[Information support for the bioresource collection: a biological information system «NeuroOnc¼]. / Informatsionnaya podderzhka bioresursnoi kollektsii: biologicheskaya informatsionnaya sistema «NeiroOnk¼.

The manuscript is devoted to development of information support system for a bioresource collection - biological information system «NeuroOnc¼. Architecture and main functions of system are presented. This system was formed in the project «Development of bioresource collection of tumors of the human nervous system with molecular genetic certification for personalized treatment of patients with neuro-oncological diseases¼. The purpose of this project was not only formation of bioresource collection, but also development of various molecular genetic methods for analysis of biospecimens in context of clinical researches. Biological information systems created to support the work of bioresource collections in hospitals should become a natural part of information infrastructure. Information support of bioresource collections cannot imply only «warehouse¼ functions. This system should have tools to support various scientific and clinical researches. Biological information systems can sometimes expand medical information systems but remain sufficiently autonomous. It is advisable to develop biological information systems in large specialized companies that can support their products for many years.

[Is it possible to detect surface antigen CD133 on patient-derived glioblastoma continuous cell cultures using fluorescent aptamers?] / Vozmozhna li detektsiya poverkhnostnogo antigena CD133 na perevivaemykh kul'turakh kletok glioblastomy patsientov s pomoshch'yu fluorestsentnykh aptamerov?

Theranostics combines diagnostics and therapeutic exposure. Regarding glioblastomas, theranostics solves the problem of detecting and destroying tumor stem cells resistant to irradiation and chemotherapy and causing tumor recurrence. Transmembrane surface antigen CD133 is considered as a potential marker of tumor stem cells. OBJECTIVE: To detect CD133 in patient-derived glioblastoma continuous cell cultures using fluorescence microscopy and modified aptamers (molecular recognition elements) anti-CD133. MATERIAL AND METHODS: To detect CD133, we used mousey fluorescence monoclonal antibodies anti-CD133 MA1-219, FAM-modified DNA aptamers anti-CD133 AP-1-M and Cs5. Non-aptamer DNA oligonucleotide NADO was used as a negative control. Detection was performed for three samples of patient-derived glioblastoma continuous cell cultures coded as 1548, 1721 and 1793. RESULTS: MA1-219 antibodies brightly stained cell culture 1548, to a lesser extent - 1721. There was diffuse staining of cell culture 1793. Cs5-FAM aptamer stained cells in a similar way, but much weaker. AP-1-M-FAM aptamer interacted with cells even weaker and diffusely stained only cell culture 1793. Non-aptamer NADO did not stain cell culture 1548 and very weakly diffusely stained cell culture 1793. CONCLUSION: For both molecular recognition elements (MA1-219 antibody and Cs5 aptamer), 3 cell culture samples can be arranged in the following order possibly reflecting CD133 status decrease: strong signal for cell culture 1548, much weaker for 1721, even weaker for 1793. Only cell culture 1548 can be considered CD133 positive with combination of Cs5+ and NADO signals. Cell culture 1793 is CD133 false positive with combination of Cs5+ and NADO+ signals.

[National and world experience in functioning of centers for collective use of biological resource collections of tumors of the central nervous system]. / Analiz mirovogo i otechestvennogo opyta funktsionirovaniya tsentrov kollektivnogo pol'zovaniya bioresursnymi kollektsiyami opukholei tsentral'noi nervnoi sistemy.

