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Aim of the study: a systematic analysis of the modern literature data on the nivolumab monotherapy efficacy in patients with metastatic colorectal cancer (mCRC). Material and methods. The review summarizes the results of clinical studies of the nivolumab efficacy in patients with mCRC between 2012 and 2022. The current approaches to assessing the tumor response in patients treated with immune checkpoint inhibitors are considered, including response patterns and criteria. Results. Data analysis showed that the use of nivolumab in mCRC patients had significant clinical benefits. Nivolumab monotherapy was shown to improve survival in patients with high microsatellite instability (MSI) or deficiencies in mismatch repair (dMMR) that progressed during standard chemotherapy. Numerous clinical studies indicate the atypical response to nivolumab. Traditional response criteria, such as RECIST do not always adequately assess the therapeutic efficacy of nivolumab in patients with mCRC. Conclusion. To improve the efficacy of mCRC treatment, standardized approaches based on the proposed specific criteria for response to immunotherapy, including immune related RECIST, immune RECIST, and immune-modified RECIST must be developed.

Introduction. In modern oncology, the identification of sentinel lymph nodes (SLN), the first nodes that stand on the way of malignant tumor metastasis, is of increasing interest. Detection of SLN followed by morphological examination allows personalizing the surgical intervention for early breast cancer, melanoma, head and neck tumors, neoplasms of the cervix and endometrium. Currently, there is an active development of specific radiopharmaceuticals for SLN imaging. Within the framework of the grant from the Federal Target Program "Pharma-2020", an original radiopharmaceutical using gamma aluminum oxide – [99mТс]-Al2O3 was developed. Preclinical studies have been demonstrated its effectiveness and safety. Pharmacokinetic studies of [99mTc]-Al2O3 showed that 24 hours after its subcutaneous administration, about 12 % of the administered dose is accumulated in the SLN, which gives possibility for its detection.Aim. To study the possibility of clinical [99mTc]-Al2O3 using for visualization of SLN in breast, larynx and laryngopharyngeal cancer.Materials and methods. The definition of SLN was carried out in 55 patients with breast cancer and 30 patients with malignant tumors of the larynx and laryngopharynx. The study included peritumoral radiopharmaceutical injection, single-photon emission computed tomography with qualitative and quantitative analysis of the images and radioguided surgery detection of lymph nodes with their subsequent morphological examination.Results and discussion. Clinical studies have shown that radionuclide imaging of SLN using [99mTc]-Al2O3 is characterized by high sensitivity in breast cancer, larynx and laryngopharyngeal cancer patients (94.5 and 90 %, respectively), due to the high-intensity accumulation of this radiopharmaceutical in the lymph nodes. The optimal time point for SPECT and radioguided examination is an interval of 18–20 hours after injection of [99mTc]-Al2O3, which allows visualizing the maximum possible number of lymph nodes with the most optimal level of radioactivity for their detection.Conclusion. Application of radionuclide imaging of SLN with the use of [99mTc]-Al2O3 as a radiopharmaceutical is useful in planning surgical treatment of patients with tumors of the breast, larynx and laryngopharynx to determine the extent of surgery.

Background. The neutrophil to lymphocyte ratio (NLR) is a prognostic marker in various carcinomas, including breast cancer. The NLR reflects the balance of systemic immunity and is associated with survival in patients with solid tumors.Aim. This study retrospectively evaluated the significance of the NLR and the absolute lymphocyte count in patients with breast cancer who received eribulin therapy.Materials and methods. The prognostic significance of the NLR and the absolute lymphocyte count in 33 patients with metastatic breast cancer treated with eribulin in 2020–2021 was analyzed.Results. The median follow-up time for patients was 9 [6; 15] months. Twenty-six of 33 (78.8 %) patients progressed. Seven of 33 (21.2 %) patients were censored due to therapy discontinuation, complete discontinuation after 1 course was required in 3 (9.1 %) patients and was associated with the development of hematological toxicity: 1 (3 %) case of a combination of grade 3 leucopenia and grade 3 thrombocytopenia, 2 (6 %) cases of grade 3 neutropenia. According to the analysis results, the NLR was a statistically significant risk factor for progression in patients on eribulin therapy, both without taking into account the influence of other factors (univariate model) and with the underlying influence of the absolute neutrophil count and the absolute lymphocyte count: hazard ratio (95 % confidence interval) was 1.21 [1.04; 1.41], p = 0.015 and 1.30 [1.07; 1.57], p = 0.008, respectively. There was no statistically significant effect of the absolute neutrophil count and the absolute lymphocyte count in both univariate and multivariate models. To illustrate the impact of SNL on the onset of progression, patients were divided into two subgroups based on median SNL: SNL˂ 2.46 and SNL ≥2.46. The median survival in patients with SNL ≥2.46 was 9 months, and in patients with SNL˂ 2.46 it was 15 months.Conclusion. The results of the pilot study state the NLR is a potential prognostic marker of long-term treatment with eribulin for patients with metastatic breast cancer, and can be used in clinical practice.

Objective: To identify the morphological patterns of development and prevention of experimental epidural fibrosis based on the shape of the dural sac in the area of laminectomy. Methods: Male Wistar rats aged 4-5 months underwent laminectomy at the level of L6-S1. The animals were divided into two groups with 7 animals per group. In the main group (Group A) the animals were treated with Antiadhesin® gel applied to the wound to prevent the development of epidural fibrosis, while in the group of comparison (Group B), the gel was not applied. Another 7 healthy animals were used as a control group. The animals were taken out of experiment on the 28th day. Histological slides stained with hematoxylin-eosin were used to measure the width and length of the dural sac, its area, perimeter, and calculate its deformity index. Results: In group B at the level of laminectomy, the ratio of the width to length of the dural sac was significantly higher than in the control group (p

