Oncology during the New Coronavirus Infection Pandemic.

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.

Kidney Injury Molecule 1 (KIM-1): a Multifunctional Glycoprotein and Biological Marker (Review).

KIM-1 (kidney injury molecule 1) is a transmembrane glycoprotein also known as HAVcr-1 and TIM-1 belongs to the T-cell immunoglobulin and mucin domain family (TIM) of proteins. TIM glycoproteins are presented on the immune cells and participate in the regulation of immune reactions. KIM-1 differs from other members of its family in that it is expressed not only by immunocompetent cells but epithelial cells as well. Cellular and humoral effects mediated by KIM-1 are involved in a variety of physiological and pathophysiological processes. Current understanding of the mechanisms determining the participation of KIM-1 in viral invasion, the immune response regulation, adaptive reactions of the kidney epithelium to acute ischemic or toxic injury, in progression of chronic renal diseases, and kidney cancer development have been presented in this review. Data of clinical researches demonstrating the association of KIM-1 with viral diseases and immune disorders have also been analyzed. Potential application of KIM-1 as urinary or serological marker in renal and cardiovascular diseases has been considered.

On normalizing of urinary KIM-1 level to urine creatinine in patients with renal cell cancer.

KIM-1 (kidney injury molecule 1), a marker of acute kidney injury, is produced by epithelial cells of renal proximal tubules. Elevated KIM-1 levels in urine and plasma are associated with renal cell carcinoma (RCC). The aim of this study was to compare the significance of non-normalized uKIM-1 values and those normalized to urine creatinine, as urinary biomarkers in RCC. The uKIM-1, urine creatinine and their ratio (uKIM-1/Cre) were studied in 118 RCC patients and 58 apparently healthy subjects. The median of uKIM-1 in the healthy group was 0.71 ng/ml (1st and 3rd quartiles were 0.35 and 1.23, respectively) and in RCC patients it was 2.36 (1.43; 5.93) ng/ml. The medians of uKIM-1/Cre were 0.77 (0.49; 1.18) and 2.42 (1.41; 4.61) ng/mgCre, respectively. Stage I RCC is statistically significantly different from stages II-III and stage IV using uKIM-1/Cre values (p = 0.0056 and p = 0.0012, respectively); using uKIM-1 values significant differences occur only when comparing stages I and IV (p = 0.015). In both healthy individuals and RCC patients, uKIM-1/Cre levels were slightly lower in subgroups younger than 50 years than in subgroups older than 50 years, whereas a similar trend was observed for uKIM-1 only in patients. In healthy men and male patients, uKIM-1 levels were higher than in the corresponding groups of women (the differences were not statistically significant), but the use of uKIM-1/Cre values eliminated the gender differences. A high correlation was found between the concentrations of uKIM-1 and urine creatinine in three healthy subjects followed up for 3 weeks (Spearman's correlation coefficients were 0.758, 0.825 and 0.933, respectively). The data obtained are clear evidence of the need for normalization uKIM-1 to urine creatinine in RCC patients.

Primary 3D Culture of Human Thyroid Follicle-Like Structures in Platelet Lysate-Based Gel.

The results of 3D culturing of human thyroid follicle-like structures in a gel based on platelet lysate at the gel-air interface are presented. During culturing up to 4 months, no new follicle-like structures were formed and none were destroyed. During the first 2 months, most follicle-like structures increased in size; then, their grown decelerated, but they retained viability. Ki-67+ cells were observed in the majority of follicle-like structures. Most of them produced thyroglobulin. Follicle-like structures get closer, the number of contacts between them increased, and cluster appeared. Thus, the developed 3D culturing system in a gel based on platelet lysate is an adequate approach for maintaining structure and functional activity of human follicle-like structures in vitro for at least 2 months.

Physicochemical and biological characteristics of chitosan/κ-carrageenan thin layer-by-layer films for surface modification of nitinol.

Thin films based on the natural polysaccharides κ-carrageenan (Carr) and chitosan (Chit) were formed by layer-by-layer deposition technique. Surface topography and mechanical characteristics (Young's modulus, adhesion strength) of the polymer films with different number of layers were determined using various modes of atomic force microscopy (AFM). Polymer films were used to deposit on the surface of nitinol (NiTi) plates. The creation of polysaccharide coatings on nitinol led to a change in surface properties, such as hydrophilicity and root mean square roughness. in vitro cytotoxicity assay for nitinol plates with and without polymer coating by the MG-63 osteoblast-like cell line was conducted and was shown that all the studied samples are not toxic. A decrease in cytotoxicity for samples with a polymer film consisting of 4 layers of chitosan and carrageenan was shown as compared to an uncoated nitinol plates.

Insitu magnesium calcium phosphate cements formation: From one pot powders precursors synthesis to in vitro investigations.

