Radiation-induced lung injury is one of the most serious complications of radiation therapy in patients with malignant thoracic neoplasms. It results from accumulation of radiation dose in the lung tissue and can lead to development of various pathological changes in the lungs, such as fibrosis, pneumonitis and pulmonary hypertension. Post-radiation lung injury can significantly reduce the patient’s quality of life and worsen the prognosis. Aim. This literature review analyzes the causes of radiation-induced lung injury, describes the main clinical manifestations and diagnostic methods, and also discusses the possibilities of treatment and prevention of this complication. Conclusion. In recent years, significant progress has been made in understanding the multifactorial pathophysiological mechanisms of radiation-induced lung injury. There is still a need for further studies of the specific prognostic factors. Non-invasive methods to diagnose the functional state of the respiratory system also deserve attention. Promising areas of future research and development include individual clinical monitoring and monitoring of lung function, specific methods of treatment, prevention and reduction of the consequences of radiation-induced lung injury. Development in this areas will help to create a unified system of prevention and rehabilitation of radiation-induced lung injury as part of complex treatment.

The aim of the study was to develop and validate a software package (SP) for computer simulation of the procedure for examining patients with lung cancer by SPECT/CT and assessing the accuracy of reconstruction of tumor lesions. Material and Methods . Lung scintigraphy for a patient with peripheral squamous cell carcinoma of the upper lobe of the right lung was performed using a two-detector gamma camera GE Discovery NM/CT 670 DR (USA) with high-resolution collimators for an energy of 140 KeV and a radiopharmaceutical (RP) 99m Tc-Technetril (MIBI, Diamed, Moscow). The data obtained were subjected to computer processing using a specialized Xeleris 4.0 system from GE (USA). The SP included a program for generating a voxel phantom (“virtual patient”), a program for modeling the “raw” data acquisition (“virtual tomograph”) and an image reconstruction based on the OSEM algorithm (Ordered Subset Expectation Maximization). In order to validate the created SP, computer simulation of the above clinical case was performed. The semi-quantitative comparative image analysis was based on a tumor/background score. Results . There was a good correlation between clinical “raw” data recorded from a real patient and projection data calculated by the Monte Carlo method from a “virtual patient”. The results of the comparative analysis showed that the tumor/background assessment was underestimated in the reconstructed images. Conclusion . The problem of the accuracy of the tumor lesions reconstruction by using standard OSEM reconstruction algorithms has not been studied. This issue is important in the management of patients with tumor lesions of the lungs and requires study and systematization. The SP will be used in further studies to analyze errors and artifacts in images of tumor lesions, as well as to develop approaches to overcome them.

The case of a patient with newly diagnosed peripheral cancer of the right lung, involving the pleura, in whom the local extent of the process initially detected by X-ray CT was significantly extended from the data of the SPECT with 99mTc-technetryl. In particular, with SPECT/CT before the start of radiation therapy (RT), involved lymph nodes were detected both in the lower edge of the root of the right lung, and in paraaortic and paratracheal location. The SPECT/CT with 99mTc-technetryl was carried out with dual-detector gamma-camera GE Discovery NM/CT 670 DR (GE Medical) in a quantitative mode, with calibration and calculation of indexes of standardized uptake values (SUV) and % uptake of the administered activity by the primary tumor and metastatically involved lymph nodes. The values of the volume of tumor tissue were, respectively, for the tumor and the largest proximal metastatically involved lymph node 154.2 cm3 and 12.9 cm3, % of the activity absorbed by the tumor tissue − 0.498 and 0.030 %, and SVP ‒ 2.19 and 2.5.With subsequent external radiation therapy (in total 40 Gy, 2 Gy 5−6 times a week) the irradiation fields were planned in such a way that all affected lymph nodes were within their borders. A control SPECT/CT study carried out immediately after the RT showed a decrease in the volume of tumor tissue in the primary node down to 58 cm3, % of the activity absorbed by the tumor tissue to 0.090 %, and SVP ‒ to 1.15. Reliable imaging of lymph nodes after LT was not observed. After 6.5 months, no evidencies for relapse or continued tumor growth were detected with a control X-ray CT performed on an outpatient visit with contrast enhancement. Thus, SPECT/CT with 99mTc-technetryl in lung cancer is a vital method for clarifying the diagnosis and assessment of the extent of the tumor process, as well as monitoring the patient. A broad inter-center assessment of abilities of the SPECT/CT with 99mTc-technetryl in lung cancer is advisable, especially when planning RT.

