Purpose of the study. To analyze the apoptosis indicators in mitochondria of brain cortex cells in female С57ВL/6 mice in the dynamics of B16/F10 melanoma growth alone and in combination with comorbidity, i.e. chronic neurogenic pain.

Materials and methods. Female С57ВL/6 mice (n = 168) were used in the experiment. Groups accounted: intact group (n = 21); control group (n = 21) with a model of chronic neurogenic pain (CNP); comparison group (n = 63) with B16/F10 melanoma transplanted subcutaneously; main group (CNP + B16/F10) (n = 63). Levels of cytochrome C (ng/mg protein), caspase 9 (ng/mg protein), Bcl‑2 (ng/mg protein), AIF (ng/mg protein), calcium (Ca 2+) (mMol/g protein) were measured by ELISA in mitochondrial samples. Statistical analysis was performed using the Statistica 10.0 program.

Results. In a week of the tumor growth in presence of comorbidity, i.e. CNP, levels of calcium in murine brain cortex mitochondria were 1.4 times higher (p < 0.05) than in the comparison group at the same time; in 2 weeks the levels declined by 80.1 times and after 3 weeks declined by 37.7 times. Compared to the values in the comparison group AIF levels in animals with CNP+B16/F10 were lower by 25 and 1.8 times (p < 0.05) at weeks 1 and 3, respectively. Higher levels of Вcl‑2 in the group with CNP + B16/F10 were registered at weeks 2 and 3 by 2 and 1.4 times (p < 0.05), respectively. Levels of cytochrome C were decreased in animals with CNP+B16/F10 at weeks 1–3 by 3.2, 1.5 (p < 0.05) and 2.8 times, respectively. Caspase 9 in CNP+B16/F10 after 3 weeks exceeded the values in the comparison group by 2.6 times.

Conclusions. Combination of CNP and melanoma at an early stage in the animal body promotes the accumulation of calcium and suppression of AIF and cytochrome C in mitochondria of the brain cortex. By the terminal stage of tumor growth in presence of comorbidity (CNP), suppression of most units of the respiratory chain of mitochondria of brain cortex cells is formed.

Purpose of the study. To study the intensity of lipid peroxidation (LPO) and indicators of antioxidant protection in the liver of rats of different sexes with combined pathology – the growth of Guerin's carcinoma in presence of experimental type 1 diabetes mellitus.

Materials and methods. The levels of malondialdehyde (MDA) and diene conjugates (DC), the activities of superoxide dismutase (SOD) and catalase, and the levels of vitamins A and D were studied by conventional spectrophotometric methods in liver tissue samples from males and females with alloxan‑induced diabetes mellitus (DM), transplanted Guerin’s carcinoma (GC) and in animals with combined pathologies (GC growth in presence of diabetes mellitus), as well as in intact rats.

Results. The levels of both LPO markers in intact females were significantly higher than in males: MDA by 3 times, DC by 2 times. The development of DM led to an increase in the content of MDA and DC in the liver of males compared with intact animals, which indicated an intensification of LPO. At the same time, there was an almost twofold increase in SOD activity, a decrease in catalase activity, and an increase in the ratio of enzymes by 2.8 times. In females, there was no increase in LPO in the liver; there was only a less pronounced increase in SOD activity than in males. At the same time, SOD activity in males was 37 % higher than in females, and catalase activity, on the contrary, was lower by 33 %, which caused a twofold excess of the ratio of enzymes in males relative to females. Among animals with GC, only males had an increase in SOD by 2.5 times, a decrease in catalase activity, and an increase in the SOD/Catalase ratio by 3 times relative to intact animals, which may be due to pronounced sex differences the SOD activity and SOD/Catalase ratio in males were 3–4 times higher than that of females. The levels of MDA and DC in males with GC growing in presence of DM remained elevated, although to a somewhat lesser extent than in DM alone, while in females both indicators were reduced. The ratio of vitamins E and A increased only in males. SOD activity and SOD/Catalase coefficient in animals of both sexes with combined pathologies were significantly lower than in groups with only DM or GC.

