Patrick Breheny
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View article: EHE cell cultures are a platform for mechanistic and therapeutic investigation
EHE cell cultures are a platform for mechanistic and therapeutic investigation Open
Epithelioid hemangioendothelioma (EHE) is a difficult to treat vascular sarcoma defined by TAZ-CAMTA1 (TC) or YAP-TFE3 (YT) fusion proteins. Human cell lines needed to further understand the pathogenesis of EHE have been lacking. Herein, w…
View article: Penalized mixed models to adjust for batch effects and unobserved confounding in high dimensional regression
Penalized mixed models to adjust for batch effects and unobserved confounding in high dimensional regression Open
Confounding can lead to spurious associations. Typically, one must observe confounders in order to adjust for them, but in high-dimensional settings, recent research has shown that it becomes possible to adjust even for unobserved confound…
View article: Alternative Likelihood Approximations for High-Dimensional Intervals for Lasso
Alternative Likelihood Approximations for High-Dimensional Intervals for Lasso Open
Classical frequentist approaches to inference for the lasso emphasize exact coverage for each feature, which requires debiasing and severs the connection between confidence intervals and the original lasso estimates. To address this, in ea…
View article: Spontaneous peripheral oxygen desaturation and apnea events in mice vary by strain and inspired oxygen level
Spontaneous peripheral oxygen desaturation and apnea events in mice vary by strain and inspired oxygen level Open
Mouse models of chronic intermittent hypoxia are widely used in research to understand the role of sleep apnea in disease pathogenesis. Mice exposed to periodic reductions in F I O 2 model arterial desaturations observed in humans and reca…
View article: EHE cell cultures: a platform for mechanistic and therapeutic investigation
EHE cell cultures: a platform for mechanistic and therapeutic investigation Open
Epithelioid hemangioendothelioma (EHE) is a difficult to treat vascular sarcoma defined by TAZ- CAMTA1 or YAP-TFE3 fusion proteins. Human cell lines needed to further understand the pathogenesis of EHE have been lacking. Herein, we describ…
View article: plmmr: an R package to fit penalized linear mixed models for genome-wide association data with complex correlation structure
plmmr: an R package to fit penalized linear mixed models for genome-wide association data with complex correlation structure Open
Correlation among the observations in high-dimensional regression modeling can be a major source of confounding. We present a new open-source package, plmmr, to implement penalized linear mixed models in R. This R package estimates correla…
View article: PI3K regulates TAZ/YAP and mTORC1 axes that can be synergistically targeted
PI3K regulates TAZ/YAP and mTORC1 axes that can be synergistically targeted Open
/Summary Purpose Sarcomas are a heterogeneous group of cancers with few shared therapeutic targets. PI3K signaling is activated in various subsets of sarcomas, representing a shared oncogenic signaling pathway. Oncogenic PI3K signaling has…
View article: Familial Oculoauriculovertebral Spectrum: A Genomic Investigation of Autosomal Dominant Inheritance
Familial Oculoauriculovertebral Spectrum: A Genomic Investigation of Autosomal Dominant Inheritance Open
Objective Oculoauriculovertebral spectrum (OAVS) encompasses abnormalities on derivatives from the first and second pharyngeal arches including macrostomia, hemifacial microsomia, micrognathia, preauricular tags, ocular, and vertebral anom…
View article: Distinct odorant receptor response patterns to aliphatic odorants in freely behaving mice
Distinct odorant receptor response patterns to aliphatic odorants in freely behaving mice Open
In mammals, odors are encoded by a combinatorial code determined by the pattern of responses across hundreds of odorant receptors expressed monogenically and monoallelically in olfactory sensory neurons. The compositions of these receptor …
View article: Supplementary Table S3 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression
Supplementary Table S3 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression Open
Supplementary Table S3. Cluster of differentiation (CD) markers used to delineate immune cell populations after gating on CD45+ live cells.
