background. The analysis of the quality of medical care for children with cancer is based on statistical data. Evaluation of the results obtained is also the basis of the strategy for the development of medical care for this category of patients. aim: analysis of the main parameters characterizing medical care for children with cancer in the Siberian Federal District. material and methods. The reports for 2017 on the health protection of 11/12 (91.6 %) constituent entities of the Russian Federation belonging to the Siberian Federal District were analyzed (Irkutsk Region did not provide data). results. In 2017 the number of children aged 0–17 years was 3 722 470, the number of pediatric hospital beds for children with cancer (ages 0–17 years) was 260 (0,7 per 10,000), and the average number of bed-days per year was 342.2. In 3 (25 %) constituent entities of the Russian Federation, there were no departments of pediatric oncology and in 1 (8,3 %) there were no hospital beds for children with cancer. The number of physicians, who specialized in children’s cancer was 49, of them 32 (65,3 %, 0,08 per 10,000, ages 0–17 years) had a certificate of a pediatric oncologist. In 1 (8,3 %) constituent entity of the Russian Federation, there were no pediatric oncologists. For children aged 0–17 years, the cancer incidence rate was 11.7 per 100,000 children, the cancer mortality rate was 2,2 per 100,000, and one-year mortality rate was 7,4 %. 188 (43,2 %) primary cancer patients were referred to medical institutions of the Federal District, and 17 (3,9 %) primary patients left the territory of the Russian Federation. conclusion. The low incidence and mortality rates can be explained by the lost of reliable follow-up data. It is advisable to introduce electronic health record systems. For reliable estimation of hospital bed supply for children with cancer and percent of patients referred to medical centers for treatment, it is necessary to carry out a clinical audit. Deficiency of pediatric oncologists should be eliminated by reforming the training of medical personnel.

The objective response rate to neoadjuvant chemotherapy (NAC) in patients with non-small cell lung cancer (NSCLC) is approximately 16 %. Therefore, the search for new predictive factors and markers that could precisely predict the NAC response and be relevant to the choice of the adequate treatment policy is of utmost importance. the purpose of the study was to analyze the relationship between the expression levels of chemosensitivity genes and NAC response in patients with non-small cell lung cancer. material and methods. The study included 30 patients with stage IIAIIIB NSCLC. Total RNA was isolated from normal and tumor lung tissue samples prior to NAC. The expression level of chemosensitivity genes, such as BRCA1, RRM1, ERCC1, TOP1, TOP2a, TUBB3, TYMS, and GSTP1 was evaluated by real-time reverse transcriptase quantitative PCR (RT-qPCR). results. A significant difference in the expression levels of the studied genes between patients with different NAC response was found. The objective response to therapy was observed in 67 % (10/15) of patients having no ERCC1 expression compared to those with ERCC1 expression (p<0.05). Low (less than 0.2) and high (more than 1.2) BRCA1 expression levels were associated with low rates of NAC response compared with patients whose expression level was between the lower and upper quartiles. Statistically significant differences were shown for the GSTP1 and RRM1 genes. conclusion. A comprehensive assessment of the expression of chemosensitivity genes is important not only in terms of understanding heterogeneity and complexity of the molecular biology of NSCLC, but also for more accurate prediction of response to NAC and identification of potential drug targets.

Spinal cord tumors include a variety of nosological units and are classified according to their localization and histological type. The search for literature sources in the Pubmed, EMBASE and eLibrary databases demonstrated the absence of studies devoted to study of the features and risk factors for the recurrence of intradural spinal tumors. the purpose of this study was to reveal features and risk factors of recurrence of intradural spinal tumors after microneurosurgical resection. material and methods. The study included medical records of 196 patients with intradural extramedullary and intramedullary spinal tumors. The extent of microneurosurgical tumor resection, clinical efficacy of surgery, and risk factors for recurrence of intradural spinal cord tumors were been analyzed. results. Improvement in neurologic deficit after surgery was noted in 116 (59.1 %) cases, neurologic status remained the same in 47 (24.0 %) patients, and worsening of neurological deficit was observed in 33 (16.8 %) cases. Total microneurosurgical resection of intradural spinal tumors was performed in 140 (71.4 %) patients, subtotal resection in 22 (11.2 %) patients, partial resection in 25 (12.7 %) patients and spinal cord decompression or biopsy and/or its roots were performed in 9 (4.6 %) of patients. The likelihood of recurrence-free survival of patients with benign intradural spinal cord tumors was significantly higher than that of patients with malignant tumors (p<0.001). Benign tumors (χ2=34.7, p<0.05), thoracic and lumbosacral tumors (χ2=10.3, p<0.05), low degree of neurological deficit (χ2=31.5, p<0.05), absence of syringomyelia/syringobulbia signs (χ2=13,2, p<0,05), as well as extramedullary tumors (χ2=12,6, p<0.05) allowed us to perform total degree microneurosurgical resection. Malignant tumors (χ2=34.8, p<0.05), cervical and thoracic tumors (χ2=8,4, p<0,05), high degree of neurological deficit (χ2=12,9, p<0.05), partial resection, biopsy or decompression of neural structures (χ2=9.7, p<0.05) and intramedullary tumors statistically significantly increased the risk of their recurrence. conclusion. Histological pattern, tumor localization, preoperative clinical and neurological deficit according to the McCormick classification and the extent of surgery are significant risk factors for recurrence of intradural spinal tumors.