Background. By 2020, breast cancer (BC) has become the most frequent malignancy in the world. The most common type of BC is HR+/HER2-negative cancer,2540% of which harbors PIK3CA mutations that affect the catalytic subunit of the PI3K protein. PIK3CA alterations are actionable, as such neoplasms can be treated with a combination of fulvestrant and the PI3K inhibitor alpelisib. As PIK3CA mutations have an extremely versatile effect on the characteristics of a tumor cell, numerous associations of PIK3CA mutations and various clinico-pathological characteristics of BC can be traced. Aim. Our aim was to clarify the information on the frequency and spectrum of PIK3CA mutations in Russian patients with HR+/HER2- advanced BC, and to study the association of PIK3CA mutations with clinical and pathological parameters of BC. Materials and methods. Tissue samples from 694 patients with HR+/HER2- advanced BC (mixed population of primary metastatic and relapsed tumors) who received any line of anti-cancer treatment in Dec 2020 to June 2021 in Russian Federation were analyzed by high-resolution melting, allele-specific PCR, digital droplet PCR and Sanger sequencing (exons 7,9, and 20 of the PIK3CA gene). Mutation rates in different BC subgroups were compared using the Fishers exact test. The age at diagnosis in patients with different PIK3CA status was compared using the MannWhitney U-test. The relationship between the PIK3CA status and the degree of tumor differentiation was compared using the CochraneArmitage test for trends. Luminal A and B BC expression subtypes were distinguished with surrogate IHC markers according to St.-Gallen recommendations (2013). Results. Mutations were identified in 220/694 (32%) BC patients. The three most frequent missense substitutions in the PIK3CA gene (p.E542K, p.E545K, and p.H1047R) accounted for 190/220 (86%) mutations. Associations of PIK3CA mutations with luminal A subtype of BC, low proliferation index, small size of the primary tumor, and absence of signs of hereditary cancer were revealed. Associations of mutations in the kinase domain of PIK3CA (p.H1047R) with late recurrence of locally advanced BC and with non-Slavic ethnic origin of patients were found. Conclusion. PIK3CA mutation rate of 32% confirms high prevalence of mutation in Russian population, with some differences reflecting the ethnic origin of patients.

Background. Triple negative breast cancer has no specific treatment sites for chemotherapy and is unfavorable in terms of prognosis. One of the drugs widely used in this cohort of patients is eribulin, which in addition to its antimitotic effect has an effect on the tumor microenvironment. The search for biological criteria that will allow predicting the effectiveness of the drug is assumed relevant since it will help to select patients who may receive the most benefit from certain therapy regimens.Objective: identification of immunological predictors of the therapeutic effectiveness of eribulin in patients with locally advanced or metastatic triple-negative breast cancer.Materials and methods. The study included 20 patients with locally advanced and metastatic triple negative breast cancer. 50 % had a short-term response (progression-free survival 6 months). Seven-color immunofluorescence was used to determine the subpopulation composition of tumor-infiltrating lymphocytes and their PD1 expression. Image acquisition and analysis were performed using the Vectra® 3.0 system and InForm® software (Akoya Biosciences, USA).Results. It has been shown that the ratio of the number of PD1-negative to PD1-positive CD20+ B-lymphocytes less than 5.5 associated with the long-term effectiveness of eribulin in patients with locally advanced or metastatic triple negative breast cancer.Conclusion. The results showed that the ratio of the number of PD1-negative to PD1-positive CD20+ B-lymphocytes can be considered as a possible marker to predict the effectiveness of eribulin in patients with breast cancer.

Introduction. Overexpression of Her2/neu is detected in 15–20 % of patients with breast cancer and associated with an aggressive form of disease and low overall and disease-free survival rates. Currently, immunohistochemical studies (IHC) and methods of in situ hybridization are used to assess Her2/neu status. One of significant drawbacks of this detection is the impossibility of simultaneous assessment of the receptor status of the primary tumor and metastatic sites. The increasing popularity of radionuclide methods using recombinant proteins as a targeting module have already demonstrated their effectiveness in solving this question at the initial stages of clinical research.The purpose of this study is to demonstrate a clinical case of assessing the extent of breast cancer in a patient with overexpression of Her2/neu using a radiopharmaceutical based on targeted protein molecules labeled with technetium-99m.Description of the clinical case. A patient diagnosed with stage IIIA right breast cancer (T2N2M0), multicentric growth and metastases in right axillary and subclavian lymph nodes at the diagnostic stage was injected intravenously with 99mTc-ADAPT6 radiopharmaceutical. The drug was prepared in the Department of Nuclear Medicine of Research Cancer Institute (Tomsk) immediately before its administration. Planar scintigraphy and singlephoton emission tomography of the chest organs were performed 2 hours after injection of 99mTc-ADAPT6 radiopharmaceutical. In addition to the previously described tumors, 3 foci of hyperfixation of the tracer in the projection of the 5th rib on the right along the middle-clavicular line, as well as in the projection of the 8 and 9 thoracic vertebrae (Th VIII, IX) were found. Computed tomography of the chest organs and bone scintigraphy with 99mTc-pyrophosphate showed no metastases in the 5th rib on the right and Th VIII, IX. Magnetic resonance imaging of the thoracic spine revealed 2 metastatic foci in Th VIII, IX. Planar scintigraphy with 99mTc-pyrophosphate and CT performed 6 months after injection of 99mTc-ADAPT6 revealed previously described foci in the projection of the thoracic spine (Th VIII, IX) and 5 ribs on the right along the mid-clavicular line. Conclusion. The results demonstrated during the study suggest that 99mTc-ADAPT6 is a promising tracer for molecular imaging of tumor foci with overexpression of the Her2/neu receptor in breast cancer patients.

The article shows the feasibility of detecting and monitoring primary breast diffuse large B-cell lymphoma using single-photon emission computed tomography (SPECT) with 99mTc-1-thio-D-glucose (99mТс-TG), a new radiopharmaceutical. The innovative radiopharmaceutical makes it possible to evaluate the metabolism of tumor tissue without using positron emission tomography. The findings of 99mTc-TG SPECT obtained during diagnosis and monitoring of the patient were confirmed by the results of computed tomography. A comprehensive examination of the patient, including 99mTc-TG SPECT, made it possible to diagnose a rare case of primary breast lymphoma. Primary breast lymphoma accounts for 1.7–2.2 % of all extranodal nonHodgkin lymphomas. Diffuse large B-cell lymphoma is the most common histological type occurring usually as a unilateral palpable tumor in middle-aged women. Extranodal lymphomas account for less than 0.5 % of all malignant neoplasms of the breast. After 6 courses of immunochemotherapy, the patient underwent 99mTc-TG SPECT, which demonstrated persistent hypermetabolic activity in the breast. The patient received radiation therapy to the remaining tumor of the left breast. The patient is in remission and followed up at the Cancer Research Institute of Tomsk National Research Medical Center. Thus, 99mTc-TG SPECT is believed to be a promising method for visualizing primary breast lymphomas and assessing their treatment outcomes. It is an alternative to the standard approach using 18F-FDG positron emission tomography. The method compares favorably with positron emission tomography with its wide availability and low cost of study.