Conclusions. The data showed that diabetes mellitus changes the specificity of oncogenesis depending on the sex of the animals. Males with the growth of Guerin's carcinoma in presence of diabetes in conditions of inhibition of SOD activity and a decrease in the ratio of conjugated enzymes of the first line of antioxidant defense demonstrate an intensification of LPO accompanied by an increase in the non‑enzymatic unit of the antioxidant system, while there is no increase in LPO in females, and the indicators of antioxidant activity change to a lesser extent.

Purpose of the study. Assessment of albumin and endogenous intoxication levels in patients with locally advanced cervical cancer receiving immunotherapy with dendritic cell vaccine.

Materials and methods. The study included 27 patients with advanced cervical cancer (CC) divided into 3 groups: 1) patients receiving dendritic cell vaccine (DCV) during primary chemoradiation treatment; 2) patients with the disease progression receiving DCV during second‑line chemotherapy; 3) patients with advanced disease with contraindications for chemo‑radiation treatment receiving DCV only. The comparison group included 20 healthy women. All groups were tested for levels of medium‑weight molecules (MWM₂₅₄ and MWM₂₈₀), total and effective concentrations of albumin (TCA and ECA), toxicity index (TI) characterizing the sorption capacity of albumin, and the coefficient of intoxication (CI) reflecting the balance between the accumulation and binding of toxic ligands.

Results. Initial elevation of MWM was observed in all patients. Levels of MWM₂₅₄ were the highest in patients with progression. TI in patients with primary and progressive CC was increased before the treatment by 1.7 and 2.2 times, and after CT (without DCV) – by 2.6 and 3.8 times. In group 3, TI was increased by 4 times, and CI by 2.5 times, being 81 % higher than in group 1. In primary patients, TI after 6 and 7 DCVs was similar to the normal values, and CI was increased during the treatment because of the accumulation of MWM₂₅₄ due to disintegration of tumor masses in these patients, and then it was normalized after 7 DCVs. CI in patients of groups 2 and 3 decreased after each DCV session. 4 and more DCVs restored the functional activity of albumin and normalized the MWM content.

Conclusion. Administration of DCV (at least 7–8 sessions) in CC patients receiving anticancer treatment or as monotherapy decreases endotoxicosis and restores detoxification capacity of albumin.

Purpose of the study. Was to reveal the antitumor effect of 2‑(6,8‑dimethyl‑5‑nitro‑4‑chloroquinoline‑2‑yl)‑5,6,7‑trichloro‑1,3‑tropolone in subcutaneous PDX models of human lung cancer.

Material and methods. The studied tropolone was synthesized using a method of expanding the o‑quinone cycle. Assess to it’s toxic effects was given by the survival and changes in the health status of female Balb/c Nude mice. Antitumor tropolone effects were studied in subcutaneous patient‑derived xenograft (PDX) models of human squamous cell lung cancer in Balb/c Nude mice. The average volumes of tumor nodes and tumor growth inhibition (TGI %) rate were taken into account. Biochemical blood tests and histological analysis of the tumor material were performed in recipient mice.

Results. An analysis of acute tropolone toxic effects did not reveal the lethal dose. The maximal TGI was observed on day 36 of the experiment in group 5 which have received 2.75 mg/g tropolone and accounted 73.5 % for females and 74.4 % for males. The average tumor volumes in females of this group were 431.3 ± 1,1 mm³ on day 33 of the experiment, in males – 428.9 ± 1,7 mm³ on day 30, and then the tumor volumes declined. The biochemical analysis of blood and histological examination of the tumor tissue of recipient mice reflect the severity of the antitumor effect on the dose of the studied tropolone.

Conclusion. The research demonstrated the antitumor activity of 2‑(6,8‑dimethyl‑5‑nitro‑4‑chloroquinoline‑2‑yl)‑5,6,7‑trichloro‑1,3‑tropolone against subcutaneous PDX models of human NSCLC. The revealed tendencies can be used to search for effective modes of the compound application in clinical practice.