Background. The problem of the development of liver metastases in colorectal cancer patients previously treated with curative intent surgery remains little studied. Identification of significant factors affecting the occurrence of metachronous metastasis contributes to a more accurate prediction of recurrence in this group of patients. material and methods. In our study we analyzed the incidence of liver metastases and prognostic factors in 116 colorectal cancer patients previously treated with curative intent at Irkutsk Regional Cancer Center between 2006 and 2017. The patients received combined modality treatment including neoadjuvant radiotherapy or chemoradiotherapy for localized and locally advanced rectal cancer, radical surgery and adjuvant chemotherapy. After curative treatment, 96 patients had no evidence of distant liver metastases, and 20 patients developed distant metastases. results. The incidence of liver metastases was 17 %. In most patients, metastases occurred 16.5 months after completion of curative treatment, reaching peak incidence at 12–18 months. Prognostic factors of colorectal liver metastases in colorectal cancer patients previously treated with curative intent surgery were: the stage of the tumor, tumor growth in the parirectal/mesocolic fatty tissue, and no previous preoperative chemoradiotherapy and adjuvant chemotherapy. conclusion. For early detection of liver metastases, the carcinoembryonic antigen (CEA) measurements, contrast-enhanced abdominal multislice CT, and ultrasound-guided liver biopsy were recommended to perform every 3 months in the postoperative period.

The purpose of the study was to analyze the prevalence of multidrug-resistant (MDR) pathogens (Escherichia coli and Klebsiella pneumonia) isolated from cancer patients. material and methods. 862 strains of E. coli and 1 461 strains of K. pneumoniae isolated from wound, blood, urine and other pathological materials from cancer patients treated at N.N. Blokhin National Medical Research Center of Oncology (Moscow) between 2014 and 2016 were analyzed. results. Over the last 3 years, there has been a significant increase in the number of E.coli resistant to piperacillin-tazobactam (from 8.1 to 25 %), ceftriaxone (from 15.7 to 100 %), ertapenem (from 8.1 to 97.7 %), and amikacin (c 4.5 to 14.6 %). The number of E. coli producing carbapenemases has increased from 5.8 to 20.8 % (p≤0.0001). Among K. pneumoniae, a significant increase in the number of strains resistant to piperacillin-tazobactam (from 59.7 to 89.7 %), ceftazidime (from 62.8 to 82.8 %), ceftriaxone (from 62.8 to 100 %), cefepime (from 63.1 to 83.8 %), ertapenem (from 62.1 to 100 % ), imipenem (from 30.0 to 81.0 %), and meropenem (from 53.9 to 86.8% ) is observed. conclusion. Evaluation of the frequency of isolation of MDR microorganisms over time is an essential element of epidemiological surveillance and is necessary for the correct treatment of patients with infectious complications.

