Journal: Frontiers in Immunology

Article Title: Unveiling spatial complexity in solid tumor immune microenvironments through multiplexed imaging

doi: 10.3389/fimmu.2024.1383932

Figure Lengend Snippet: Immunophenotyping panel for multiplexed tissue imaging of cancer.

Article Snippet: p53 , REA1132 , 50 , 130-119-502 , PE , Miltenyi Biotec.

Techniques: Imaging

Journal: bioRxiv

Article Title: Senescence-inhibitory Δ133p53α counteracts accelerated ageing and mortality

doi: 10.64898/2025.12.31.697195

Figure Lengend Snippet: Western blot analyses of lamin A/C and progerin, full-length p53, Δ133p53α, and p21 Waf1/Cip1 were performed in four 15-week-old Δ133p53α-expressing Group-1 mice ( CAG-133 Tam/+ ; Cre Tg/+ ; Lmna G609G/+ ), along with four each of age-matched, non-expressing control Group-2 ( CAG-133 LSL/+ ; Cre Tg/+ ; Lmna G609G/+ ) and Group-4 mice ( CAG-133 +/+ ; Cre +/+ ; Lmna G609G/+ ), as well as two age-matched wild-type mice ( CAG-133 +/+ ; Cre +/+ ; Lmna +/+ ). Results from skin ( a ), skeletal muscle ( b ), kidney ( c ), spleen ( d ), and lung ( e ) are presented. An inter-blot control (liver from a Group-1 mouse) was included in all blots. F, female; M, male. GAPDH was a loading control and used for normalization of p21 Waf1/Cip1 , progerin, and full-length p53 expression levels. Quantitative data summaries of p21 Waf1/Cip1 , progerin, and full-length p53 in Group-1, -2 and -4 mice are shown as relative values to Group-2 mice (mean ± s.d. from n = 4; open circles indicate two females, and closed circles indicate two males). P values were determined by Welch’s t -test. Two wild-type mice were used only as references and not for statistical comparisons.

Article Snippet: Primary antibodies used were as follows: anti-p53 antibodies SAPU (sheep polyclonal) and DO-11 (mouse monoclonal; Bio-Rad, MCA1704) ; anti-p21 Waf1/Cip1 (mouse monoclonal; Santa Cruz Biotechnology, sc-6246, clone F-5); anti-lamin A/C (mouse monoclonal; Santa Cruz Biotechnology, sc-376248); anti-GAPDH (mouse monoclonal; Santa Cruz Biotechnology, sc-166574); and anti-β-actin (mouse monoclonal; Thermo Fisher Scientific, MA1-91399).

Techniques: Western Blot, Expressing, Control

Journal: bioRxiv

Article Title: Senescence-inhibitory Δ133p53α counteracts accelerated ageing and mortality

doi: 10.64898/2025.12.31.697195

Figure Lengend Snippet: a,b , Top Hallmark pathways identified by Gene set enrichment analysis (GSEA). The bulk RNA-seq data were obtained from the heart ( a ) and kidney ( b ) in 9-10-month-old Group-1 and Group-3 mice (n = 5 each). Pathways are ranked by normalized enrichment score. False discovery rate < 0.10. c-g, Enrichment plots illustrate significant downregulation of the p53 pathway ( c,d ) and upregulation of the oxidative phosphorylation ( e,f ) in both heart and kidney, as well as upregulation of the glycolysis in the kidney ( g ). Enrichment plots depict running enrichment scores (ES) and the distribution of genes within each Hallmark gene set. All leading edge genes in each pathway are listed in Extended Data Table 2. h,i, qRT-PCR assays of mRNA expression of genes in the oxidative phosphorylation pathway (Ndufs6, Ndufc2, Uqcrq, Hsd17b10, and Gpx4) and an antioxidant gene Prdx1 in the heart ( h ) and kidney ( i ) of 9-10-month-old Group-1 and Group-3 mice (mean ± s.d. from n = 5, each with technical triplicate; open circles, females; closed circles, males). P values were calculated by Welch’s t -test.