Introduction. Epidural fibrosis is an urgent problem in modern spinal surgery and orthopedics. The formation of connective tissue in the epidural space after performing surgical interventions on the spinal column inevitably leads to adhesion of the latter to the dura mater and compression of neural structures, followed by the formation of clinical and neurological symptoms. The search for literary sources in domestic and foreign scientific databases has demonstrated the presence of several works studying the effectiveness of barrier methods for preventing the development of epidural fibrosis. It should be noted that the results of these studies are ambiguous and largely contradictory.The purpose was to study the effectiveness of using a spatially cross-linked polymer in the postoperative lumbar epidural fibrosis prevention in an experiment.Materials and methods. The study included 26 male Wistar rats (average body weight 338.5±9.07 g), which were divided into two groups: Group I (control, n = 12): animals underwent laminectomy at the level of vertebral bodies LVII – SI without application of spatially crosslinked polymer; Group II (experimental, n = 14): animals underwent laminectomy at the level of vertebral bodies LVII – SI followed by application of a spatially cross-linked polymer to the dura mater. The morphological and instrumental parameters were studied.Results. Significant differences were noted in the severity of epidural fibrosis (χ2 = 14.846, p = 0.003), the number of newly formed vessels (F = 14.371, p

Relevance. PIK3CA belongs to the top three most frequently mutated genes in breast cancer (BC), especially in estrogen receptor (ER) positive, HER2 negative BC subtype. With an approval of selective PI3K-alpha inhibitor, alpelisib, this alteration has become actionable in ER+HER2- tumors. The frequency and spectrum of PIK3CA alterations in various cohorts is affected by a number of factors, including the distribution of BC expression subtypes, histological types, patient age, and even ethnicity. Aim. Aim of the current study was to characterize the frequency and spectrum of PIK3CA alterations in Russian BC patients. Materials and methods. The analysis of PIK3CA exon 7, 9 and 20 mutations was performed in a cohort of Russian ER+HER2- BC patients by a combination of high-resolution melting analysis, allele-specific PCR, and digital droplet PCR. Results. PIK3CA lesions were identified in 62/206 (30%) patients. Noteworthy, 59/62 (95%) of the identified variants were represented by the three most common p.E542K, p.E545K, and p.H1047R substitutions. The analysis of clinical and morphological characteristics revealed the trends towards association of PIK3CA mutations with older age and more frequent metastatic lung involvement. Conclusion. The obtained data on the frequency and spectrum of PIK3CA somatic aberrations can be helpful when organizing molecular genetic testing of breast cancer patients and using PI3K inhibitors in Russian population.

Background. The increased incidence of inflammatory bowel disease (IBD) in the world and the lack of consensus on the causes and development mechanisms of IBD are the key elements that determine the relevance of the study. According to some authors, in the pathogenesis of the development and occurrence of ulcerative colitis, one of the leading causes is a change in the composition of the colon microflora and the impact of the products of their metabolism on the enteric system and intestinal motility.The aim was to study the qualitative and quantitative changes in the colon microbiota in rats when modeling ulcerative lesions by the original method.Materials and methods. The experimental study was carried out using male Wistar rats (n = 24). Ulcerative colitis was modeled in an original way. The quantitative and qualitative composition of the parietal microflora of the distal colon was determined.Results. When modeling ulcerative lesions of the colon using the original method, changes in the qualitative and quantitative composition of the parietal microflora of the colon were revealed. On the 3rd day there was a decrease in Lactobacillus ssp. and Escherichia coli, as well as the growth of fungal microflora and the appearance of representatives of opportunistic microflora. The changes were progressive in nature, and by the 7th day of the study revealed a marked reduction of the total parietal concentration of the normal flora bacteria and an increased percentage and absolute number of representatives of conditionally pathogenic microflora. By the 10th day of the experiment, with a small increase in the total number of parietal bacteria, the predominant microorganisms were Bacteroides ssp. (26.8%) and Peptococcus ssp. (27.6%).

The purpose of the study was a comparative experimental assessment of long-term toxic effects of cytostatic drugs (epirubicin, etoposide, platidiam, carboplatin, paclitaxel) on the female reproductive function and search for pharmacological ways to reduce them.Material and Methods. Experiments were carried out on 200 outbred male rats, Wistar stock, 2.5 months old. Antitumor drugs were administered once, intravenously, in maximum tolerated dose. The reproductive status in rats was assessed 90 and 180 days after injection of cytostatic drugs. Correction of ovariotoxicity of cytostatic drugs was carried out using a recombinant human granulocyte colony stimulating factor (rhG-CS F, Neupomax, FARMSTA NDA RT-UfaVITA OJSC , Russia) and liquid extract of Scutellaria Baikalsky («GNTsLS », Kharkov). The mating and fertility ability of female rats as well as pre- and post-implantation fetal mortality were determined. Ovarian reserve was evaluated using morphological analysis of the ovaries using quantitative assessments of structural damage. Concentration of anti-Muller hormone in the blood of adult rats-females receiving etoposide and rhG-CS F were evaluated by enzyme immunoassay (IFA, ELISA , Cloud clone, Corp. Wuhan). Statistical processing of obtained experimental data was performed using Mann-Whitney U-test and Fisher angular transformation.Results. The mating and fertility ability of animals was found to be persisted. However, signs of early depletion of the ovarian reserve and a decrease in reproductive potential were observed. The risk of early menopause was increased to a greater extent after using epirubicin, etoposide and paclitaxel, and to a lesser extent after platidiam and carboplatin. The reproductive potential of animals was reduced due to increased fetal death. Platinum-containing drugs were found to be the most toxic. G-CS F was the effective drug for protecting the ovarian reserve from cytostatic effects. The use of Scutellaria baicalensis extract increased the reproductive potential of animals by reducing the rate of embryonic death.

Background. Violation of the regeneration of the tracheal wall after undergoing reconstructive surgeries remains an urgent problem of modern surgery. One of the reasons for the violation of the regeneration processes is insufficient blood supply to the organ. Finding new ways to improve blood flow is a promising area of research.Aim. To evaluate the effectiveness of VEGF effect on the regeneration of the anterior tracheal surface in the early postoperative period.Materials and methods. The study included 60 male Wistar rats at the age of 10 months. All animals underwent tracheal reconstructive surgery; the animals were divided into three groups: group 1 – without medicinal film, group 2 – with prolonged-release medicinal film, group 3 – with prolonged-release medicinal film containing VEGF. The sampling of histological material was carried out on days 3, 7 and 21 of the study, using morphometry to determine the thickness of the tracheal wall, the thickness of the postoperative scar, the area of the surgical intervention zone, the area of the vessels, the ratio of the thickness of the postoperative scar to the wall thickness trachea and the ratio of the area of the vessels to the area of the surgical intervention zone.Results. It was revealed that when exposed to a long-acting medicinal film containing VEGF, significant histological changes occurred on day 7 of the study. In groups 1 and 2, healing occurred by day 21 and was accompanied by defects of the mucous membrane and cartilage. On day 7 in group 3, there was a complete epithelialization of the tracheal wall, an increase in the number of newly formed vessels and glands in the area of surgical intervention. Healing was carried out with a thin postoperative scar without defects in all layers of the tracheal wall.Conclusion. The results obtained indicate the stimulating effect of VEGF on the regeneration of the tracheal wall in the early postoperative period after undergoing reconstructive surgery. The use of VEGF reduces the time of postoperative wound healing and preserves the anatomical structure of the tracheal wall.

