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Background: Due to non-vascularized and aneural structure, articular cartilage has limited self-repairing capacity. The aim of this study was to investigate the revitalization of inflammatory injured articular cartilage matrices by human nasal chondrocytes (hNC)., Materials and Methods: Cartilage matrix was prepared by devitalization of articular cartilage samples obtained intraoperatively from an adult patient undergoing knee joint replacement. hNC were obtained from native tissues by enzymatic digestion with further expansion over two passages. The obtained nasal chondrocytes were used to seed decellularized scaffolds, which were then cultured in vitro for 7, 14, or 21 days in chondrogenic medium. Migration was observed by histologic staining with fast green, safranin-O, and hematoxylin and scanning electron microscopy. Biochemical analysis was performed to determine the glycosaminoglycan (GAG) and DNA content of the cartilage using dimethylmethylene blue and CyQuant Cell Proliferation Assay Kit., Results: We seeded healthy and inflamed cartilage with nasal chondrocytes and found that the cells actively invade mainly pathologically altered cartilage. The results of biochemical quantitative analysis showed that the amount of DNA significantly increased by day 7 and decreased by day 14, while the quantitative values of GAGs had the opposite trend. Histological staining showed that cartilage formation occurred on day 7, intercellular spaces were filled with de novo synthesized cartilage matrix with significantly low GAG content on day 14, and newly formed GAG-rich cartilage was observed on day 21. The obtained data on cartilage regeneration were confirmed by scanning electron microscopy., Conclusions: Our preliminary results showed that human nasal chondrocytes are capable of infiltrating the pathologically altered extracellular matrix of articular cartilage damaged by arthritis, thereby promoting its repair to a physiologically relevant state., Competing Interests: Declarations. Ethics approval and consent to participate: The study was conducted according to the guidelines of the Declaration of Helsinki. All human samples were collected after obtaining written informed consent from the individuals and/or their relatives, and approval from the Local Ethical Commission (EKNZs; Ref.# 78/07). All human samples were collected with informed consent given by the involved individuals and/or relatives. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Combined proton-neutron therapy can be the best opportunity for neutron radiation therapy due to highly conformal proton irradiation and high relative biological effectiveness of neutrons. The study compares 4 schemes of sequential in vitro exposure of Chinese hamster fibrosarcoma cells B14-150 to 14.5 MeV neutrons and a scanning beam of protons. Treatment efficiency increased with increasing the contribution of the neutron component to the total dose from 30 to 40% and the delivery of the neutron dose as the first fraction in the two-fraction proton-neutron exposure., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

This work presents the method of synthesis and physicochemical characterization of isothiourea and cinnamic acid original derivative α-cyano-4-hydroxycinnamate 1-cyclohexanoy-l-2-ethylisothiourea (T1114). In studies of the cytotoxic and antitumor activity of T1114, it has been found that the combination in one molecular structure of NOS-inhibitory fragment (1-cyclohexanoyl-2-ethylisothiourea) and a fragment inhibiting monocarboxylate lactate transporters (MCT) (α-cyano-4-hydroxycinnamic acid) does not modify the cytotoxic activity of bifunctional NOS/MCT-inhibitor T1114 in vitro. But in vivo inhibition of NOS and MCT is able to realize effects on the tumor microenvironment and hypoxic tumor cells. Such structural and functional modification has significantly extended the antitumor activity of the new NOS/MCT inhibitor. The bifunctional compound not only realized a more pronounced antitumor effect, but also prevented the development of hypoxic adaptation in solid Ehrlich carcinoma and acquired the ability to overcome the resistance of mouse cervical cancer (RShM-5). Therefore, the combination of NOS-inhibitory, anti-vasculogenic and hypoxia-oriented toxic effects can create new opportunities in antiangiogenic therapy of malignant neoplasms., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

In this study, the optimal engraving parameters were determined through the analysis of scanning electron microscopy (SEM) data, as follows: a laser power density of 5.5 × 10 5 W/cm 2 , an irradiation rate of 0.1 mm/s, a well radius of 60 μm, a distance between well centers of 200 μm, and a number of passes for each well of 20. After 1 week of in vitro cultivation, chondrocytes were located on the surface of the scaffolds, in the sockets and lacunae of decellularized cartilage. When implanted into animals, both cellular and acellular scaffolds were able to support cartilage in-growth and complete regeneration of the defect without clear boundaries with normal tissue. Nevertheless, the scaffolds populated with cells exhibited superior biocompatibility and were not subject to rejection, in contrast to cell-free constructs.

Nanophotothermolysis (NPhT) effect is considered to be an approach for the development of highly selective modalities for anticancer treatment. Herein, we evaluated an antitumor efficacy of NPhT with intravenously injected zinc phthalocyanine particles (ZnPcPs) in murine subcutaneous syngeneic tumor models. In S37 sarcoma-bearing mice a biodistribution of ZnPcPs was studied and the high antitumor efficacy of ZnPcPs-mediated NPhT was shown, including a response of metastatic lesions. The morphological investigation showed the main role of a local NPhT-induced vascular damage in the tumor growth and tumor spread inhibition. Murine tumors of different histological origin were not equally sensitive to the treatment. The results demonstrate a potential of ZnPcPs-mediated NPhT for treatment of surface tumors., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We studied the antitumor activity of the combined use of local proton irradiation in two modes (10 and 31 Gy) with preliminary intra-tumoral injection of two types of bismuth nanoparticles differing in surface coating: coated with the amphiphilic molecule Pluronic-F127 or Silane-PEG (5 kDa)-COOH polymer. Nanoparticles were used in doses of 0.75 and 1.5 mg/mouse. In two independent series on experimental tumor model (solid Ehrlich carcinoma), bismuth nanoparticles of both modifications injected directly into the tumor enhanced the antitumor effects of proton therapy. Moreover, the radiosensitizing effect of bismuth nanoparticles administered via this route increased with the increasing the doses of nanoparticles and the doses of radiation exposure. In our opinion, these promising data obtained for the first time extend the possibilities of treating malignant neoplasms., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: To evaluate the outcomes of isolated liver chemo perfusion in patients with hepatic metastases from uveal melanoma., Materials and Methods: Cardiovascular surgeons are often involved in the treatment of oncological diseases. Isolated liver chemoperfusion requires the use a heart-lung machine. A little more than 300 operations of isolated liver chemoperfusion have been performed worldwide. From 2020 to 2023, 38 cases of isolated liver chemoperfusion were performed at the Kostroma Clinical Oncological Dispensary., Results: There were 3 deaths, 2 due to liver failure. The remaining patient had hepatic artery thrombosis, who despite emergency thrombectomy and repair of common hepatic artery succumbed to multiorgan failure. Bleeding was diagnosed in 7 patients in the postoperative period. In all cases, relaparotomy was performed to stop bleeding. Subsequently, no special features were noted. The median disease-free survival was 5.4 months. The median overall survival was 20.3 months at the time of submission of this manuscript., Conclusions: Isolated liver chemoperfusion is a safe method of regional chemotherapy and can be considered in patients with isolated hepatic metastases from uveal melanoma., Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-023-01620-6., Competing Interests: Conflict of interestThe authors declare no competing interests., (© Indian Association of Cardiovascular-Thoracic Surgeons 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

