Precision in radiotherapy requires the development of standardized, reproducible, and biologically relevant models to accurately assess the efficacy and safety of various radiobiological sources. This review presents a novel approach using precision-cut organotypic tissue slices (OTSs), or organotypic tissue cultures (OTCs), as a representative model with potential for unifying the assessment of radiobiological sources. Derived from specific organs, OTSs retain the complex architecture and multicellular environment of the tissue, providing a unique platform that bridges the gap between in vitro cell cultures and in vivo animal models. The typed OTSs can effectively mimic the in vivo physiological responses to ionizing radiation, providing insight into the mechanisms of radiation-induced damage and repair, and the potential for radiation-induced toxicity and side effects. The emerging practices for the use of OTSs in radiobiological studies include slice mechanical preparation, radiation exposure, and outcomes assessment. The prepared approach for OTS preparation promises to improve the reliability and comparability of radiobiological studies, facilitating the development of safer and more effective radiation therapies. OTSs have the potential to significantly advance our understanding and application of radiation medicine and research by providing a physiologically relevant assessment of radiobiological effects of novel ionizing radiation sources.

BackgroundProstate cancer is the most commonly diagnosed oncological disease among men not only in Russia but also worldwide, while meningioma is the one of the most commonly diagnosed primary central nervous system (CNS) intracranial tumor. However, their combination occurs quite rarely. Prostate-specific membrane antigen radioligand therapy (PSMA RLT) might be an extremely perspective treatment option for these patients as both neoplasms are characterized by PSMA expression.MethodsAfter PET/CT demonstrated a high [68Ga]68Ga-PSMA-11 uptake level in metastatic castration-resistant prostate cancer (mCRPC) and intracranial meningioma in a 77-year old patient, we performed four administrations of [225Ac]Ac-PSMA-617. evaluating the prostate-specific antigen (PSA) dynamics and the structural response by brain MRI and PET/CT with [68Ga]Ga-PSMA-11. In addition, we evaluated the patient’s complaints and his hematological indications.ResultsAfter treatment, the patient revealed a remarkable decrease in the [68Ga]Ga-PSMA-11 uptake level based on the PET/CT data, a decrease in the PSA level by 99.8%, and a decrease in the meningioma size by 90.6%. Among the unfavorable symptoms, high-grade xerostomia (CTCAE v5.0) was revealed. The hematological parameters remained stable for the whole period of observation.ConclusionsThe presented clinical case report describes a unique positive experience on the use of [225Ac]Ac-PSMA-617 therapy in mCRPC and brain meningioma, thus allowing us to expand our understanding of PSMA RLT as a method for the treatment of not only prostatic tumors but also tumors of non-prostatic locations.

The current treatment of radiation-induced skin wounds utilizes mainly conventional therapies, including topical steroids, creams, ointments, and hydrogel dressings, which do not take into account the immunologic changes that occur in the skin after radiation exposure. Therefore, it is relevant to consider alternative therapies and their impact on changes in the immune landscape of the skin. The aim of this study was to investigate the effect of allogeneic minimally manipulated keratinocytes and fibroblasts on rat skin repair and the development of immune responses. We found that the use of cell therapy compared to treatment with syntazone ointment and no treatment resulted in faster healing and a reduction in the size of radiation-induced skin wounds, area of inflammation, and edema. Additionally, in the group receiving the cell therapy application, there was an observed increase in the number of mast cells (MCs), activation of MC interaction with M2 macrophages, a reduction in the direct contact of MCs with the vascular bed, an increase in the content of collagen fibers due to the intensification of collagen fibrillogenesis, and a restoration of their histotopographic organization. Thus, the positive effect of cell therapy based on allogeneic minimally manipulated keratinocytes and fibroblasts on skin regeneration indicated that it can be used in clinical practice to improve the effectiveness of rehabilitation after radiation therapy.

