Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Cytogenetic evolution of MYCN and MDM2 amplification in the neuroblastoma LS tumour and its cell line.
|
7576957 |
1995 |
Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Non-syntenic amplification of MDM2 and MYCN in human neuroblastoma.
|
7700632 |
1995 |
Neuroblastoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Overexpression of Mdm2 in neuroblastoma (NB)(1) cell lines failed to decrease the high steady state levels of endogenous p53.
|
10488081 |
1999 |
Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
To test this hypothesis, p53 expression, location, and functional integrity was examined in neuroblastoma by irradiating 6 neuroblastoma cell lines and studying the effects on p53 transcriptional function, cell cycle arrest, and induction of apoptosis, together with the transcriptional function of p53 after irradiation in three ex vivo primary, untreated neuroblastoma tumors. p53 sequencing showed five neuroblastoma cell lines, two of which were MYCN-amplified, and that all of the tumors were wild-type for p53. p53 was found to be predominantly nuclear before and after irradiation and to up-regulate the p53 responsive genes WAF1 and MDM2 in wild-type p53 cell lines and a poorly-differentiated neuroblastoma, but not a differentiating neuroblastoma or the ganglioneuroblastoma part of a nodular ganglioneuroblastoma in short term culture.
|
11395384 |
2001 |
Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
MDM2 mediated nuclear exclusion of p53 attenuates etoposide-induced apoptosis in neuroblastoma cells.
|
11125034 |
2001 |
Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
We determined p53 function by measuring induction of p21 and/or MDM2 proteins in response to melphalan (L-PAM) in seven L-PAM-sensitive and 11 L-PAM-resistant neuroblastoma cell lines. p53 was functional in seven/seven drug-sensitive but in only 4/11 drug-resistant cell lines (P = 0.01).
|
11507071 |
2001 |
Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Strategies for pharmacologic and genetic inhibition of MDM2 may prove to be an important new therapeutic approach in neuroblastoma.
|
15927364 |
2005 |
Neuroblastoma
|
0.100 |
PosttranslationalModification
|
disease |
BEFREE |
Luciferase reporter assays confirmed the E-box-specific, MYCN-dependent regulation of the MDM2 promoter in MYCN-inducible neuroblastoma cell lines.
|
15644444 |
2005 |
Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
The observed treatment effects without the need of imposing a genotoxic burden suggest that selective MDM2 antagonists might be beneficial for treatment of neuroblastoma patients with and without MYCN amplification.
|
17018622 |
2006 |
Neuroblastoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Our aim was to determine the frequency of p53 mutations, p14(ARF) methylation, or deletion and MDM2 amplification in 23 neuroblastoma cell lines (6 derived at diagnosis and 17 derived at relapse).
|
16489014 |
2006 |
Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
We previously reported that 3 p53 wild type (wt) MYCN amplified (MNA) neuroblastoma cell lines failed to G1 arrest after DNA damage despite induction of p53, p21(WAF1) and MDM2.
|
17172827 |
2006 |
Neuroblastoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
These data support the hypothesis that elevated MDM2 levels contribute to MYCN-induced genomic instability through altered regulation of centrosome replication in neuroblastoma.
|
17363562 |
2007 |
Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
The lack of association between SNP309 and MYCN status indicates that MDM2 SNP309 may be a new independent prognostic factor for stage 4 NB.
|
18835771 |
2008 |
Neuroblastoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Data from this pilot study suggest that the MDM2 G/G and T/G-SNP309 alleles are markers of increased predisposition to tumor development and disease aggressiveness in neuroblastoma.
|
18519749 |
2008 |
Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
The MDM2 antagonist nutlin-3 sensitizes p53-null neuroblastoma cells to doxorubicin via E2F1 and TAp73.
|
19360352 |
2009 |
Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
To study the interaction of MYCN and MDM2, we generated an Mdm2 haploinsufficient transgenic animal model of neuroblastoma.
|
19649205 |
2009 |
Neuroblastoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
We review here these mechanisms for evasion of p53-mediated growth control and conclude that deregulation of the p14(ARF)-MDM2-p53 axis seems to be the principal mode of p53 inactivation in neuroblastoma, opening new perspectives for targeted therapeutic intervention.
|
19779493 |
2009 |
Neuroblastoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Antitumor activity of the selective MDM2 antagonist nutlin-3 against chemoresistant neuroblastoma with wild-type p53.
|
19903807 |
2009 |
Neuroblastoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
MDM2 SNP309, a T-to-G substitution in the MDM2 promoter associated with higher gene expression compared to wild-type, may attenuate the p53 pathway in NB, in which p53 mutations are rare.
|
19526525 |
2009 |
Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Inactivation of the p53/MDM2/p14(ARF) pathway develops during treatment and contributes to neuroblastoma relapse.
|
20145180 |
2010 |
Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
A cohort of 497 NB children, enrolled in the Italian Neuroblastoma Registry between January 1985 and December 2005 and previously investigated for the prognostic role of MDM2 SNP309, was considered for this study.
|
20232446 |
2010 |
Neuroblastoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
MDM2 is a key inhibitor of p53 and a positive activator of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) activity with an important role in neuroblastoma pathogenesis.
|
21484514 |
2011 |
Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Also, we found that the enforced overexpression of MDM2, or conversely, the inhibition of overexpressed endogenous MDM2, led to either a remarkable increase or decrease in tumor growth, respectively, in MYCN-amplified neuroblastoma (even though no p53 function was involved).
|
21862876 |
2011 |
Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Functional analysis of the p53 pathway in neuroblastoma cells using the small-molecule MDM2 antagonist nutlin-3.
|
21460101 |
2011 |
Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Our data further characterize the apoptosis-sensitive phenotype induced by MYCN, expand our understanding of the activity of MDM2-p53 antagonists and highlight Galectin-3 as a potential biomarker for the tailored p53 reactivation therapy in patients with high-risk neuroblastomas.
|
23152863 |
2012 |