Epidural fibrosis is a dynamic pathological process that develops and progresses over time and is a polyetiological and multifactorial complication in the postoperative period during spinal surgery.Aim of the study. To study the reparative process and the formation of epidural fibrosis and its effect on the shape of the dural sac in the area of laminectomy at different periods of wound healing.Materials and methods. To assess the dynamics of the formation of epidural fibrosis and the involvement of the dura mater in this process, laminectomy was performed at the level of the LVI vertebra in 35 male Wistar rats at the age of 4–5 months. The animals were divided into 5 periods of withdrawal from the experiment on days 3, 7, 14, 21, and 28. The histological material was studied by staining with hematoxylin and eosin. To assess the deformation of the dural sac, the ratio of the diameter to the length of the canal was assessed on histological preparations in the laminectomy zone, and these measurements were carried out in a group of intact animals at the level of the LVI vertebra (n = 7). Results. During the observation process, a change in the ratio of the sizes of the dural sac has been observed. In the period from days 3 to 14, the anterior-posterior size of the dural sac progressively decreases, in parallel, the transverse size increases, which leads to a change in its shape. On follow-up, some form correction occurs. It is possible that the change in the shape of the dural sac in terms of up to 14 days is due to edema, plasma saturation of tissues, as well as the growth of connective tissue. The subsequent decrease in edema and the restructuring of the newly formed connective tissue leads to a correction of the shape of the dural sac.Conclusion. In the work, the dynamics of morphological changes in the zone of formation of epidural fibrosis during laminectomy in the experiment was assessed. The dynamics of changes in the lumen of the dural sac was established. The early involvement of the dura mater in the pathological process, its interest during the entire observation period was noted. Also, histological preparations show the involvement of the nerve fibers of the cauda equina in the pathological process from the early stages after surgery: vacuolization and destruction of nerve fibers, adhesion of fibers to each other and to the dura mater, as well as activation of endotheliocytes in the vasa nervorum.

The article is devoted to identifying the specifics of Russian philosophy through the analysis of F. M. Dostoevsky and L.N. Shestov’s texts. The stylistic features of the two philosophers have been considered, their ways of philosophizing and denying of the cult of reason have been examined. The analysis is carried out using additional literature of French existentialism (were used such philosophers who wrote in similar styles as philosophical essays). To date, there are many researches in which study features of Russian philosophy. It is noted, that one of them are imagery, inseparable connection between philosophy and faith and criticism of rationalism. The excessive cult of reason leads to such problems in the history as the creation of the hydrogen bomb, the environmental crisis and so on. The revolt against reason and the state of groundlessness are a response to the processes of modern rationalization and technocratization, an attempt to go beyond the limits of the usual paradigm, to get out of the closed subjectivity. Thus, it’s necessary to define the limits of the reason and develop a new way of philosophizing, for this reason it is proposed to consider the concept of groundlessness in the philosophy of L.N. Shestov, which makes the attempt to construct a philosophy, avoiding strict logic and excessive rationality.

The purpose of the study was to provide up-to-date data on the efficacy of positron emission computed tomography (PET) for the diagnosis, assessment of tumor extension and monitoring of colorectal cancer.Material and Methods. The Medline and Pubmed databases were used for searching for publications devoted to clinical trials of diagnostic value of PET with 18F-Ftordesoxyglucose (PET with 18F-FDG).Results. Data on the value of PET with 18F-FDG in visualization of the primary tumor, detection of lymph node and distant metastases and assessment of the treatment response in patients with colorectal cancer were presented.Conclusion. PET with 18F-FDG was shown to be a promising imaging method for colorectal cancer. It is the most sensitive method in the detection of liver metastases. 18F-FDG PET is particularly superior to CT and MET in the ability to assess tumor response to treatment and predict early tumor response to therapy. The development of new radiopharmaceuticals for the diagnosis, staging, monitoring and prediction of colorectal cancer is of great importance.

Quality of life of 42 patients with locally advanced breast cancer (T2-4N0-3M0) after combined modality treatment including either neutron therapy or photon therapy was studied. The EORTC QLQ-30 (version 3.0) and EORTC QLQ -BR-23 questionnaires were used. A slight decrease in the physical and emotional state and nausea/vomiting were observed in the group of patients who received neutron therapy (n=20) as well as in the group of patients who received photon therapy (n=22). In patients of the neutron therapy group, an increase in the index of dyspnea by 6 points (with the baseline index of 15.0 ± 5.7 points) was observed. The dyspnea index decreased to 5.26 ± 2.9 points 12 months later in patients having no evidence of disease progression. Local pulmonary fibrosis was diagnosed in 2 (10 %) of 20 breast cancer patients. In photon therapy group patients, an increase in the index of dyspnea by 11 points (with the baseline index of 14.3 ± 5.1 points) was observed. In 12 months, the dyspnea index decreased to 7.1 ± 3.1 points. Local pulmonary fibrosis was diagnosed in 4 (18 %) of 22 patients. A moderate decline in the general health status was observed in both groups of patients after neutron therapy delivered to the anterior chest wall. However, all patients with locally advanced breast cancer subjectively noted the rise of the general health status 12 months after completion of treatment (78.3 ± 4.2 points, respectively). Thus, postoperative neutron therapy delivered to the anterior chest wall did not increase the frequency of complications and did not affect the quality of life of breast cancer patients.

The purpose of the study was a comparative assessment of long-term toxic effects of cytotoxic drugs (anthracycline antibiotics, topoisomerase activity inhibitors, platinum and taxane complex compounds) on male reproductive function. Material and methods. 2.5-month-old male Wistar rats were used in the experiment. The following cytotoxic drugs were administered to animals in the maximum tolerated dose: Vepesid (etoposide, Teva, Israel), Irinotecan (Campto, Rhone-Poulens, Great Britain), Carboplatin (kemokarb, Dabur India Ltd., India), Paclitaxel (mitotax, Dr. Reddy`s, India), Platidiam (Lachema, Czech Republic), Pharmorubicin (Farmitalia, Carlo Erba). The reproductive status was assessed 90 and 180 days after administration of cytotoxic drugs. The fertilizing ability, productivity of spermatogenesis and the viability of a fertilized egg were evaluated. To determine the sensitivity of different types of spermatogonia to the drugs, we studied the dynamics of the number of their cell populations 2, 5, 10, 15, 30, 90 and 180 days after starting the experiment. Results. In long-term follow-up following administration of farmorubicin and paclitaxel to male rats, a complete (pharmacorubicin) or partial (paclitaxel) decrease in the fertilizing ability due to oligospermia was detected. The decrease in spermatogenesis productivitywas reversible. In rats treated with topoisomerase activity inhibitors, the fertilizing ability was preserved, however spermatogenic failure was also seen, as judged by the total sperm number. In the long term after the administration of platinum complexes, no decline in the reproductive function was observed, and the spermatogenesis productivity corresponded to the control values. The severity of toxic effects on gonads was determined by the sensitivity of different types of spermatogonia to the action of drugs. Pharmorubicin and paclitaxel exerted a pronounced toxic effect on stem spermatogonial cells. Paclitaxel and carboplatin induced dominant lethal mutations in spermatogonia, but the likelihood of gametes bearing genetic damage incompatible with life decreased over time.