The results of a part of works carried out by the NRC Kurchatov Institute in the development of the physical and technical foundations of the technology of high-temperature gas-cooled reactor (HTGR) systems are presented. Integral components of the development of the physical and technical foundations of the HTGR technology are the improvement of methodology and software for calculations to justify the nuclear and physical part of the project and experimental studies, such as the study of neutronic characteristics of reactors of this type on a critical facility, the study of tightness of fuel samples, and materials science studies of samples in fuel quality control procedures. Maintaining the HTGR knowledge base makes it possible to consolidate the accumulated experience and identify individual critical technologies and is also used in the preparation and implementation of technological development plans aimed at obtaining missing design data.

Objective: to improve treatment outcomes in patients with infected pancreatic necrosis through the rational use of minimally invasive technologies. Materials and methods. A retrospective-prospective analysis of treatment results was conducted on 137 patients with infected pancreatic necrosis. The control group consisted of 53 patients who underwent open necrosectomy. In the main group (84 patients), a developed treatment algorithm was applied using minimally invasive technologies: puncture-draining interventions, video-assisted retroperitoneoscopy, and percutaneous necrectomy. Results. In the control group, postoperative complications developed in 50 (94.3%) patients, with a mortality rate of 54.7%. In the main group, postoperative complications were observed in 32 (38.1%) patients, with a mortality rate of 33,3%. The developed devices for necrectomy allowed for a reduction in operation time by 45.6% (p = 0.04). Conclusions: The application of the developed treatment algorithm and instrumentation using minimally invasive technologies allowed for a reduction in the frequency of postoperative complications from 94.3% to 38.1% and mortality from 54.7% to 33,3% in patients with infected pancreatic necrosis.

Objective: Traditional cell-based radiobiological methods are inadequate for assessing the toxicity of ionizing radiation exposure in relation to the microstructure of the extracellular matrix. Organotypic tissue slices preserve the spatial organization observed in vivo, making the tissue easily accessible for visualization and staining. This study aims to explore the use of fluorescence microscopy of physiologically compatible 3D tissue cultures to assess the effects of ionizing radiation. Methods: Organotypic tissue slices were obtained by vibratome, and their mechanical properties were studied. Slices were exposed by two ionizing radiation sources; electron beams (80 Gy and 4 Gy), and soft gamma irradiation (80 Gy and 4 Gy). Two tissue culture protocols were used: the standard (37°C), and hypothermic (30°C) conditions. A qualitative analysis of cell viability in organotypic tissue slices was performed using fluorescent dyes and standard laser confocal microscopy. Results: Biological dosimetry is represented by differentially stained 200-µm thick organotypic tissue sections related to living and dead cells and cell metabolic activity Conclusion: Our results underscore the ability of fluorescence laser scanning confocal microscopy to rapidly assess the radiobiological effects of ionizing radiation in vitro on 3D organotypic tissue slices.

Studies on health effects of radiation exposure to residents around the Semipalatinsk nuclear test site (SNTS), Kazakhstan, are necessary for epidemiological assessment of radiation-related health risks after low-dose irradiation. Radiation dose estimates are the principal point for radiation epidemiological studies. These estimates should be based on the most reliable initial data, used for dose estimations. The comparative critical analysis of various available archival and published initial data, namely values of historical exposure dose rates and values of soil contamination by 137Cs in considered settlements, including information about dates, times and locations of measurements, was performed with the aim to select most reliable and realistic initial data necessary for estimation of settlement-average accumulated external doses for some settlements located in the vicinity of radioactive clouds' trajectories related to the most significant tests at the SNTS. Results of estimation of accumulated external radiation dose to air, based on these selected initial data, are presented for 18 settlements. Calculated accumulated external doses were compared with retrospective instrumental dose estimates for settlements, where data on TL/OSL luminescence retrospective dosimetry with quartz-containing samples or electron spin resonance (ESR) dosimetry with tooth enamel were available. Estimation of settlement-average external radiation dose to air is the first important step necessary for the next step-individualized radiation dose estimations among different age, professional and ethnic-specific groups of population lived in the study settlements considering behavior, shielding, location and relocation factors in each population group. This is a subject of future work.

