Jean M. Mulcahy Levy
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View article: Multi‐pronged analysis of pediatric low‐grade glioma and ganglioglioma reveals a unique tumor microenvironment associated with <scp>BRAF</scp> alterations
Multi‐pronged analysis of pediatric low‐grade glioma and ganglioglioma reveals a unique tumor microenvironment associated with <span>BRAF</span> alterations Open
Pediatric low‐grade gliomas (pLGG) comprise 35% of all brain tumors. Despite favorable survival, patients experience significant morbidity from disease and treatments. A deeper understanding of pLGG biology is essential to identify novel, …
View article: BRAF/MEK inhibition induces cell state transitions boosting immune checkpoint sensitivity in BRAFV600E-mutant glioma
BRAF/MEK inhibition induces cell state transitions boosting immune checkpoint sensitivity in BRAFV600E-mutant glioma Open
Resistance to v-raf murine sarcoma viral oncogene homolog B1 (BRAF) plus mitogen-activated protein kinase kinase (MEK) inhibition (BRAFi+MEKi) in BRAFV600E-mutant gliomas drives rebound, progression, and high mortality, yet it remains poor…
View article: Loss of LDOC1 by chromatin compaction in mesenchymal tumor cells is required for PFA1 ependymoma growth
Loss of LDOC1 by chromatin compaction in mesenchymal tumor cells is required for PFA1 ependymoma growth Open
Background Posterior fossa molecular subtype A (PFA) ependymoma occurs in young children and is the deadliest subtype of pediatric ependymoma. High-risk subtypes with chromosome 1q + and/or 6q- exhibit significantly poorer outcomes compare…
View article: Combined inhibition of SHP2 overcomes adaptive resistance to type 1 BRAF inhibitors in BRAF V600E-driven high-grade glioma
Combined inhibition of SHP2 overcomes adaptive resistance to type 1 BRAF inhibitors in BRAF V600E-driven high-grade glioma Open
Background BRAF-mutant gliomas can be targeted therapeutically using BRAF-selective inhibitors, yet responses are often transient due to adaptive resistance through reactivation of RAS-ERK signaling. Here, we evaluate the role of SHP2, a c…
View article: Supplemental Table 1 from Deconvoluting Mechanisms of Acquired Resistance to RAF Inhibitors in BRAF<sup>V600E</sup>-Mutant Human Glioma
Supplemental Table 1 from Deconvoluting Mechanisms of Acquired Resistance to RAF Inhibitors in BRAF<sup>V600E</sup>-Mutant Human Glioma Open
Upstream regulators predicted in Ingenuity Pathway Analysis. All significant p<0.01) patient sample and cell line upstream regulators predicted to have changed after exposure to BRAFi, organized by tab. Analysis was conducted per-patient, …
View article: Supplementary Methods from Deconvoluting Mechanisms of Acquired Resistance to RAF Inhibitors in BRAF<sup>V600E</sup>-Mutant Human Glioma
Supplementary Methods from Deconvoluting Mechanisms of Acquired Resistance to RAF Inhibitors in BRAF<sup>V600E</sup>-Mutant Human Glioma Open
Supplementary Methods
View article: Supplemental Table 2 from Deconvoluting Mechanisms of Acquired Resistance to RAF Inhibitors in BRAF<sup>V600E</sup>-Mutant Human Glioma
Supplemental Table 2 from Deconvoluting Mechanisms of Acquired Resistance to RAF Inhibitors in BRAF<sup>V600E</sup>-Mutant Human Glioma Open
GSEA analysis of paired RNA samples. Samples were analyzed using both the C2 (Curated Gene Sets) and C6 (Oncogenic Signature Gene Sets) MSigDB Collections. Comparisons were made either between the pre- and post-BRAFi samples within the TGF…