Collective use center is an organization or structural unit with unique resource providing access to this resource for internal and third-party users. Collective use centers are a relatively new phenomenon in bioresource collections, especially collections of human biological material due to some ethical and legal issues. At the same time, the demand for human biological material continues to grow in fundamental and applied researches. The collective use center «Bioresource collection of tissues and cell cultures of tumors of the human nervous system for fundamental and applied researches¼ has worked since October 14, 2022. This center has access to unique collection of the Laboratory of Neurosurgical Anatomy and Conservation of Human Biological Tissues of the Burdenko Neurosurgical Center. OBJECTIVE: To analyze the experience of collective use center and biobank of the Burdenko Neurosurgical Center compared to national and international data on functioning of collective use centers specializing in tumors of the human central nervous system. MATERIAL AND METHODS: We reviewed the PubMed and e-Library databases using the following keywords: core facilities brain tumors, repository of collective use brain tumors, biobank of CNS tumors, central nervous system tumor collection centers. We also analyzed the organizations registered on the portal of scientific and technical infrastructure of the Russian Federation. RESULTS: We analyzed 275 publications devoted to collective use centers and biobanks. These biobanks do not position themselves as collective use centers but actively realize biological material for researches. Structure of institutions presented on the portal of scientific and technical infrastructure of the Russian Federation is characterized. The collective use center «Bioresource collection of tissues and cell cultures of tumors of the human nervous system for fundamental and applied researches¼ has access to biobank of the Burdenko Neurosurgical Center. To date, the biobank contains more than 8478 aliquots of tumor tissue frozen at ultra-low temperature (-196°C) and obtained from 1993 patients. Considering available data, we established the basic principles of work in collective use centers with bioresource collections. CONCLUSION: Collective use centers with bioresource collections of tumors of the central nervous system are rare. There is only one collective use center organized at the Burdenko Neurosurgical Center on the portal of scientific and technical infrastructure of the Russian Federation. At the same time, there is an urgent need to increase their number and activity in Russia and other countries worldwide. You can use the resource of brain tumor collections by leaving a request on the official website of this organization in the «Collective use center¼ section.

[Covalently conjugated DNA aptamer with doxorubicin as in vitro model for effective targeted drug delivery to human glioblastoma tumor cells]. / Kovalentno kon"yugirovannyi DNK-aptamer s doksorubitsinom kak in vitro model' effektivnogo adresnogo vozdeistviya na opukholevye kletki glioblastomy cheloveka.

Targeted delivery of chemotherapeutic agents with aptamers is a very effective method increasing therapeutic index compared to non-targeted drugs. OBJECTIVE: To study the effectiveness of in vitro therapeutic effect of covalently conjugated GR20 DNA aptamer with doxorubicin on glioblastoma cells compared to reference culture of human fibroblasts. MATERIAL AND METHODS: A Sus/fP2 cell culture was obtained from glioblastoma tissue sample to analyze the effectiveness of conjugate. A linear culture of human dermal fibroblasts (mesenchymal stem cells) DF1 was used as a control. To assess antiproliferative activity of covalently conjugated GR20 aptamer with doxorubicin, we used the MTS test. The Cell Index was measured using the xCelligence S16 cell analyzer assessing viability of cell cultures by recording changes in real time. RESULTS: Human glioblastoma Sus/fP2 cells reduce own proliferative potential by 80% when exposed to doxorubicin (0.5 µM, 72 hours, MTS test), by 9% when exposed to GR20 aptamer (10 µM, 72 hours, MTS test) and by 26% when exposed to covalently conjugated DOX-GR20 (0.5 µM, 72 hours, MTS test). A long-term study of proliferative potential of Sus/fP2 cells on the xCelligence S16 analyzer revealed a significant decrease in the number of cells under the effect of doxorubicin and covalently conjugated DOX-GR20. Effectiveness of covalently conjugated DOX-GR20 is halved. GR20 aptamer at a concentration of 10 µM and its conjugate with doxorubicin DOX-GR20 at a concentration of 1 µM have no negative effect on cells of the control culture of DF1 fibroblasts, while doxorubicin is toxic for these cells. MTS test and xCelligence S16 cell analyzer found no decrease in metabolic activity of DF1 cells and their ability to proliferate. CONCLUSION: We established obvious antiproliferative effect of covalent conjugate DOX-GR20 on continuous human glioblastoma cell culture Sus/fP2 without toxic effect on the reference culture (dermal fibroblasts DF1).

[Genetic factors in degenerative disc disease]. / Rol' geneticheskikh faktorov v razvitii degenerativno-distroficheskogo porazheniya mezhpozvonkovykh diskov.

