William J.E. Frye
A5026472811- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Histone Deacetylase Inhibitors Research
- Sarcoma Diagnosis and Treatment
- Protein Degradation and Inhibitors
- Lung Cancer Treatments and Mutations
- Cancer Research and Treatments
- Drug Transport and Resistance Mechanisms
- Click Chemistry and Applications
- PI3K/AKT/mTOR signaling in cancer
- Cancer Mechanisms and Therapy
- Peptidase Inhibition and Analysis
- MicroRNA in disease regulation
- Barrier Structure and Function Studies
- Ferroptosis and cancer prognosis
- Quinazolinone synthesis and applications
- Cell Adhesion Molecules Research
- Caveolin-1 and cellular processes
- HER2/EGFR in Cancer Research
- Adenosine and Purinergic Signaling
- RNA Interference and Gene Delivery
- Melanoma and MAPK Pathways
- Renal and related cancers
- Glioma Diagnosis and Treatment
National Cancer Institute
2022-2025
Center for Cancer Research
2022-2025
National Institutes of Health
2022-2025
Abstract Background A principal protective component of the mammalian blood–brain barrier (BBB) is high expression multidrug efflux transporters P-glycoprotein (P-gp, encoded by ABCB1 ) and ABCG2 (encoded on lumenal surface endothelial cells. The zebrafish P-gp homolog Abcb4 expressed at BBB phenocopies human P-gp. Comparatively little known about four homologs gene: abcg2a , abcg2b abcg2c abcg2d . Here we report functional characterization brain tissue distribution homologs. Methods To...
Aim: Ferroptosis is a non-apoptotic form of cell death caused by lethal lipid peroxidation. Several small molecule ferroptosis inducers (FINs) have been reported, yet little information available regarding their interaction with the ATP-binding cassette (ABC) transporters P-glycoprotein (P-gp, ABCB1) and ABCG2. We thus sought to characterize interactions FINs P-gp ABCG2, which may provide oral bioavailability brain penetration predict drug-drug interactions. Methods: Cytotoxicity assays...
Abstract In malignant glioma, cytotoxic drugs are often inhibited from accessing the tumor site due to blood-tumor barrier (BTB). Ibrutinib, FDA-approved lymphoma agent, inhibits Bruton tyrosine kinase (BTK) and has previously been shown independently impair aortic endothelial adhesion increase rodent glioma model survival in combination with therapy. Yet additional research is required understand ibrutinib’s effect on BTB function. this study, we detail baseline BTK expression cells its...
Abstract Purpose: PAX-fusion negative rhabdomyosarcoma (FN RMS) is driven by alterations in the RAS/MAP kinase pathway and partially responsive to MEK inhibition. Overexpression of IGF1R its ligands also observed FN RMS. Preclinical clinical studies have suggested that itself an important target Our previous revealed preclinical efficacy MEK1/2 inhibitor, trametinib, BMS-754807, but this combination was not pursued clinically due intolerability murine models. Here, we sought identify a...
Abstract Histone deacetylase inhibitors (HDACi) are part of a growing class epigenetic therapies used for the treatment cancer. Although HDACis effective in T-cell lymphomas, solid tumors with this drugs has not been successful. Overexpression multidrug resistance protein P-glycoprotein (P-gp), encoded by ABCB1, is known to confer HDACi romidepsin vitro, yet increased ABCB1 expression associated patients, suggesting that other mechanisms arise clinic. To identify alternative romidepsin, we...
Ferroptosis is a form of cell death caused by direct or indirect inhibition glutathione peroxidase 4 that leads to lethal lipid peroxidation. Several small molecule ferroptosis inducers (FINs) have been reported, yet little information available regarding resistance mechanisms, particularly their interaction with the ATP-binding cassette (ABC) transporters P-glycoprotein (P-gp, ABCB1) and ABCG2. Given role ABC play in absorption, distribution, excretion many drugs, characterizing these...
Abstract Background A principal protective component of the mammalian blood-brain barrier (BBB) is high expression multidrug efflux transporters P-glycoprotein (P-gp, encoded by ABCB1 ) and ABCG2 (encoded on lumenal surface endothelial cells. The zebrafish P-gp homolog Abcb4 expressed at BBB phenocopies human P-gp. Comparatively little known about four homologs gene: abcg2a , abcg2b abcg2c abcg2d . Here we report functional characterization brain tissue distribution homologs. Methods To...
ABSTRACT Histone deacetylase inhibitors (HDACis) are part of a growing class epigenetic therapies used for the treatment cancer. While elevated levels efflux pump P-gp associated with in vitro resistance to romidepsin, this mechanism does not translate clinic. We developed romidepsin-resistant cell line independent function that acts upstream deacetylation process. found expression methyltransferase METTL7A is necessary resistance, and naïve cells can drive thiol-containing HDACis....
<p>Supplemental Table S8 contains information about METTL7A and METTL7B in T-cell lymphoma tissue microarray samples</p>
<p>Supplemental Table S2 contains information about the cross-resistance profile of MCF7 DpVp300 cells for multiple drugs</p>
<p>Figure S2 contains cell cycle analysis and cytotoxicity data for MCF7 DpVp300 cells showing they are resistant to romidepsin do not overexpress P-gp</p>
<p>Figure S1 contains chemical structures of select HDAC inhibitors</p>
<p>Supplemental Table S8 contains information about METTL7A and METTL7B in T-cell lymphoma tissue microarray samples</p>
<p>Supplemental Table S7 contains information about the normal tissue expression of METTL7A and METTL7B</p>
<p>Figure S3 contains gene ontology analysis, motif and nucleosome density from the RNA-seq ATAC-seq data.</p>
<p>Figure S4 contains cytotoxicity assay and immunoblot data from the MCF7 DpVp300 cell lines showing that expression of METTL7A confers resistance.</p>
<p>Figure S1 contains chemical structures of select HDAC inhibitors</p>
<p>Supplemental Table S1 contains information about the chemical structures of HDACi</p>
<p>Figure S2 contains cell cycle analysis and cytotoxicity data for MCF7 DpVp300 cells showing they are resistant to romidepsin do not overexpress P-gp</p>
<div>Abstract<p>Histone deacetylase inhibitors (HDACi) are part of a growing class epigenetic therapies used for the treatment cancer. Although HDACis effective in T-cell lymphomas, solid tumors with this drugs has not been successful. Overexpression multidrug resistance protein P-glycoprotein (P-gp), encoded by <i>ABCB1</i>, is known to confer HDACi romidepsin <i>in vitro</i>, yet increased <i>ABCB1</i> expression associated patients,...
<div>Abstract<p>Histone deacetylase inhibitors (HDACi) are part of a growing class epigenetic therapies used for the treatment cancer. Although HDACis effective in T-cell lymphomas, solid tumors with this drugs has not been successful. Overexpression multidrug resistance protein P-glycoprotein (P-gp), encoded by <i>ABCB1</i>, is known to confer HDACi romidepsin <i>in vitro</i>, yet increased <i>ABCB1</i> expression associated patients,...
<p>Figure S6 contains cell cycle analysis of cells overexpressing METTL7A.</p>
<p>Figure S4 contains cytotoxicity assay and immunoblot data from the MCF7 DpVp300 cell lines showing that expression of METTL7A confers resistance.</p>