Aim. The aim of the study was to evaluate the ability of pMEL-TCI and pMEL-A0201 DNA-constructs encoding artificial polyepitope melanoma antigens to induce antitumor T cell immune response ex vivo. material and methods. Dendritic cells were obtained from peripheral blood mononuclear cells of HLA-A02:01-positive donors; DCs transfected with target DNA vaccine constructions were co-cultured with autologous T lymphocytes to stimulate anti-tumor effector T cells. Specific activity of ex vivo stimulated PBMC was assessed (1) by their ability to cause lysis of human melanoma Mel Is cells, and (2) by the level of their granzyme-producing activity. A recombinant plasmid encoding the full-length MART-1 melanoma antigen was used as a positive control. results. All DNA vaccine constructions as well as positive control construction were found to be able to stimulate specific anti-tumor immune responses of autologous PBMC ex vivo, and these PBMC were found to induce melanoma Mel Is cells lysis. Both the efficiency of induced cytotoxic responses and the level of granzymes production stimulated with DCs transfected with pMel-A0201 significantly exceeded those stimulated with DCs transfected with either pMel-TCI or with DNA construction encoding the full-length MART-1 protein. The cytotoxicity level correlates with the level of granzyme B production in CD8+ T lymphocytes. conclusion. DNA vaccine constructions encoding artificial polypeptides composed of tumor antigen epitopes can stimulate the antitumor cytotoxic response. This approach can be used as the basis for the development of new methods of immunotherapy for cancer.

Resveratrol, genistein and quercetin from the group of polyphenols from secondary plant metabolites reveal cancer preventive and antivirus effects realized via their pleiotropic influence on the different macromolecules in cells. These compounds can interact with DNA without the formation of covalent bonds. This process is usually followed by changes in spatial, physical-chemical and structural DNA characteristics that can result in disfunction of DNA metabolism enzymes and chromatin destabilization. Similar effects were described for anticancer drug Curaxine CBL0137 in association with activation of interferon-α signaling. We demonstrated dose-dependent stimulating effects of resveratrol, genistein and quercetin on interferon-α signaling using HeLa cells expressed mCherry protein with interferon-stimulated response elements (ISRE) in promoter. Furthermore, it was shown by live-cell fluorescent microscopy in HT1080 cells with mCherry-labeled histone H1.5 that described polyphenols induced the redistribution of this linker histone in cell nuclei. The data obtained suggest an existence of DNA-dependent mechanism of anticancer effects of plant polyphenols and a need for further study of crosslinks between the polyphenols’ influence on chromatin structure and the changes in genome function, in particular, induction of interferon- interferon-α signaling.

Objective: to compare the morphological and functional properties of mesenchymal stem cells from mammary tissues and chemically-induced mammary tumor tissues. material and methods. The study included 25 female Wistar rats. In 20 rats, mammary carcinoma was induced by intramammary injection of N-methyl-N-nitrosourea after estrus synchronization with chorionic gonadotropin. The control group consisted of 5 rats. Mammary carcinoma was verified histologically and immunohistochemically. To examine, whether the cells isolated from normal tissue and tumor tissue belonged to mesenchymal stem cells, FACS Canto II flow cytofluorometer was used. The functional properties of mesenchymal stem cells were evaluated in MTT assay by the level of nitric oxide production in normal and by hydrogen peroxide-induced hypoxia. The levels of prolactin, luteinizing hormone and estradiol E2 in urine were studied using solid-phase enzyme-linked immunosorbent assay. results. Chemically-induced mammary tumor according to histological and immunohistochemical studies corresponded to luminal B type breast cancer in humans. In rats that developed mammary tumors, the urine prolactin levels after synchronization of estrus were increased. In rats that did not develop tumors, the levels of prolactin and luteinizing hormone were decreased, but the levels of estradiol E2 were increased. More mesenchymal stem cells with CD45-/CD90+phenotype were obtained from the breast tumor tissue. Mesenchymal stem cells from tumor tissue showed increased proliferative potential and were more resistant to hypoxia. conclusion. Tumor- associated mesenchymal stem cells having high proliferative potential and resistance to hypoxia were obtained from chemically-induced mammary tumor tissue. Morphologic and functional differences in mesenchymal stem cells obtained from mammary breast tissue and tumor tissue require further studies.

