Glioblastoma is the most malignant and invasive brain tumor with extremely poor prognosis. p53-inducible gene 3, a downstream molecule of the tumor suppressor p53, has been found involved in apoptosis and oxidative stress response.
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.
A human glioblastoma cell line with repressible expression of the p53 protein did not show any difference in MTH-68/H sensitivity in its p53-expressing and p53-depleted states, indicating that the apoptotic process induced by MTH-68/H does not depend on p53.
A protein folding molecular imaging biosensor monitors the effects of drugs that restore mutant p53 structure and its downstream function in glioblastoma cells.
A stereotactic core biopsy revealed glioblastoma with immunostaining suggestive of histone H3K27M and TP53 mutation, consistent with diffuse intrinsic pontine glioma.
A subpopulation of cells were present in the low-grade tumours that contained the same p53 gene mutation predominant in the cells of the recurrent tumours that had progressed to glioblastoma.
A trend of inverse relationship between patient survival and the number of tumor cell nuclei with immunohistochemically detectable p53 protein was seen in glioblastoma cases: 20.5 +/- 12.7 versus 13.7 +/- 6.3 months (mean +/- SD) in instances with > or > or = 25% positive cells, respectively.
A tumor-targeting nanomedicine carrying the p53 gene crosses the blood-brain barrier and enhances anti-PD-1 immunotherapy in mouse models of glioblastoma.
Additionally, such gains or amplifications were present in all tumor samples where the initial histopathological diagnosis was glioblastoma and immunohistochemical study disclosed p53 tumor suppressor protein negative and epidermal growth factor receptor positive immunoreactivity; such glioblastomas possessing p53 tumor suppressor protein positive and epidermal growth factor receptor negative immunoreactivity seldom displayed any gain.
Although TP53 wild-type glioblastoma cell lines are similarly sensitive to AMG232 and RG7112, we found that four TP53 wild-type out of ten patient-derived glioblastoma cells are much more sensitive to AMG232 than RG7112 (average IC<sub>50</sub> of 76 nM vs. 720 nM).
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.
Analysis of human specimens showed that miR-34a expression is down-regulated in glioblastoma tissues as compared with normal brain and in mutant p53 gliomas as compared with wild-type p53 gliomas. miR-34a levels in human gliomas inversely correlated to c-Met levels measured in the same tumors.
ARs were significantly higher in higher-grade astrocytic tumors than in lower-grade tumors (Mann-Whitney U test: P = 0.0003), although wide variability in each group resulted in overlapping between the groups. p53 protein immunopositivity (more than 25% of nuclei) was found in 15 of 32 glioblastoma cases, while in the remaining 17 none or only a low percentage (up to 6%) of the nuclei were positive.
Because p53 has emerged as a master metabolic regulator, we hypothesized that the presence of wild-type p53 in glioblastoma cells could confer a selective advantage to these cells under the adverse conditions of the glioma microenvironment.