View article: Supplementary Figure 3 from Deconvoluting Mechanisms of Acquired Resistance to RAF Inhibitors in BRAF<sup>V600E</sup>-Mutant Human Glioma
Supplementary Figure 3 from Deconvoluting Mechanisms of Acquired Resistance to RAF Inhibitors in BRAF<sup>V600E</sup>-Mutant Human Glioma Open
Increased RTK expression and activity in AM38 resistant cells. (A) RTK array for parental (left) and resistant (right) AM38 cells. (B) Immunoblot of cell lysates from parental (P) and resistant (R) AM38. (C) Fold change in RNA expression b…
View article: Supplementary Figure 2 from Deconvoluting Mechanisms of Acquired Resistance to RAF Inhibitors in BRAF<sup>V600E</sup>-Mutant Human Glioma
Supplementary Figure 2 from Deconvoluting Mechanisms of Acquired Resistance to RAF Inhibitors in BRAF<sup>V600E</sup>-Mutant Human Glioma Open
Frequency of co-mutations in BRAF and genes of interest in 35,231 patients in pan-cancer cohorts found in cBioPortal. The bar graph represents the number of patients with each pair of alterations as found in dataset and the circles represe…
View article: Supplemental Table 3 from Deconvoluting Mechanisms of Acquired Resistance to RAF Inhibitors in BRAF<sup>V600E</sup>-Mutant Human Glioma
Supplemental Table 3 from Deconvoluting Mechanisms of Acquired Resistance to RAF Inhibitors in BRAF<sup>V600E</sup>-Mutant Human Glioma Open
GSEA subgroup analysis of paired RNA samples. Subgroups were analyzed based on the presence (Enriched in post-txt mutant) or absence (Enriched in post-txt non-mutant) of a genomic alteration at time of recurrence. Subgroup analysis was als…
View article: Supplementary Figure 1 from Deconvoluting Mechanisms of Acquired Resistance to RAF Inhibitors in BRAF<sup>V600E</sup>-Mutant Human Glioma
Supplementary Figure 1 from Deconvoluting Mechanisms of Acquired Resistance to RAF Inhibitors in BRAF<sup>V600E</sup>-Mutant Human Glioma Open
Venn diagram detailing the gene lists used to assemble the ten most commonly mutated genes in glioblastoma.
View article: Data from Deconvoluting Mechanisms of Acquired Resistance to RAF Inhibitors in BRAF<sup>V600E</sup>-Mutant Human Glioma
Data from Deconvoluting Mechanisms of Acquired Resistance to RAF Inhibitors in BRAF<sup>V600E</sup>-Mutant Human Glioma Open
Purpose:Selective RAF-targeted therapy is effective in some patients with BRAFV600E-mutated glioma, though emergent and adaptive resistance occurs through ill-defined mechanisms.Experimental Design:Paired pre-/post- RAF inhibitor (RAFi)-tr…
View article: Supplementary Figure 4 from Deconvoluting Mechanisms of Acquired Resistance to RAF Inhibitors in BRAF<sup>V600E</sup>-Mutant Human Glioma
Supplementary Figure 4 from Deconvoluting Mechanisms of Acquired Resistance to RAF Inhibitors in BRAF<sup>V600E</sup>-Mutant Human Glioma Open
GSEA comparing paired pre-/post- treatment glioma with BRAF V600E mutations (n=10) against BRAF wild type (n = 4) specimens. Highlighted are selected groups of similar differentially expressed gene sets. WT = wild type
View article: The assessment of therapeutic autophagy inhibition in NF1 mutated tumor cells
The assessment of therapeutic autophagy inhibition in NF1 mutated tumor cells Open
MAPK pathway activation is found across central nervous system tumors. Neurofibromin 1 (NF1) protein is a GTPase-activating protein and tumor suppressor that negatively regulates RAS protein activity. A NF1 loss of function mutation result…