Compound T1089—a novel nitrogen mustard based on an indole-3-carboxylic acid derivative (ICAD)—has been synthesized. The ICAD used as the basis for T1089 is a TLR agonist capable of activating an antitumor immune response. This study describes the synthesis method and presents the results of preliminary investigations of this compound. This research included an assessment of acute toxicity in mice, in vivo clastogenic activity evaluated via the bone marrow chromosome aberration (BMCA) test in mice, in vitro cytotoxicity determined by the MTT assay against human lung carcinoma A549 cells, and in vivo antitumor effects (ATEs) in models of conventional chemotherapy (CCT) of solid tumors in mice. The bifunctional alkylating agent cyclophosphamide (CPA) was used as a reference drug. Toxicological studies revealed that T1089 belongs to toxicity class III (moderately toxic), with acute toxicity values (LD16 and LD50) in mice following intraperitoneal (i.p.) administration being 191 and 202 mg/kg, respectively. The alkylating activity and clastogenic potential of T1089 were demonstrated by its effects in the BMCA test, which were comparable to those of CPA. A single i.p. administration of CPA and T1089 at a dose of 0.064 mmol/kg induced similar stimulation of structural mutagenesis associated with DNA strand breaks. The frequency of karyocytes with aberrations increased 20-fold compared to the control, primarily due to a rise in chromatid breaks and fragments, and to a lesser extent, due to an increase in exchange-type aberrations. In vitro cytotoxicity studies indicated differences in the mechanisms of alkylating activity between CPA and T1089. According to the MTT assay, the cytotoxic effects of CPA were observed only at concentrations exceeding 2 mM (IC50 = 4.2 ± 0.3 mM), corresponding to lethal in vivo doses, which is expected since the formation of CPA’s alkylating metabolite requires hepatic microsomal enzymes. In contrast, significant cytotoxic effects of T1089 were observed at much lower concentrations (15–50 μM, IC50 = 33.4 ± 1.3 μM), corresponding to safe in vivo doses. Differences were also observed in the in vivo ATEs of CPA and T1089 in the Ehrlich solid carcinoma (ESC) CCT model. Following seven i.p. administrations at 48 h intervals (33 mg/kg), both compounds exhibited increasing toxicity, manifested as cumulative body weight loss in treated mice. However, despite the aggressive CCT regimen, ESC showed low sensitivity to CPA. The ATE of CPA developed slowly, reaching a significant level only after four injections, and even after seven administrations, tumor inhibition (TI) did not exceed 30%. In contrast, ESC was significantly more sensitive to T1089 under the same CCT conditions. The ATE of T1089 exhibited a cumulative pattern but developed more rapidly and to a greater extent. A significant antitumor effect was observed after just two injections, with maximal efficacy (TI = 53%) achieved after four injections and sustained until the end of the observation period. A high ATE of T1089 was also observed in the B-16 melanoma CCT model. Following six i.p. administrations at 48 h intervals (28 mg/kg), T1089 treatment was associated with minimal toxicity. Despite this mild CCT regimen, melanoma exhibited high sensitivity to T1089. Maximal ATE (TI = 56%) was achieved after two injections, and subsequent administrations maintained a consistently high efficacy (TI = 52–55%) until the end of the study. In summary, preliminary findings demonstrate that T1089 possesses alkylating activity characteristic of bifunctional agents, accompanied by high in vitro cytotoxicity and in vivo ATEs in CCT models (at high doses). Given that the ICAD used as the basis for T1089 is a TLR agonist capable of stimulating antitumor immunity, T1089 can be considered a dual-action alkylating agent with combined antitumor effects. These results justify further investigation of T1089 in conventional and metronomic chemotherapy regimens, particularly in combination with immune checkpoint inhibitors and antitumor vaccines.

