Childhood Medulloblastoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Expression and association between PRMT5 and MYC in primary medulloblastoma tumors were investigated using publicly available databases.
|
31694585 |
2019 |
Childhood Medulloblastoma
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
JHU-083 treatment caused decreased growth and increased apoptosis in human MYC-expressing medulloblastoma cell lines.
|
31340195 |
2019 |
Childhood Medulloblastoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Therefore, our data provide insights about the mechanisms underlying BETi effects and the appearance of resistance and support the therapeutic use of combined cell-cycle inhibitors with BETi in MYC-amplified medulloblastoma.
|
31160565 |
2019 |
Childhood Medulloblastoma
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
Critically, G207 delivered to the cerebellum was able to target/treat the highly aggressive MYC-overexpressed group 3 murine medulloblastoma increasing survival vs controls.
|
30918335 |
2019 |
Childhood Medulloblastoma
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
Current preclinical models do not represent the full scale of group 3 and group 4 heterogeneity: all of existing group 3 cell lines are MYC-amplified and most mouse models resemble MYC-activated MBs.
|
30876441 |
2019 |
Childhood Medulloblastoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Combined functional genomic and chemical screens identify SETD8 as a therapeutic target in MYC-driven medulloblastoma.
|
30626740 |
2019 |
Childhood Medulloblastoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
MK-8628 showed therapeutic efficacy against in vitro and in vivo models of MYC-amplified medulloblastoma by inducing apoptotic cell death and cell cycle arrest.
|
30611741 |
2019 |
Childhood Medulloblastoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
This study highlights B7-H3 as a viable target in MB angiogenesis, and that the expression of miR-29 can inhibit B7-H3 and sensitize MB cells to treatment with MYC-inhibiting drugs.
|
31382461 |
2019 |
Childhood Medulloblastoma
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
We performed analysis of GABR and MYC expression in MB tumors and used molecular, cell biological, and whole-cell electrophysiology approaches to establish presence of a functional 'druggable' GABA<sub>A</sub>R in group 3 cells.
|
30725256 |
2019 |
Childhood Medulloblastoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
We find that higher MYC levels are associated with increased EZH2, and pharmacological blockade of EZH2 is a potential therapeutic strategy for aggressive medulloblastoma with elevated MYC.
|
30632221 |
2019 |
Childhood Medulloblastoma
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
High MYC mRNA expression and MYC gene amplification in MB have been considered as indicators of poor prognosis.
|
30901604 |
2019 |
Childhood Medulloblastoma
|
0.400 |
PosttranslationalModification
|
disease |
BEFREE |
Functional analysis of enriched pathways highlighted cell-cycle progression and protein synthesis as therapeutic targets for MYC-like medulloblastoma.
|
29562177 |
2018 |
Childhood Medulloblastoma
|
0.400 |
GeneticVariation
|
disease |
BEFREE |
In addition, the combination treatment significantly prolonged survival as compared to single-agent therapy in orthotopically transplanted human Group 3 MB with MYC amplifications.
|
29511348 |
2018 |
Childhood Medulloblastoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Human MYC-amplified (Med8A and D283) and non-amplified (UW228-2 and ONS76) MB cell lines were incubated for 2, 4 or 6 h with increasing doses (0-100 μg/ml) of 5-ALA, and PPIX accumulation was determined by flow cytometry.
|
30445362 |
2018 |
Childhood Medulloblastoma
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
In cell lines, SHH MB, which are low-MYC expressing, demonstrated both constitutive and inducible expression of PD-L1 while those in Group 3/4 that expressed high levels of MYC had only inducible expression.
|
29721192 |
2018 |
Childhood Medulloblastoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Results also demonstrated that the MYC-amplified MB lines showed a higher sensitivity to combined therapies compared to non-MYC-amplified cell lines.
|
29682173 |
2018 |
Childhood Medulloblastoma
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
The BET inhibitor JQ1 suppressed MYC expression in a human G3 MB cell line (HD-MB03) and CRISPR-Myc, but not in Retro-Myc MBs.
|
29880921 |
2018 |
Childhood Medulloblastoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Most children with medulloblastoma fall within the standard-risk clinical disease group defined by absence of high-risk features (metastatic disease, large-cell/anaplastic histology, and MYC amplification), which includes 50-60% of patients and has a 5-year event-free survival of 75-85%.
|
30392813 |
2018 |
Childhood Medulloblastoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Furthermore, combination therapy with S3-NTDi and cisplatin significantly decreased highly aggressive MYC-amplified MB cell growth and induced apoptosis by downregulating STAT3 regulated proliferation and anti-apoptotic gene expression.
|
29280516 |
2018 |
Childhood Medulloblastoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
To identify targetable vulnerabilities, we employed inhibitor screening that revealed mTOR inhibitor hypersensitivity in the MYC-overexpressing medulloblastoma cell line, D341.
|
28409891 |
2017 |
Childhood Medulloblastoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Novel MYC-driven medulloblastoma models from multiple embryonic cerebellar cells.
|
28504719 |
2017 |
Childhood Medulloblastoma
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
TEAD4's co-activator, YAP1, and the downstream targets, MYC and CCND1, were also found to be upregulated in AT/RT when compared to medulloblastoma.
|
27966820 |
2017 |
Childhood Medulloblastoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
In line with these findings we show for MYC-amplified medulloblastoma a profound reduction in activity of the oncogenes STAT3 and AKT.
|
28159923 |
2017 |
Childhood Medulloblastoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
DiSCoVER analysis predicted that aggressive MYC-driven Group 3 medulloblastoma would be sensitive to cyclin-dependent kinase (CDK) inhibitors.
|
27012813 |
2016 |
Childhood Medulloblastoma
|
0.400 |
Biomarker
|
disease |
BEFREE |
Historical risk stratification criteria for medulloblastoma rely primarily on clinicopathological variables pertaining to age, presence of metastases, extent of resection, histological subtypes and in some instances individual genetic aberrations such as MYC and MYCN amplification.
|
27040285 |
2016 |