The paper presents an experimental model of the development of degenerative-dystrophic processes in the intervertebral disc at LVI - St level, worked out by specialists of Irkutsk Scientific Centre of Surgery and Traumatology. For the purposes of the research we used the techniques of laminectomy and LVI facetectomy.Materials and methods. The experiment was conducted on ten Wistar male rats using microsurgical instruments and binocular optics with a 6-fold magnification. The reliability and effectiveness of the obtained model were evaluated by X-ray and histological research methods. Spondylograms assessed the level, volume of surgical intervention and the likelihood of LVI spondylolisthesis occurrence relative to St against the background of impaired spinal support function created surgically on the day 15 of the experiment. The histological picture of degenerative changes in the intervertebral disc was assessed on the week 16 and 24 after the animals were sacrificed.Results. An X-ray examination on the day 15 revealed LVI spondylolisthesis relative to SI in 4 out of 10 experimental animals. To assess the nature of degenerative-dystrophic changes in the intervertebral disc, five rats were sacrificed at the 16th week and five - at the 24th week. When analyzing the obtained histological data, we noted the progression of degenerative-dystrophic changes in the intervertebral disc occurring by the 24th week.Conclusion. The designed model for the development of degenerative-dystrophic changes in the intervertebral disc is in direct correlation with the violation of the integrity of the posterior supporting complex with the subsequent formation of spondylolisthesis and instability in this segment. Histological studies in the intervertebral disc reliably confirmed the formation and progression of degenerative-dystrophic changes in the intervertebral disc at the LVI-SI level from the 16th to the 24th week of the experiment. The obtained experimental model of the formation of degenerative-dystrophic changes without mechanical damage to the intervertebral disc will allow clinicians to obtain information about the primary changes in the intervertebral disc, to study the mechanisms of development and the course of degenerative changes in the intervertebral disc on the model of disturbance of the back supporting complex with pathological changes in the biomechanics of the spine after laminectomy and facetectomy. Understanding and knowledge of the pathogenesis of degenerative-dystrophic disease of the spine will allow specialists to exercise an etiopathogenically reasonably approach to the issues of prevention and treatment.

Introduction. The purpose of this study was to evaluate the feasibility of using 99mTc-TG SPECT in the detection and staging of malignant lymphoma.Materials and methods. Fifteen patients with newly diagnosed malignant lymphoma underwent 99mTc-TG SPECT. Six patients had Hodgkin’s lymphoma and 9 patients had aggressive forms of non-Hodgkin’s lymphoma (NHL): diffuse large B-cell lymphoma (7 cases), B-cell follicular lymphoma (1 case), and lymphoma from B cells in the marginal zone (1 case). Stage IIA was diagnosed in 5 patients, stage IIB in 1, stage IIIA in 1, stage IVA in 4 and stage IVB in 4 patients.Results. Pathological 99mTc-TG uptake in lymph nodes was observed in 14 (93 %) of the 15 patients. In one patient, the enlarged submandibular lymph node (16 mm in size) detected by CT was not visualized by 99mTc-TG SPECT. This false-negative result was likely to be associated with increased accumulation of 99mTc-TG in the oropharyngeal region. There were difficulties in the visualization of paratracheal, para-aortic and paracardial lymph nodes. These difficulties were associated with a high blood background activity, which persisted even 4 hours after intravenous injection of 99mTc-TG. Software-based SPECT and CT image fusion allowed visualization of these lymph nodes. The pathological 99mTc-TG accumulation in axillary, supraclavicular, infraclavicular and cervical lymph nodes was observed most often. Extranodal involvement was seen in 9 patients. 99mTc-TG SPECT identified extranodal hypermetabolic lesions in 7 (78 %) of these patients. In one patient, hypermetabolic lesion in the lung detected by 99mTc-TG SPECT was not detected on CT image. CT identified bone marrow involvement in the pelvic and scapula in 1 patient. The use of 99mTc-TG SPECT allowed the visualization of hypermetabolic bone tissue lesions in this patient (Figure 4). In addition, in a patient with intact bone tissue on CT, 99mTc-TG SPECT detected hypermetabolic lesions in the iliac bone.Conclusion. 99mTc-1-Thio-D-glucose demonstrated increased uptake in nodal and extranodal sites of lymphoma. The results indicate that SPECT with 99mTc-1-Thio-D-glucose is a feasible and useful tool in the detection and staging malignant lymphoma.

The purpose of the study was a systematic literature review of imaging assessment of lymph node metastasis in patients with laryngeal and hypopharyngeal cancer.Material and methods. In order to review the most relevant scientific literature available, we searched Elibrary, Medline databases (from January 2005 to December 2017). Of 735 identified studies, 32 were assessed.Results. The role of ultrasonography, spiral computer tomography, magnetic resonance tomography, positron emission tomography in the assessment of regional metastatic spread in patients with laryngeal and hypopharyngeal cancer was analyzed. All these imaging techniques failed to reliably identify clinically occult lymph node metastases. However, the choice of treatment options for laryngeal and hypopharyngeal cancer depends considerably on the diagnostic accuracy. In this context, the concept of sentinel lymph nodes deserves special attention.Conclusion. Further studies of the sentinel lymph node concept using various radiopharmaceutical drugs in the detection of preclinical regional metastasis in patients with laryngeal and hypopharyngeal cancer are required.

The study is devoted to reparative regeneration of supporting tissue in the area of the defect using the methods of acupuncture with stimulation of biological active points when modeling delayed apposition of fragments. Material and methods. The work was performed using laboratory animals of the Chinchilla rabbits, at the age of 6 months. The delayed apposition of shin bone fragments was simulated in all animals. In the dynamics of the study, an assessment of radiological and morphological changes in the area of the bone defect was performed. After the fragments were compared and fixed using animal randomization methods, the animals were divided into two groups – the control and the main group, in which the biologically active points were stimulated. Results and discussion. The evaluation of the supporting tissue regeneration in the defect zone under the influence of proposed biologically active points combination by the method of acupuncture within the conditions of delayed apposition of shin bone fragments has revealed physiological change of regeneration phases with the formation of differentiated bone tissue and bone marrow elements to the 50th day of the study. The 2 fold predominance of bone tissue, 2 fold — the bone marrow substance, a decrease in cartilage tissue, the absence of fibrous connective tissue have been revealed compared with the control group, where the slowdown in the physiological change of regeneration phases and the formation of regenerate supporting tissue in the form of pseudarthrosis have been revealed.