BACKGROUND:The main type of treatment of unresectable NSCLC is chemoradiotherapy, which has a relatively high toxicity. One option allowing to reduce the toxicity of this approach may be immunocorrective therapy. The appointment of this type of treatment should be warranted in terms of patient's immune system response. This confirms the importance of verifying systemic immune disorders in primary patients with NSCLC. GOAL:To assess the features of the population of immune cells in peripheral blood in patients with stage IIIB, IIIC primary NSCLC and to identify any signs of secondary immunodeficiency in this cohort. METHODS:We analyzed the frequencies of circulating T cells (CD3+, CD4+, CD8+), B-cells (CD19+), NK-cells (CD3-CD16+CD56+ cell), and NKT-cells (CD3+CD56+ cells) within CD45+ cells (lymphocytes) in 80 patients with stage IIIB-IIIC NSCLC, and in 40 healthy controls using eight-color flow cytometry. RESULTS:In patients with stages IIIB-IIIC primary NSCLC, changes within immunocompetent blood cells were found. Moreover, it was unveiled that quantitative changes affected all major immunocompetent cells. A decrease in the proportion of CD4+ T cells and B lymphocytes and an increase in the number of NK and NKT cells were found. Also, an increase in the number of double-positive CD4+CD8+ T cells was revealed, as well as a significant increase in the proportion of B1a (CD5+CD19+) cells among B lymphocytes (qualitative disorders). CONCLUSION:The revealed multidirectional changes among immunocompetent peripheral blood cells in patients with locally advanced NSCLC (stages IIIB-IIIC) can be beyond doubt considered as signs of systemic immune disorders in this cohort (secondary immunodeficiency).

To understand the biological effects of residual radioactivity after the atomic bomb explosion in Hiroshima and Nagasaki, we previously investigated the effects of 56Mn, a major residual radioisotope. Our rat study demonstrated that inhalation exposure to 56MnO2 microparticles affected gene expression in the lungs, testes, and liver, despite the low radiation doses. Because 56Mn is a β- and γ-emitter, the differential effects between β- and γ-rays should be clarified. In this study, 31Si, a β-emitter with a radioactive half-life similar to that of 56Mn, was used to determine its effects. Male Wistar rats were exposed to sprayed neutron-activated 31SiO2 microparticles, stable SiO2 microparticles, or X-rays. The animals were examined on days 3 and 14 after irradiation. The expression of radiation-inducible marker genes, including Ccng1, Cdkn1a, and Phlda3, was measured in the spleen, lungs, and liver. Furthermore, the expressions of pathophysiological marker genes, including Aqp1, Aqp5, and Smad7 in the lungs and Cth, Ccl2, and Nfkb1 in the liver, were determined. Impacts of 31SiO2 exposure were observed mainly in the liver, where the expression of Cth markedly increased on post-exposure days 3 and 14. Our data suggest that internal exposure to β-emitted microparticles has significant biological effects and its possible roles as residual radiation after atomic bombing.

The purpose of the study. To estimate the number of patients with the preservation of relative dose intensity (RDI) ≥ 80 % of first-line antitumor therapy in patients with unresectable non-small cell lung cancer (NSCLC), and to compare the effectiveness of therapy in groups with optimal and lower RDI.Patients and methods. The study included 30 patients (25 men and 5 women) with locally advanced unresectable NSCLC. The median age was 57 years. The main criterion for inclusion in the study was morphologically verified NSCLC with stage IIIB-IIIC of the disease. All patients underwent simultaneous chemoradiotherapy. According to the histogenesis of the tumor process, patients with a squamous cell variant prevailed.Results. The data obtained from 22 (73.3 %) patients who retained a relative dose intensity of RDI > 80 % demonstrated that given dose intensity is sufficient to achieve a stable antitumor effect. In 8 (26.7 %) cases, however, the RDI was less than 80 %, which affected the effectiveness of the treatment. The median follow-up for overall survival (OS) was 29.2 months, progression-free survival (PFS) was 15.1 months, and local control was 21.9 months. in all patients included in the analysis. The indicators of OS in the second year had an advantage in the group of patients with RDI < 80 % and amounted to 73.3 % compared with 60.5 % in patients with RDI > 80 %. PFS was higher in the group of patients with high dose intensity, in the first year of follow-up it was 75.6 % compared with the group of patients with RDI < 80 % (62.5 %), in the second year of follow-up, PFS was 27.2 % and 20.8 %, respectively. Local control was 90.2 % in the first year in the group of patients with RDI > 80 % and 62.5 % in the group of patients with RDI < 80 %. The second year of follow-up demonstrated the advantage of the group of patients with RDI >80 % in terms of local control and amounted to 48.1 % versus 34.7 %, respectively.Conclusion. The results obtained show that maintaining relative dose intensity at a high level has a positive effect on survival rates and local control of patients with locally advanced unresectable NSCLC. However, there is a cohort of patients who did not receive the planned amount of treatment, due to the high toxicity of simultaneous chemoradiotherapy. It is necessary to develop new approaches to concomitant therapy aimed at reducing the toxicity of the combined treatment and achieving maximum antitumor effect.