About 7% of all cancer deaths are caused by pancreatic cancer (PCa). PCa is known for its lowest survival rates among all oncological diseases and heterogenic molecular profile. Enormous amount of genetic changes, including somatic mutations, exceeds the limits of routine clinical genetic laboratory tests and further stagnates the development of personalized treatments. We aimed to build a mutational landscape of PCa in the Russian population based on full exome next-generation sequencing (NGS) of the limited group of patients. Applying a machine learning model on full exome individual data we received personalized recommendations for targeted treatment options for each clinical case and summarized them in the unique therapeutic landscape.

Objective: To investigate the effect of two fractionation regimens on survival in patients with Grade IV gliomas depending on rapid early progression (REP)., Material and Methods: Fractionation with prescribed doses of 2 and 3 Gy was alternately used in 140 patients with morphologically confirmed Grade IV glioma using a pairwise modeling strategy., Results: REP was diagnosed in 60 (42.9%) out of 140 patients with Grade IV gliomas and 55 (45.5%) out of 121 patients with glioblastomas. Fatal outcome was observed in 111 (79.3%) patients, 99 (70.7%) ones died from progression of glioma. In case of no REP, the median overall survival as of December 2023 was 32.20 (95% CI 25.7-38.7) months, with REP - only 16.03 (95% CI 13.5-18.6) months ( p <0.0001). Median survival was slightly lower in patients with glioblastoma - 28.2 and 16.5 months, respectively ( p <0.0001)., In patients with Grade IV gliomas and no REP, 3 Gy ( n =40) fractionation regimen was followed by median overall survival 44.98 (95% Cl 15.3-74.6) months, 2 Gy ( n =40) - 20.99 (95% CI 9.2-32.7) months ( p =0.027). In case of glioblastoma, differences between fractionation regimes lose significance - medians 33.7 and 19.7 months, respectively ( p =0.081). According to multivariate analysis, 3 Gy fractionation regimen is more effective than standard radiotherapy ( p =0.009) in patients without REP, while significance of isoeffective doses <59.5Gy≥ is slightly lower ( p =0.020). Radiotherapy on the background of temozolomide is equally important ( p =0.007)., In patients with grade 4 gliomas and REP, 3 Gy ( n =30) fractionation regimen was followed by median overall survival 17.18 (95% CI 14.2-20.2) months, 2 Gy ( n =30) - 12.88 (95% CI 5.4-20.3) months ( p =0.849). In case of glioblastoma, Cox model classification matrix looks as follows: fractionation variant ( p =0.423), isoeffective dose <59.5Gy≥ ( p <0.0001), temozolomide during radiotherapy ( p =0.701), functional status ( p =0.485)., Conclusion: In patients with Grade IV gliomas and no REP, 3 Gy fractionation regimen has significant advantages over standard radiotherapy regarding overall survival. In case of more aggressive course of tumor (REP), higher single dose does not improve treatment outcomes. Isoeffective dose ≥59.5Gy is of great importance.

A 72-year-old female patient with chronic kidney disease stage presented with multiple parathyroid adenomas and tertiary hyperparathyroidism. SPECT/CT with 99m Tc-MIBI revealed accumulation of radiopharmaceuticals in 2 out of 4 parathyroid glands. Ultrasound established localization of all parathyroid glands. Subtotal parathyroidectomy with excision of 3 glands and resection of half of the fourth gland was performed. Intraoperative indocyanine green angiography was performed to identify all parathyroid glands and remnant perfusion. There was normal parathyroid function after 6 months.

The therapeutic efficacy of a Russian radiopharmaceutical 177 Lu-DOTA-PSMA was studied in vivo using male BALB/c nu/nu (nude) mice with prostate carcinoma 22Rv1 xenografts by tumor growth inhibition criterion. The mean tumor volumes in mice treated with 177 Lu-DOTA-PSMA were significantly lower than in animals of the control group. There were no significant differences in the values of tumor growth inhibition between the groups of animals receiving 3.7 or 7.4 MBq of 177 Lu-DOTA-PSMA., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

Nuclear medicine presents one of the most promising modalities for efficient non-invasive treatment of a variety of cancers, but the application of radionuclides in cancer therapy and diagnostics is severely limited by their nonspecific tissue accumulation and poor biocompatibility. Here, we explore the use of nanosized metal-organic frameworks (MOFs) as carriers of radionuclides to order to improve their delivery to tumour. To demonstrate the concept, we prepared polymer-coated MIL-101(Cr)-NH 2 MOFs and conjugated them with clinically utilized radionuclide 188 Re. The nanoparticles demonstrated high loading efficacy of radionuclide reaching specific activity of 49 MBq mg -1 . Pharmacokinetics of loaded MOFs was investigated in mice bearing colon adenocarcinoma. The biological half-life of the radionuclide in blood was (20.9 ± 1.3) h, and nanoparticles enabled it to passively accumulate and retain in the tumour. The radionuclide delivery with MOFs led to a significant decrease of radioactivity uptake by the thyroid gland and stomach as compared with perrhenate salt injection, which is beneficial for reducing the side toxicity of nuclear therapy. The reported data on the functionalization and pharmacokinetics of MIL-101(Cr)-NH 2 for radionuclide delivery unveils the promising potential of these MOFs for nuclear medicine., (© 2023 IOP Publishing Ltd.)

