Glioma growth can cause pervasive changes in the functional connectivity (FC) of brain networks, which has been associated with re-organization of brain functions and development of functional deficits in patients. Mechanisms underlying functional re-organization in brain networks are not understood and efforts to utilize functional imaging for surgical planning, or as a biomarker of functional outcomes are confounded by the heterogeneity in available human data. Here we apply multiple imaging modalities in a well-controlled murine model of glioma with extensive validation using human data to explore mechanisms of FC disruption due to glioma growth. We find gliomas cause both local and distal changes in FC. FC changes in networks proximal to the tumor occur secondary to hemodynamic alterations but surprisingly, remote FC changes are independent of hemodynamic mechanisms. Our data strongly implicate hemodynamic alterations as the main driver of local changes in measurements of FC in patients with glioma.
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http://dx.doi.org/10.1177/0271678X18803948 | DOI Listing |
Viruses
January 2025
Surgical Neurology Branch, NINDS, NIH 10 Center Drive, Bethesda, MD 20892, USA.
Glioblastoma multiforme (GBM) is a devastating, aggressive primary brain tumor with poor patient outcomes and a five-year survival of less than 10%. Significant limitations to effective GBM treatment include poor drug delivery across the blood-brain barrier, drug resistance, and complex genetic tumor alterations. Gene therapy uses a mechanism different from other GBM therapies to reduce tumor growth and enhance antitumor immunity.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Molecular Neurotherapeutics Laboratory, National Neuroscience Institute, Singapore 308433, Singapore.
Glioblastoma (GBM) is an aggressive brain tumor characterized by extensive metabolic reprogramming that drives tumor growth and therapeutic resistance. Key metabolic pathways, including glycolysis, lactate production, and lipid metabolism, are upregulated to sustain tumor survival in the hypoxic and nutrient-deprived tumor microenvironment (TME), while glutamine and tryptophan metabolism further contribute to the aggressive phenotype of GBM. These metabolic alterations impair immune cell function, leading to exhaustion and stress in CD8+ and CD4+ T cells while favoring immunosuppressive populations such as regulatory T cells (Tregs) and M2-like macrophages.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznań, Poland.
Adult-type diffuse gliomas are characterized by inevitable recurrence and very poor prognosis. Novel treatment options, including multimodal drugs or effective drug combinations, are therefore eagerly awaited. Tinostamustine is an alkylating and histone deacetylase inhibiting molecule with great potential in cancer treatment.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou 730030, China.
The aim of this study was to investigate the inhibitory effect of nintedanib (BIBF) on glioblastoma (GBM) cells and its mechanism of action and to optimize a drug delivery strategy to overcome the limitations posed by the blood-brain barrier (BBB). We analyzed the inhibition of GBM cell lines following BIBF treatment and explored its effect on the autophagy pathway. The cytotoxicity of BIBF was assessed using the CCK-8 assay, and further techniques such as transmission electron microscopy, Western blotting (WB), and flow cytometry were employed to demonstrate that BIBF could block the autophagic pathway by inhibiting the fusion of autophagosomes and lysosomes, ultimately limiting the proliferation of GBM cells.
View Article and Find Full Text PDFMicroorganisms
January 2025
Scientific and Educational Center, Molecular Bases of Interaction of Microorganisms and Human of the Center for Personalized Medicine of Federal State Budgetary Scientific Institution, Institute of Experimental Medicine, Acad. Pavlov Street, 12, 197022 Saint Petersburg, Russia.
Background: Cancer remains a leading cause of mortality globally. Conventional treatment modalities, including radiation and chemotherapy, often fall short of achieving complete remission, highlighting the critical need for novel therapeutic strategies. One promising approach involves the oncolytic potential of Group A (GAS) strains for tumor treatment.
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