Article Snippet: Primary antibodies used were as follows: anti-p53 antibodies SAPU (sheep polyclonal) and DO-11 (mouse monoclonal; Bio-Rad, MCA1704) ; anti-p21 Waf1/Cip1 (mouse monoclonal; Santa Cruz Biotechnology, sc-6246, clone F-5); anti-lamin A/C (mouse monoclonal; Santa Cruz Biotechnology, sc-376248); anti-GAPDH (mouse monoclonal; Santa Cruz Biotechnology, sc-166574); and anti-β-actin (mouse monoclonal; Thermo Fisher Scientific, MA1-91399).

Techniques: RNA Sequencing, Phospho-proteomics, Quantitative RT-PCR, Expressing

Journal: Antioxidants

Article Title: Saposhnikovia divaricata Inhibits Inflammation, Oxidative Stress, and Ferroptosis to Alleviate DSS-Induced Ulcerative Colitis

doi: 10.3390/antiox15020258

Figure Lengend Snippet: Network pharmacology analysis identifies p53 as a core ferroptosis-related target of FF in UC. ( A ) Venn diagram illustrating the intersection of FF compound targets with ferroptosis- and UC-related targets. ( B ) Protein–protein interaction (PPI) network of the common targets. Node size and color intensity represent the degree of connectivity, with TP53 (p53) identified as the core target. ( C ) Compound-target-pathway network diagram. The inner pink nodes represent the 38 intersecting targets linking FF, UC, and ferroptosis. ( D ) Gene Ontology (GO) enrichment analysis of the common targets, categorized into Biological Process (BP, red), Cellular Component (CC, green), and Molecular Function (MF, blue). ( E ) Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.

Article Snippet: The p53 antibody was obtained from Boster Biological Technology Co., Ltd. (Pleasanton, CA, USA, Item #BM0101).

Techniques:

Journal: Antioxidants

Article Title: Saposhnikovia divaricata Inhibits Inflammation, Oxidative Stress, and Ferroptosis to Alleviate DSS-Induced Ulcerative Colitis

doi: 10.3390/antiox15020258

Figure Lengend Snippet: FF modulates the expression of ferroptosis-related proteins in colon tissue via the p53 pathway. ( A ) Representative immunohistochemical (IHC) images of p53, SLC7A11, and GPX4 expression in colon sections (scale bar = 50 μm). ( B – D ) Quantitative analysis of the relative protein expression levels of p53 (B), SLC7A11 (C), and GPX4 (D). Data are presented as the mean ± SD ( n = 3 independent experiments). ### p < 0.001 versus the control (CON) group; * p < 0.05, ** p < 0.01, *** p < 0.001 versus the DSS model group.

Article Snippet: The p53 antibody was obtained from Boster Biological Technology Co., Ltd. (Pleasanton, CA, USA, Item #BM0101).

Techniques: Expressing, Immunohistochemical staining, Control

Journal: International Journal of Cancer

Article Title: Bcl-2 with loss of apoptosis allows accumulation of genetic alterations: A pathway to metastatic progression in human breast cancer

doi: 10.1002/(sici)1097-0215(20000320)89:2<142::aid-ijc7>3.0.co;2-b

Figure Lengend Snippet: FIGURE 1 – Percentage of tumors with Bcl-2 over-expression according to the number of accumulated oncogene alterations (c-Myc, EGFR and c-erbB-2) and p53 status (mutated vs. non-mutated tumors).