The purpose of the study was to analyze the antitumor activity of magnetic bimetallic Ag-Fe nanoparticles having the structure of Yanus particles produced by the electrical explosion of wires. material and methods. For the synthesis of bimetallic Ag-Fe nanoparticles, a simultaneous electric explosion of silver and iron wires in an argon atmosphere was used. The morphology and size of the nanoparticles and their agglomerates were determined by transmission electron microscopy. To determine the average size of nanoparticles, particle size distribution histograms approximated by log-normal distribution were plotted. The phase composition was determined using x-ray method. The cytotoxic effect of the nanoparticles was evaluated by MTT assay using mouse neuro-2a (N2a) neuroblastoma cell lines and J774 histiocytic sarcoma cell lines. results. In case of simultaneous electric explosion of silver and iron wires in an argon atmosphere, the spherical 72 nm particles were obtained. Silver and iron were shown to be unevenly distributed in particles. There were areas enriched with one of the components with clear boundaries of phase separation or Janus nanoparticles. On the diffractogram of the sample, the main reflections correspond to the phases of metallic Ag and Fe. Aqueous suspensions of monometallic Ag and Fe nanoparticles reduced cell viability to a lesser extent than bimetallic nanoparticles. Ag-Fe nanoparticles showed the highest dose-dependent antitumor activity. The higher corrosion rate of bimetallic Ag-Fe particles compared to monometallic nanoparticles was due to the larger contact area between metallic phases in Janus nanoparticles, which determined a larger number of corrosion centers in bimetallic nanoparticles. conclusion. As a result of an electric explosion of wires from immiscible metals of iron and silver, bimetallic Ag-Fe nanoparticles with Janus particle structure were obtained. Ag-Fe nanoparticles exhibite higher antitumor activity than the individual metals from which they are composed and are a promising material for the fight against cancer cells.

To study the mechanisms underlying the effects of intraperitoneal chemoperfusion and to develop the optimal chemoperfusion regimen, an animal model of peritoneal carcinomatosis closely resembles a human model of peritoneal carcinomatosis is required. In our study, the model of peritoneal carcinomatosis in rats with ascitic ovarian cancer was used. material and methods. There were three groups of rats with ascitic ovarian cancer: 1 – the control group (n=15) having no treatment; 2 – rats receiving normothermic intraperitoneal chemoperfusion with cisplatin, 40 mg/kg (n=12); 3 – rats receiving hyperthermic intraperitoneal chemoperfusion with cisplatin, 20 mg/kg (n=14). All animals were euthanized with subsequent autopsy. results. Ascitic ovarian cancer developed in 100 % of the animals injected with the tumor cells. The median overall survival of rats in the control group was 9.5 days. At autopsy, all rats had ascites, and rats surviving 15‒17 days after the tumor cell injection had white tumor nodes measuring 1–3 mm in the greater omentum, intestinal mesentery, parietal and visceral peritoneum. The nodes were histologically verified as metastases of low-differentiated ovarian tumor. In 2 and 5 rats from groups 2 and 3 respectively, metastases in paratracheal lymph nodes and tumor hydrothorax were detected with no evidence of peritoneal carcinomatosis. The median survival of rats in groups 2 and 3 was significantly higher than that in the control group, being 37.5 and 25.5 months, respectively (р=0,256). conclusion. This in vivo study proved that localization of ascitic ovarian tumor, development of the tumor in all animals injected with tumor cells, fast ascites progression and peritoneal carcinomatosis make this ascitic ovarian cancer an adequate preclinical model of peritoneal carcinomatosis to study intraperitoneal chemoperfusion. Further studies are needed to understand the reasons and mechanisms of the tumor hydrothorax development in rats after intraperitoneal chemoperfusion.

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.

Introduction. Metastatic melanoma is characterized by clinical and morphological heterogeneity and plasticity. Rare cases of metastatic melanoma are known, that have no visual expression of melanocytic markers. Contradictory histology of such melanomas requires a differential diagnosis from morphologically similar non- melanocytic tumors, sarcoma or lymphoma. objective is to describe the extraordinary cases of metastatic melanomas with low expression of differentiation markers. material and methods. 15 melanoma cases with unusual clinical and morphological characteristics were included in the study. These tumors were examined by pathologist and cytologist, by immunohistochemical and FISH analyses, mutations in BRAF, NRAS and KIT genes were detected by PCR. results. Some primary tumors were amelanotic, therefore, they were difficult for differential tumor diagnosis. Most frequently, primary tumors were located on the back, shin or head. In 4 patients the primary focuses were not detected. Metastatic lesions were as large nodular tumors in soft tissues of the back or lower limb. Most tumors belong to mixed or spindle-cell histological types. Spindle-shaped cells were also revealed by cytological analysis. BRAF gene mutations were identified by genetic analysis in 27 % of tumors, NRAS and KIT gene mutations were not detected. In 4 cases FISH analysis was performed to detect EWSR1 gene rearrangements, but it did not confirm the diagnosis of sarcoma. conclusion. The results indicate the presence of a heterogeneous group of melanoma cases, which have a number of morphological and molecular features that bring them closer to sarcomas.