View article: CNSC-25. CONCURRENT IMMUNE CHECKPOINT BLOCKADE ENHANCES THE SURVIVAL BENEFIT OF CLINICALLY RELEVANT MAPK PATHWAY INHIBITORS IN A T CELL-DEPENDENT MANNER
CNSC-25. CONCURRENT IMMUNE CHECKPOINT BLOCKADE ENHANCES THE SURVIVAL BENEFIT OF CLINICALLY RELEVANT MAPK PATHWAY INHIBITORS IN A T CELL-DEPENDENT MANNER Open
BACKGROUND Despite the availability of targeted therapies, gliomas carrying the BRAFV600E mutation remain challenging to treat. Combined pharmacologic BRAFV600E and MEK inhibition is clinically used in patients with BRAFV600E mutant glioma…
View article: LGG-57. BH3 MIMETICS IMPROVE RESPONSE TO AUTOPHAGY INHIBITION IN BRAFV600E GLIOMAS
LGG-57. BH3 MIMETICS IMPROVE RESPONSE TO AUTOPHAGY INHIBITION IN BRAFV600E GLIOMAS Open
BACKGROUND Autophagy inhibition improves the effectiveness of RAF pathway inhibition (RAFi) and overcomes resistance mechanisms. Mechanistic links between autophagy and apoptotic cell death may explain this ability. BH3 mimetics with autop…
View article: LGG-12. INTEGRATED CLINICAL AND MOLECULAR CHARACTERIZATION OF 200 DISSEMINATED PEDIATRIC LOW-GRADE GLIOMAS
LGG-12. INTEGRATED CLINICAL AND MOLECULAR CHARACTERIZATION OF 200 DISSEMINATED PEDIATRIC LOW-GRADE GLIOMAS Open
Pediatric low-grade gliomas (PLGG) have excellent outcomes overall but are a major clinical challenge when disseminated. Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a recognised entity both clinically and pathologically, however m…
View article: ETMR-22. IDENTIFICATION OF 5-FLUROURACIL AS A SELECTIVE THERAPY IN A NOVEL EP300::BCOR FUSION GLIOMA TUMOR MODEL
ETMR-22. IDENTIFICATION OF 5-FLUROURACIL AS A SELECTIVE THERAPY IN A NOVEL EP300::BCOR FUSION GLIOMA TUMOR MODEL Open
INTRODUCTION BCL6 corepressor gene (BCOR)-altered glioma brain tumors are a newly identified entity which include cases involving a gene fusion with histone acetyltransferase EP300. Treatment strategies for BCOR-fusion gliomas have not yet…
View article: CP-12. PHASE 0 AND FEASIBILITY SINGLE-INSTITUTION CLINICAL TRIAL OF INTRAVENOUS TOCILIZUMAB FOR ADAMANTINOMATOUS CRANIOPHARYNGIOMA
CP-12. PHASE 0 AND FEASIBILITY SINGLE-INSTITUTION CLINICAL TRIAL OF INTRAVENOUS TOCILIZUMAB FOR ADAMANTINOMATOUS CRANIOPHARYNGIOMA Open
BACKGROUND Adamantinomatous craniopharyngioma (ACP) is a devastating skull-base tumor believed to derive from epithelial remnants of the primordial craniopharyngeal duct (Rathke’s pouch), which gives rise to the anterior pituitary gland. A…
View article: Abstracts of the 100th Annual Meeting June 6–9, 2024 Olympic Valley, California
Abstracts of the 100th Annual Meeting June 6–9, 2024 Olympic Valley, California Open
Background: Clinical trials of anti-Aβ monoclonal antibodies in Alzheimer disease (AD) infer target engagement from Aβ positron emission tomography (PET) and/or fluid biomarkers such as cerebrospinal fluid (CSF) Aβ42/40.However, these biom…
View article: Multi-pronged analysis of pediatric low-grade glioma reveals a unique tumor microenvironment associated with BRAF alterations
Multi-pronged analysis of pediatric low-grade glioma reveals a unique tumor microenvironment associated with BRAF alterations Open
Pediatric low-grade gliomas (pLGG) comprise 35% of all brain tumors. Despite favorable survival, patients experience significant morbidity from disease and treatments. A deeper understanding of pLGG biology is essential to identify novel, …
