Arnold J. Levine
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View article: Neoantigenic properties of TP53 variants influence cancer risk in individuals with Li-Fraumeni syndrome
Neoantigenic properties of TP53 variants influence cancer risk in individuals with Li-Fraumeni syndrome Open
European Commission, Fondation MSDAvenir, BMBF, Deutsche Kinderkrebsstiftung, European Regional Development Fund, Région Normandie, NIH, Mark Foundation, and Hertz Foundation.
View article: Genomic landscape of virus-associated cancers
Genomic landscape of virus-associated cancers Open
It has been estimated that 15%-20% of human cancers are attributable to infections, mostly by carcinogenic viruses. The incidence varies worldwide, with a majority affecting developing countries. Here, we conduct a comparative analysis of …
View article: Neoantigenic properties of<i>TP53</i>variants modify cancer risk in individuals with Li-Fraumeni syndrome
Neoantigenic properties of<i>TP53</i>variants modify cancer risk in individuals with Li-Fraumeni syndrome Open
STRUCTURED ABSTRACT Importance Li-Fraumeni Syndrome (LFS) is an heterogenous cancer predisposition caused by pathogenic TP53 variants, characterized by a lifelong high risk of a broad spectrum of cancers. At least certain pathogenic TP53 v…
View article: Supplementary Tables S1-S4 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary Tables S1-S4 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
Supplementary Table S1. Sensitivity of Various Cell Lines to Reactivator Compound PC14586. Supplementary Table S2. Cell Line Information for Cells Used in the Paper. Supplementary Table S3. Antibodies Used to Detect Specific Antigens in Tu…
View article: Figure 5 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Figure 5 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
Pharmacologic activation of WT p53 inhibited tumor growth and induced immunologic cell changes in tumors. A, Average tumor volume (mm3; left), AUC analysis of tumor growth (middle), and percentage of body weight change (right) in C57Bl/6 m…
View article: Supplementary File S6 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S6 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
p53 pathway profiling analysis in T3M-4 cells treated by PC14586 (5 µM) vs. DMSO control (16 h).
View article: Supplementary Figures S1-S7 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary Figures S1-S7 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
Supplementary Figure S1. Functional Characterization of p53-Y220C Reactivator Compounds. Supplementary Figure S2. Reactivator Compounds are Active Only in p53-Y220C Cell Lines. Supplementary Figure S3. Selective Restoration of Wild-Type (W…
View article: Figure 1 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Figure 1 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
Functional characterization of p53-Y220C reactivator compounds and restoration of WT p53 function in cells. A, Structure of p53 reactivators and biochemical properties. The concentration of the test compound required to increase Y220C-DBD …
View article: Supplementary File S12 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S12 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
The restoration of the p53 signaling pathway in vivo was assessed via p53 pathway profiling analysis in NUGC-3 xenografted tumors after 6 days of 100-mg/kg PC14586 administration.
View article: Supplementary File S16 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S16 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
GSEA analysis using MSigDB Hallmark gene sets collection (H) for all detected genes demonstrated the regulation of genes for immune and inflammatory response in vivo in NUGC-3 xenograft tumors following 8 h of treatment with 100 mg/kg PC14…
View article: Figure 2 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Figure 2 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
Selective restoration of WT p53 transcriptional responses by PC14586 in cells. A, Quantification of CDKN1A (p21) and MDM2 mRNA by qRT-PCR in p53-Y220C, other p53 hotspot mutants, p53 WT, and p53 KO cell lysates following 5 hours of treatme…
View article: Figure 4 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Figure 4 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
PC14586 restored multiple facets of dynamic WT p53 transcriptional responses in vivo. A, Time-dependent effects of PC14586 on gene expression of key p53 targets, CDKN1A, MDM2, and BIRC5, with repeat daily administration across 6 days in th…
View article: Supplementary File S4 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S4 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
p53 pathway profiling analysis in NUGC-3 cells treated by PC14586 (5 µM) vs. DMSO control (5 h).
View article: Supplementary File S15 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S15 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
The immune pathway changes with PC14374 administration in vivo based on the Nanostring data from Hupki-MT373 tumors treated with vehicle versus PC14374 at 150 or 300 mg/kg for 2Q7D×2 or 2Q7D×3.
View article: Supplementary File S10 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S10 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
Annotated gene differential expression (DE) analysis from RNA-seq data in 4 cell lines (NUGC-3, T3M-4, NUGC-3 KO, and SJSA-1) treated with rezatapopt (PC14586, 5 µM) versus DMSO (5 and 16 h).
View article: Supplementary File S14 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S14 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
GSEA analysis of DEGs shows the restoration of WT p53 transcriptional responses by PC14586 in vivo in NUGC-3 xenografted tumors over 6 days of 100-mg/kg PC14586.
View article: Supplementary File S13 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S13 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
Annotated analysis of differential gene expression (DE) from RNA-seq data in NUGC-3 xenografted tumors over 6 days of 100 mg/kg PC14586 administration.
View article: Supplementary File S3 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S3 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
p53 pathway profiling analysis in NUGC-3 KO cells treated by PC14586 (5 µM) vs. DMSO control (16 h).
View article: Figure 3 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Figure 3 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
Pharmacologic activation of WT p53 in p53-Y220C xenografts induced p53 signaling and inhibited tumor growth. A and B, PC14586 was administered orally at the indicated doses to p53-Y220C–expressing (A) NUGC-3 and (B) T3M-4 mouse xenografts.…
View article: Supplementary File S9 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S9 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
p53 pathway profiling analysis in SJSA-1 cells treated by PC14586 (5 µM) vs. DMSO control (16 h).
View article: Data from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Data from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
Restoration of the tumor suppressor function of tumor-associated p53 mutants, including the Y220C substitution, has posed a significant challenge for therapeutic discovery. In this study, we describe rezatapopt (PC14586), part of a series …
View article: Supplementary File S5 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S5 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
p53 pathway profiling analysis in T3M-4 cells treated by PC14586 (5 µM) vs. DMSO control (5 h).
View article: Supplementary File S8 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S8 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
p53 pathway profiling analysis in SJSA-1 cells treated by PC14586 (5 µM) vs. DMSO control (5 h).
View article: Supplementary File S2 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S2 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
p53 pathway profiling analysis in NUGC-3 KO_p53i cells induced with doxycycline (50 ng/ml) vs. PBS control (12.5 h).
View article: Supplementary File S7 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S7 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
p53 pathway profiling analysis in NUGC-3 KO cells treated by PC14586 (5 µM) vs. DMSO control (5 h).
View article: Supplementary File S11 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S11 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
The restoration of WT p53 transcriptional responses by PC14586 in p53-Y220C–expressing cells (NUGC-3 and T3M-4) at 5 and 16 h was assessed through GSEA analysis for DEGs.
View article: Figure 6 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Figure 6 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
Responses of two patients with solid tumors harboring TP53 Y220C mutations receiving rezatapopt. A–C Patient with advanced small cell lung carcinoma from the PYNNACLE phase I study. A, CT scans at baseline and 12 weeks showing a reduction …
View article: Supplementary File S1 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Supplementary File S1 from Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator Open
p53 pathway profiling analysis in NUGC-3 cells treated by PC14586 (5 µM) vs. DMSO control (16 h).