The search for markers applicable for efficient differential diagnosis and personalized therapy is a priority task of experimental neuro-oncology. Modern molecular methods allow us to analyze human biopsy material; however, further actions with this extracted tumor tissue are limited. Relevant and sophisticated CNS tumor models are required for precise therapy development. Although it is possible to use human biomaterial to create 2D and 3D cultures and implant them into xenograft animals, the data generated from such models is limited. Due to changes in the classification of the CNS tumors in 2021, a representative model should have not only morphological similarity to human tumors but also key genetic aberrations for studying the mechanisms of carcinogenesis and personalized therapy (such as PDGFRa, Olig1/2, Sox2, and Mki67) for different glioma models such as astrocytoma, oligodendroglioma, and glioblastoma. On the basis of a unique scientific facility “The Collection of experimental tumors of the nervous system and neural tumor cell lines” (Avtsyn Research Institute of Human Morphology of “Petrovsky National Research Center of Surgery”), there is a biobank of chemically induced transplantable tumors of laboratory animals. Their properties, mechanisms, and progression closely correlate with malignant CNS neoplasms in humans. These are potentially useful for identifying novel signaling pathways associated with oncogenesis in the nervous system and personalizing therapeutic approaches. In our work, we characterized a tissue-transplantable brain tumor strain of rat glioma101.8 using MRI, IHC, scRNA-seq, and qPCR-RT methods. According to this study, the cellular composition of the tissue-transplantable rat glioma 101.8 strain was determined, as well as the major genetic signature characteristics of each cell population of this tissue-transplantable strain and its microenvironment.

Glioblastoma (GBM) is a highly aggressive human neoplasm with poor prognosis due to its malignancy and therapy resistance. To evaluate the efficacy of antitumor therapy, cell models are used most widely, but they are not as relevant to human GBMs as tissue models of gliomas, closely corresponding to human GBMs in cell heterogeneity. In this work, we compared three different tissue strains of rat GBM 101.8 (induced by DMBA), GBM 11-9-2, and GBM 14-4-5 (induced by ENU). Materials and methods: We estimated different gene expressions by qPCR-RT and conducted Western blotting and histological and morphometric analysis of three different tissue strains of rat GBM. Results: GBM 101.8 was characterized by the shortest period of tumor growth and the greatest number of necroses and mitoses; overexpression of Abcb1, Sox2, Cdkn2a, Cyclin D, and Trp53; and downregulated expression of Vegfa, Pdgfra, and Pten; as well as a high level of HIF-1α protein content. GBM 11-9-2 and GBM 14-4-5 were relevant to low-grade gliomas and characterized by downregulated Mgmt expression; furthermore, a low content of CD133 protein was found in GBM 11-9-2. Conclusions: GBM 101.8 is a reliable model for further investigation due to its similarity to high-grade human GBMs, while GBM 11-9-2 and GBM 14-4-5 correspond to Grade 2–3 gliomas.

This work describes a sapphire cryo-applicator with the ability to sense tissue freezing depth during cryosurgery by illumination of tissue and analyzing diffuse optical signals in a steady-state regime. The applicator was manufactured by the crystal growth technique and has several spatially resolved internal channels for accommodating optical fibers. The method of reconstructing freezing depth proposed in this work requires one illumination and two detection channels. The analysis of the detected intensities yields the estimation of the time evolution of the effective attenuation coefficient, which is compared with the theoretically calculated values obtained for a number of combinations of tissue parameters. The experimental test of the proposed applicator and approach for freezing depth reconstruction was performed using gelatin-based tissue phantom and rat liver tissue in vivo. It revealed the ability to estimate depth up to 8 mm. The in vivo study confirmed the feasibility of the applicator to sense the freezing depth of living tissues despite the possible diversity of their optical parameters. The results justify the potential of the described design of a sapphire instrument for cryosurgery.

Background: This study aimed to develop a superior aptamer-based therapeutic for targeted glioblastoma intervention by conducting a comparative analysis of two DNA aptamers: the original U2 sequence, selected against glioblastoma cells exhibiting high EGFRvIII expression, and its modified, shortened, and stabilized variant, Gol1. Methods: The effects of the investigated aptamers on primary human glioblastoma cells with graded receptor expression levels and on a rat 101/8 glioblastoma tissue model were rigorously studied. Results: The results demonstrated the significant superiority of the stabilized Gol1 aptamer, which exhibited exceptional binding affinity for the EGFRvIII receptor. Pronounced antiproliferative and antimigratory effects against EGFRvIII-positive human tumor cells, ultimately inducing complete cell death. Transcriptomic analysis revealed a sophisticated dual mechanism of action for Gol1: the specific activation of neuronal differentiation genes concurrent with the suppression of key alternative splicing factors. Crucially, in vivo confirmation showed highly selective accumulation of the FAM-labeled Gol1 aptamer exclusively within tumor tissue, with a maximum concentration gradient observed in the invasive border zone and a complete absence of accumulation in intact brain parenchyma. Conclusions: These comprehensive findings confirm that the Gol1 aptamer constitutes a highly promising and versatile platform for developing novel targeted theranostic strategies against glioblastoma, offering a precise approach for both diagnostic imaging and therapeutic intervention.