OBJECTIVE: To analyze available literature data on the role of genetic factors in degenerative disc disease. METHODOLOGY: We reviewed the PubMed, MEDLINE, Cohrane Library, e-Library databases using the following keywords: degenerative spine lesions, intervertebral disc herniation, pathogenesis, genetic regulation. RESULTS: Searching depth was 2002-2022. We reviewed 84 references. Exclusion criteria: duplicate publications, reviews without detailed description of results, opinions. Finally, we included 43 the most significant studies. CONCLUSION: There are literature data on proinflammatory cytokines, growth factors and osteodestructive processes in pathogenesis of degenerative disc disease. However, there is only fragmentary information about the role of genetic regulation of these processes. Some factors, such as microRNA, TGF-b, VEGF, MMP are still poorly understood.

[The Structure, Expression, and Non-Canonical Functions of Human rDNA: The Role of Non-Coding Regions].

The genes coding for the rRNAs seem evolutionary conserved on the first glance, but astonish one with their variability in the structure and a variety of functions on closer examination. The non-coding parts of rDNA contain regulatory elements, protein binding sites, pseudogenes, repetitive sequences, and microRNA genes. Ribosomal intergenic spacers are not only in charge with the nucleolus morphology and functioning, namely, the rRNA expression and ribosome biogenesis, but also control nuclear chromatin formation thus mediating cell differentiation. The alterations in the expression of these non-coding regions of rDNA in response to environmental stimuli underlie the keen sense of a cell to various types of stressors. Malfunctioning of this process may result in a wide range of pathologies from oncology to neurodegenerative disease and mental illness. Here, we observe to-date materials on the structure and transcription of the ribosomal intergenic spacer in humans and its role in rRNA expression, in-born disease development, and cancer.

Changes in Oncogene Expression in Experimental Glioblastoma 101.8 Rats during Therapy with PLGA Nanoparticles Loaded with Doxorubicin.

We compared the expression of the main glioblastoma oncogenes during therapy with doxorubicin (Dox) and Dox in nanoparticles based on a copolymer of lactic and glycolic acids (Dox-PLGA) at a delayed start of treatment. Late initiation of Dox-PLGA therapy of glioblastoma showed an increase in the expression of multiple drug resistance genes, such as Abcb1b and Mgmt, and a decrease in Sox2 expression. Increased expression of other oncogenes (Melk, Wnt3, Gdnf, and Pdgfra) were observed during both Dox and Dox-PLGA therapy. These changes indicate increased tumor aggressiveness and its resistance to cytostatics at the late start of therapy.

[Prognostic model for assessing the human glioma cell malignancy grade based on MDM2, MELK, SOX2, CDK4, DR5 and OCT4 gene expression]. / Prognosticheskaya model' dlya otsenki stepeni zlokachestvennosti kul'tury kletok gliomy cheloveka na osnovanii issledovaniya ekspressii paneli genov MDM2, MELK, SOX2, CDK4, DR5 i OCT4.

Glioma cell cultures are used in basic researches of tumor processes, personalized medicine for selecting treatment regimens depending on individual characteristics of patients and pharmacology for assessing the effectiveness of chemotherapy. Suppression of glioma culture growth without reduction of malignancy grade is common. Drug cancellation may be followed by substitution of precursor cells by more malignant clones. Therefore, analysis of culture cell malignancy grade is important. In the future, intraoperative analysis of glioma cell malignancy grade can be used to select individual therapy. OBJECTIVE: We analyzed the relationship between expression of marker genes TUBB3, CD133, CDK4, CDK6, CIRBP, DR4, DR5, EGFR, FGFR, FSHR, GDNF, GFAP, L1CAM, LEF1, MAP2, MDM2, MELK, NANOG, NOTCH2, OCT4, OLIG2, PDGFRA, PDGFA, PDGFB and SOX2 and glioma cell malignancy grade, as well as created appropriate prognostic model. MATERIAL AND METHODS: We analyzed expression of 25 marker genes in 22 samples of human glioma cultures using quantitative real-time PCR. Statistical analysis was performed using the IBM SPSS Statistics 26.0 software. We used the Kolmogorov-Smirnov and Shapiro-Wilk tests to assess distribution normality. Nonparametric Jonckheere-Terpstra and Spearman tests were applied. RESULTS: We obtained a prognostic model for assessing the grade III and IV glioma cell malignancy based on expression of marker genes MDM2, MELK, SOX2, CDK4, DR5 and OCT4. Predictive accuracy was 83% (Akaike information criterion -55.125).

