V V Kudelkina, M V Gulyaev, A S Khalansky, E A Miroshnichenko, O V Makarova, T Kh Fatkhutdinov, A M Kosyreva
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引用次数: 0
Abstract
The aim of this study was to morphologically, molecularly, and immunologically characterize two new transplantable glioblastoma (GB) tissue models, designated M2 GB and M6 GB.
Materials and methods: Two new chemically induced, easily transplantable tissue mouse models of high-grade glioma have been created and characterized. M2 GB and M6 GB tissues were orthotopically transplanted to immunocompetent C57BL/6 mice. The clinical and morphological characteristics of tumor growth, as well as the intratumoral immune response and target gene expression were assessed.
Results: Clinical manifestations of M2 GB and M6 GB growth in mice include motility disorders, cachexia, and priapism. Morphologically, M2 GB and M6 GB are characterized by diffuse proliferation, cellular and nuclear polymorphism, and high mitotic activity with pathological mitotic patterns corresponding to the aggressive nature of the mentioned tumors. Both tumors were significantly infiltrated with CD3+ T lymphocytes (~32%) and F4/80+ macrophages (~28-50%). M2 GB showed a higher content of F4/80+ macrophages compared to M6 GB. The Cdkn2a, S100b, Mki67, Pten, Vegfa, Hif1a, Sox2, Abcb1, and Gfap genes were overexpressed in both tumors. Expression of the Cd133, Tp53, and Pdgfra genes was increased in M2 GB. High expression of Pi3k and Gdnf was seen in M6 GB. Expression of Cd44, Pi3k, Hif1a, Gdnf, and Egfr was higher in M6 GB tissues compared to M2 GB, whereas expression of Cdkn2a, Tp53, Cd133, and Pdgfra was higher in M2 GB tissues compared to M6 GB.
Conclusion: The M2 GB and M6 GB models of transplanted tissues reproduce key characteristics of human GB, including similar intracellular immune profiles, clinical and morphological features, and gene expression patterns, which are important for further research in neurological oncology. These models can be used to develop diagnostic and treatment methods and to study tumor genesis.
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