Purpose of the study. Was was the creation of a Patient Derived Xenograft (PDX) model of non‑small cell lung cancer in immunodeficient mice adapted to growth in immunodeficient mice.

Materials and methods. The study was performed using the tumor material from 14 donors implanted subcutaneously to 132 immunodeficient Balb/c Nude mice. Xenografts were maintained until the third passage. PDXs in the third passage from 3 patients were used to assess the model sensitivity to cisplatin. A histological analysis and genetic tests for the presence of EGFR mutations were performed for donor tumors from 3 patients and the corresponding xenografts in the third passage.

Results. We observed a noticeable PDX growth already on the 8th day after the tumor material implantation. Successful xenograft engraftment was noted in 21 of 42 mice (50 %), which were rather successful results. A comparative histological analysis of tumor material from 3 patients showed that the PDX models retained the original histotype. We also demonstrated the identity of the EGFR mutations in the established xenografts from 3 patients and the donor tumors, which proved the value of these PDX models for preclinical studies of substances with potential antitumor activity. The analysis of the xenograft sensitivity to cytostatic cisplatin showed a statistically significant decrease in the growth rate in the xenografts obtained from 2 out of 3 patients, in comparison with the control.

Conclusions. The created PDX models can be recommended as test systems for preclinical studies of the effectiveness of new pharmacological substances with potential antitumor activity.

Purpose of the study. Was to study the results of magnetic resonance imaging (MRI) of the patients with malignant neoplasms (MN) of the rectum after transanal full‑layer resection of the tumor.

Materials and methods. MRI images of the pelvis of 25 patients with rectal cancer after organ–preserving surgical treatment in the volume of full‑layer excision of the tumor for the period from 2015 to 2020 of the MRI department of the A. Tsyb Medical Radiological Research Centre, the Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation; 13 patients received additional treatment in the volume of chemoradiotherapy and brachytherapy; 13 patients underwent dynamic studies to assess the process after treatment.

The MRI picture was evaluated by T2‑WI in three planes and DWI with an ADC map in the pelvic region and aimed at the excision zone of the tumor.

Indications for MRI were the exclusion of continued tumor growth in the surgical intervention area and clinical manifestations of suture failure in the tumor excision area.

Results. All patients were divided into two groups: 11 patients with a normal course of the postoperative period where visualized a zone of scar changes in the area of surgical intervention with a low intensity signal in the T2‑WI mode, without signs of true diffusion restriction, hyper‑ and the average intensity of the signal and 14 patients with identified deviations from the normal picture: of these 10 patients with a relapse after surgical treatment, who had additional formations with signs of pathological MR signal, true diffusion restriction, which were regarded as recurrent formations in the tumor excision zone, as well as 4 patients in the tumor excision zone, a defect in the rectal wall was visualized against the background of a low intensity signal from the zone of fibrous changes, with the formation of liquid leaks, indicating the insolvency of the seams.

Conclusion. The method of MRI can be recommended as the method of choice for assessing the pelvic region after transanal endoscopic microsurgery (TEM), which allows for high accuracy to exclude continued tumor growth; to assess the pelvic region for the presence of distant metastases; to determine the defect of the walls in the excision zone of tumors. MRI provides safe dynamic control.

Purpose of the study. Surgical treatment of extended strictures and obliterations of the ureter is still a complicated problem of modern urology. The aim of the study was to analyze our own experience of ureteral replacement plastic surgery with buccal graft, i.e buccal ureteroplasty (BU) with its extended strictures/obliterations.

Patients and methods. We’ve observed 25 patients who underwent BU. The lower third of the ureter was affected in 3 (12.0 %) cases, the lower third and the mouth of the ureter was affected in 7 people (28.0 %), the middle third in 2 (8.0 %), the upper third in 5 patients (20.0 %), the combined lesion of the upper third of the ureter and the pelvic‑ureteral segment (PUS) was in 8 (32.0 %) patients. All patients underwent repeated operations on a ureter, all revealed a significant comorbid background. The surgery was performed with a tubularized buccal graft in 13 (52.0 %), the onlay technique was applied in 12 (48.0 %). Laparoscopic surgery was performed in 10 (40.0 %) patients, surgical aid was carried out in an open way in 15 (60 %).

