Aim . To study the role of CT perfusion in the differential diagnosis of histological subtypes of supratentorial malignant gliomas and to determine the degree of their malignancy. Materials and methods . The study included 34 patients (20 men and 14 women, with an average age of 52 years) with newly detected supratenorial glial tumors, who subsequently underwent neurosurgical treatment in the NMIC of neurosurgery with histological verification of the diagnosis. Depending on the histological diagnosis, three groups of patients were identified: 1) anaplastic astrocytomas, 2) glioblastomas, 3) anaplastic oligodendrogliomas. The CT-perfusion protocol was performed on a 64-slice Optima 660 (GE) scanner and consisted of three separate parts: a low-dose axial CT of the brain with a slice thickness of 5 mm (90 kV), a perfusion protocol performed according to a prolonged scheme, with two consecutive continuous series of scans, and a post-contrast series of CT images in a spiral scanning mode. In addition, all patients underwent an MRI examination (using a Signa Hdxt 3.0 T (GE) MR scanner, in T2, T2-FLAIR, SWAN, DWI, and T1 modes before and after contrast enhancement). Results . The study demonstrated that anaplastic astrocytomas are characterized by significantly low absolute and normalized hemodynamics parameters (BF, BV, PS) when compared with glioblastomas, and significantly low absolute maximum values of blood flow (BF) and blood volume (BV) when compared with the group of anaplastic oligodendrogliomas. CT perfusion using the normalized permeability index (PS) can reliably differentiate glioblastomas and anaplastic oligodendrogliomas. Perfusion parameters, both absolute and normalized, did not show statistically significant differences in the differential diagnosis of various molecular and genetic subtypes of anaplastic astrocytomas. Conclusion . CT perfusion using all hemodynamic parameters demonstrated high reliability and efficacy in distinguishing between glioblastomas and anaplastic astrocytomas. Further research is required to evaluate the effectiveness of the method in distinguishing glioblastomas from anaplastic oligodendrogliomas.

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. To study the antitumor effect of doxorubicin combined with nitrosorbide on intracranial experimental glioblastoma 101/8 in rats. 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. 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. Nitric oxide donor nitrosorbide considerably potentiated the antitumor effect of doxorubicin against intracranial 101/8 glioblastoma in rats.

Культуры глиом имеют широкий спектр применения: в фундаментальных исследованиях опухолевых процессов, персонализированной медицине для подбора схем лечения, учитывающих индивидуальные особенности пациента, а также в фармакологии для оценки эффективности действия лекарственных средств на опухоль. При этом часто отмечается подавление роста культуры глиомы в целом без снижения степени злокачественности. При отмене препаратов может происходить вытеснение пула предшествующих клеток более злокачественными клонами, поэтому важное значение имеет определение степени злокачественности клеток в культуре. В дальнейшем изучение степени злокачественности клеток культуры глиомы, полученной от пациента во время операции, может быть использовано для подбора персонализированной терапии, наилучшим образом подходящей данному пациенту. ЦЕЛЬ ИССЛЕДОВАНИЯ Изучение связи между экспрессией маркерных генов TUBB3, CD133, CDK4, CDK6, CIRBP, DR4, DR5, EGFR, FGFR, FSHR, GDNF, GFAP, L1CAM, LEF1, MAP2, MDM2, MELK, NANOG, NOTCH2, OCT4, OLIG2, PDGFRA, PDGFA, PDGFB и SOX2 и степенью злокачественности клеток в культурах глиом и создание прогностической модели в виде уравнения на основе регрессионного анализа. МАТЕРИАЛ И МЕТОДЫ С помощью количественной полимеразной цепной реакции в реальном времени была проанализирована экспрессия 25 маркерных генов в 22 образцах культур глиом человека, полученных от пациентов, проходивших лечение в ФГАУ «Национальный медицинский исследовательский центр нейрохирургии им. акад. Н.Н. Бурденко» Минздрава России. При статистической обработке полученных данных, проведенной с помощью программного обеспечения IBM SPSS Statistics 26.0 (StatSoft Inc., США), для оценки нормальности распределения анализировали критерии Колмогорова—Смирнова и Шапиро—Уилка, при сравнительной статистике использовали непараметрические критерии Джонкхиера—Терпстры и Спирмена. РЕЗУЛЬТАТЫ Была получена прогностическая модель для определения степени злокачественности клеток в культурах глиом III и IV Grade с помощью оценки экспрессии маркерных генов MDM2, MELK, SOX2, CDK4, DR5 и OCT4 с прогностической точностью 83% (информационный критерий Акаике равен —55,125).