Background. The number of reproductive-aged women with cancer, who desire child bearing, has increased with improvements in cancer detection and treatment. Cancer treatments have the potential to cause germline mutations that might increase the risk of cancer in the progeny of cancer patients. the aim of the study was to assess the feasibility of reducing the long-term side effects of Etoposide on the progeny of rats using Glutaxim. material and methods. Forty-five white outbred female Wistar rats, 2.5-month-old, were divided into 3 groups. Group I consisted of 15 intact rats. Group II comprised 15 rats treated with cytostatic drug (the control group). Group III consisted of 15 rats treated with Glutoxim® (Glutayil-Cysteinyl-Glycine, Pharma Vam Ltd., Russia) at a dose of 50 μg/kg 5 days before and 5 days after receiving cytostatic drug. results. An increase in the number of fetuses with external hemorrhages and pathological changes in internal organs was found in the progeny of female rats receiving Etoposide 3 months before mating. The progeny experienced a decrease in the rate of formation of sensory-motor reflexes, ability to learn and adaptive behavior. All studied parameters did not differ from background values in the progeny of female rats treated with combination of Etoposide and Glutoxim. conclusion. Glutaxim is the effective drug for correction of pathological changes in the progeny of female rats receiving cytostatic drugs.

The work is devoted toanew suture in the formation of tracheo-tracheal anastomosis. Despite the improvement of surgical technique in tracheal interventions, the number of postoperative complications (insufficiency and stenosis of anastomosis) remains high, with postoperative lethality reaching 18.2 %. The main problem is the lack of a unified point of view on the choice of the method of anastomosis, in particular, inclusion in the mucosal suture. Several variants of tracheo-tracheal anastomosis are suggested, but a large number of complications testify to the shortcomings of the methods used.The aim of this work is to optimize the imposition of a continuous single-row suture for the formation of tracheo-tracheal anastomosis with a shortening of the trachea.Materials and methods. The study was carried out on the basis of the scientific department of experimental surgery with the vivarium of Irkutsk Scientific Centre of Surgery and Traumatology using Wistar rats, and approved by the ethical committee.Results. A technique for the formation of tracheo-tracheal anastomosis with the use of an original continuous singlerow suture with a shortening of the trachea was developed. Step by step a sequence of operations from access to the cervical trachea to the formation of an anastomosis.Conclusion. The discussed version of the seam in the formation of tracheo-tracheal anastomosis makes it possible to accurately compare and reliably stabilize the sewn ends of the trachea.

Paraneoplastic neurological syndrome involves the concurrent development of cancer and neurologicaldiseases. Breast cancer is the second most common cancer associated with paraneoplastic damage to the central and peripheral nervous system. Autoimmune genesis of the disease is characterized by the presence of highly specific onconeural antibodies, which selectively affect neurons in the brain cord, spinal cord and spinal ganglia, and cause the onset of neurological symptoms within 2 years before cancer is detected. Six well-characterized onconeural antibodies detected in the blood serum of breast cancer patients can be used for the laboratory diagnosis of paraneoplastic neurological syndrome. Of them, anti-Hu, anti-CV2 and anti-amphiphysin antibodies cause polyneuropathy most often. Anti-Yo antibody is usually associated with cerebellar degeneration. Multiple neuronal autoantibodies can be simultaneously detected in a patient. Removal of the tumor may lead to stabilization and even partial regression of the neurological symptoms in 70 % of patients. Therefore, the surgical treatment of cancer should consider not only the tumor extension, but also the severity and progression of neurological deficit. We present a case of paraneoplastic cerebellar degeneration and paraneoplastic polyneuropathy in a 50-year-old woman with the neurological symptoms appeared 5 months before breast infiltrating ductal carcinoma was detected. The current approaches to the diagnosis of paraneoplastic neurological syndrome, as well as feasibility of radical removal of the tumor due to progression of neurological deficit were discussed.

The article presents the clinical cases of the targeted therapy regorafenib in metastatic colorectal cancer (mCRC) in Russia. Russian oncologists’ experience has not only confirmed the results of international clinical trials, but also clearly demonstrated the possibility of regorafenib long-term administration on the back of high efficacy and manageable safety profile.

Introduction. The choice of adequate treatment for cancer patients and their survival rates signifcantly depend on the precise detection of the primary tumor and the assessment of the extent of cancer involvement. Despite advances in the treatment of laryngeal/hypopharyngeal cancer, many aspects of this problem are still unresolved. The purpose of the study. Diagnostic capabilities of nuclear medicine imaging in the detection and assessment of the spread of laryngeal/hypopharyngeal cancer were studied. Material and methods. The study included 40 patients with histologically verifed laryngeal/ hypopharyngeal cancer, 10 patients with tumor recurrence after completion of therapy and 20 patients with benign laryngeal lesions. Single photon emission computed tomography (SPECT) was performed 20 minutes after the injection of 99mTc-methoxy-isobutyl-isonitrile (MIBI). Sentinel lymph nodes (SLNs) were detected in 26 patients after submucosal injections of 99mTc-Tehneft or 99mTc-Alotech around the tumor. In 18 hours after the injection of 99mTc-Tehneft and 99mTc-Alotech, SPECT was performed. In 24 hours after the injection of 99mTc-Tehneft and 99mTc-Alotech, intraoperative SLN detection was performed using Gamma Finder II. Results. SPECT with 99mTc-MIBI revealed laryngeal and hypopharyngeal tumors in 38 of the 40 patients. The 99mTc-MIBI uptake in metastatic lymph nodes was visualized in 2 (17 %) of the 12 patients. 28 SLNs were detected by SPECT and 31 SLNs were identifed using the intraoperative gamma probe. The percentage of lymphotropic radiopharmaceuticals in the SLN was 5–10 % of the radioactivity in the injection site by SPECT and 12–33 % by intraoperative gamma probe detection. Conclusion. SPECT with 99mTc-MIBI is an effective tool for the diagnosis of laryngeal/hypopharyngeal cancer. The sensitivity, specifcity and accuracy of this technique were 95, 80 and 92 %, respectively. The use of 99mTc-Tehnefte and 99mTc-Alotech for the detection of SLN in laryngeal/hypopharyngeal cancer patients was characterized by high effcacy, while intraoperative detection was more sensitive, being 80 and 100 %, respectively.

