This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol-3-OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma.
Mean Ki-67 labeling index was 29% (range, 1.5%-80%). p53 mutation was present in 20/36 GBs (55%), whereas OLIG2 expression was positive in 29/36 GBs (80.5%).
The experiments were conducted with human glioblastoma cell lines, which differ in regard to their p53 status, namely U87 (wild-type) and U251 (mutated).
While CT did not impact on the release of Hsp70, fractionated RT resulted in significantly increased extracellular concentrations of Hsp70 in p53 mutated and WT glioblastoma cells.
In an effort to shed light on consequences mediated by p53 inactivation in gliomas, we established the Tet-On system for p53 in the LN-Z308 glioblastoma cell line.
Analysis of Fas mRNA levels in a glioblastoma cell line containing a p53 mutation and an inducible wild-type p53 gene showed little difference under induced and noninduced conditions, suggesting that in glioblastomas, Fas expression is not directly linked to the p53 status.
DNA-damage regulated autophagy modulator 1 (DRAM1) is known as a target of TP53-mediated autophagy, and has been reported to promote the migration and invasion abilities of glioblastoma stem cells.
Specifically, targeting cellular pathways frequently altered in glioblastoma, such as the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), the p53 and the retinoblastoma (RB) pathways, or epidermal growth factor receptor (EGFR) gene amplification or mutation, have failed to improve outcome, likely because of redundant compensatory mechanisms, insufficient target coverage related in part to the blood brain barrier, or poor tolerability and safety.
We have taken advantage of the Nf1-/+;Trp53-/+cis mouse model of astrocytoma/glioblastoma to map genetic loci affecting whether astrocytomas are found in the spinal cord.
Manganese superoxide dismutase (MnSOD) is a malignant astrocytoma specific biomarker and associated with adverse prognosis in p53 expressing glioblastoma.
Tp53-gene transfer induces hypersensitivity to low doses of X-rays in glioblastoma cells: a strategy to convert a radio-resistant phenotype into a radiosensitive one.
The present case is unusual in four aspects: (i) it arose from a low-grade ganglioglioma in the absence of previous radiation or chemotherapy, which is the fourth reported case; (ii) the original tumor showed a high proliferative index on flow cytometry but a low Ki-67 labeling index, implying that the application of flow cytometry might play a certain role in predicting biological and clinical behavior of low grade gangliogliomas; (iii) p53 mutation and deletion appeared in the secondary glioblastoma, which was not shown in the original well-differentiated ganglioglioma; and (iv) the transformed glioblastoma showed p16 inactivation detected by methylation and deletion, which are relatively uncommon genetic events in secondary glioblastomas.
Synthetic small interfering RNA was used to knock down mutant TP53 in T98G and U138 cells, which are human glioblastoma cells with a P53 mutation, by screening of exons 4-8.
This study focused on the in vitro application of magnetic nanoparticles to deliver Tp53 as a gene of interest to glioblastoma (U87) cells across a simulated BBB model that comprised KB cells.
MIR517C inhibits autophagy and the epithelial-to-mesenchymal (-like) transition phenotype in human glioblastoma through KPNA2-dependent disruption of TP53 nuclear translocation.
Even though TP53 mutations were more frequent among younger patients with glioblastoma, they had no statistically significant effect on survival after adjustment for age (P = 0.62).
Isogenic derivatives of glioblastoma cells differing only in p53 function were prepared using a retroviral vector expressing a dominant negative mutant of p53 (mt p53).