Article Snippet: Bcl-2, c-Myc, c-erbB-2, p53, EGFR and hormone receptor (PR, ER) expression Expression of these genes was assessed by immuno-histochemistry (IHC) using appropriate antibodies: the monoclonal antibody (MAb) anti-Bcl-2 124 (ICI, Cambridge Research Biochemicals, Northwich, UK) at 1:200 dilution; MAb to p53, clone BP-53-12-1 (Biogenex, San Ramon, CA); MAb Ab-6, clone DO-1 (Oncogene Science, Uniondale, NY); MAb Ab-1, clone 9E10 (Oncogene Science), which reacts with human c-Myc at 1:100 dilution; MAb anti-C-erbB-2, clone CB11 (Biogenex) at 1:80 dilution; MAb anti-EGFR, clone E30 (Merck, Darmstadt, Germany) at 1:15 dilution.

Techniques: Over Expression

Journal: International Journal of Cancer

Article Title: Bcl-2 with loss of apoptosis allows accumulation of genetic alterations: A pathway to metastatic progression in human breast cancer

doi: 10.1002/(sici)1097-0215(20000320)89:2<142::aid-ijc7>3.0.co;2-b

Figure Lengend Snippet: FIGURE 2 – Percentage of tumors with p53 over-expression according to the number of accumulated oncogene alterations (c-Myc, EGFR and c-erbB-2) and histological grade (I/II or III).

Article Snippet: Bcl-2, c-Myc, c-erbB-2, p53, EGFR and hormone receptor (PR, ER) expression Expression of these genes was assessed by immuno-histochemistry (IHC) using appropriate antibodies: the monoclonal antibody (MAb) anti-Bcl-2 124 (ICI, Cambridge Research Biochemicals, Northwich, UK) at 1:200 dilution; MAb to p53, clone BP-53-12-1 (Biogenex, San Ramon, CA); MAb Ab-6, clone DO-1 (Oncogene Science, Uniondale, NY); MAb Ab-1, clone 9E10 (Oncogene Science), which reacts with human c-Myc at 1:100 dilution; MAb anti-C-erbB-2, clone CB11 (Biogenex) at 1:80 dilution; MAb anti-EGFR, clone E30 (Merck, Darmstadt, Germany) at 1:15 dilution.

Techniques: Over Expression

Journal: Cancer Discovery

Article Title: Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator

doi: 10.1158/2159-8290.CD-24-1421

Figure Lengend Snippet: 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 binding to the DNA from a consensus p53 response element by 1.5-fold (SC 150 ) was measured by the TR-FRET assay; the binding constant (Kd) was determined by surface plasmon resonance (SPR), and the structural stabilization shown by the Tm was determined through a thermal shift assay, as described in Methods. n.d., not determined. B, X-ray crystal structure of the Y220C−PC10709 complex, PDB code 9BR3 . The Y220C protein is shown as a gray cartoon representation with key residues highlighted as stick models. The hydrogen bonds between specific amino acids in the Y220C protein and PC10709 are indicated by dashed red lines. C, Induction of WT p53 antibody reactivity in cells. NUGC-3 cells were treated with PC14586 for 2 hours, followed by IP of p53 with either WT p53 (PAb1620) or mutant p53 (PAb240) cross-reacting antibodies. Changes in WT and mutant cross-reacting p53 levels were detected by Western blotting of the IP samples with the nonspecific 7F5 p53 antibody. D, Fold change in ELISA, normalized to the vehicle control of mutant (PAb240 antibody) and WT (PAb1620 antibody) p53 protein levels in NUGC-3 cells treated for 2 hours with increasing doses of the Y220C reactivator compounds. E, Biotinylated oligonucleotides corresponding to p53 response elements and a negative control (scramble) oligonucleotide were immobilized on an MSD plate and incubated with a cellular lysate from NUGC-3 cells treated with rezatapopt (PC14586; 2 hours). An increase in sequence-specific DNA binding of p53-Y220C was detected with a total p53 antibody. F, A 5-day MTT proliferation assay was performed as described in the Methods section using the four p53 reactivator compounds in NUGC-3 (p53-Y220C), T3M-4 (p53-Y220C), SJSA-1 (p53 WT), and NUGC-3 KO (p53 KO) cells. Proliferation rates and reactivator compound IC 50 s are presented for each cell line. G, The incorporation of EdU and IC 50 was measured following a 24-hour treatment with increasing doses of the reactivator compounds in the indicated cell lines. H, Quantitation of the expression of fluorescently tagged proteins at specific phases of the cell cycle in NUGC-3, T3M-4, and SJSA-1 cells stably expressing the Incucyte Cell Cycle Lentivirus after a 24-hour treatment with 5 µmol/L reactivator compounds and ( I ) increasing concentrations of rezatapopt (PC14586). J, PC14586 IC 50 values across various cell lines, including those harboring the TP53 Y220C mutation or other p53 hotspot mutations, p53 KO cell lines, and p53 WT cell lines, were obtained from a 5-day MTT assay. K, Western blot analysis of p21 and MDM2 protein expression in NUGC-3 and T3M-4 cells following 5-hour PC14586 treatment. Data in D–I were from three experiments, data in J were from two experiments, and graphs were plotted as mean ± SD.