Laryngeal and hypopharyngeal cancer takes the leading position among malignant head and neck tumors, representing one of the most important and socially significant problems in modern oncology. Approaches to the treatment of locally advanced laryngeal or hypopharyngeal cancer have changed significantly in the recent years, due to new anticancer drugs and the widespread use of the best types of chemotherapy combined with surgery and radiotherapy.

Skin melanoma is a malignant tumor originating in the cells of the melanocytic system, which is characterized by an aggressive clinical course, significant metastatic potential and unfavorable prognosis. These features of the tumor stipulate the need to improve measures to optimize early diagnosis of tumors. The article presents cases of pigmented skin melanoma to demonstrate the variability of clinical manifestations of this tumor requiring dermatologist skills in the differential diagnostics of neoplasms.

Histocytosis X is a rare disease of unknown etiology involving the reticuloendothelial system. We present a case of a 32 year-old man diagnosed with Pulmonary Histocytisis X. The CT image of the lungs showed disseminated disease with the formation of cyst-like cavities, which were histologically verified using lung biopsy.

Short-term results of using Orbis II Paxman device for prevention of chemotherapy-induced alopecia were analyzed. A total of 98 sessions of scalp cooling were performed in 32 patients. Twenty-four (80 %) scalpcooled patients had good hair preservation. The level of comfort during the procedure was 87 %. Patients with breast cancer underwent 55 scalp cooling sessions. Good hair preservation was observed in 88% of cases. Grade 1 and 2 alopecia was observed in 12% of patients. Thus, the data obtained confirm that the use of scalp cooling methods can improve the quality of life for patients receiving chemotherapy.

The problem of regeneration of bone structure and joint cartilage is one of the priority programs of scientific research. Regulation of bone formation at the damage is carried out by complex set of factors. A reflection of the regeneration processes is the dynamics of blood parameters, among which are the indicators of inflammatory reaction of the organism, and condition of phagocytosis system. One way to control the severity of impaired reparative regeneration is the analysis of immunological tests of the first order. The aim of our study was to investigate nonspecific resistance of the organism for any breach of reparative regeneration of bone in the lower leg. The study was performed on rabbits "Chinchilla" which simulated the breach of the terms of reparative regeneration. We assessed leukocyte profile and indicators of phagocytosis in experimental animals. Status of the phagocytic activity of blood neutrophils was evaluated on the following parameters: phagocytic index, phagocytic number, nitroblue tetrazolium test, the concentration of circulating immune complexes. We found broken shin bone reparative regeneration of rabbit at fiftieth day of observations is accompanied by leukocytosis with increased segmented neutrophils and a decrease in lymphocytes, inhibition of phagocytosis, and violation of the elimination of circulating immune complexes.

Toxic effects of combined cisplatin and docetaxel treatment on the granulocytic hemopoiesis were studied in 45 patients with stage II–IV non-small cell lung carcinoma. The patients received intravenous injections of docetaxel at a dose of 75 mg/m2 followed by cisplatin 75 mg/m2. Blood parameters were assessed during 3 courses of chemotherapy. To estimate the state of granulocytic hemopoiesis, the hematological, cultural and functional methods were used. The study showed that the reactivity of granulocytopoiesis was maintained at a high level, namely, there was a significant activation of the central signals of granulocytic hematopoiesis, resulting in the accumulation of immature and mature myelokaryocytes in the bone marrow and increase in the bone marrow pool of mature neutrophils, as well as in increase in the number of bone marrow progenitor cells granulocytopoiesis in terms of acceleration of their maturing.

Managing bone tissue regeneration is a key problem in traumatology and orthopedics. The researches proved that thyroid hormones affect hemostasis and reparative regeneration of bone tissue favorably and promote osteogenesis and bone consolidation. The aim of this research is to study the influence of disturbed reparative regeneration on the concentration of thyroid hormones in blood in the dynamics. Experimental research on rabbits (n = 12) with modelling of disturbed reparative regeneration revealed disorder in thyroid hormones synthesis and different directions of T3 and unbound T3 production on the 35th day when the maximum decrease of T3 (2 times) and unbound T3 (1.5 times) compared to normal values was registered. The analysis of production of T4 and unbound T4 revealed suppression of the values from the 1st to 50th day and gradual increase in unbound T4 from the 50th day. The most significant manifestation of thyroid gland reaction on the disturbed reparative regeneration of shin bones was the decrease in T3 and peripheral conversion of thyroid hormones up to 50th day with formation of false joint in these terms.

We studied capabilities of confocal laser scanning microscopy in the analysis of lipid droplets volume and of quantity of functional mitochondria and reactive oxygen species production in liver cells for early diagnosis of cytochemical disturbances at dyslipoproteinemia (16 days of experiment). The results showed the increase of lipid droplets volume in hepatocytes, decrease of functional mitochondria and increase of reactive oxygen species production. We evaluated the potential of real-time PCR method in the analysis of mitochondrial DNA of blood plasma at early stages of dyslipoproteinemia and in experimental infarction. On the background of registered blood lipid metabolism disorders and structural and functional changes in liver cells, we determined the tendency to three-time increase in concentration of circulating cell-free mtDNA on the 16th day of dyslipoproteinemia as compared to the control data. We used a model of myocardial infarction to show statistically significant increase in the level of circulating cell-free blood mtDNA from 48 hours after adrenaline injection and we found that this level maintained up to 144 hours after adrenaline injection. Obtained data can serve as a basis for creation of technologies for diagnostic monitoring of atherosclerosis and myocardial infarction severity.

We studied distal colon of Wistar rats including descending transverse colon and rectum. Feature of distal colon in the left flexure are short mesenterium growing in size towards rectum, common mesenterium with small intestine attached to it on the right side and ligament forming left flexure and attached to it on the left side. It was found that one of the variants of normal blood supply is the absence of a. mesenterica caudalis. In this case blood supply comes from arterial arch formed by a. rectalis media and a. colica media. Moreover, in the classic variant of blood supply we revealed a variation in the amount of straight branches that go to this segment of colon wall from left colic and superior rectal arteries (from 3 to 5 from each artery). The structural features of rectum is weak expression of rectal ampulla that causes the depletion of fecal masses immediately after passing into rectum. Crypt compartment of colon of Wistar rats consists by 80,6 % of obligatory flora represented with Bacteroides ssp., Lactobacillus spp., Bifidobacterium spp., Enterococcus faecalis, E. coli (lac+), Grampositive rods. Facultative flora is represented with Proteus mirabilis, Peptococcus spp., Candida spp., Staphylococcus epidermidis, Citrobacter freundii and makes 19,4 %.

A low level of functional properties of E. coli isolated from the mouth cavity of lung cancer patients indicated the disturbed symbiotic relationship between Escherichia and macro-organism. This evidence is followed by intensification of biological properties of E.coli, causing the parasitism and bacterial pathogenicity.