[Molecular markers of neuro-oncogenesis in patients with glioblastoma]. / Molekulyarnye markery neiroonkogeneza pri glioblastome golovnogo mozga.

The problem of current treatment approaches to brain gliomas is short-term life expectancy in these patients. Apparently, it is required to change treatment approach via analysis of glioma stem cells rather cells with overexpression of marker genes. This review is devoted to similarities and differences between neurogenesis and neuro-oncogenesis characterized with molecular markers (CD133 as an example). The role of tumor stem cells and their relationship with neural stem cells are considered regarding development of glioma. The authors analyzed CD133 as a marker of glioma stem cells. In the future, stem cells will be important target for eradication during target therapy. A single molecular marker cannot characterize tumor stem cells as supported by CD133 studies. A set of molecular markers specific for certain cell type is required, and their combination will provide more accurate establishment of tumor stem cells.

[The role of glial cell line-derived neurotrophic factor isoforms in human glial tumors]. / Rol' izoform neirotroficheskogo faktora glial'noi kletochnoi linii (GDNF) v glial'nykh opukholyakh cheloveka.

Glial cell line-derived neurotrophic factor (GDNF) has a wide range of actions and positively affects viability, proliferative activity and migratory ability of cells in nervous system. That is why GDNF is being considered as a therapeutic molecule in the treatment of neurodegenerative diseases, in particular Parkinson's disease. However, GDNF has the same effect on high-grade glioma cells promoting their growth, resistance to therapy and dissemination. Expression of this factor in tissues and cultures of gliomas is up to five times higher than in intact brain matter. It was revealed that epigenetic modifications in GDNF gene promoter contribute to overexpression. Target suppression of GDNF gene transcription slows down growth of glioma and decreases cell migration. This review is devoted to the effect of GDNF on glioma cells, causes and consequences of its overexpression. Further analysis of expression and function of various GDNF isoforms in glial tumors may be valuable to develop new treatment methods for these dangerous diseases.

[Protein CD133 as a tumor stem cell marker]. / Belok CD133 kak marker opukholevykh stvolovykh kletok.

The CD133 protein is a large transmembrane glycoprotein. Despite multiple studies, the role of CD133 protein in cells is still poorly understood. Nevertheless, there is an association of CD133 protein with neoplastic transformation. This review summarizes data on CD133 protein, its structure, regulation of expression, molecular interactions and representation in cells that have undergone malignant transformation. Available data suggest that CD133 may have a great potential for predicting survival in various solid tumors. This protein can also be a marker of glioma.

[Principles of biobanking and biobanks of central nervous system tumors in world practice]. / Printsipy biobankirovaniya i biobanki opukholei nervnoi sistemy v mirovoi praktike.

Biobanks of central nervous system tumors are created in parallel with development of modern technologies for evaluation of molecular features of human diseases. In modern world practice, no one doubts that creation of biobanks of tumors is necessary and critical for personalized medicine. An important aspect of recent improvements in biobanks has been the expansion of tumor sample storage conditions. Development of cell technologies has made it possible to create cell cultures from tumor material that made it possible to evaluate further therapy before affecting the patient himself. Biobanks have become especially attractive in the study of brain tumors, where the peculiarity of location and blood-brain barrier complicate treatment approaches. This review describes the approaches to creation of biobanks of CNS tumors in world practice, sample storage conditions, ethical and legal regulation of biobanks, as well as experience of biobanking in different countries.

[Cell cultures in assessing radioresistance of glioblastomas]. / Ispol'zovanie kletochnykh kul'tur dlya otsenki radiorezistentnosti glioblastom.

To date, no modern methods of treatment allow overcoming malignant potential of glial neoplasms and significant increase of survival. Analysis of glioblastoma radioresistance using cancer cell cultures is one of the perspective directions, as radiotherapy is standard and available treatment method for these neoplasms. This review summarizes current studies identifying many factors of radioresistance of glial tumors, such as hypoxia, microenvironment and metabolic features of tumor, stem cells, internal heterogeneity of tumor, microRNA, features of cell cycle, DNA damage and reparation. We obtained data on involvement of various molecular pathways in development of radioresistance such as MEK/ERK, c-MYC, PI3K/Akt, PTEN, Wnt, JAK/STAT, Notch, etc. Changes in activity of RAD51 APC, FZD1, LEF1, TCF4, WISP1, p53 and many others are determined in radioresistant cells. Further study of radioresistance pathways will allow development of specific target aptamers and inhibitors.