Composite poly-L-lactide acid-based scaffolds with hydroxyapatite (HAp) content up to 75 wt.% were fabricated via solution blow spinning. The influence of HAp concentration on structure, wettability, mechanical properties and chemical and phase composition of the produced materials was examined. It was found that with an increase of HAp content the average fiber diameter was increased, the uniaxial strength and relative elongation were reduced, while the phase composition and surface wettability did not change. The performance of the scaffolds during implantation in the parietal bone of a rat skull for a period from 15 to 90 days was studied. The materials have shown high ability to integrate with both soft and hard tissues. It was found that scaffolds with 25 wt.% HAp content significantly enhance osteogenesis during scarification (damage) of the periosteum. Overall, the fabricated scaffolds proved to be highly efficient for replacing bone defects in long tubular bones.

Objective – to analyze the utility of additive manufacturing in orthopedic oncology practice. Materials and methods. We describe the first experience of using individual implants manufactured by a 3D-printer. Between October 2019 and February 2021, nine patients were operated on for primary and metastatic tumors of long and short bones of the extremities in the Department of Oncology, E.N. Meshalkin National Medical Research Center. All patients have undergone segmental resections with simultaneous replacement of bone defects with individual titanium grafts. Patients were active one day postoperatively. They were followed up for 1–16,5 months with X-ray monitoring every 3 months. Results. All patients survived. In 8 out of 9 individuals, surgical wounds healed by primary intention. All study participants had pain resolution, and their limb function was restored. One patient had postoperative complication (infection). One patient required repeated surgery due to migration of the graft head. Conclusion. Our first experience with individual grafts manufactured using a 3D-printer is quite promising. Therefore, this technique can be implemented into routine clinical practice.

Cancer is the second leading cause of death worldwide behind cardiovascular diseases. Late stage of cancer at diagnosis and low efficacy of traditional cancer treatments result in low survival rate in cancer patients. Modern techniques to kill tumor cells are therefore needed. Over the last decade novel anticancer treatments have emerged from advances in our understanding of tumor cell biology, and a number of molecular and biologic targets have been identified. Chimeric antigen receptor T cell (CAR-T cell) therapy is a novel adoptive immunotherapy, which is used predominantly in the treatment of hematological malignancies. Moreover, it has been evidenced that cells of the innate immune system are key players at initiating and regulating adaptive immune responses. Studies focusing on innate immune cells for cancer immunotherapy show promising results. In this review, we describe functions of natural killer cells and analyze the rationale for using natural killer cells in cancer therapy.

This work represents the results of the study of the surrounding tissues reaction to the implantation of bioresorbable implants formed by the solution blow spinning from polylactic acid and ultrafine calcium phosphate powders, depending on the time and place of implantation. Using scanning electron microscopy it is shown that implants formed from randomly interwoven fibers have interconnected open porosity. It was established that the addition of calcium phosphate ultrafine powders does not cause changes in the formed implants structure. Histological investigation of tissue specimens from the implantation site revealed a high ability of created implants to successful integration with surrounding tissue after 15 days from the moment of implantation. Complete or partial implant resorption with substitution by own tissues was registered at 90 days after implantation. It was established that implantation of composite bioresorbable implants on the ilium bone stimulates the osteogenic process better than the implantation on skull bone within the same period. It was defined that scarification of the outer cortical plate in implant contact points with bone tissue increases the implants ability to stimulate osteogenic process. It was shown that the composite implants filled with calcium phosphate dibasic dehydrate in ultrafine powder form have the largest ability to stimulate osteogenesis.

Cancer is the second leading cause of death worldwide behind cardiovascular diseases. Late stage of cancer at diagnosis and low efficacy of traditional cancer treatments result in low survival rate in cancer patients. Modern techniques to kill tumor cells are therefore needed. Over the last decade novel anticancer treatments have emerged from advances in our understanding of tumor cell biology, and a number of molecular and biologic targets have been identified. Chimeric antigen receptor T cell (CAR-T cell) therapy is a novel adoptive immunotherapy, which is used predominantly in the treatment of hematological malignancies. Moreover, it has been evidenced that cells of the innate immune system are key players at initiating and regulating adaptive immune responses. Studies focusing on innate immune cells for cancer immunotherapy show promising results. In this review, we describe functions of natural killer cells and analyze the rationale for using natural killer cells in cancer therapy.