Background/Objectives: Glioblastoma is an aggressive brain tumour with a poor prognosis and limited therapy. The truncated aptamer GR20, derived from aptamer U31, was developed to retain EGFR binding while reducing size. This study evaluated how aptamer truncation, while maintaining its tertiary structure, affects its antiproliferative activity against human glioma cells. Methods: Five transplantable human glioblastoma cell cultures (BU73, G22, G23, G01, Sus/fP2) were used. Aptamer binding was assessed by flow cytofluorimetry, intracellular accumulation was tracked by confocal microscopy. Changes in stemness and malignancy gene expression were evaluated by real-time PCR. Protein expression levels were assessed by immunocytochemistry. Proliferative activity was measured using the MTS assay. Results: GR20 retained EGFR binding and demonstrated more than two-fold higher binding efficiency to glioblastoma cells than antibodies or the U31 aptamer. Both aptamers accumulated in cells after 2 h of incubation. GR20 significantly reduced the expression of stemness genes (CD133, OCT4) and malignancy genes (EGFR, PDGFRα, TP53) but showed modest antiproliferative effects (9–11% reduction). U31 exhibited stronger antiproliferative activity, reducing Sus/fP2 viability by 31% and 58%. Molecular dynamics showed that U31 maintains a “multi-loop” conformational state absent in GR20. Conclusions: Although the truncated GR20 still binds to the EGFR and is taken up by cells, its antiproliferative activity is reduced compared to U31. The multi-loop conformation present in U31 but missing in GR20 appears to enhance activity, identifying this motif as a promising target for future aptamer optimization.

Nucleolus-oriented protein nucleolin plays a significant role in the life of a normal mammalian cell. However, nucleolin is also actively expressed in cells of malignant tumors. At the same time, its expression in different types of cancer is significantly increased compared with normal cells. It is interesting that nucleolin localization often varies in tumor cells, namely in the cytoplasm and on the cell membrane. This fact is considered to be a poor prognostic indicator. This work is devoted to the study of the distribution of nucleolin in human glioblastoma cells. Glioblastoma is one of the most aggressive malignant tumors with an absolutely unfavorable prognosis. These tumors have a high proliferative potential, but in addition they are often characterized by invasive properties. Research on lineage cells does not let to fully study these properties of glioblastoma, since lineage cells are very different from the actual tumor. In our study, we used two primary cell cultures of human glioblastoma with varying degrees of invasiveness of the original tumors. The main interest was directed at studying the localization of nucleolin and its correlation with the invariability of the N- and C-termini of the corresponding protein. Particular attention was paid to the significance of the unaltered C-terminus of nucleolin for its distribution in the cells of transplanted human glioblastoma cultures derived from patient tissues. The aim of this work is to find the relationship between the deformation of the N- or C-terminal sequences of nucleolin and its localization.We showed that in glioblastoma cells, with a high degree of invasion, nucleolin is found in the cytoplasm and close to the cell membrane, and the distribution of nucleolin with undeformed C and N-terminal does not match.

Transgenic clones of mouse embryonic stem cells of the RI line were -received by transfection of plasmid linear vectors. The changes in the transgene structure during its integration into the genome of the target cells were investigated. Displacements were found on the flanks of the integrated transgene. It was found that multicopy tandem structures are formed in head- -tail orientation at the transgene integration. It was noted that the number of copies of the integrated transgenes varies considerably, but the introduction of DNA fragments from the nuclear shells into the flanks of the transgene normalizes the number of its copies.