We performed a retrospective analysis of ultrasound scans in 42 patients with cutaneous melanoma of the extremities in planning the closure of skin defects with skin fascial island flaps supplied by perforating vessels. First, the primary melanoma focus was scanned by ultrasound to reveal characteristics of the skin, tumor and adjacent tissues. Then we detected perforating vessels to mark them and to select the sites for the island flaps. Ultrasound examination was performed using the IU 22 PHILIPS, GE Logiq E9 and Supersonic imagine AIxPLORER MultiWave Systems with linear multi-frequency sensors (517 MHz) in the B-mode, color and power Doppler to visualize the blood flow. We clarified the criteria of the necessary and sufficient parameters according to Doppler ultrasound visualization for surgical treatment of cutaneous melanoma of the extremities by the suggested method in preoperative period, as well as monitoring of the flap state after surgery. The transfer of flaps on perforating vessels did not cause blood flow disorders in them: the mean arterial blood flow velocity was 13.1 ± 4.7 cm/sec before surgery and 12.8 ± 5.4 cm/sec after it. The maximal venous flow velocity was on average 7.0 ± 1.3 cm/sec before surgery and 6.2 ± 0.8 cm/sec after it. Thus, triplex ultrasound significantly facilitates the selection and individual design of the flap with the inclusion of feeding vessels of sufficient potential, helps in planning the operation, reduces the risk of failure and improves the results of treatment. This method contributes to the radicalization of surgical intervention with a simultaneous decrease in the risk of postoperative complications and acceleration of medical and social rehabilitation of patients.

Purpose: to present different modalities of biliary decompression and specific antitumor treatment of hilar cholangiocarcinoma (Klatkin tumor). material and methods. The review was based on 318 publications available from Pubmed, Medline, Elibrary, etc. in the interval time between 19212018. results. Hilar cholangiocarcinoma is a rare hepatobiliary malignancy with dismal prognosis demonstrating slow periductal infiltrative growth, late metastasis and causing death mainly due to local complications. Percutaneous transhepatic biliary drainage (PTBD) is the optimal way of biliary decompression for malignant hilar strictures nowadays. PTBD is the safest, technically accessible technique with reproducible results. Transpapillary decompression in Klatskin tumor patients is technically feasible in 40 % of cases only. Biliary resection accompanied by major hepatectomy is considered the only curative modality to the date, but its results aren’t satisfactory a well as the majority of patients aren’t seemed the surgical candidates. Thus the locoregional technologies, i.e. radiation therapy, radiofrequency ablation and photodynamic therapy (PDT), are widely spread. PDT should be preferred over other local modalities due to safety, efficiency, possibility of reinterventions, technical and economic accessibility. conclusion. Modern approaches to the management of Klatskin tumor do not differ much from the those proposed by the first researchers in the middle of the xxth century and comes down to the biliary stricture dilatation and the sustenance of the normal bile passage as long as possible. However, despite the strategic stagnation, significant tactical successes were achieved thus allowing significant prolongation of survival in previously considered incurable patients.

Ovarian cancer is a highly heterogeneous disease characterized by multiple histological subtypes. High- grade serous ovarian carcinoma is the most common histological subtype of ovarian cancer. The majority of ovarian cancer patients present with malignant ascites at diagnosis. Peritoneal dissemination is one of the most unfavorable factors for tumor progression and recurrence. A more precise visualization of peritoneal carcinomatosis can be achieved by transabdominal ultrasound. However, the prognostic factors associated with malignant ascites in ovarian cancer are currently not well understood. Among the clinical parameters, the volume of ascites has the greatest information in terms of prognosis of disseminated ovarian cancer. Ovarian cancer with small-volume ascites has a more favorable therapeutic prognosis. Ascites is an easily accessible and valuable source of cellular and extracellular components contained in it that are involved in ovarian carcinogenesis. Ascites represents an accessible and valuable source of material to identify signals that influence tumor growth. At present, among the soluble high- and low molecular components of ascites, an active search for additional prognostic and predictor factors is being conducted, providing insights into the molecular mechanisms for clinical phenotypes of ovarian cancer.