Immune responses to tissue-engineered grafts made of xenogeneic materials remain poorly studied. The scope of current investigations is limited by the lack of information on orthotopically implanted grafts. A deeper understanding of these processes is of great importance since innovative surgical approaches include the implantation of xenogeneic decellularized scaffolds seeded by cells. The purpose of our work is to study the immunological features of tracheal repair during the implantation of tissue-engineered constructs based on human xenogeneic scaffolds modified via laser radiation in rabbits. The samples were stained with hematoxylin and Safranin O, and they were immunostained with antibodies against tryptase, collagen II, vimentin, and CD34. Immunological and inflammatory responses were studied by counting immune cells and evaluating blood vessels and collagen. Leukocyte-based inflammation prevailed during the implantation of decellularized unseeded scaffolds; meanwhile, plasma cells were significantly more abundant in tissue-engineered constructs. Mast cells were insignificantly more abundant in tissue-engineered construct samples. Conclusions: The seeding of decellularized xenogeneic cartilage with chondrocytes resulted in a change in immunological reactions upon implantation, and it was associated with plasma cell infiltration. Tissue-engineered grafts widely differed in design, including the type of used cells. The question of immunological response depending on the tissue-engineered graft composition requires further investigation.

Treatment of a wide variety of defects in the oral and maxillofacial regions requires the use of innovative approaches to achieve best outcomes. One of the promising directions is the use of gene-activated materials (GAMs) that represent a combination of tissue engineering and gene therapy. This approach implies that biocompatible materials will be enriched with gene-carrying vectors and implanted into the defect site resulting in transfection of the recipient's cells and secretion of encoded therapeutic protein in situ. GAMs may be presented in various designs depending on the type of material, encoded protein, vector, and way of connecting the vector and the material. Thus, it is possible to choose the most suitable GAM design for the treatment of a particular pathology. The use of plasmids for delivery of therapeutic genes is of particular interest. In the present review, we aimed to delineate the principle of work and various designs of plasmid-based GAMs and to highlight results of experimental and clinical studies devoted to the treatment of periodontitis, jaw bone defects, teeth avulsion, and other pathologies in the oral and maxillofacial regions.

Reliable methods for identifying rodents play an important role in ensuring the success of preclinical studies. However, animal identification remains a trivial laboratory routine that is not often discussed, despite the fact that more than 6 million rodents are used in animal studies each year. Currently, there are extensive regulations in place to ensure adequate anesthesia and to reduce animal suffering during experiments. At the same time, not enough attention is paid to the comfort of rodents during routine identification procedures, which can be painful and cause some complications. In order to achieve the highest ethical standards in laboratory research, we must minimize animal discomfort during the identification phase. In this article, we discuss traumatic methods of identification and describe several painless methods for marking in long-term experimental studies. The use of non-traumatic and non-invasive methods requires the renewal of marks as they fade and additional handling of the rodents. Laboratory personnel must be trained in stress-minimizing handling techniques to make mark renewal less stressful.

Proton and ion radiation therapy, when used both as single radiation and in mixed radiation mode, have a number of advantages over the conventional γ-therapy that are determined by physical characteristics of accelerated particles. The paper presents the results of an in vitro study of the effectiveness of sequential exposures of Chinese hamster tumor cells B14-150 to proton (p) and 12 C ion beams. We used 4 irradiation schemes differing by the sequence of exposure and the contribution of each radiation to the total dose. Synergism was shown for 12 C ions dose contribution of 45% (taking into account the coefficient of relative biological efficiency) and the sequence 12 C→p., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

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 (IC 50 = 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., (Copyright ® 2023 National Research University Higher School of Economics.)

Background: The aim of study was to evaluate survival outcome and limb function in cancer patients with proximal limbs metastasis. Associated factors on survival outcome and limb function were identified. The comparative analysis between intramedullary nailing and prosthesis surgery in cancer patients with proximal limb metastasis was performed., Methods: In this five-center retrospective study, patients diagnosed with limbs metastasis were collected. Descriptive statistics was used and log-rank test was performed to analyze the survival in subgroups. The Cox proportional hazards regression analysis was performed to identify the independent prognostic factors. The Musculoskeletal Tumor Society (MSTS) scoring system was used to evaluate limb function after surgery, and t test or analysis of variance (ANOVA) was utilized in subgroup analysis., Results: A total of 316 patients with limb metastasis were included with mean age at 61.0 years. The most common primary tumor was breast, followed by renal cancer and lung cancer. The median overall survival was 24.0 months and the 1-, 3- and 5-year survival rates were 86.9%, 34.7% and 6.8%, respectively. Primary tumor type, visceral metastasis and chemotherapy were proved to be the independent prognostic factors. The mean Musculoskeletal Tumor Society (MSTS) score was 20.5, significant difference was observed in subgroup of solitary/multiple bone metastasis, with/without pathological fracture, and type of surgery., Conclusion: The present study concluded that primary tumor type, visceral metastasis and chemotherapy were three factors affecting the survival of patients. Compared with intramedullary nailing, the patients underwent prosthesis surgery showed better limb function, this procedure should be encouraged in patients with indication., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Current abdominal surgery has several approaches for biliary reconstruction. However, the creation of functional and clinically applicable bile duct substitutes still represents an unmet need. In the paper by Miyazawa and colleagues, approaches to the creation of bile duct alternatives were summarized, and the reasons for the lack of development in this area were explained. The history of bile duct surgery since the nineteenth century was also traced, leading to the conclusion that the use of bioabsorbable materials holds promise for the creation of bile duct substitutes in the future. We suggest three ideas that may stimulate progress in the field of bile duct substitute creation. First, a systematic analysis of the causative factors leading to failure or success in the creation of bile duct substitutes may help to develop more effective approaches. Second, the regeneration of a bile duct is delicately balanced between epithelialization and subsequent submucosal maturation within limited time frames, which may be more apparent when using quantitative models to estimate outcomes. Third, the utilization of the organism's endogenous regeneration abilities may enhance the creation of bile duct substitutes. We are convinced that an interdisciplinary approach, including quantitative methods, machine learning, and deep retrospective analysis of the causes that led to success and failure in studies on the creation of bile duct substitutes, holds great value. Additionally, more attention should be directed towards the balance of epithelialization and submucosal maturation rates, as well as induced angiogenesis. These ideas deserve further investigation to pave the way for bile duct restoration with physiologically relevant outcomes., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

