в легкие. Проведено 2 противорецидивных курса полихимиотерапии второй линии, решением консилиума врачей проведен первый этап хирургического лечения: резекция левой подвздошной кости с замещением дефекта временным цементным спейсером. В послеоперационном периоде больной проведено 8 курсов адъювантной полихимиотерапии, ДГТ на область обоих легких (СОД 12 Гр) и зону первичного очага (СОД 46 изоГР), 12 курсов поддерживающей терапии. Выполнен отсроченный реконструктивно-пластический этап хирургического лечения – удаление временного цементного спейсера с установкой индивидуальной тазовой стабилизирующей системы. Больная находится под наблюдением 25 мес после комплексного лечения, жалоб не предъявляет, передвигается самостоятельно, двигательная функция левого тазобедренного сустава сохранена в полном объеме.Заключение. Использование нестандартных высокотехнологичных подходов в хирургическом лечении саркомы Юинга неблагоприятных локализаций в сочетании с химиолучевой терапией позволяет достичь удовлетворительных результатов при лечении больных с распространенным опухолевым процессом и сохранения высокого уровня качества жизни.

Work within the COVID-19 pandemic — the experience of the biobank of the National Medical Research Center of Oncology

Aim. To present the main results and changes in the work of the biobank of the National Medical Research Center of Oncology during the pandemic of coronavirus disease 2019 (COVID-19).Material and methods. The paper presents a dynamic analysis of the delivery of fresh frozen biological samples from operated patients for three quarters of 2019 and 2020, as well as considers possible ways to implement research projects to collect and deposit materials for the biobank within the COVID-19 pandemic. The work included persons over 18 years old, with primary gastrointestinal cancers, who, upon hospitalization, gave informed consent to transfer biological material tothe biobank. One of the inclusion criteria was the presence of a negative nasopharyngeal swabs tested for SARS-CoV-2 by the polymerase chain reaction. Data calculation and comparative analysis of the results was carried out using the Microsoft Office Excel software package.Results. It was revealed that in the first quarter of 2019, 34% of biological samples were received from the total amount for the year, while in 2020 — 50%; in the second quarter of 2019 — 35%. The second quarter of 2020 was characterized by change in the schedule of work of institutions due to the COVID-19 pandemic, which led to a 56% decrease in the number of samples compared to the same period in 2019 and amounted to 14% of material collected for the three quarters of2020. In the third quarter of 2020, the flow was restored and amounted to 65 patients, which corresponds to 36% of material collected in this year and is more than in 2019 by 23%.Conclusion. a critical decrease in the deposited material in the second quarter of 2020 indicated the need to adapt the current biobanking rules inRussia in general and the studied biobank in particular. Possible adaptation ways may consist in the creation of joint projects between groups of scientists from different organizations, taking into account the requirements of information and biological safety. This problem and ways to solve it were widely discussed at international and Russian platforms, including the 4th meeting of the National Association of Biobanks and Biobanking Specialists, dedicated to the organization of biobanking during the COVID-19 pandemic

CELL MEDIATED IMMUNITY IN PATIENTS WITH STAGE II–IV COLORECTAL CANCER WITH OR WITHOUT CIRCULATING TUMOR CELLS

Nowadays, circulating tumor cells (CTCs) are considered to be one of the most important mechanisms of tumor dissemination. Detection of CTCs in patients` blood is estimated as a prognostic factor for various tumors including colorectal cancer (CRC). However, CTCs may also be a source of tumor antigens capable of inducing both immune response and tolerance and participating in «immmunoediting». The aim of the study was to assess the parameters of cell-mediated immunity in patients with stage IIIV CRC with respect to the presence or absence of CTCs. Materials and Methods. We studied the parameters of cell-mediated immunity in 60 patients with stage IIIV CRC with respect to the presence or absence of CTCs. Before treatment, we evaluated the CTC levels in patients’ blood using CellSearch System™ and lymphocyte subsets: Т-В-NК-cells, T-reg, CD4+ and CD8+ expressing markers of activation (CD69+, СD38+, CD25+, HLA-DR+ СD95+); naïve and memory T-lymphocytes (CD45RA-/CD45RO+); NК-cells expressing CD335, perforin and granzyme B using flow cytometry (FACSCantoII, BD). Results. A difference in the immunologic parameters between patients with CTCs and without CTCs depending on the stage of CRC was found. In СTС-positive patients with locally-advanced CRC, increase in the parameters of innate immunity (CD335+ NK-cells, neutrophils` respiratory burst) and activated Th (CD38+, CD25+, HLA-DR+) was found, while in СTС-positive patients with generalized CRC, suppression of cytotoxic lymphocytes of both innate (CD56/16+) and adaptive (CD8+CD25+) immunity was observed, which is, apparently, an unfavorable prognostic factor. Conclusion. The presence of CTC in CRC patients is accompanied by some immunologic changes rather stimulating Thlink and innate immunity factors in II-III stages and doubtlessly suppressive in patients with IV stage

Expression of E- and N-cadherins in tumor in luminal, primary operable breast cancer without Her2/neu overexpression in postmenopausal women as a prognostic factor

Purpose of the study. Evaluation of the expression of E- and N-cadherins in tumor tissues in postmenopausal patients with primary operable luminal breast cancer (BC) without Her2/neu overexpression for inclusion in the panel of a comprehensive assessment of tumor biological parameters for the disease prognosis.Patients and methods. The study included 120 patients divided into two groups: patients with luminal A and luminal B subtypes. To evaluate the prognostic significance of E- and N- cadherins in both groups of patients, we analyzed expression levels and correlation using the Mann- Whitney U-test and Spearman correlation criterion; overall survival, progression-free and tumor- specific one, at various values of the studied biomarkers — by the Kaplan- Meier method.Results. The differences in the mean expression levels were not statistically significant (p>0,05). E-cadherin was twice higher in luminal A BC (55.4±5.2) compared to luminal B BC (28.1±4.9), N-cadherin in luminal A BC (12.8±5.3) was 1.3 times lower than in luminal B BC (17.06±5.4). Patients with luminal B BC demonstrated a tendency to the loss of E-cadherin and increased expression of N-cadherin, which is often associated with poor prognosis. However, the correlation between these markers was not statistically significant (p>0,05).Conclusions. Thus, despite the differences in levels of E- and N-cadherin expression, these markers did not show their prognostic significance, and therefore, they were not included in the panel for a comprehensive assessment of tumor biological parameters when determining the prognosis of luminal breast cancer without Her2/neu overexpression in postmenopausal women