Overall, these results indicate that SPARCL1 overexpression might be instrumental for the generation of CSC-derived preclinical models of GBM in which the main pathognomonic hallmarks of GBMs are retrievable, making them suitable for effective preclinical testing of therapeutics.
We used whole-exome and RNA sequencing in a patient with glioblastoma multiforme to identify a rearrangement between TTYH3, encoding a membrane-resident, calcium-activated chloride channel, and BRAF intron 1, resulting in a TTYH3-BRAF fusion protein that retained all features essential for BRAF autoinhibition.
We found that emodin, an inhibitor of phosphoglycerate mutase 1 derived from natural substances, significantly suppressed the glycolysis rate and IR-induced GBM migration in in vivo orthotopic xenograft mouse models.
Our findings demonstrate that CYP46A1 is a critical regulator of cellular cholesterol in GBM and that the CYP46A1/24OHC axis is a potential therapeutic target.
Moreover, our bis-indole-derived NR4A2 antagonists represent a novel class of anti-cancer agents with potential future clinical applications for treating GBM.
The cell type-dependent selectivity of this compound appears to arise at least in part from redox-dependent formation of a proapoptotic derivative, termed cRIPGBM, in GBM CSCs. cRIPGBM induces caspase 1-dependent apoptosis by binding to receptor-interacting protein kinase 2 (RIPK2) and acting as a molecular switch, which reduces the formation of a prosurvival RIPK2/TAK1 complex and increases the formation of a proapoptotic RIPK2/caspase 1 complex.
These data demonstrate that Fbln7 is overexpressed by endothelial cells and pericytes of the abnormal microvessels in GBM, and suggest that Fbln7 may contribute to the aberrant vessel formation by modulation of the angiopoietin-1/angiopoietin-2-Tie2 axis.
Taken together, our findings indicate that the NIX-mediated mitophagic pathway may represent a key therapeutic target for solid tumors, including glioblastoma.
The mRNA expression profile of GAMs displayed an upregulation of factors that are considered as pro-inflammatory M1 (eg, CCL2, CCL3L3, CCL4, PTGS2) and anti-inflammatory M2 polarization markers (eg, MRC1, LGMN, CD163, IL10, MSR1), the latter rather being associated with phagocytic functions in the GBM microenvironment.
Based on the random survival forest model, we identified UDP-glucose pyrophosphorylase 2 (UGP2) (upregulated gene) had a significant effect on GBM prognosis.
These findings are relevant to GBM patients because a low level of FGL2 expression with concurrent high GM-CSF expression is associated with higher CD8B expression and longer survival.
Impaired circulating myeloid CD1c+ dendritic cell function in human glioblastoma is restored by p38 inhibition - implications for the next generation of DC vaccines.
The current study aimed to investigate whether miR-193a-5p influences cell proliferation and migration through the mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathway by targeting neuro-oncological ventral antigen 1 (NOVA1) in glioblastoma.
To investigate whether and how TMEM168 functioned in the tumorigenesis of human GBM cells, two human GBM cell lines (U87 and U373) were used for study.