Results. Severe complications according to the Clavien‑Dindo classification, requiring hospitalization of patients in the intensive care unit with organ dysfunction, as well as lethal outcomes were absent. The follow‑up period of patients ranged from 1 to 57 months (an average of 14.7 months). One patient after laparoscopic BU with a tubular graft had a short (1 mm) stenosis in the anastomosis area for 6 months of follow‑up, which was successfully eliminated by laser endoureterotomy. During the entire follow‑up period, residual hydronephrosis was recorded in 4 patients (16.0 %) against the background of complete patency of the anastomosis. A control flexible ureteroscopy performed in 16 (64.0 %) patients did not reveal rejection of the buccal graft. There are still 20 patients under our supervision.

Conclusion. Our experience shows that the implementation of BU is possible on any part of the VMP using various techniques. This operation can be regarded as the "second" line of surgical treatment of strictures and obliterations of the ureter, especially after unsuccessful attempts of other reconstructions in a group of patients with severe concomitant pathology.

Purpose of the study. The study's objective is to investigate the expression level of tissue and serum markers of oncogenesis and nephrofibrosis transforming growth factor beta (TGF‑β) and matrix metalloproteinase‑9 (MMP‑9) in patients operated for various stages of renal cell carcinoma.

Materials and methods. The study prospectively included medical data of 60 patients with kidney cancer with T1–3N0M0 who received surgical treatment in the Clinic of Urologynamed after S. R. Mirotvortsev of the State Medical University from 2016 to 2019. The patients were divided into 3 groups: Group 1 included 20 patients who underwent laparoscopic kidney resection; Group 2–20 patients who underwent laparoscopic nephrectomy; Group 3–20 patients who underwent open nephrectomy. The control group consisted of 15 healthy volunteers without chronic kidney diseases. All patients signed an informed consent to participate in the study. All patients at the preoperative stage, in the early (7–10 days) and remote postoperative periods (after 1 and 2 years) were tested by solid‑phase ELISA on a StatFax 4200 analyzer using eBiosence and Cloud‑Clone Corp reagent kits for the serum concentration of oncogenesis markers MMP‑9 and TGF‑β1.

Results. Initial increase of MMP‑9 concentration was detected in all groups of PCC patients compared to the control group (p ≤ 0.05). According to the results of ROC analysis, this indicator has high specificity and sensitivity for prognosis of preoperative stage of renal cell carcinoma. The sensitivity and specificity of MMP‑9 were 87.5 % and 62 %, respectively, and the diagnostically significant level of MMP‑9 was 958 ng/ml. A comprehensive analysis of the content of MMP‑9 and TGF‑β1 oncogenesis markers in serum and tumor cells revealed the correlation of these indicators in various biological objects.

Conclusion. Markers of oncogenesis and nephrofibrosis TGF‑β1 and MMP‑9 provide an opportunity for non‑invasive monitoring of tumor progression and probability of metastasis in the clinical setting. Serum MMP‑9 are a reliable predictor of tumor growth. Serum TGF‑β1 concentration isn't a sufficiently reliable marker of tumor progression.

Purpose of the study. Was to assess the prospects for the use of vacuum aspiration biopsy in terms of breast cancer diagnosis in patients with focal breast changes categorised by 3 and 4a according to the BIRADS scale.

Materials and methods. In the period from February 2020 to July 2021, 41 (n = 41) the patient with nodules of 3 and 4a categories according to BIRADS has been passed 41 vacuum aspiration biopsies (VAB) (n = 41) under local infiltration anesthesia with ultrasound navigation. The 17 % (n = 7) of the nodular neoplasms were represented by multiple lesions. The ultrasound examination was mandatory for all the patients and the 17 % (n = 7) was combined with mammography. Invasive diagnostics of tissue material from tumors subject to VAB was previously performed in 5 patients. Trephine biopsy was also performed in 4 cases and the fine needle aspiration biopsy (TAB) was performed in 1 case. Tissue atypia was not detected in all cases.