[Cell cultures of human CNS tumors as in vitro model for individualized therapeutic approach]. / Kletochnye kul'tury opukholei TsNS cheloveka kak in vitro model' dlya individual'nogo podkhoda k terapii.

Tumor cell lines and cultures are widely used in biomedical research. They are excellent model systems for analysis of oncological mechanisms and understanding the biology of tumor cells. Cell cultures are used to develop and test new anticancer drugs, radiosensitizers and radiotherapy methods. Clinical application of tumor cell cultures is directly related to development of personalized medicine. Using tumor cell culture in a particular patient, physicians can select treatment considering molecular genetic characteristics of patient and tumor. In addition, it is possible to choose the optimal drug or radiotherapy regimen with obvious effectiveness in certain cell culture. This review describes the advantages of such an approach.

[Multimodal method of tissue differentiation in neurooncology using Raman spectroscopy, fluorescence and diffuse reflectance spectroscopy]. / Mul'timodal'nyi metod differentsiatsii tkanei v neiroonkologii s ispol'zovaniem spektroskopii kombinatsionnogo rasseyaniya, fluorestsentsii i diffuznogo otrazheniya.

BACKGROUND: There is a need to expand the possibilities of urgent analysis of intracranial tumor type during resection. These measures are necessary to improve resection quality with preservation of intact tissues and avoiding recurrence and neurological impairment in postoperative period. OBJECTIVE: To create optical-spectral method for differentiating the intracranial tumor types. MATERIAL AND METHODS: We used a combination of certain methods such as fluorescence spectroscopy to analyze the content of endogenous and exogenous fluorophores in samples, diffuse reflectance spectroscopy to analyze structural integrity of tissues according to light scattering and blood filling according to hemoglobin spectrum absorption, as well as spontaneous Raman spectroscopy detecting individual molecular components of tissues. The study was conducted at the Laboratory of Neurosurgical Anatomy and Conservation of Biological Materials of the Burdenko Neurosurgical Center and included 93 tissue samples from 60 patients diagnosed with glioblastoma (n=28), meningioma (n=12), astrocytoma (n=9), oligodendroglioma (n=5), and metastasis (n=6). RESULTS: Different types of intracranial tumors that cannot be differentiated using one of the considered spectroscopy modes can be distinguished in another one. Thus, we can conclude possible advantages of combined optical-spectral approach.

[Nitric oxide donor nitrosorbide potentiates the antitumor effect of doxorubicin against experimental glioblastoma]. / Donor oksida azota izosorbida dinitrat povyshaet protivoopukholevyi effekt doksorubitsina pri khimioterapii eksperimental'noi glioblastomy.

BACKGROUND: Doxorubicin is a well-known antitumor drug that is not employed for chemotherapy of brain tumors. Indeed, doxorubicin does not penetrate across the blood-brain barrier in therapeutic concentrations. OBJECTIVE: To study the antitumor effect of doxorubicin combined with nitrosorbide on intracranial experimental glioblastoma 101/8 in rats. MATERIAL AND METHODS: Male Wistar rats (n=86) with intracranial implanted glioblastoma 101/8 received doxorubicin (i.v. 1.5 mg/kg thrice) alone or in combination with nitrosorbide (i.v or orally, 0.5 mg/kg thrice) in 2, 5 and 8 days after implantation. Efficacy was assessed considering survival and brain tumor volume in 14 days after tumor implantation. RESULTS: Combination of doxorubicin and nitrosorbide significantly increased survival (57% and 155%, respectively) and slowed down tumor growth (16±12 and 8±6 mm3, respectively) compared to doxorubicin alone. Effectiveness of nitrosorbide alone was trivial. CONCLUSION: Nitric oxide donor nitrosorbide considerably potentiated the antitumor effect of doxorubicin against intracranial 101/8 glioblastoma in rats.

[Risk of Multiple Sclerosis: Analysis of Interactions Between Variants of Nuclear and Mitochondrial Genomes].