Calcium phosphate cements are of great interest for researchers and their applications in medical practice expanded. Nevertheless, they have a number of drawbacks including the insufficient level of mechanical properties and low degradation rate. Struvite (MgNH4PO4) -based cements, which grew in popularity in recent years, despite their neutral pH and acceptable mechanical performance, release undesirable NH4 + ions during their resorption. This issue could be avoided by replacement of ammonia ions in the cement liquid with sodium, however, such cements have a pH values of 9-10, leading to cytotoxicity. Thus, the main goal of this investigation is to optimize the composition of cements to achieve the combination of desirable properties: neutral pH, sufficient mechanical properties, and the absence of cytotoxicity, applying Na2HPO4-based cement liquid. For this purpose, cement powders precursors in the CaO-MgO-P2O5 system were synthesized by one-pot process in a wide composition range, and their properties were investigated. The optimal performance was observed for the cements with (Ca + Mg)/P ratio of 1.67, which are characterized by newberyite phase formation during setting reaction, pH values close to 7, sufficient compressive strength up to 22 ± 3 MPa (for 20 mol.% of Mg), dense microstructure and adequate matrix properties of the surface. This set of features make those materials promising candidates for medical applications.

[Endoscopic closure of septal perforation in children with a vascularized flap on the ethmoidal artery]. / Éndoskopicheskoe zakrytie perforatsii peregorodki nosa u detei vozvratnym transseptal'nym loskutom na vetviakh reshetchatykh arterii.

In the article, a new method of septal perforation closing in children with a flap on the ethmoid artery under endoscopic control is described. Unlike conventional endoscopic procedures described technique allows to close the perforation bilaterally. Using the author's technique, 6 children with septal perforation aged from 13 to 17 years (mean age 15.2±2.1) were operated on. In all patients, the perforation was completely closed. Thus, the method has shown high efficiency and safety, which allows it to be widely used in pediatric practice.

Elimination of a Viscumin-Ferromagnetic Nanoparticles Conjugate from the Tumor Nodule in Mice.

External magnetic field is characterized by low toxicity and existence of magnetic properties, which contributes to an interest in the development of products from ferromagnetic nanoparticles (FNP) for antitumor therapy. Previously we synthesized a conjugate of ferromagnetic magnetite nanoparticles and viscumin (mistletoe lectin I, MLI), which exhibits the antitumor activity. Studying the pharmacological properties of this conjugate (FNP-MLI) was directed to the evaluation of FNP-MLI elimination after intratumor injection in mice. The elimination rate of FNP-MLI was much lower than that of native plant MLI. The presence of FNP-MLI was not accompanied by undesired changes in the tumor tissue. The use of a FNP-MLI conjugate allowed us to prolong the time of MLI presence in tissues without increasing the dose of exogenous lectin. These features contribute to the prolongation of an immunomodulatory effect of MLI.

Analysis of Reparative Activity of Platelet Lysate: Effect on Cell Monolayer Recovery In Vitro and Skin Wound Healing In Vivo.

Platelet lysate prepared from donor platelet concentrate and pooled according to a developed technique stimulates migration of multipotent mesenchymal stromal cells of the human adipose tissue and promotes healing of the monolayer defect in cultures of human fibroblasts and multipotent mesenchymal stromal cells in vitro in concentrations close those of fetal calf serum (5-10%). Lysate of platelets from platelet-rich rat blood plasma stimulated healing of the skin defect by promoting epithelialization and granulation tissue formation. The regenerative properties of platelet lysate in vivo increased with increasing its concentration.

Some Physical, Chemical, and Biological Parameters of Samples of Scleractinium Coral Aquaculture Skeleton Used for Reconstruction/Engineering of the Bone Tissue.

Physical and chemical (phase and chemical composition, dynamics of resorption, and strength properties), and biological (cytological compatibility and scaffold properties of the surface) properties of samples of scleractinium coral skeletons from aquacultures of three types and corresponding samples of natural coral skeletons (Pocillopora verrucosa, Acropora formosa, and Acropora nobilis) were studied. Samples of scleractinium coral aquaculture skeleton of A. nobilis, A. formosa, and P. verrucosa met the requirements (all study parameters) to materials for osteoplasty and 3D-scaffolds for engineering of bone tissue.

Criteria of biocompatibility of materials for bone defect repair.

We analyzed and systematized the criteria of biocompatibility of materials intended for reconstruction of bone defects on the basis of previously studied synthetic, natural, and composite biomaterials (carbonate hydroxyapatite, calcium phosphate cement, silica, natural corals, freshwater pearls, chitosan/carbonate hydroxyapatite) in the model of subcutaneous implantation to small laboratory animals.

Scleractinium coral aquaculture skeleton: a possible 3D scaffold for cell cultures and bone tissue engineering.

Cytocompatibility of 5 coral aquaculture skeleton species derived from two families (Acroporidae and Pocilloporidae) was studied over the course of in vitro culturing in continuous human fibroblast culture by the MMT test. Biocompatibility and capacity of scaffold to "transfer" cell cultures (specifically, multipotent mesenchymal stromal cells) to sites of implantation were studied in vivo by subcutaneous implantation of skeletal fragments to rats. All coral skeleton aquaculture specimens were cytocompatible (nontoxic and with surface matrix characteristics satisfactory for cells), biocompatible, and could be tried as 3D matrices for bone tissue engineering.