It is known that the saturation ratio of transferrin (Tf) with iron in human blood is an important clinical parameter. Specific antibodies can be used to analyze subtle changes in the relative abundance of different forms of transferrin potentially associated with a pathological process. Recently, the authors of this study were able to obtain and characterize highly specific single-domain antibodies (nanobodies) that predominantly recognize the iron-saturated (holo-Tf) or iron-unsaturated (apo-Tf) form of transferrin. In this work, under conditions closer to physiological than in the previous experiments, we further demonstrated that these unique nanobodies have extremely high differential binding specificity for different forms of Tf in different human biological fluids. Using these nanobodies, we were able to analyze for the first time relative abundance of the transferrin forms in urine samples from the patients with bladder cancer (BC). We have shown that increase in the concentration of total Tf in the urine samples normalized for creatinine is associated with the degree of progress and growth of malignancy of BC. In the samples of healthy donors and in the early stages of BC (G1), Tf is detected in much smaller amounts (compared to the later stages) and only with additional concentration of the studied samples. For most of the studied urine samples from the BC patients, it is expected (as previously shown in the case of Tf in the blood of terminal ovarian cancer patients) that the concentration of apo-Tf is clearly higher than holo-Tf, especially in the case of the most advanced muscle-invasive BC. It was a surprise for us that approximately equal amounts of apo-Tf and holo-Tf were found in the urine samples of some patients with BC. We hypothesized that the holo-Tf fraction in this case could be largely represented by the "secondary complexes" formed by apo-Tf in combination with ions other than Fe3+, which accumulate in the urine of some cancer patients and are able to bind to apo-Tf, changing its conformation towards holo-Tf. By using inductively coupled plasma mass spectroscopy (ICP-MS), we obtained first results confirming our hypothesis. Preparation of the holo-Tf in these urine samples was found to be highly enriched in zinc and nickel. Also, relative enrichment in cadmium has been observed in this preparation, but at much lower concentrations. The obtained data indicate that the used nanobody, while recognizing predominantly the iron-saturated form of transferrin (holo-Tf), is also capable of binding transferrin in association with other metal ions that are different from iron. This ability could potentially open up new possibilities for investigation of relative abundance of various metal ions in association with transferrin in human biological fluids in normal and pathological conditions.

The influence of various morphological, anatomical, genetic and other factors on the local recurrence-free survival of patients who have undergone different renal cell cancer (RCC) treatment is still a rather complex, ambiguous and controversial issue for practicing oncourologists. This review evaluates the effect of several factors on both recurrence-free survival and local recurrence-free survival. The review includes articles, clinical cases, literature reviews, and meta-analyses highlighting the analysis of independent and interrelated predisposing factors for developing local recurrence of RCC from 1984 to 2020. The PubMed, Web of Science, and Scopus databases were searched in English, Spanish, and German. A review of the literature showed the role of the following indices in the local recurrence RCC: microvascular invasion ( p  = 0.001), tumor necrosis ( p  = 0.0001), high malignancy (Fuhrman III or IV) (HR = 38.3, 95% CI 3.1-467, p  = 0.004) as histological factors, tumor size as an anatomical factor. Thus, the authors state that every centimeter of the tumor increases the risk of local recurrence ( p  < 0.05). A group from the Mayo Clinic showed the equivalence of different treatment methods in local RCC recurrence. Thus, in the group of patients with cT1a stage kidney cancer, the 5-year local recurrence-free survival rates were 97.7% (96.7-98.6), 95.9% (92.3-99.6), and 95.9% (92.3-99.6) for renal resection, RFA, and cryoablation, respectively. Surgical margin status is the most studied and controversial marker of local renal cell carcinoma recurrence. Researchers found a direct effect of PSM on the risk of local RCC recurrence ( p  < 0.01). The personalized approach with the search and evaluation of predisposing factors for the local recurrence, as well as further selection of the most optimal treatment, will allow oncourologists to improve both the effectiveness of primary treatment and the recurrence-free survival of patients.

Bones are the fourth most frequent site of metastasis from malignant tumors, including breast cancer, prostate cancer, melanoma, etc. The bioavailability of bone tissue for chemotherapy drugs is extremely low. This requires a search for new approaches of targeted drug delivery to the tumor growth zone after surgery treatment. The aim of this work was to develop a method for octacalcium phosphate (OCP) bone graft functionalization with the cytostatic drug cisplatin to provide the local release of its therapeutic concentrations into the bone defect. OCP porous ceramic granules (OCP ceramics) were used as a platform for functionalization, and bisphosphonate zoledronic acid was used to mediate the interaction between cisplatin and OCP and enhance their binding strength. The obtained OCP materials were studied using scanning electron and light microscopy, high-performance liquid chromatography, atomic emission spectroscopy, and real-time PCR. In vitro and in vivo studies were performed on normal and tumor cell lines and small laboratory animals. The bioactivity of initial OCP ceramics was explored and the efficiency of OCP functionalization with cisplatin, zoledronic acid, and their combination was evaluated. The kinetics of drug release and changes in ceramics properties after functionalization were studied. It was established that zoledronic acid changed the physicochemical and bioactive properties of OCP ceramics and prolonged cisplatin release from the ceramics. In vitro and in vivo experiments confirmed the biocompatibility, osteoconductivity, and osteoinductivity, as well as cytostatic and antitumor properties of the obtained materials. The use of OCP ceramics functionalized with a cytostatic via the described method seems to be promising in clinics when primary or metastatic tumors of the bone tissue are removed.

Since an extensive genome research has started, basic principle "one gene-one protein-one function" was significantly revised. Many proteins with more than one function were identified and characterized as "moonlighting" proteins, which activity depend not only on structural peculiarities but also on compartmentation and metabolic environment. It turned out that "housekeeping" glycolytic enzymes show important moonlight functions such as control of development, proliferation, apoptosis, migration, regulation of transcription and cell signaling. Glycolytic enzymes emerged very early in evolution and because of the limited content of genomes, they could be used as ancient regulators for intercellular and intracellular communication. The multifunctionality of the constitutively expressed enzymes began to serve cancer cell survival and growth. In the present review we discuss some moonlight functions of glycolytic enzymes that important for malignant transformation and tumor growth., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shegay, Shatova, Zabolotneva, Shestopalov and Kaprin.)