Article Snippet: The 96-well ELISA plates were coated with WT p53 (150 ng/well; PAb1620; Caprico Biotechnologies, Cat. # 102201, RRID: AB_3662135), mutant p53 (100 ng/well; PAb240; Novus Biologicals, Cat. # NB200-103, RRID: AB_10001083), or total p53 (3.13 ng/well; PAb1801; Novus Biologicals, Cat. # NB200-104, RRID: AB_10001307) antibodies and incubated overnight at 4°C.

Techniques: Functional Assay, Concentration Assay, Binding Assay, SPR Assay, Thermal Shift Assay, Mutagenesis, Western Blot, Enzyme-linked Immunosorbent Assay, Control, Negative Control, Incubation, Sequencing, Proliferation Assay, Quantitation Assay, Expressing, Stable Transfection, MTT Assay

Journal: Cancer Discovery

Article Title: Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator

doi: 10.1158/2159-8290.CD-24-1421

Figure Lengend Snippet: 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 treatment with rezatapopt (PC14586). Data for the top four cell lines were representative results of three biological repeats, data for other cell lines were from two biological repeats, and graphs were plotted as mean ± SD. A.U., arbitrary unit. B, Scatter plots showing expression levels of genes involved in the p53 signaling pathway in cells following treatment with rezatapopt (PC14586). RNA samples extracted from p53-Y220C–expressing cells (NUGC-3), p53 KO cells (NUGC-3 KO) treated with rezatapopt (PC14586; 5 µmol/L, 16 hours), and NUGC-3 KO_p53i cells induced with doxycycline (50 ng/mL, 12.5 hours) were profiled by the Qiagen RT 2 p53 pathway qRT-PCR panel. Scales are in log 10 (relative expression to housekeeping genes; n = 3). C, Scatter plots of log 2 (transcripts per million + 0.01) and volcano plots of −log 10 (FDR) versus log 2 (fold change) from RNA-seq analysis of expressed genes from p53-Y220C and p53 KO cell lines following DMSO and rezatapopt (PC14586; 5 µmol/L) treatment (16 hours). Genes enriched in gene sets of Fischer direct p53 targets (upregulated), Fischer DREAM Targets (downregulated), DEGs excluding the above-enriched genes (upregulated and downregulated), and non-DEGs were sequentially overlaid as indicated. D, Top enriched gene sets from GSEA of the Molecular Signatures Database C2 collection curated gene sets in the indicated RNA-seq data (NUGC-3 treated with 5 µmol/L PC14586 versus DMSO for 16 hours) from DEGs (Walden stat preranked). The number of overlapping genes from the upregulated DEGs enriched in both the Fischer direct p53 targets gene set, and each listed gene set was divided by the total number of genes in each listed gene set and then multiplied by 100 to obtain the overlap with Fischer_Direct_p53_Targets (%). Overlap with Fischer DREAM targets (%) was calculated in a similar manner, except using the downregulated DEGs. To calculate enrichment (%), the number of genes from the DEGs with the indicated direction of regulation enriched in each gene set was divided by the total number of genes in each listed gene set and multiplied by 100. Normalized enrichment scores (NES) and percentages (%) were plotted on the upper and lower x -axes. All gene sets shown had enrichment of FDR q value ( q ) <0.001. Note that the names of gene sets were shortened. See Supplementary File S11 for details. E, Examples of the GSEA enrichment plots from D . F, Schematic representation of p53 in the transcriptional repression of cell-cycle genes via retinoblastoma-E2F and DREAM complexes. CDK, cyclin-dependent kinase; RBL, retinoblastoma-like proteins p107 (RBL1) and p130 (RBL2).