Urine of prostate cancer (PCa) carries miRNAs originated from prostate cancer cells as a part of both nucleoprotein complexes and cell-secreted extracellular vesicles. The analysis of such miRNA-markers in urine can be a convenient option for PCa screening. The aims of this study were to reveal miRNA-markers of PCa in urine and design a robust and precise diagnostic test, based on miRNA expression analysis. The expression analysis of the 84 miRNAs in paired urine extracellular vesicles (EVs) and cell free urine supernatant samples from healthy donors, patients with benign and malignant prostate tumours was done using miRCURY LNA miRNA qPCR Panels (Exiqon, Denmark). Sets of miRNAs differentially expressed between the donor groups were found in urine EVs and urine supernatant. Diagnostically significant miRNAs were selected and algorithm of data analysis, based on expression data on 24-miRNA in urine and obtained using 17 analytical systems, was designed. The developed algorithm of data analysis describes a series of steps necessary to define cut-off values and sequentially analyze miRNA expression data according to the cut-offs to facilitate classification of subjects in case/control groups and allows to detect PCa patients with 97.5% accuracy.

Background Prostate cancer (PCa) is one of the major cancers in men, but discrepancy between incidence and mortality calls for a careful approach to screening and diagnosis. Controversy between US Preventive Services Task Force recommendations and the outcomes clinical trials illustrate that the shortcomings of existing biomarkers and high demand in novel approaches for prostate cancer screening. Recent studies have suggested miRNAs as new candidates for cancer biomarkers. In this study, we have investigated the use of miRNAs found in cell-free nucleoprotein complexes and urine extracellular vesicles (EVs) as prostate cancer biomarkers. Methods Urine extracellular vesicles were isolated by standard ultracentrifugation protocols. Cell-free supernatant containing nucleoprotein complexes was obtained after 17.000g centrifugation. miRNA from supernatant and urine EVs were isolated as described previously (Lekchnov et al, Anal Biochem, 2016) and profiled using customized miRCURY LNA miRNA qPCR panels (Exiqon Ltd). Results Profiling of the expression of 84 miRNAs in paired samples of urine supernatant and urine EVs of 10 healthy donors (HD), 10 PCa patients and 10 patients with benign prostatic hyperplasia (BPH) has identified subsets of miRNAs differentially expressed between the groups. Using ratio-based normalization miRNA pairs with significantly different expression were selected and verified in an independent sample of 15 HD, 15 PCa and 15 BPH patients. To facilitate highly specific PCa detection a stepwise diagnostic algorithm based on miRNA expression in HD group (median ± 2SD cut off values) and hierarchical analysis of analytical systems was proposed (Bryzgunova et al, PLoS One, 2019). Diagnostic panels developed using miRNA profiling data and comprised of 24 miRNAs (17 miRNA ratios) could classify PCa and BPH patients and HD with 100% specificity and 97.5% accuracy. Diagnostic system based on the expression of 5 miRNA pairs in urine (miR-30a: miR-125b, miR-425: miR-331, miR-29b: miR-21, miR-191: miR-200a, miR-331: miR-106b) can be potentially used to identify PCa. Conclusions The data shows promise of urine cell-free and vesicle cargo miRNA as prostate cancer biomarkers. Legal entity responsible for the study The authors. Funding The study was supported by the Russian Science Foundation (no. 16-15-00124). Pavel P. Laktionov acknowledges financial support within the framework of the Russian state funded budget project # АААА-А17-117020210026-2 to the ICBFM SB RAS. Disclosure All authors have declared no conflicts of interest.

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.

Urine of prostate cancer patients contains tumor-specific biopolymers, including protein- and microvesicles-associated miRNAs that can potentially be used as oncomarkers. Previously we have characterized urinary extracellular vesicles and demonstrated diagnostic potential of their miRNAs. In this study, we have performed a comparative analysis of 84 miRNA in paired samples of urine microvesicles and urine supernatant from healthy men, patients with benign prostate hyperplasia, and prostate cancer patients using miRCURY LNA miRNA qPCR Panels. In all groups of patients, miRNA subsets characterized by different distribution between the urinary fractions have been found. In this context, two groups of miRNAs have been identified, which are involved in several signaling pathways including those associated with prostate cancer development.