We evaluated antitumor efficacy of photodynamic therapy of murine Ehrlich carcinoma and rat sarcoma M-1 with new photosensitizers 13 1 -N-(4-aminobutyl)amydo chlorine e6 (1), 13 2 -(5-guanidylbutanamido)-chlorine e6 (2), and 13 2 -(5-biguanidylbutanamido)-chlorine e6 (3). The inhibiting effect of the photodynamic therapy was evaluated by the following parameters: tumor growth inhibition, complete regression of the tumors, and absolute growth rate of the tumor nodes in animals with the continued neoplasia growth. The criterion of cure was the absence of tumors up to 90 days after the therapy. It is shown that the studied photosensitizers have high antitumor activity in the photodynamic therapy of the Ehrlich carcinoma and sarcoma M-1., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

Gelatin methacryloyl (GelMA) has recently attracted increasing attention. Unlike other hydrogels, it allows for the adjustment of the mechanical properties using such factors as degree of functionalization, concentration, and photocrosslinking parameters. In this study, GelMA with a high degree of substitution (82.75 ± 7.09%) was synthesized, and its suitability for extrusion printing, cytocompatibility, and biocompatibility was studied. Satisfactory printing quality was demonstrated with the 15% concentration hydrogel. The high degree of functionalization led to a decrease in the ability of human adipose-derived stem cells (ADSCs) to adhere to the GelMA surface. During the first 3 days after sowing, proliferation was observed. Degradation in animals after subcutaneous implantation was slowed down.

Uveal melanoma accounts for 80% of all ocular melanomas, and 30-60% of patients have metastases to the liver. A few patients are candidates for liver resection, and this disease is associated with poor prognosis. There are few data on optimal management of metastatic uveal melanoma. Isolated hepatic perfusion is a perspective method for regional treatment of inoperable metastatic liver lesions with uveal melanoma. We present a patient with uveal melanoma who underwent previous enucleation of the eye. Cancer progressed 15 years later as an isolated inoperable metastatic liver lesion. The patient underwent isolated liver perfusion with melphalan, hyperthermia and oxygenation. Subsequently, the patient received systemic therapy with pembrolizumab. Partial response was achieved 1 month after the procedure. There was no progression for 20 months after surgery under systemic therapy with pembrolizumab. Thus, isolated liver chemoperfusion with melphalan is advisable in these patients.

Objective: To analyze the influence of continued growth of glioblastoma between surgery and radiotherapy on subsequent survival., Material and Methods: Fractionation with a prescribed dose of 2 and 3 Gy was alternately applied using a pairwise modeling strategy in 140 patients with morphologically confirmed glioblastoma (grade 4). Early progression of disease between microsurgery and radiotherapy was diagnosed in 60 patients, and no tumor growth was noted in 80 patients., Results: The minimum period of early progression was 0.33 months, maximum - 4.27 months (median 1.1 (95.0% CI: 0.9-1.3)). The most significant predictors of early progression were resection quality ( p <0.0001), large residual tumor ( p =0.003) and no MGMT promoter methylation ( p =0.001). IDH1 status did not affect early progression. In residual tumor ≥1.2 cm 3 , the median period of early progression was 1.9 months ( n =70; 95% Cl: 1.3-2.5), <1.2 cm 3 - 3.5 months ( n =70; p =0.019). After resection of less than 76% of tumor, this value was 1.1 months ( n =28), ≥76% - 3.1 months ( n =112; p =0.006). Without tumor growth, the median overall survival was 33.41 months ( n =80; 95% Cl: 27.1-39.7), with early progression - 16.03 months ( n =60; 95% Cl: 13.5-18.6; p <0.0001). This predictor was significant for fractionation with a prescribed dose of 3 Gy ( p <0.0001) and standard radiotherapy (2 Gy; p =0.028). By December 2022, 26 out of 40 patients without early progression survived two years after treatment (3 Gy) (65%, median not reached). In case of fractionation with a prescribed dose of 2 Gy, 20 patients survived this period (50%, median reached)., Conclusion: Almost half of patients with newly diagnosed glioblastoma develop early progression between microsurgery and radiotherapy. Therefore, patients with and without early progression should be probably assigned to different prognostic groups regarding overall survival.

Objective: To evaluate the effectiveness of ICG angiography in patients with papillary thyroid cancer (PTC) undergoing transoral endoscopic thyroidectomy (TOETVA) and selective neck dissection (level VI)., Material and Methods: A retrospective analysis included 20 patients with PTC who underwent TOETVA with selective neck dissection (level VI) between September and December 2022. ICG was administered intravenously (5 mg ´ 3 times). We analyzed parathyroid glands by visual examination and ICG angiography. Fluorescence of all glands was assessed., Results: Twenty patients underwent ICG angiography during TOETVA. A total of 68 parathyroid glands were identified. Only 76.5% (52/68) of parathyroid glands were identified at initial visual examination. ICG angiography additionally localized 12 glands that improved detection to 94.1% (64/68). At least one well-vascularized parathyroid gland was demonstrated by ICG angiography in 16 patients. In all these patients, serum parathyroid hormone was normal in 1 and 10 days after surgery. Two out of four patients who failed to identify a well-vascularized parathyroid gland developed transient hypoparathyroidism. There were no intraoperative and postoperative complications associated with ICG angiography., Conclusion: ICG angiography was simple, safe and effective for better identification and preservation of parathyroid glands in patients with PTC undergoing TOETVA. This method was valuable for assessing the viability and function of parathyroid glands and predicting postoperative hypocalcemia.

Isolated hepatic perfusion is one of the possible approaches for unresectable liver metastases of uveal melanoma. This technique is rare in modern oncology because of extremely difficult technique and high risk of intra- and postoperative complications. Thus, minimizing surgical trauma and increasing safety and reproducibility of this technique are important. There were 36 procedures of isolated «open» hepatic perfusion. The authors describe the first experience of endovascular hepatic perfusion. Advantages and clinical prospects of this method are shown.

Primary liver cancer and colorectal cancer liver metastases are among the leading causes of cancer-related mortality worldwide. Surgery is one of the main methods of treatment to achieve the best results in overall and recurrence-free survival. The main objectives in this surgery are preoperative planning, assessment of functional viability of liver parenchyma and total resection with low complication rate. Post-resection liver failure is one of the most formidable and often fatal complication following functional failure of liver remnant. Thus, preoperative assessment of liver functional reserves is a necessary step for adequate selection of patients and safe surgery. Passive liver tests, such as biochemical parameters or clinical scales, do not accurately reflect the actual functional component of liver parenchyma. The most accurate method is dynamic quantitative test of liver, such as indocyanine green clearance. The authors discuss the practical aspects of preoperative assessment of liver functional reserves using indocyanine green, as well as the concept and technical foundations of fluorescent imaging in hepatobiliary surgery.

