Molecular chaperones, especially 70 kDa heat shock protein, in addition to their intracellular localization in cancer cells, can be exposed on the surface of the plasma membrane. We report that the membrane-associated chaperone mHsp70 of malignant brain tumors is required for high migratory and invasive activity of cancer cells. Live-cell inverted confocal microscopy of tumor samples from adult (n = 23) and pediatric (n = 9) neurooncologic patients showed pronounced protein expression on the membrane, especially in the perifocal zone. Mass spectrometry analysis of lipid rafts isolated from tumor cells confirmed the presence of the protein in the chaperone cluster (including representatives of other families, such as Hsp70, Hsc70, Hsp105, and Hsp90), which in turn, during interactome analysis, was associated with proteins involved in cell migration (e.g., Rac1, RhoC, and myosin-9). The use of small-molecule inhibitors of HSP70 (PES and JG98) led to a substantial decrease in the invasive potential of cells isolated from a tumor sample of patients, which indicates the role of the chaperone in invasion. Moreover, the use of HSP70 inhibitors in animal models of orthotopic brain tumors significantly delayed tumor progression, which was accompanied by an increase in overall survival. Data demonstrate that chaperone inhibitors, particularly JG98, disrupt the function of mHsp70, thereby providing an opportunity to better understand the diverse functions of this protein and offer aid in the development of novel cancer therapies. Significance: Membrane-bound mHsp70 is required for brain tumor cell migration and invasion and therefore could be employed as a target for anticancer therapies.

Glioblastoma (GBM) is one of the most aggressive and lethal malignancy of the central nervous system. Temozolomide is the standard of care for gliomas, frequently results in resistance to drug and tumor recurrence. Therefore, further research is required for the development of effective drugs in order to guarantee specific treatments to succeed. The aim of current study was to investigate the effects of nerve growth factor (NGF), human cathelicidin (LL-37), protegrin-1 (PG-1), and temozolomide on bioenergetic function of mitochondria, clonogenicity, and migration of human U251 glioma cells. Colony formation assay was used to test the ability of the glioma cells to form colonies in vitro. The U251 glioma cells migration was evaluated using wound-healing assay. To study the mitochondrial metabolism in glioma cells we measured oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) using a Seahorse XF cell Mito stress test kit and Seahorse XF cell Glycolysis stress kit, respectively. We revealed that LL-37, NGF, and TMZ show strong anti-tumorigenic activity on GMB. LL-37 (4 μM), TMZ (155 μM), and NGF (7.55 × 10⁻³ μM) inhibited 43.9%–60.3%, 73.5%–81.3%, 66.2% the clonogenicity of glioma U251 cells for 1–2 days, respectively. LL-37 (4 μM), and NGF (7.55 × 10⁻³ μM) inhibited the migration of U251 glioma cells on the third and fourth days. TMZ also inhibited the migration of human glioma U251 cells over 1–3 days. In contrast, PG-1 (16 μM) stimulated the migration of U251 glioma cells on the second, fourth, and sixth days. Anti-mitogenic and anti-migration activities of NGF, LL-37, and TMZ maybe are relation to their capacity to reduce the basal OCR, ATP-synthetase, and maximal respiration of mitochondria in human glioma U251 cells. Glycolysis, glycolytic capacity and glycolytic spare in glioma U251 cells haven`t been changed under the effect of NGF, LL-37, PG-1, and TMZ in regard to control level. Thus, LL-37 and NGF inhibit migration and clonogenicity of U251 glioma cells, which may indicate that these compounds have anti-mitogenic and anti-migration effects on human glioma cells. The study of the mechanisms of these effects may contribute in the future to the use of NGF and LL-37 as therapeutic agents for gliomas.

Craniosynostosis is a craniofacial anomaly, characterized by premature fusion of one or more of the cranial sutures. Each suture and their combination correspond to a special type of deformation.Purpose. The study aimed at indicating the difficulties of early diagnostics of various forms of the craniosynostosis and evaluating the quality of treatment of patients with this disease depending on their age.Material and methods. A survey of parents with craniosynostosis who were treated at the Almazov National Medical Research Centre in 2018–2019 was conducted. The parents of 107 patients were surveyed. The main objectives of our research were: to evaluate the timeliness of diagnosis of craniosynostosis at primary health care at patient’s place of residence; to compare the methods of diagnosis verification and to present the results of the parents’ subjective assessment of the results of surgical treatment at the early and long-term postoperative period.Results. The median age of children when they were diagnosed with craniosystosis was 5 months, the median age of patients when they underwent a surgical treatment was 16 months. The median duration of the catamnesis was 6 months. We revealed that the preliminary diagnosis was established by a neurologist and pediatrician only in 21% of cases. Only at 28% of cases, children were directed to neurosurgeon, who confirm the diagnosis. In 38 (35.3%) cases, patient’s parents independently sought medical advice. The diagnosis was verified by the results of the computer tomography in 55% of patients. on because primary care specialists due to the lack of primary care specialists’ awareness about the diagnosis of craniosynostoses and attempts at long-term monitoring and conservative treatment. The timeliness of detection of craniosynostosis in the newborn period and in the|first month of life can significantly improve the cosmetic and functional outcomes of the disease.

Summary. The membrane-bound heat shock protein mHsp70 is selectively expressed on the surface of tumor cells, but not on normal cells; it makes mHsp70 a promising target for theranostics of malignant tumors. Objective: in vivo visualization of mHsp70-positive cells in malignant human brain tumors. Materials and methods: intraoperative sampling of histological material was carried out from 7 patients with malignant tumors and from 3 patients with epilepsy. Localization of Hsp70 was determined using live confocal microscopy. To identify intergroup differences in the intensity of green pixels (Hsp70), the Kruskal-Wallis test was applied. Results. A method for intravital staining of tumor samples and image registration by the laser scanning confocal microscopy was developed. High expression of mHsp70 was found in tumor cells compared to control cells in the brain tissue of patients with epilepsy. Conclusion. For the first time, in vivo visualization of mHsp70-positive cells in malignant brain tumors was performed. The results indicate the possibility of using mHsp70 as a marker of tumor cells.

Brain tumors are the most common group of neoplasms in children, which is in the top-3 causes of infant mortality from oncopathology.   The aim of the study is to make a literature review of modern approaches to the personalization of treatment of CNS tumors in children based on the study of molecular genetics, immunohistochemical and imagingт characteristics. The article provides a description of the most common types of neoplasms of the nervous system — low grade gliomas (LGG), high grade gliomas (HGG), mixed glioneural tumors, etc. The molecular genetics, immunohistochemical, visualization characteristics of each type of gliomas are described. Modern information on prognosis and treatment of tumors is also given in the publication. The prognosis of the course of LGG/GNT in children depends more often on the patient’s age, histology, and location of the tumor, as well as its molecular profile. Older patients have a more favorable prognosis than younger children. Well-visualized tumors located superficially have a better outcome than diffuse gliomas, as well as deeply located tumors. Detection of BRAF mutations and FGFR rearrangements may indicate a better prognosis than in the presence of SNV. Local mutations of BRAF with concomitant deletion of CDKN2A, as well as mutations with H3.3 pK27 are the most dangerous.