Results. The removed lesions were benign in 85.3 % (n = 35) of the cases. Breast cancer was diagnosed in 4.8 % of cases (n = 2), cancer in situ was diagnosed in 9.7 % (n = 4). The cases of invasive cancer were observed in both BIRADS categories, while in situ cancer was diagnosed in only 4a BIRADS categories. The residual tissue of the formation was detected in 1 case (n = 1). During the procedure, no complications were revealed. Moreover, in the early postoperative period, seroma formation has occurred in 2 patients 4.8 % (n = 2). All the patients noted the satisfactory tolerance to the manipulation.

Conclusion. The data obtained suggest that vacuum aspiration biopsy has a high diagnostic accuracy and certain advantages in this category of patients, in particular cases of urgent need to conduct more precise invasive diagnostics without performing the excisional biopsy examination.

The tumor lesions of the reproductive system organs carry the leading position in the structure of gynecological diseases. One of the rare tumors that can affect the organs of the reproductive system is pecoma, which is a tumor of mesenchymal origin. Because of it’s rare occurrence the gynecologists often misinterpret available clinical data and the results of patient`s examination, diagnosing and treating the tumor as a myoma before having received the results of the histological examination. Our article describes a clinical case of a patient who had a preliminary diagnosis of uterine fibroids, and because of this fact the planned surgical treatment was carried out. But a retroperitoneal tumor originating from the uterine vein was detected during the surgery. The diagnosis of sclerosing pecoma was established by histological and immunohistochemical studies. The article analyzes the clinical features of the patient`s disease, as well as the available results of instrumental methods of examination which can lead to final diagnosis of pecoma, also difficult issues of diagnosis and tactics of diagnostic search are noted.

The literature data on the frequency of detection of pecomas, the features of their structure are presented. It is marked, that there is also a possibility of pecoma`s localization in various organs, for example, lungs, liver, kidneys, as well as in soft tissues. The possibility of multiple lesions – pecomatosis is emphasized. It is noted that among the pelvic organs the uterus is affected most often, but furthermore, the pelvic lymph nodes, the broad ligament, the omentum, the peritoneum of the pelvis and the rectum wall can be also involved in the pathological process. Risk factor of pecomas malignancy is discussed separately, the presence of three types of pecomas is determined. This fact significantly effects the probability of relapse of the tumor after surgical removal and, respectively, the tactics of postoperative follow‑up of such patients.

The tumor of the upper sulcus of the lung is an atypical form of cancer, which is characterized by invasion into the aperture of the chest and mediastinum, which in turn determines the manifestation of the disease of neurological symptoms.

Tactical approaches in the treatment of this disease are well known. To date, complex treatment is used, which includes neoadjuvant chemoradiotherapy followed by surgical treatment. This approach gives the best result in terms of prognosis and survival of patients.

Considering the local invasion, planning the surgical stage in the treatment of this group of patients is a difficult task and requires a multidisciplinary approach to determine the optimal surgical tactics.

This paper presents our own clinical observation of the successful surgical treatment of a 54‑year‑old patient with a tumor of the upper sulcus of the right lung. In order to adequately visualize the pathological process, safety and convenience of surgical intervention, Hemi‑Clamshell access was used, which combined the advantages of sternotomy and thoracotomy. Taking into account the topical location of the tumor, the greatest technical difficulties during the operation arose when performing mobilization of the upper lobe of the right lung, adequate lymph dissection near large arterial and venous vessels, removal of part of the chest wall of the pleural cavity dome.

Also, one of the important issues when planning surgical treatment of this group of patients is to determine the indications for restoring the skeletal function of the chest after rib resection. In our case, despite the resection of the posterior segments of the I–III ribs, all the muscles of the anterior chest wall were preserved, which took over part of the skeletal function of the chest. There was no development of paradoxical breathing in the postoperative period.

Surgical interventions of this amount should be performed in specialized thoracic oncology clinics and multidisciplinary medical institutions. At the same time, a multidisciplinary approach of doctors of various specialties, the experience of the operating team in performing such operations and the appropriate anesthesiological and resuscitation service is needed.