Human platelet lysate as a promising growth-stimulating additive for culturing of stem cells and other cell types.

We compared the composition and biological activity of fetal calf serum and platelet lysate from donor platelet concentrate. In platelet lysate, the concentrations of alkaline phosphatase, lactate dehydrogenase, creatinine, and mineral metabolism parameters were lower, while parameters of lipid and protein metabolism were higher than in fetal calf serum. The concentrations of growth factors (platelet-derived (AA, AB, BB), vascular endothelial, insulin-like, and transforming growth factor ß) in platelet lysate 1.7-148.7-fold surpassed the corresponding parameters in fetal calf serum. After replacement of fetal calf serum with platelet lysate in the culture medium (0, 25, 50, 75, and 100%), the count of multipotent mesenchymal stromal cells on day 7 (in comparison with day 1) increased by 154.8, 206.6, 228.2, 367.7, and 396.5%, respectively. Thus, platelet lysate can be an adequate non-xenogenic alternative for fetal calf serum.

In vitro study of matrix surface properties of porous granulated calcium phosphate ceramic materials made in Russia.

We performed in vitro screening of monophasic (hydroxyapatite, beta-tricalcium phosphate, carbonate-substituted hydroxyapatite with 0.59 and 5.9 wt% substitution with CO(3)(2-)) and biphasic (hydroxyapatite-tricalcium phosphate with various percentage of the components 80/20, 60/40, 20/80, silicon-substituted hydroxyapatite with 0.79 wt% SiO(2)) porous granulated ceramics composed of calcium phosphate powders synthesized by methods of heterophasic interaction of reagents and precipitation from aqueous solutions using MTT test and cultured human fibroblasts. Acute toxicity of materials (24-h incubation with cell culture) and matrix properties (3, 5, 7, 14, 18, 21, 28 days in culture) were evaluated. We selected a batch of materials obtained by precipitation from aqueous solutions, which were non-toxic and were characterized by good matrix properties (for cells). Biphasic ceramics with hydroxyapatite-tricalcium phosphate ratio of 80/20 exhibited best characteristics, and ceramics on the basis of silicon-substituted hydroxyapatite showed moderate characteristics.

Study of in vivo biocompatibility and dynamics of replacement of rat shin defect with porous granulated bioceramic materials.

Biocompatibility of porous granulated bioceramic materials (hydroxyapatite, beta-tricalcium phosphate, hydroxyapatite-b-tricalcium phosphate complex (80:20 wt%), carbonate-containing hydroxyapatite, and silicon-containing hydroxyapatite) was shown in a subcutaneous test on BDF1 mice. Dynamic (up to 8 months) observation showed gradual replacement of the granular substance with de novo forming bone tissue with hemopoiesis foci on a model of fenestral defect in the shin bone in Wistar rats. By the rate of resorption, the materials rank as follows: silicon-containing hydroxyapatite

Study of growth parameters and potentialities of differentiation of multipotent mesenchymal stromal cells from rat bone marrow in vitro.

The dynamics of growth and proliferative activity of the population of multipotent mesenchymal stromal cells from rat bone marrow was studied during 7 passages. The efficiency of colony formation, the morphology of multipotent mesenchymal stromal cells, and the possibility of spontaneous and induced differentiation were studied. The rat bone marrow fibroblast-like multipotent mesenchymal stromal cells are capable of clonal growth; their proliferative activity and the yield remained high until passage 4, but then decreased. Induction of osteo- or adipogenic differentiation of bone marrow multipotent mesenchymal stromal cells increased the percentage of morphologically modified cells carrying specific markers.

[Application of cell technologies to tissue defect closure in oncology].

In vivo and in vitro experiments on the application of cell technologies to tissue defect closure were conducted; autologic mesenchymal stem cells on 3-demensional matrices were used. The authors analyze the results of the application of bioengineering tissue equivalents for the closure of soft tissue and upper airway defects after extensive resections performed in 52 oncological patients. Tissue equivalents with stem cells provide engraftment and long-term graft functioning; they also modify wound surface, thus stimulating wound epithelization. In this study the application of tissue equivalents led to wound healing and functional recovery in 87% of patients.

[The radiobiologycal approaches of the individual prognosis of the radiotherapy efficacy of the tumor deseases].

The results of several years standing investigations about the develop of the way to the individual prognosis of tumour sensitivity to radiotherapy are brought. The initial level of proliferative activity of different tumour types of individual patients--carcinoma of oropharingeal zone, stomach, oesophagys, rectum, glioblastoma have been studied. It was shown that for the several tumours the high initial level of proliferative activity is the indication of good prognosis. For the all tumours studied the significant decreasing of proliferative activity in the beginning of the radiation treatment is the good prognostic factor of tumour regression (decreasing of volume on 70-100%) or the strong damages of tumour tissue (III-IV grade of patomorphosis). The data of literature of last years are discussed and the proposal is that for the determination of prognostic factors the multiparameter analysis is need.