Objective: To investigate the impact of resection quality on subsequent survival of patients with glioblastoma., Material and Methods: There were 141 patients with morphologically confirmed glioblastoma (grade 4). Fractionation with the prescribed dose of 2 and 3 Gy was alternately used (pairwise modeling strategy). Total resection was performed in 29.8% of patients (EOR: 100%; n =42), subtotal - 56.7% (EOR: 70-99%; n =80). Extent of resection 1-69% was registered in 19 patients (13.5%)., Results: As of December 2022, 124 out of 141 patients (87.9%) were diagnosed with primary progression, 101 (71.6%) ones died. We analyzed the threshold role of EOR. The most informative level was 70% ( p =0.002). EOR 100% was followed by median overall survival about 32.2 months (95% Cl: 15.3-49.1), EOR 70-99% - 21.3 months (95% Cl: 15.1-27.5), EOR 1-69% - 10.3 months (95% Cl: 3.8-16.9; p =0.003). Fractionation mode with the prescribed dose of 3 Gy partially eliminated significance of EOR ( p =0.148) in contrast to standard fractionation ( p =0.015). Tumor growth in the interval between surgery and radiotherapy (REP) reduces significance of EOR ( p =0.042). Inclusion of second-line therapy with bevacizumab in multivariate analysis model (OR=0.488; p =0.002) makes EOR less significant (OR=0.749; p =0.085) in contrast to REP (OR=2.482; p <0.0001)., Conclusion: To date, the principle of maximum safe resection remains fundamental in neurosurgery. EOR about 70% is sufficient regarding overall survival, but total resection should be sought if possible.

The aim of the study was to compare type I collagen-based and methacryloyl gelatin-based (GelMA) hydrogels by their ability to form hyaline cartilage in animals after subcutaneous implantation of scaffolds., Materials and Methods: Chondrocytes were isolated from the costal cartilage of newborn rats using 0.15% collagenase solution in DMEM. The cells was characterized by glycosaminoglycan staining with alcian blue. Chondrocyte scaffolds were obtained from 4% type I porcine atelocollagen and 10% GelMA by micromolding and then implanted subcutaneously into the withers of two groups of Wistar rats. Histological and immunohistochemical studies were performed on days 12 and 26 after implantation. Tissue samples were stained with hematoxylin and eosin, alcian blue; type I and type II collagens were identified by the corresponding antibodies., Results: The implanted scaffolds induced a moderate inflammatory response in both groups when implanted in animals. By day 26 after implantation, both collagen and GelMA had almost completely resorbed. Cartilage tissue formation was observed in both animal groups. The newly formed tissue was stained intensively with alcian blue, and the cells were positive for both types of collagen. Cartilage tissue was formed among muscle fibers., Conclusion: The ability of collagen type I and GelMA hydrogels to form hyaline cartilage in animals after subcutaneous implantation of scaffolds was studied. Both collagen and GelMA contributed to formation of hyaline-like cartilage tissue type in animals, but the chondrocyte phenotype is characterized as mixed. Additional detailed studies of possible mechanisms of chondrogenesis under the influence of each of the hydrogels are needed., Competing Interests: Conflicts of interest. The authors claim that there are no conflicts of interest.

(1) Background: There are no reliable and widely available markers of functional iron deficiency (FID) in cancer. The aim of the study was to evaluate the role of transferrin (Tf) as a marker of cancer of the ovary (CrO) and related FID. (2) Methods: The study groups consisted of 118 patients with CrO and 69 control females. Blood serum iron status was determined on a Beckman Coulter AU (USA) analyzer. Tf quantification was performed by immunoturbidimetry. The relative contents of apo- and holo-Tf (iron-free and iron-saturated Tf, respectively) were determined in eight patients and a control female by immunochromatographic analysis based on the use of monoclonal single-domain antibodies (nanobodies). (3) Results: Four groups of patients with different iron statuses were selected according to ferritin and transferrin saturation values: absolute iron deficiency (AID) (n = 42), FID (n = 70), iron overload (n = 4), normal iron status (n = 2). The groups differed significantly in Tf values (p < 0.0001). Lower values of Tf were associated with FID. Furthermore, FID is already found in the initial stages of CrO (26%). Immunosorbents based on nanobodies revealed the accumulation of apo-Tf and the decrease in holo-Tf in patients with CrO. (4) Conclusions: Tf may be a promising tool for diagnosing both CrO and associated FID.

Transfer of regenerative approaches into clinical practice is limited by strict legal regulation of in vitro expanded cells and risks associated with substantial manipulations. Isolation of cells for the enrichment of bone grafts directly in the Operating Room appears to be a promising solution for the translation of biomedical technologies into clinical practice. These intraoperative approaches could be generally characterized as a joint concept of tissue engineering in situ. Our review covers techniques of intraoperative cell isolation and seeding for the creation of tissue-engineered grafts in situ, that is, directly in the Operating Room. Up-to-date, the clinical use of tissue-engineered grafts created in vitro remains a highly inaccessible option. Fortunately, intraoperative tissue engineering in situ is already available for patients who need advanced treatment modalities.

Numerous clinical studies have shown a wide clinical potential of mesenchymal stromal cells (MSCs) application. However, recent experience has accumulated numerous reports of adverse events and side effects associated with MSCs therapy. Furthermore, the strategies and methods of MSCs therapy did not change significantly in recent decades despite the clinical impact and awareness of potential complications. An extended understanding of limitations could lead to a wider clinical implementation of safe cell therapies and avoid harmful approaches. Therefore, our objective was to summarize the possible negative effects observed during MSCs-based therapies. We were also aimed to discuss the risks caused by weaknesses in cell processing, including isolation, culturing, and storage. Cell processing and cell culture could dramatically influence cell population profile, change protein expression and cell differentiation paving the way for future negative effects. Long-term cell culture led to accumulation of chromosomal abnormalities. Overdosed antibiotics in culture media enhanced the risk of mycoplasma contamination. Clinical trials reported thromboembolism and fibrosis as the most common adverse events of MSCs therapy. Their delayed manifestation generally depends on the patient's individual phenotype and requires specific awareness during the clinical trials with obligatory inclusion in the patient' informed consents. Finally we prepared the safety checklist, recommended for clinical specialists before administration or planning of MSCs therapy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://sci.amegroups.com/article/view/10.21037/sci-2022-025/coif). The authors have no conflicts of interest to declare., (2022 Stem Cell Investigation. All rights reserved.)