Extraskeletal osteosarcoma is a rare malignant tumor with histologic similarities to primary bone osteosarcoma. However, there are distinct differences in epidemiology, imaging features, biological characteristics, prognosis, and management compared with osteogenic osteosarcoma. Extraskeletal osteosarcoma is usually characterized as high-grade neoplasm with clinically aggressive behavior, poor prognosis, frequent recurrence/lymphogenic metastatsis, and resistence to chemotherapy. A noteworthy feature of extraskeletal osteosarcoma is the fact that almost all existing biological phenomena described in mesenchymal oncopathology (except primary-multiple lesions) are present in this tumor, namely: secondary malignancy, association with syndromes, partial spontaneous regression of the tumor, dedifferentiation, bone invasion, biphasic pathology. In this paper, we have discussed in detail the tumor morphology, histological subtypes, prognostic factors and differential diagnosis.

В последнее время возросла популярность роботассистированных операций. Появляются публикации по использованию роботических комплексов daVinci в торакальной, абдоминальной и кардиохирургии [1— 4]. Большинство публикаций принадлежат американским и европейским авторам. Основная масса роботических вмешательств выполняется при онкоурологической патологии. Своевременное выявление и лечение рака почки, предстательной железы, мочевого пузыря обеспечивает хорошие результаты. Роботические вмешательства являются альтернативой лапароскопическим операциям при этих заболеваниях [3, 5—9]. Но опыт подобных вмешательств в России не-

Presence of tumor-derived cell-free miRNA in biological fluids as well as simplicity and robustness of cell-free miRNA quantification makes them suitable markers for cancer diagnostics. Based on previously published data demonstrating diagnostic potentialities of miR-205 in blood and miR-19b as well as miR-125b in urine of prostate cancer patients, bioinformatics analysis was carried out to follow their involvement in prostate cancer development and select additional miRNA-markers for prostate cancer diagnostics. Studied miRNAs are involved in different signaling pathways and regulate a number of genes involved in cancer development. Five of their targets (CCND1, BRAF, CCNE1, CCNE2, RAF1), according to the STRING database, act as part of the same signaling pathway. RAF1 is regulated by miR-19b and miR-125b, and it was shown to be involved in prostate cancer development by DIANA and STRING databases. Thus, other microRNAs regulating RAF1 expression such as miR-16, -195, -497, and -7 (suggested by DIANA, TargetScan, MiRTarBase and miRDB databases) can potentially be regarded as prostate cancer markers.

Background. Dysphagia is the main clinical symptom in patients with locally advanced esophageal carcinoma and proximal part of the stomach. Esophageal stenting is a highly effective and safe method to restore esophageal lumen patency. Published data indicate a high rate of stent-related complications. Material and methods. A retrospective, two-centered study included 166 patients (102 males and 64 females), who underwent endoscopically-guided esophageal stenting from 2004 to 2015. The age of the patients ranged from 36 to 92 years. Expandable metal stents were used for all patients. In most cases (81.3%), drug-eluting stents (22 mm diameter, 120 mm length) were preferable. Treatment outcomes and complications were analyzed. Results. Complications during stent placement (incorrect stent disclosure) were observed in 7 patients. All these complications were eliminated by relocating the stent to the desired position. Postoperative complications were noted in 29 patients (stent migration in 9 patients, stent fracture and migration in 2 patients, stent obstruction in 1 patient, destruction of stent coating and fragmentation in 5 patients, and dysphagia recurrence due to continuing tumor growth in 11 patients). All stent-related complications were corrected by re-endoscopy. Conclusions. The data obtained indicate the need for lifelong surveillance of patients after stenting.

Melanoma is one of the most dangerous forms of skin cancer. Aggressive growth with a high risk of distant metastasis is the cause of the high death rate from skin melanoma worldwide. Melanoma that has metastasized beyond the lymph nodes requires more aggressive treatment. The standard treatment modalities including surgery, radiation therapy and chemotherapy are not very effective for most patients. The aggressive nature of this disease sustains an urgent need for more effective treatment methods. Immunotherapy is currently one of the most promising approaches for fighting cancer cells. The review analyses the main immunotherapeutic approaches to melanoma treatment, including therapeutic vaccines based on tumor cells, synthetic peptides and polyepitopic immunogens. Many of these vaccines are currently being studied in various clinical trials.