|
Glioblastoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
We have examined the relative roles of the two major phospholipid products of PI3K activity, phosphatidylinositol 3,4-biphosphate [PtdIns(3,4)P2] and phosphatidylinositol 3,4,5-triphosphate [PtdIns(3,4,5)P3], in the regulation of PKB activity in glioblastoma cells containing high levels of both of these lipids due to defective PTEN expression.
|
10958682 |
2000 |
|
Glioblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Downregulation of uPA inhibits migration and PI3k/Akt signaling in glioblastoma cells.
|
12545160 |
2003 |
|
Glioblastoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Here, we report on the analysis of 17 genes related to the Pi3k/Akt signalling pathway for genetic alteration and aberrant expression in a series of 103 glioblastomas.
|
14655756 |
2003 |
|
Glioblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
These results suggest that genetic alterations of class IA PI3K subunit genes can occasionally play a role in human glioblastoma by activating the PI3K-AKT signaling pathway independently of PTEN mutation.
|
15605984 |
2004 |
|
Glioblastoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
PI3K-AKT pathway negatively controls EGFR-dependent DNA-binding activity of Stat3 in glioblastoma multiforme cells.
|
16007122 |
2005 |
|
Glioblastoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Glioblastomas frequently carry genetic alterations resulting in an aberrant activation of the phosphoinositol-3-kinase (Pi3k)/protein kinase B (Akt) signalling pathway, including most notably phosphatase and tensin homolog (PTEN) mutation, epidermal growth factor receptor (EGFR) amplification and rearrangement, as well as carboxyl-terminal modulator protein (CTMP) hypermethylation [Knobbe et al., (2004) Hypermethylation and transcriptional downregulation of the carboxyl-terminal modulator protein gene in glioblastomas.J Natl Cancer Institute, 96, 483-486].
|
16150119 |
2005 |
|
Glioblastoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Recently, a large-scale mutational analysis of eight PI3K and eight PI3K-like genes revealed somatic mutations in PIK3CA, which encodes the p110alpha catalytic subunit of class IA PI3K, in several types of cancer, including glioblastoma multiforme.
|
17050665 |
2006 |
|
Glioblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Inhibition of PI3K in U87MG glioblastoma cells, which have activated PI3K/Akt activity secondary to phosphatase and tensin homologue deleted on chromosome 10 (PTEN) mutation, with LY294002 blunted the induction of HIF-1alpha protein and its targets vascular endothelial growth factor and glut1 mRNA in response to hypoxia.
|
16849522 |
2006 |
|
Glioblastoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Mutation or deletion of PTEN has been found in as high as 80% of glioblastomas, which harbor aberrant cell signaling passing through the phosphatidylinositol-3-kinase (PI3K) and Akt (PI3K/Akt) survival pathway.
|
17616812 |
2007 |
|
Glioblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
These results suggest that the EGFR/PTEN/PI3K pathway is frequently altered in glioblastomas and is a promising target for therapy, in particular for primary glioblastomas.
|
17235514 |
2007 |
|
Glioblastoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Introduction of normal PTEN together with H-Ras(G12V) into U251 glioblastoma cells reduced the PI3K-dependent activation of Akt, but had no effect on vacuolation.
|
17210246 |
2007 |
|
Glioblastoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Rapamycin has anticancer activity in PTEN-deficient glioblastoma and warrants further clinical study alone or in combination with PI3K pathway inhibitors.
|
18215105 |
2008 |
|
Glioblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Our results uncover CD95 as an activator of PI3K and, most importantly, as a crucial trigger of basal invasion of glioblastoma in vivo.
|
18328427 |
2008 |
|
Glioblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
For example, combining gefitinib with inhibitors of the PI3K/AKT pathway show enhanced cytotoxicity in glioblastoma derived cell lines.
|
18566746 |
2008 |
|
Glioblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
In conclusion, PI3K inhibitors are promising agents in the treatment of glioblastomas, especially when used in combination with ionizing radiation.
|
18413797 |
2008 |
|
Glioblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
By identifying class I PI3K inhibitors as powerful agents in enhancing the lethality of DNA-damaging drugs, to which GBMs are usually considered unresponsive, our findings have important implications for the design of rational combination regimens in overcoming the frequent chemoresistance of GBM.
|
19633683 |
2009 |
|
Glioblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
The phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway is altered in most glioblastoma multiforme.
|
19549905 |
2009 |
|
Glioblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
The suggested dependence of glioblastoma tumors on PI3K signaling implies that PI3K inhibitors should lead to effective killing of these cancer cells, but that has been shown not to be the case.
|
19076776 |
2009 |
|
Glioblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Our findings suggest that there is p70S6K-mediated, cross-inhibitory regulation between the MEK/ERK and PI3K/mTOR pathways, in which each contribute to the maintenance of the self-renewal and tumorigenic capacity of glioblastoma CSLCs.
|
20857497 |
2010 |
|
Glioblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Thus, HOXA9 activation is a novel, independent, and negative prognostic marker in GBM that is reversible through a PI3K-associated epigenetic mechanism.
|
20068170 |
2010 |
|
Glioblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
These findings suggest that the PI3K/mTor signaling pathway is critical for the maintenance of glioblastoma CSLC properties, and targeting both mTor and PI3K of CSLCs may be an effective therapeutic strategy in glioblastoma.
|
20861085 |
2010 |
|
Glioblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
In addition, we demonstrate that the extracellular signal-regulated kinase (ERK)1/2 pathway is only partially implicated in the modulation of CXCL12-induced glioblastoma cell movement, whereas the phosphoinositol-3 kinase (PI3K) pathway is not involved.
|
20392929 |
2010 |
|
Glioblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
In the present study, we report decreased cell proliferation and invasive ability upon the LY294002-induced inhibition of PI3K in both U251 and LN229 human glioblastoma cells in vitro.
|
20888802 |
2010 |
|
Glioblastoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Genetic analyses demonstrated that EGFR-Ras and PI3K induce fly glial neoplasia through activation of a combinatorial genetic network composed, in part, of other genetic pathways also commonly mutated in human glioblastomas.
|
21538561 |
2011 |
|
Glioblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
CsA, comparably to pharmacological inhibitors of PI3K/Akt signaling (LY294002, A443654), reduced motility of glioblastoma cells, diminished MMP-2 gelatinolytic activity and MMP-2 and MT1-MMP expression.
|
21276823 |
2011 |