The paper examines the violations of monotonicity and semiconvergence of the inverse optimization problem to equilibrium iterative solutions under conditions of physical density discontinuities in therapy planning techniques. Additionally, it addresses aspects of quasi-Newton iterations of the obtained solution in both voxel representation and continuous approximation. Examples include radiation treatment plans for patients treated with proton beam at the Prometheus therapeutic facility at the A. Tsyb Medical Radiological Research Center, Obninsk, Kaluga oblast, Russia. The presented aspects of the theory and its applications form the basis of the dose-anatomical planning program.

The role of surface antigens of Yersinia pestis in reception of the phage L-413C was evaluated experimentally. Based on the methods of phage inactivation after its co-incubation with soluble or bead-bounded antigens, the importance of the plague microbe LPS in the phage reception was confirmed, and the inability to bind the capsular antigen F1, Ail protein, and two autotransporters YapF and YapM was shown. The native and recombinant PsaA, being solved, significantly inhibited the lytic activity of the phage in contrast to the bead-bound antigens. The knockout EV cells (ΔpsaA) are able to bind the phage particles as well as the wild strain. The use of three methods to evaluate the role of the PsaA antigen in phage L-413C reception gave contradictory results. On the one hand, the reactive domains of PsaA are able to interact with phage particles in solution. At the same time, these domains appear to determine nonspecific binding of the PsaA protein to the underlying bacterial cell structures or polystyrene microsphere, preventing phage adhesion.

BACKGROUND: Transoral endoscopic thyroidectomy (TE) by the vestibular access is an advanced technique in modern domestic oncology as it enables to have a perfect cosmetic results without any asymmetry caused by the scar strain on the visualized surface of the neck skin. CLINICAL CASE DESCRIPTION: The article presents the first Russian experience, obtained in the research and clinical institution specializing in oncological diseases, in the application of transoral endoscopic TE by the vestibular access in children suffering of differentiated thyroid cancer. 9 children with thyroid cancer (TC), who were hospitalized to the A. Tsyb Medical Radiological Research Center from July 5, 2022, till December 20, 2022, were taken in the study. Tumor stage was estimated by the International Classification TMN TC (UICC, 8th ed., 2017): cT1a — 6 patients, cT1b — 3 patients. The age ranged from 6 to 17 y.o., average 15.2±1.1 (5 boys, 4 girls). All patients survived endoscopic surgery on the thyroid gland (TG) by the vestibular access: 6 patients — hemithyroidectomy (HTE) and 3 patients — TE, selective cervical lymphadenectomy (level VI). All nine endoscopic surgeries on the thyroid gland by the vestibular access were successful, without conversion. In all patients, paratracheal, pretracheal and prelaryngeal groups of lymph nodes on the lesion side (level VI) were removed. Surgery duration ranged from 59 to 143 minutes, average 95±20.5 minutes. No complications, such as laryngeal nerve paresis or hypoparathyroidism, were observed. Intradermal hematoma and chin skin paresthesia were registered as local postoperative complications which did not require any treatment. All patients were satisfied with their cosmetic outcomes. CONCLUSION: Transoral endoscopic thyroidectomy by the vestibular access is a safe and feasible alternative surgical intervention for neoplasms in the carefully selected infants so as to avoid scar formations on the frontal neck surface. Transoral endoscopic interventions in the thyroid gland and regional lymphatic regions by the vestibular access should be performed only in highly specialized oncological centers equipped with modern endoscopic devices.