The role of lactic acid (lactate) in cell metabolism has been significantly revised in recent decades. Initially, lactic acid was attributed to the role of a toxic end-product of metabolism, with its accumulation in the cell and extracellular space leading to acidosis, muscle pain, and other adverse effects. However, it has now become obvious that lactate is not only a universal fuel molecule and the main substrate for gluconeogenesis but also one of the most ancient metabolites, with a signaling function that has a wide range of regulatory activity. The Warburg effect, described 100 years ago (the intensification of glycolysis associated with high lactate production), which is characteristic of many malignant tumors, confirms the key role of lactate not only in physiological conditions but also in pathologies. The study of lactate's role in the malignant transformation becomes more relevant in the light of the "atavistic theory of carcinogenesis," which suggests that tumor cells return to a more primitive hereditary phenotype during microevolution. In this review, we attempt to summarize the accumulated knowledge about the functions of lactate in cell metabolism and its role in the process of carcinogenesis and to consider the possible evolutionary significance of the Warburg effect.

The use of radiation with low and high linear energy transfer (LET) in the same treatment regimen is promising in terms of increasing the efficiency and reducing the severity of radiation complications. Here we studied combined effect of protons (LET≈3 keV/μm) and heavy recoils (HR) induced by 14.5 MeV neutrons (LET≈290 keV/μm) on B14-150 fibrosarcoma cells. Comparison of the 4 irradiation schemes with different high-LET/low-LET dose ratios and the irradiation sequences revealed higher effectiveness of the combined action in the HR→protons sequence and with increasing HR dose contribution to 40% of the total dose. The observed effects were due to differences in the recovery of damages induced in cells by radiations with low and high LET., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

Diabetic foot ulcer (DFU) is one of the most severe complications of diabetes mellitus, often resulting in a limb amputation. A cell-based therapy is a highly promising approach for an effective DFU treatment. However, there is no consensus regarding the most effective cell type for DFU treatment. Various cell types contribute to chronic wound healing via different mechanisms. For example, application of keratinocytes can stimulate migration of native keratinocytes from the wound edge, while mesenchymal stem cells can correct limb ischemia. To assess the effectiveness of a certain cell type, it should be administered as a monotherapy without other substances and procedures that have additional therapeutic effects. In the present review, we described therapeutic effects of various cells and provided an overview of clinical studies in which stem and somatic cell-based therapy was administered as a monotherapy. Topical application of somatic cells contributes to DFU healing only, while injection of mesenchymal stem cells and mononuclear cells can break a pathophysiological chain leading from insufficient blood supply to DFU development. At the same time, the systemic use of mesenchymal stem cells carries greater risks. Undoubtedly, cell therapy is a potent tool for the treatment of DFU. However, it is vital to conduct further high-quality clinical research to determine the most effective cell type, dosage and way of administration for DFU treatment. Ischemia, neuropathy and neuro-ischemia are underlying factors of diabetic foot ulcer. Stem and somatic cells monotherapy can improve chronic wound healing via different mechanisms., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A number of single-domain antibodies (nanobodies) obtained previously to major marker blood proteins were tested as tools to preprocess urine samples from patients with bladder cancer. Nanobody-based tools demonstrated unique possibilities for noninvasive diagnostic studies along with other conventional methods, such as electrophoresis and, in prospect, mass spectrometric analysis. A testing of 22 samples from bladder cancer patients showed that the development of bladder cancer is accompanied by an increase in the urine contents of major blood proteins, including those known as potential bladder cancer biomarkers. New nanobody-based immunosorbents allow both specific enrichment and specific removal of particular antigenic proteins and subproteomes associated with them from a biological fluid. The isolation of immune complexes from the urine of a particular patient is of particular interest. An initial study of the complexes showed not only increased contents of IgA and IgG at advanced stages of the disease, but also many other components, which provide potential biomarkers of the pathological process in a particular patient. It is intended to use the approaches proposed in this work in a future larger-scale study of urine samples from patients with bladder cancer at different stages of the disease in order to identify new promising biomarkers of bladder cancer.

Fast neutron therapy, which previously has demonstrated effective results, but along with a large number of complications, can again be considered a promising treatment method in the treatment of cancer. One of the ways of analyzing the relative biological efficiency and accurate biological dose of fast neutrons in body tissues is to improve the algorithms of computational biology and mathematical modeling. A high-performance computing code was written which allows to estimate in real-time mode the biological dose of the proton component from the action of neutron radiation with an energy of 14.8 MeV. A comparative analysis of the computing performance on various video cards was also performed., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

Photodynamic therapy (PDT) is an effective treatment for a number of solid malignancies. In this work, the antitumor efficacy of photodynamic therapy for murine B16 melanoma with intravenous administration of a new photosensitizer (PS) based on the chlorin e 6 conjugate with a prostate-specific membrane antigen (PSMA) was studied in vivo. We have previously published the data obtained in the first part of the study: the dynamics of PS accumulation in the tumor and surrounding tissues and the antitumor efficacy of the photodynamic therapy, which was evaluated by the regression parameters and morphological characteristics of the tumors-including by the complete regression of the tumors, the absolute growth rate of the tumors among the mice with continued tumor growth, and an increase in life expectancy compared to the control. The criterion for a complete cure was the absence of signs of tumor recurrence within 90 days after therapy. The conducted studies demonstrated the high efficiency of the new photosensitizer for the photodynamic therapy of B16 melanoma. This article presents a continuation of this work, including histological studies of the zones exposed to laser irradiation on the 21st day after treatment and an assessment of the therapeutic potential of photodynamic therapy for the destruction of tumor cells. Pathological studies in the zones of photodynamic exposure revealed that the effectiveness of the PDT depended on the PS dose and the laser irradiation parameters.