View article: Tumor and immune cell types interact to produce heterogeneous phenotypes of pediatric high-grade glioma
Tumor and immune cell types interact to produce heterogeneous phenotypes of pediatric high-grade glioma Open
Background Pediatric high-grade gliomas (PHGG) are aggressive brain tumors with 5-year survival rates ranging from <2% to 20% depending upon subtype. PHGG presents differently from patient to patient and is intratumorally heterogeneous,…
View article: Genetic Predictors of Neurocognitive Outcomes in Survivors of Pediatric Brain Tumors
Genetic Predictors of Neurocognitive Outcomes in Survivors of Pediatric Brain Tumors Open
Purpose : Neurocognitive deficits are common in pediatric brain tumor survivors. The use of single nucleotide polymorphism (SNP) analysis in DNA repair genes may identify children treated with radiation therapy for brain tumors at increase…
View article: HGG-18. SINGLE CELL RNA-SEQ ANALYSIS OF PEDIATRIC HIGH-GRADE GLIOMA PATIENT SAMPLES IDENTIFIES COMMON GLIAL AND IMMUNE CELL TYPES THAT HELP TO EXPLAIN HETEROGENEITY AND TUMORIGENESIS
HGG-18. SINGLE CELL RNA-SEQ ANALYSIS OF PEDIATRIC HIGH-GRADE GLIOMA PATIENT SAMPLES IDENTIFIES COMMON GLIAL AND IMMUNE CELL TYPES THAT HELP TO EXPLAIN HETEROGENEITY AND TUMORIGENESIS Open
BACKGROUND Pediatric high-grade gliomas (PHGG) are aggressive, undifferentiated central nervous system (CNS) tumors. PHGG comprises subtypes that differ phenotypically, histologically and by cellular composition. Despite intensive research…
View article: LGG-22. CHARACTERIZATION OF THE TUMOR MICROENVIRONMENT IN PEDIATRIC LOW-GRADE GLIOMA
LGG-22. CHARACTERIZATION OF THE TUMOR MICROENVIRONMENT IN PEDIATRIC LOW-GRADE GLIOMA Open
BACKGROUND Pediatric low-grade gliomas (pLGGs) are the most common brain tumors in children. Although pLGGs represent a significant number of patients with slow-growing, often curable tumors, they are also affected by neurologic injuries, …
View article: Supplementary Figure 5 from Interleukin-6/STAT3 Pathway Signaling Drives an Inflammatory Phenotype in Group A Ependymoma
Supplementary Figure 5 from Interleukin-6/STAT3 Pathway Signaling Drives an Inflammatory Phenotype in Group A Ependymoma Open
S3I-201 effects on cell cycle EPN cell line 811 and apoptosis in EPN cell line 723.
View article: Supplementary Figure 5 from Autophagy Inhibition Improves Chemosensitivity in BRAF<sup>V600E</sup> Brain Tumors
Supplementary Figure 5 from Autophagy Inhibition Improves Chemosensitivity in BRAF<sup>V600E</sup> Brain Tumors Open
PDF file 31K, Autophagic flux by flow cytometry in vemurafenib treated cells
View article: Supplementary Figure 4 from Interleukin-6/STAT3 Pathway Signaling Drives an Inflammatory Phenotype in Group A Ependymoma
Supplementary Figure 4 from Interleukin-6/STAT3 Pathway Signaling Drives an Inflammatory Phenotype in Group A Ependymoma Open
Concentration of cytokine secretion from flow sorted disaggregated tumor samples.
View article: Data from Interleukin-6/STAT3 Pathway Signaling Drives an Inflammatory Phenotype in Group A Ependymoma
Data from Interleukin-6/STAT3 Pathway Signaling Drives an Inflammatory Phenotype in Group A Ependymoma Open
Ependymoma (EPN) in childhood is a brain tumor with substantial mortality. Inflammatory response has been identified as a molecular signature of high-risk Group A EPN. To better understand the biology of this phenotype and aid therapeutic …