Purpose. To estimate the possibility of trimethylhydrasine propionate using for prevention of acute doxorubicin-induced cariotoxicity in breast cancer patients. Material and methods. The study included 72 women (mean age – 51 ± 2.1 years) with breast cancer without significant pathology of the cardiovascular system. Main group consisted of 32 patients (mean age – 52 ± 2.2 years), which were injected intravenously trimethylhydrasine propionate 1000 mg 1 times/day for three days prior to chemotherapy. 40 patients of the control group (mean age – 50 ± 2.5 years) did not receive of cardioprotective therapy before chemotherapy. For the cancer treatment of these patients used doxorubicin in dose of 50 mg/m2 per course in combination with various drugs. All patients were studied by GATE SPECT before starting chemotherapy and at 1 hour after the first administration of doxorubicin. Results. Before the start of chemotherapy, none of the patients showed perfusion defects and contractility disorders. Baselines left ventricular contractility in control group and in main group was not different. After doxorubicin administration in the control group there was a decrease in left ventricular ejection fraction (LVEF) – from 65.5 ± 9.8 % to 61.8 ± 7.2 % (p

The present study shows significance of onco-neural antibodies as markers of paraneoplastic polyneuropathy in early cancer detection. Symptoms of polyneuropathy occurred at least 6 months before tumor detection in 2/3 patients, neuronal antibodies were detected in blood serum of more than 50 % of patients.

From 2007 to 2011, 39 patients with locally advanced breast cancer (T2-4N0-3M0-1) received multimodality treatment including neo-and adjuvant chemotherapy, radical or segmented mastectomy, neutron therapy to the area of postoperative cicatrix and external beam radiotherapy to the areas of regional spread. Neutron therapy delivered to the area of postoperative cicatrix was well tolerated by all patients. The overall 4-year and relapse-free survival rates were 86,2 ± 6,8 % and 92,7 ± 4,9 %, respectively

In the last decade, molecularly-targeted therapy is the most intensively developing treatment modalities in oncology. The main targets for this therapy are many elements of apoptosis signaling pathways and cell cycle regulation, the damage of which is associated with a malignant growth. One of the available molecular targets is the epidermal growth factor receptor (EGFR), which activation occurs in lung cancer, colorectal cancer, squamous cell carcinoma of the head and neck , breast cancer, melanomas, etc. To block oncogenic EGFR signaling, target drug as small molecule tyrosine kinase inhibitors, peptide associated cytotoxins and antiEGFR monoclonal antibodies were created. However, there are a number of studies (FLEX, SATURN, INTEREST, IPASS), where the expected and observed clinical cure rates of target drugs are not the same, including primary goal - increasing time to tumor progression. As the cause of inconsistency of treatment results may be lack the selection of patients with the additional molecular damages (mutations or genetic polymorphisms), providing the sensitivity and /or resistance to therapeutic agent. The most important reason for discrepancy between the real and the expected treatment effect of target drugs is the phenomenon of intratumoral heterogeneity, that is manifested as coexist of cells with different biological properties, due to genetic, epigenetic, phenotypic peculiarities of tumor clones within the tumor. Search for new driver targets and the creation of drugs directed against them, development of multitarget approach are perspective to improve the effectiveness of targeted therapy. In addition, it is important to use molecular testing to monitor the treatment efficacy, because therapy can drive the tumor clonal evolution, leading to the emergence of resistant cell clones.

The comparative analysis of immediate and long-term clinical outcomes in 68 patients with stage III non-small cell lung cancer was carried out. The study group comprised 36 patients who received 2 cycles of neoadjuvant vinorelbin/carboplatin-containing chemotherapy with subsequent assessment of objective response. If complete and partial responses were achieved and in cases with stable disease, patients underwent radical surgery followed by 3 cycles of the same regimen of adjuvant chemotherapy. The control group consisted of 32 patients who underwent surgery alone. The results obtained showed efficacy of the combined modality treatment due to significant decrease in the rate of local recurrences, distant metastases and increase in the rate of overall survival as compared to the group with surgery alone.

The role of high-field magnetic resonance imaging in diagnosis and assessment of invasion and local spread of bladder cancer has been presented.

Parameters of epitheliocytes in buccal mucosal smears of lung cancer patients were analyzed. The study results showed disturbances in the process of maturation and differentiation of the oral mucosal epithelium, significant structural and functional changes in buccal epitheliocytes, which were more pronounced after chemotherapy

The effect of recombinant human granulocyte colony-stimulating factor (filgrastim) on hematopoietic recovery was studied. The study included 77 patients with stage III–IV breast cancer who received chemotherapy with oxorubicin/docetaxel. Filgastrim was administered to 30 patients in the intervals between chemotherapy courses. The drug was injected subcutaneously at a dose of 300 mg, twice, on days 8 and 12 days from the last administration of docetaxel. Blood parameters were assessed within 3 cycles of chemotherapy. Filgastrin was shown to stimulate bone marrow granulocytopoiesis depressed by cytostatic drugs. The effect was realized on the level of committed precursors, morphologically differentiated bone marrow and peripheral blood cell elements, being the result of stimulation of the proliferative activity of hematopoietic progenitor cells of granulocytopoiesis under the influence of humoral factors released by cells of the microenvironment, as well as, to a large extent, the acceleration of the maturation of these cells.

The aim of research: the studying of blood lipid spectrum, C-reactive protein concentration, and free circulating mitochondrial DNA changes in the course of aorta atherosclerosis development in early steps of high-cholesterol diet in experiment. Material and methods. Dyslipidemia was induced by high-cholesterol diet in rabbits “Chinchilla”. The C-reactive protein level and lipid spectrum was analyzed with Beckman synhron 4 multianalyzer (Beckman coulter, USA). The mitochondrial DNA level was registered by real-time PCR. The ultra structure of aorta surface was studied by scanning electron microscopy. Results. It was shown that in the blood of experimental animals is formed the Beckman imbalance of atherogenic and antiatherogenic cholesterol fractions (on 2 days of dyslipidemia) and iselevated the C-reactive protein level (on the 8 days). Concurrently, on the 16 days of study, we registered the leucocyte adhesion on the aorta surface in the areas of connections with arteria, which could be focuses of atherosclerotic plaque development. The level of free circulating mitochondrial DNA showed the tendency to 3-fold elevation in comparing with control. However, this data predetermined the prospects of blood plasma mitochondrial DNA level studying on the more late stages of dyslipidemia. Conclusion. In the whole, the detected complex of biochemical disturbances of blood and ultrastructural changes of aorta surface in the course of early steps of high-cholesterol diet maybe prospective model of early events of atherosclerosis for pre-clinical translational research in the development of new technologies for diagnostics, prophylaxis, and treatment of lipid metabolism disturbances and atherosclerosis.