|
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
The performance of the proposed methodology is investigated by applying a state-feedback controller to two GRN models: a melanoma WNT5A Boolean network and a p53-MDM2 negative feedback loop Boolean network, when the cost of the undesirable states, and thus the identity of the undesirable genes, is learned using the proposed methodology.
|
29993697 |
2020 |
|
melanoma
|
0.500 |
AlteredExpression
|
disease |
BEFREE |
The protein levels of p53 and p21 increased upon the treatment with albendazole and fenbendazole, indicating activation of the p53-p21 pathway, while the levels of Mdm2 and MdmX decreased in melanoma and breast cancer cells overexpressing these proteins.
|
31181622 |
2019 |
|
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
Our findings provide a rationale for cotargeting CDK4/6 and MDM2 in melanoma.
|
31413145 |
2019 |
|
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
Besides the identification of well-recognized driver mutations of <i>BRAF</i> (3.1%), <i>RAS</i> family (6.2%), <i>NF1</i> (7.8%), and <i>KIT</i> (23.1%) in MMs, our study also found that (i) mutations and amplifications in the transmembrane nucleoporin gene <i>POM121</i> (30.8%) defined a patient subgroup with higher tumor proliferation rates; (ii) enrichment of structural variations between chromosomes 5 and 12 defined a patient subgroup with significantly worse clinical outcomes; (iii) over 50% of the MM patients harbored recurrent focal amplification of several oncogenes (<i>CDK4, MDM2,</i> and <i>AGAP2</i>) at 12q13-15, and this co-occurred significantly with amplification of <i>TERT</i> at 5p15, which was verified in the validation cohort; (iv) the PDX trial demonstrated robust antitumor effects of palbociclib in MMs harboring <i>CDK4</i> amplification.
|
30782616 |
2019 |
|
melanoma
|
0.500 |
AlteredExpression
|
disease |
BEFREE |
Targeting negative regulation of p53 by MDM2 and WIP1 as a therapeutic strategy in cutaneous melanoma.
|
29235570 |
2018 |
|
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
ATM Dependent DUSP6 Modulation of p53 Involved in Synergistic Targeting of MAPK and p53 Pathways with Trametinib and MDM2 Inhibitors in Cutaneous Melanoma.
|
30577494 |
2018 |
|
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
Antagonists of MDM2-p53 interaction are emerging anti-cancer drugs utilized in clinical trials for malignancies that rarely mutate p53, including melanoma.
|
29030058 |
2017 |
|
melanoma
|
0.500 |
AlteredExpression
|
disease |
BEFREE |
In a word, via increasing hnRNPA1 level and then reducing the expression of MDM2, estradiol prevented carcinogenesis in melanomas.
|
28035066 |
2017 |
|
melanoma
|
0.500 |
AlteredExpression
|
disease |
BEFREE |
Melanoma tumors usually retain wild-type p53; however, its tumor-suppressor activity is functionally disabled, most commonly through an inactivating interaction with mouse double-minute 2 homolog (Mdm2), indicating p53 release from this complex as a potential therapeutic approach.
|
28092675 |
2017 |
|
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
Our data present, for the first time, preliminary evidence that inherited abnormalities on TP53, MDM2 and BCL2 genes, enrolled in apoptosis pathways, have a pivotal role in differences of outcomes in women and men with CM.
|
28050764 |
2017 |
|
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
Flow cytometry and confocal analysis were performed on C26 colon carcinoma (HDM2 positive) and B16F0 melanoma (HDM2 negative) cells.
|
28565974 |
2017 |
|
melanoma
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
The dysplastic nevus phenotype, present in the majority of our hereditary melanoma cases and also in some sporadic cases, further enhanced the effect of the MDM2 GG genotype on melanoma risk (P=0.005).
|
24625390 |
2014 |
|
melanoma
|
0.500 |
AlteredExpression
|
disease |
BEFREE |
The effects of miR-18b overexpression on the p53 pathway and on melanoma cell growth were reversed by MDM2 overexpression.
|
23365201 |
2013 |
|
melanoma
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Dual targeting of BRAF(V600E) and Hdm2 with vemurafenib and Nt-3, respectively, synergistically induced apoptosis and suppressed melanoma viability in vitro and tumor growth in vivo.
|
23812671 |
2013 |
|
melanoma
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
A number of genes previously recognized to have an important role in the development and progression of melanoma were identified including homozygous deletions of CDKN2A (13 of 39 samples), CDKN2B (10 of 39), PTEN (3 of 39), PTPRD (3 of 39), TP53 (1 of 39), and amplifications of CCND1 (2 of 39), MITF (2 of 39), MDM2 (1 of 39), and NRAS (1 of 39).
|
22250051 |
2012 |
|
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
Specifically, we used a combination of RNA interference and two structurally independent small molecule inhibitors of the p53-MDM2 interaction to assess the relative requirement of both proteins for the viability of normal melanocytes and a broad panel of melanoma cell lines.
|
21743494 |
2012 |
|
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
Moreover, we also found that the melanoma growth suppression mediated by mitogen-activated protein kinase/extracellular signal-regulated kinase inhibition was potentiated by HDM2 antagonism.
|
21993556 |
2012 |
|
melanoma
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Investigation of the effect of MDM2 SNP309 and TP53 Arg72Pro polymorphisms on the age of onset of cutaneous melanoma.
|
22336942 |
2012 |
|
melanoma
|
0.500 |
Biomarker
|
disease |
BEFREE |
The data suggest that the ability of sorafenib to activate GSK-3β and alter the intracellular distribution of p53 may be exploitable as an adjunct to agents that prevent the HDM2-dependent degradation of p53 in the treatment of melanoma.
|
21929745 |
2011 |
|
melanoma
|
0.500 |
AlteredExpression
|
disease |
BEFREE |
Finally, we show that overexpression of SPARC renders cells more resistant to the p53-mediated cytotoxic effects of the DNA-damaging drug actinomycin-D. Our study indicates that SPARC functions through activation of Akt and MDM2 to limit p53 levels and that acquired expression of SPARC during melanoma development would confer survival advantages through suppression of p53-dependent apoptotic pathways.
|
21685937 |
2011 |
|
melanoma
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
MDM2 SNP309 and p53 Arg72Pro in cutaneous melanoma: association between SNP309 GG genotype and tumor Breslow thickness.
|
20535124 |
2010 |
|
melanoma
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
We evaluated the effect of MDM2 SNP309 and its interaction with the p53 Arg72Pro polymorphism on pigmentary phenotypes and skin cancer risk in a nested case-control study within the Nurses' Health Study (NHS) among 219 melanoma cases, 286 squamous cell carcinoma (SCC) cases, 300 basal cell carcinoma (BCC) cases, and 873 controls, and among controls from other studies.
|
18814047 |
2009 |
|
melanoma
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Prospectively enrolled melanoma patients (N = 227) were evaluated for MDM2 SNP309 and the related polymorphism, p53 Arg72Pro.
|
19318491 |
2009 |
|
melanoma
|
0.500 |
AlteredExpression
|
disease |
BEFREE |
We speculated that guanine at position 309 (G309) of the Mdm2 promoter might be a cause of Mdm2 overexpression in MM patients, and associated with increased risk of MM.
|
19455066 |
2009 |
|
melanoma
|
0.500 |
Biomarker
|
disease |
CTD_human |
Treatment of melanoma cells with DW1/2 was instead found to decrease levels of Mdm2 and Mdm4.
|
17210701 |
2007 |