Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Genomic coamplification of CDK4/MDM2/FRS2 is associated with very poor prognosis and atypical clinical features in neuroblastoma patients.
|
31756773 |
2020 |
Neuroblastoma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
New inhibitor of the TAp73 interaction with MDM2 and mutant p53 with promising antitumor activity against neuroblastoma.
|
30664963 |
2019 |
Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Preclinical evaluation of the first intravenous small molecule MDM2 antagonist alone and in combination with temozolomide in neuroblastoma.
|
30536898 |
2019 |
Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Oridonin induces Mdm2-p60 to promote p53-mediated apoptosis and cell cycle arrest in neuroblastoma.
|
31339234 |
2019 |
Neuroblastoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
The present study evaluated the effect of ethanolic extract of <i>Nardostachys jatamansi</i> roots (NJ<sub>et</sub>) on MYCN mediated regulation of expression of MDM2 and p53 proteins in neuroblastoma cell lines, IMR-32 and SK-N-MC.
|
28216878 |
2019 |
Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Although MDM2 has been validated as a promising target in preclinical models, no MDM2 inhibitors have yet entered clinical trials for neuroblastoma patients.
|
29416773 |
2018 |
Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Together, combined inhibition of ALK and MDM2 may provide an effective treatment for <i>TP53</i> wild-type neuroblastoma with <i>ALK</i> aberrations.
|
28425916 |
2017 |
Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
The Neuroblastoma New Drug Development Strategy (NDDS) has: 1) established a group with expertise in drug development; 2) prioritised targets and drugs according to tumour biology (target expression, dependency, pre-clinical data; potential combinations; biomarkers), identifying as priority targets ALK, MEK, CDK4/6, MDM2, MYCN (druggable by BET bromodomain, aurora kinase, mTORC1/2) BIRC5 and checkpoint kinase 1; 3) promoted clinical trials with target-prioritised drugs.
|
28604107 |
2017 |
Neuroblastoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Importantly, neuroblastoma maintains both an active p53 and an aberrant mTOR signaling.<b>Experimental Design:</b> Using an orthotopic xenograft model and modulating p53 levels, we investigated the antitumor effects of the mTORC1 inhibitor temsirolimus in neuroblastoma expressing normal, decreased, or mutant p53, both as single agent and in combination with first- and second-generation MDM2 inhibitors to reactivate p53.<b>Results:</b> Nongenotoxic p53 activation suppresses mTOR activity.
|
28821555 |
2017 |
Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
In conclusion, these data strongly support the further evaluation of dual BCL2/MDM2 targeting as a therapeutic strategy in neuroblastoma.
|
28915653 |
2017 |
Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
In summary, our data strongly suggest that MDM2-specific inhibitors like SAR405838 may serve not only as a stand-alone therapy, but also as an effective adjunct to current chemotherapeutic regimens for treating NB with an intact MDM2-p53 axis.
|
27764791 |
2016 |
Neuroblastoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
The presence of SNP309 does not affect MDM2 expression in neuroblastoma.
|
24391119 |
2014 |
Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
The role of the MDM2 antagonist, p14(ARF), in controlling the TP53-MDM2 balance in neuroblastoma is unresolved.
|
23343716 |
2013 |
Neuroblastoma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Here we establish the role of these conjugates in activating p53 pathway by phosphorylation at Ser15, 20 and 46 residues and downregulate key oncogenic proteins such as MYCN and Mdm2 in IMR-32 neuroblastoma cells.
|
23992861 |
2013 |
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 |
Neuroblastoma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Our results indicate that MDM2 has a p53-independent role in the regulation of both MYCN mRNA stabilization and its translation, suggesting that MDM2-mediated MYCN expression is one mechanism associated with growth of MYCN-associated neuroblastoma and disease progression.
|
21822304 |
2012 |
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 |
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 |
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 |