Red bone marrow and autologous bone tissue (bone fragments and bone chips) of the donor were harvested intraoperatively during autoplasty of talus bone defect. Titanium chips were obtained by grinding a fragment of a microporous titanium-coated hip arthroplasty (Zimmer). Bone marrow mononuclear cells were isolated in the operating room, and bone and titanium fragments were incubated with a suspension of mononuclear cells. The quality of revitalization was assessed by fluorescence microscopy and histological examination after culturing of adherent cells on the bone and titanium fragments. During culturing on bone chips, bone marrow mononuclear fraction cells demonstrated significantly higher metabolic activity than bone marrow cells (p=0.04). Mononuclear fraction cells were also capable of stable colonization of titanium fragments with the formation of composite tissue model., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

The development of technologies for using the Novac-11 pulsed electron accelerator in radiation therapy of animals with spontaneous neoplasms requires dosimetric and radiobiological studies. The studies were performed on cultured Chinese hamster V-79 fibroblasts after irradiation with 10 MeV electrons in a dose range up to 12 Gy and 60 Co γ-radiation. Chemical dosimeters FBX and Fricke were used as additional test-systems. The depth dose curves were measured and the maximum dose depth of the electron beam was determined in tissue-equivalent phantoms. Cell survival and the data of chemical dosimetric systems showed that the effects of electron irradiation did not differ from that of 60 Co γ-radiation. It was concluded that the use of Novac-11 in the therapy of animals with spontaneous neoplasms is advisable., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

The aim of this study was to verify the applicability of high-concentration collagen-based bioink with MSC (ADSC) and decellularized ECM granules for the formation of cartilage tissue de novo after subcutaneous implantation of the scaffolds in rats. The printability of the bioink (4% collagen, 2.5% decellularized ECM granules, derived via 280 μm sieve) was shown. Three collagen-based compositions were studied: (1) with ECM; (2) with MSC; (3) with ECM and MSC. It has been established that decellularized ECM granules are able to stimulate chondrogenesis both in cell-free and MSC-laden scaffolds. Undesirable effects have been identified: bone formation as well as cartilage formation outside of the scaffold area. The key perspectives and limitations of ECM granules (powder) application have been discussed.

The COVID-19 pandemic has served as a catalyst for a whole layer of scientific research, including in Russia, where, since 2020, international multicenter studies have been conducted on the impact of the coronavirus infection on the course of oncological diseases, as well as on the development and application of new clinical methods in oncology. In the years 2020-2022, new methods of nuclear medicine based on the targeted effect of ionizing radiation of radiopharmaceuticals began to be actively developed, in particular, new domestic radiopharmaceuticals (RPs) for diagnostics and therapy and methods of intra-arterial radioembolization developed by RPs with 90Y and 188Re of primary and metastatic tumors of various localization. New methods of radiation therapy have been introduced into clinical practice, including remote radiation therapy with "fast" neutrons, which makes it possible to overcome the resistance of a tumor to radiation and drug treatment. In addition, the search for and introduction into clinical practice of new approaches in the field of gene therapy and the use of oncolytic viruses continues. Platforms for complex pharmacogenomic analysis based on global knowledge and deep machine learning are being used in Russia, allowing for the precise selection of the most effective therapy. New multidisciplinary technologies are being developed., Competing Interests: The authors declare that they have no conflicts of interest., (© Pleiades Publishing, Ltd. 2022, ISSN 1019-3316, Herald of the Russian Academy of Sciences, 2022, Vol. 92, No. 4, pp. 456–463. © Pleiades Publishing, Ltd., 2022.Russian Text © The Author(s), 2022, published in Vestnik Rossiiskoi Akademii Nauk, 2022, Vol. 92, No. 8, pp. 722–730.)

This article presents a method of organ-preserving surgical treatment of laryngeal cancer, which has been developed and used since 1991 at the Tsyba Medical Radiological Research Center, Branch of the National Medical Research Center of Radiology of the Ministry of Health of Russia. The indications for this method are tumors affecting the middle part of the larynx, limiting its mobility, extending to the anterior commissure, laryngeal ventricle, vestibular fold, lower larynx and one arytenoid cartilage, but retaining mobility in the scooper-cricoid articulation., Objective: To increase the functional safety of the larynx and improve the quality of life of patients with laryngeal cancer by using the developed method of organ-preserving surgical intervention in combined treatment., Material and Methods: The study included 197 patients who were operated on by the same method for a primary tumor or in connection with a relapse of the disease. At the first stage, all primary patients underwent a course of radiation or chemoradiation therapy 40-50 Gy. In 78 patients with recurrent laryngeal cancer who underwent resection of the larynx, the previous treatment was carried out in the form of a full course of radiation or chemoradiation therapy with a above 60 Gy., Results: Wound healing by primary intention in patients with preoperative irradiation was observed in 92.4% of cases. With resections for a primary tumor, restoration of functions was observed in 115 (96.6%) patients, and with resections of recurrent tumors - in 71 (91%) patients. Three-year disease-free survival in these patients was 74.4%., Conclusion: The presented data showed the high efficiency of the method. This is evidenced by the course of the postoperative period, functional and oncological results are comparable, and in some cases exceed those of other researchers.

Materials and Methods: Experimental animals ( n  = 135) were divided into 5 groups: I - control ( n  = 10); II - 2IR ( n  = 35; 2 Gy); III - 2IR + LP-PRP + IGF-1 ( n  = 30); IV - 2IR + LP-PRP ( n  = 30); V - LP-PRP ( n  = 30)., Results: Electron irradiation reduces the number of germ cells in comparison with the control group. After injection of LP-PRP + rhIGF-1 significantly increased the number of germ cells, Sertoli and Leydig cells, the height of germinal epithelium, area and diameter of seminiferous tubules., Conclusion: LP-PRP + rhIGF-1 has a normalizing effect on structural and functional disorders of the testis caused by electron irradiation.

We studied the possibility of using sodium deoxyribonucleate (Derinat) for improving the efficiency of co-transplantation of mesenchymal (MSC) and hematopoietic stem cells (HSC) to female F1(CBA×C57BL/6) mice with bone marrow aplasia caused by exposure to γ-radiation. It was found that immunomodulator Derinat enhanced the effect of co-transplantation, in particular, triple post-irradiation administration of Derinat accelerated hematopoiesis recovery judging from the parameters of peripheral blood, total cellularity of the bone marrow and spleen, and animal survival. Single or double administration of Derinat prior to irradiation was ineffective. The optimal result was obtained when the following scheme was applied: MSC→HSC with an interval of 48 h starting during the first hours after irradiation and triple administration of Derinat (in 10-15 min, 3 and 7 days after irradiation) in a dose of 3 mg/mouse., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)