Study objective was to reflect the current state of the early kidney damage markers clinical significance in patients with urolithiasis. Authors performed a literature review of articles (original studies and reviews) published between 2018 and February 2022 on the study of pro‑inflammatory, profibrotic and angiogenic factors in urolithiasis. Bibliographic, informational and semantic source search methods in Google Scholar, PubMed, Scopus and Embase databases were used. Analysis of a legalistic and systematic sources was carried out.

Proteinuria, serum creatinine and glomerular filtration rate are now accepted as the main diagnostic markers of renal lesions. These markers already allow to reveal lesions at the stage of chronic kidney disease, when the lesion process is practically irreversible. Today it is most relevant to conduct the search for biomarkers of acute and chronic renal lesions at patients with urolithiasis to detect pathological changes in the kidneys and to determine their nature at an early stage of diagnosis.

Improved diagnostic techniques destined to provide a detailed picture of the development of the pathological process in patients with urolithiasis will make it possible to prevent renal failure development at an early stage in this category of patients.

The analysis results of work in the conditions of a pandemic of a new coronavirus infection pandemic showed that patients with malignant neoplasms (ZNO) belong to a group of high risk of infection and severe course of this infectious disease. The incidence of COVID‑19 complications in this group of patients is 3.5 times higher than in the general population, which is largely due to the immunosuppressive effect of both oncological diseases themselves and their treatment.

Many attempts have been held to identify and validate other risk factors for severe COVID‑19. Epidemiological data indicate that elderly patients with chronic diseases, including diabetes mellitus (DM), arterial hypertension (AH), obesity, are susceptible to a more severe course of COVID‑19 with a higher frequency of deaths. A number of studies have noted a higher incidence of severe forms of the infectious process and a higher level of COVID‑19‑associated mortality in men. Currently new aspects of the influence of hormonal changes, including iatrogenic ones, on the course of coronavirus infection are being identified. In particular, the data of clinical studies demonstrate a correlation between the level of testosterone in the blood serum and the level of inflammatory cytokines, the features of viral entry into cells, the course of the disease as a whole. This is especially important for understanding the features of the new coronavirus infection in patients with prostate cancer (PC), including for the development of a therapeutic algorithm, indications and contraindications to certain methods of treating PC in a pandemic, as well as ways of additional therapeutic effects when combined with PC and COVID‑19.

The review presents the results of studies on the potential mechanisms of increased susceptibility of men to SARS‑CoV‑2 and discusses the search for new therapeutic targets in COVID‑19, discusses the features of the course of COVID‑19 in patients with PC depending on the level of androgens, including androgen deprivation therapy (ADT).

Purpose of the study. Explore organizational tools for managing health system resources to fight the COVID‑19 pandemic in Kazakhstan.

Materials and methods. The analysis of regulatory documents (5 decrees of the chief sanitary doctors and 2 orders of the Ministry of Health of the Republic of Kazakhstan) regulating measures for the COVID‑19 pandemic was carried out. These legal acts were approved in the first months after the declaration of the state of emergency in the country after the detection of the first cases of coronavirus infection in Kazakhstan. These laws and regulations governed the provisions and measures to combat COVID‑19. And also the analysis of measures for the introduction of quarantine or restrictions based on the monitoring of the R number of the virus was carried out.

Results. The article discusses the issues of resource provision to contain the spread of COVID‑19 in the country. The analysis of the regulatory legal acts regarding the types of assistance provided to the population to prevent the spread of infection, as well as the treatment strategy for patients suffering coronavirus infection. These laws regulate the introduction, weakening/strengthening or cancellation of restrictive measures in the regions, mainly related to the activities of organizations and public places where there is a high concentration of the population, as well as the movement of masses of people.

Conclusion. The study showed what types of assistance are provided to the population to halt the COVID‑19 pandemic, ranging from tactics at the outpatient level to the deployment of care at the inpatient level. In addition, the monitoring of the R value of the virus can be a working tool for the authorities in the introduction of quarantine measures.