There is increasing evidence that the interaction of the mitochondrial and nuclear genomes substantially affects the risk of neurodegenerative diseases. The role of mitonuclear interactions in the development of multiple sclerosis, a severe chronic neurodegenerative disease of a polygenic nature, is poorly understood. In this work, we analyzed the association of multiple sclerosis with two-component mitonuclear combinations that include each of seven polymorphic variants of the nuclear genome localized in the region of the UCP2, and KIF1B genes and in the PVT1 locus (MYC, PVT1, and MIR1208 genes) and each often polymorphisms of the mitochondrial genome, as well as individual genetic variants that make up these combinations. Association of the individual components of these combinations with multiple sclerosis was also evaluated. 507 patients with multiple sclerosis and 321 healthy individuals were enrolled in the study, all participants were ethnic Russians. Two mitonuclear combinations associated with multiple sclerosis were identified: the UCP2 (rs660339)*A + MT-ATP6 (rs193303045)*G combination was characterized by p-value = 0.015 and OR= 1.39 [95% CI 1.05-1.87], and the PVT1 (rs2114358)*G + MT-ND1 (rs1599988)*С combination - by p-value = 0.012 and OR = 1.77 [95% CI 1.10-2.84]. Only one of the individual components of these combinations, allele rs660339*A of the nuclear gene UCP2 encoding uncoupling protein 2 of the mitochondrial anion carrier family, was independently associated with multiple sclerosis (p = 0.028; OR = 1.36 [95% CI 1.01-1.84]). This study expands the current understanding of the role of mitonuclear interactions and variance of nuclear genes, whose products function in mitochondria, and in risk of MS.

[Intraosseous metastasis of K27-mutant glioma]. / Vnutrikostnoe metastazirovanie K27-mutantnoi gliomy.

Glioma metastasis outside the central nervous system is a quite rare phenomenon. The disease in a young woman manifested itself as back pain and loss of vision in the left eye. Magnetic resonance imaging (MRI) revealed a tumor of the optic nerve; positron emission tomography showed multiple secondary bone changes. At the same time, MRI detected no signs of neoplasm in the midline brain structures (the brain stem and subcortical nuclei) and spinal cord. Two biopsies (superior iliac spine trephine biopsy and optic nerve tumor biopsy) were performed. There were similar histological tumors; the optic nerve tumor was found to have K27M mutation in the H3F3A gene, whereas the metastatic tumor lacked this mutation (possibly due to the quality and quantity of DNA isolated from the tumor cells). The interesting features of this case are the simultaneous detection of primary and metastatic tumors before receiving any treatment and the absence of the K27M mutation in the H3F3A gene in the metastasis.

[Theranostics for glioblastoma with monoclonal antibodies to the epidermal growth factor receptor]. / Perspektivy teranostiki glioblastomy s pomoshch'yu monoklonal'nykh antitel k retseptoru epidermal'nogo faktora rosta EGFR.

A review is devoted to analysis of the prospects of theranostics for multiform glioblastoma with monoclonal antibodies to the epidermal growth factor receptor (EGFR). Treatment of various malignancies demonstrated high potential of the use of EGFR. However, in case of glioblastoma, the effectiveness of monoclonal antibodies to EGFR is constrained by the absence of informative criteria for assessing the effectiveness of diagnosis and treatment of disease.

[Secondary prevention of chronic tonsillitis exacerbations by bacteriophage medications]. / Vtorichnaia profilaktika obostrenii khronicheskogo tonzillita bakteriofagal'nymi sredstvami.

Chronic tonsillitis is one of the most common diseases to modern people, which treatment requires a preventative care course approach. The general purpose of the present research could be framed as follows: to estimate clinical efficiency of bacteriophage medications, in the case of 'Ostophag' mixture for preventative care. Study population consisted eighty people. Participants were divided into two groups (forty patients in each) both diagnosed compensated and decompensated forms of chronic tonsillitis with pathogenic microflora in the lacunae of the palatine tonsils. In the first group we built monotherapy on bacteriophage medications use, whereas in the second one monotherapy was founded on antiseptic implication. The results of the present investigation showed high efficiency of bacteriophage medications a means of chronic tonsillitis salvage care.