View article: Supplementary Figure S1 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression
Supplementary Figure S1 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression Open
Supplementary Figure S1. Combination therapy co-targeting CDK4/6 and MEK acts synergistically against MPNST cells in vitro
View article: Supplementary Figure S2 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression
Supplementary Figure S2 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression Open
Supplementary Figure S2. Dual CDK4/6-MEK inhibition synergistically suppresses the growth of some, but not all, MPNST PDXs in immune deficient mice
View article: Supplementary Figure S4 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression
Supplementary Figure S4 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression Open
Supplementary Figure S4. Predicted immune cell composition of human PNFs, ANNUBPs, and MPNSTs based on CIBERSORT analyses.
View article: Supplementary Table S1 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression
Supplementary Table S1 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression Open
Supplementary Table S1. Antibody sources and conditions for western blotting, IF, and IHC
View article: Supplementary Figure S6 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression
Supplementary Figure S6 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression Open
Supplementary Figure S6. Analysis of helper (CD4) and pan (CD3) T cells in combination therapysensitive versus combination therapy-resistant MPNSTs
View article: Supplementary Figure S5 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression
Supplementary Figure S5 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression Open
Supplementary Figure S5. Evaluation of differentially expressed genes (DEGs) and tumor infiltrating immune cells (plasma cells and B cells) in drug-treated de novo MPNSTs.
View article: Supplementary Figure S4 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression
Supplementary Figure S4 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression Open
Supplementary Figure S4. Predicted immune cell composition of human PNFs, ANNUBPs, and MPNSTs based on CIBERSORT analyses.
View article: Supplementary Figure S7 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression
Supplementary Figure S7 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression Open
Supplementary Figure S7. Analyses of p-RB1, Ki67, and PD-L1 in combination therapy-sensitive and - resistant MPNSTs and PD-L1 in NF1 patient tumors.
View article: Supplementary Figure S1 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression
Supplementary Figure S1 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression Open
Supplementary Figure S1. Combination therapy co-targeting CDK4/6 and MEK acts synergistically against MPNST cells in vitro
View article: Supplementary Table S2 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression
Supplementary Table S2 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression Open
Supplementary Table S2. Antibodies and dyes used for immunophenotyping by flow cytometry.
View article: Data from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression
Data from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression Open
Purpose: Malignant peripheral nerve sheath tumors (MPNSTs) are lethal, Ras-driven sarcomas that lack effective therapies. We investigated effects of targeting CDK4/6, MEK, and/or programmed death-ligand 1 (PD-L1) in preclinical MPNST model…
View article: Supplementary Figure S3 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression
Supplementary Figure S3 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression Open
Supplementary Figure S3. Tumor growth kinetics of individual de novo MPNSTs during therapy
View article: Supplementary Figure S3 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression
Supplementary Figure S3 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression Open
Supplementary Figure S3. Tumor growth kinetics of individual de novo MPNSTs during therapy
View article: Supplementary Table S4 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression
Supplementary Table S4 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression Open
Supplementary Table S4. Primers for qRT-PCR analyses
View article: Supplementary Figure S8 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression
Supplementary Figure S8 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression Open
Supplementary Figure S8. Additional MPNST analyses for CDK4/6-MEK inhibition plus anti-PD-L1 therapy study.
View article: Supplementary Table S3 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression
Supplementary Table S3 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression Open
Supplementary Table S3. Cluster of differentiation (CD) markers used to delineate immune cell populations after gating on CD45+ live cells.
View article: Supplementary Figure S2 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression
Supplementary Figure S2 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression Open
Supplementary Figure S2. Dual CDK4/6-MEK inhibition synergistically suppresses the growth of some, but not all, MPNST PDXs in immune deficient mice
View article: Supplementary Table S5 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression
Supplementary Table S5 from CDK4/6-MEK inhibition in MPNSTs causes plasma cell infiltration, sensitization to PD-L1 blockade, and tumor regression Open
Supplementary Table S5. Abbreviated list of top kinase inhibitory compounds predicted to be effective against MPNSTs from C-Map analyses of the MPNST transcriptome from NF1 patients.