For many decades, neutrons have been actively used in the treatment of various cancer diseases. In the light of recent advances in conventional photon therapy, interest in neutrons has almost faded, despite their unique biological features. At the same time, neutron-capture therapy is actively developing, the concept of which is based on the high precision of the treatment method, allowing to minimize the toxicity of the treatment. Another way of using neutrons deserves attention – as sources for contact brachytherapy. In Russia, various neutron therapy methods have been studied in depth, ranging from fundamental aspects to direct wide use in various clinical situations. Such capabilities were provided by the extensive research infrastructure of particle physics, and its accessibility to researchers and clinicians. In the modern clinical perspective, neutron therapy can be an effective treatment option for certain clinical indications. Such cases are traditionally referred to as radioresistant tumors, which are considered to be low sensitive to irradiation. This mini-review recall the history of the use of neutrons since their discovery and to the present days, as well it discusses their role in the further development of radiotherapy.

Objective . To analyze cosmetic results in reconstruction of defects in the distal anatomical parts of the nose. Materials and methods . The results of 103 reconstructions in patients with acquired defects of the external nose with loss of distal anatomical parts were studied. The evaluation of cosmetic results was performed using a 5-point scale of the NAFEQ (Nasal Appearance and Function Evaluation Questionnaire). Complication rate and assessments in groups with median and lateral localization of the defect (33 and 70 patients, respectively) depending on the method of reconstruction were compared. Results . Complication rate in the reconstruction of median defects (4 cases, 12.1%) and lateral defects (2 cases, 2.9%) did not have a statistically significant difference (Fisher’s exact two-tailed test, p=0.066). With median defects, a decrease in assessment of cosmetic results was more often noted in indications of “nasal tip”, “nasal alar”, and “nasal back”; with lateral defects – “nostril size”, “nasal alar”, “nasal back”. The estimates of the tip and back of the nose were statistically significantly higher after the reconstruction of lateral defects than median ones, p=0.004 and p<0.001, respectively. There was no statistically significant difference between the groups in the estimates of the nasal alar and the nostril size. The indicator “total appearance of the nose” did not have a statistically significant difference in the groups, p=0.129. The results for the indicators “nostrilя size”, “color of the outer nose”, “total appearance of the nose” were statistically significantly higher when using a puzzle flap compared with alternative methods. The estimates of the “nasal tip” index were statistically significantly higher following reconstruction with a frontal flap compared with nasal flaps. Conclusion . The complication rate in the reconstruction of the distal subunits of the nose was 5.8% and had no difference in the median and lateral localizations of the defect. Cosmetic results differed when assessed by individual measures. The assessment of the total appearance of the nose had no significant difference in the median and lateral localizations of the defect. The use of a puzzle flap and a forehead flap presented better results for the particular subunits.

The coronavirus disease (COVID-19) pandemic has brought into sharp relief the threat posed by coronaviruses and laid the foundation for a fundamental analysis of this viral family, as well as a search for effective anti-COVID drugs. Work is underway to update existent vaccines against COVID-19, and screening for low-molecular-weight anti-COVID drug candidates for outpatient medicine continues. The opportunities and ways to accelerate the development of antiviral drugs against other pathogens are being discussed in the context of preparing for the next pandemic. In 2012–2015, Tsyshkova et al. synthesized a group of water-soluble low-molecular-weight compounds exhibiting an antiviral activity, whose chemical structure was similar to that of arbidol. Among those, there were a number of water-soluble compounds based on 5-methoxyindole-3-carboxylic acid aminoalkyl esters. Only one member of this rather extensive group of compounds, dihydrochloride of 6-bromo-5-methoxy-1-methyl-2-(1-piperidinomethyl)-3-(2-diethylaminoethoxy)carbonylindole, exhibited a reliable antiviral effect against SARS-CoV-2 in vitro. At a concentration of 52.0 μM, this compound completely inhibited the replication of the SARS-CoV-2 virus with an infectious activity of 106 TCID50/mL. The concentration curves of the analyzed compound indicate the specificity of its action. Interferon-inducing activity, as well as suppression of syncytium formation induced by the spike protein (S-glycoprotein) of SARS-CoV-2 by 89%, were also revealed. In view of its synthetic accessibility − high activity (IC50 = 1.06 µg/mL) and high selectivity index (SI = 78.6) − this compound appears to meets the requirements for the development of antiviral drugs for COVID-19 prevention and treatment.