Article Snippet: The 96-well ELISA plates were coated with WT p53 (150 ng/well; PAb1620; Caprico Biotechnologies, Cat. # 102201, RRID: AB_3662135), mutant p53 (100 ng/well; PAb240; Novus Biologicals, Cat. # NB200-103, RRID: AB_10001083), or total p53 (3.13 ng/well; PAb1801; Novus Biologicals, Cat. # NB200-104, RRID: AB_10001307) antibodies and incubated overnight at 4°C.

Techniques: Quantitative RT-PCR, Expressing, RNA Sequencing

Journal: Cancer Discovery

Article Title: Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator

doi: 10.1158/2159-8290.CD-24-1421

Figure Lengend Snippet: 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. Analysis includes tumor volume (mm 3 ) measurements starting on day 1 of dosing (top left), AUC of tumor growth (top right), or percentage of body weight change (bottom). Each data point is the average tumor volume (left panel) or average percentage of body weight change (right). Percentage of TGI or regression is relative to starting volume. n = 10/group. Data shown are mean ± SEM. C, Fold change normalized to vehicle (V) control of mutant (PAb240 antibody), WT (PAb1620 antibody), and total (PAb1801 antibody) p53 protein levels using MSD in NUGC-3 xenograft tumors. Indicated time points are after the dose on day 4 of daily oral administration of vehicle at 25, 50, and 100 mg/kg PC14586. Consolidated vehicles from 7, 24, and 48 hours of 2QD × 1 treatments, n = 12; PC14586, n = 4/group. Data shown are mean ± SEM. Detectable plasma levels (μmol/L) are shown by the red symbol and designated on the right y- axis. D, Fold change in protein expression of p53 downstream targets using MSD (p21, MDM2) and normalized to vehicle control or ELISA (MIC-1) and normalized to vehicle control and tumor volume (mm 3 ) in tumor samples described in C . Data shown are mean ± SEM. E, Representative IHC images of Ki-67, p21, and MDM2 in the NUGC-3 xenograft model after 4 days of vehicle at 50 or 100 mg/kg PC14586 daily administration. Scale bars are 100 µm, 20× objective. Bar graphs represent the average percentage of positive stained cells on days 1 and 4 following the administration of 50 and 100 mg/kg PC14586. Symbols represent individual samples. Error bars show SEM. Statistical significance relative to vehicle was determined using one-way ANOVA with Dunnett’s multiple comparisons test (adjusted P value * < 0.01; *** 0.0001; **** <0.0001). QD, once daily.

Article Snippet: The 96-well ELISA plates were coated with WT p53 (150 ng/well; PAb1620; Caprico Biotechnologies, Cat. # 102201, RRID: AB_3662135), mutant p53 (100 ng/well; PAb240; Novus Biologicals, Cat. # NB200-103, RRID: AB_10001083), or total p53 (3.13 ng/well; PAb1801; Novus Biologicals, Cat. # NB200-104, RRID: AB_10001307) antibodies and incubated overnight at 4°C.

Techniques: Activation Assay, Expressing, Control, Mutagenesis, Clinical Proteomics, Enzyme-linked Immunosorbent Assay, Staining

Journal: Cancer Discovery

Article Title: Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator

doi: 10.1158/2159-8290.CD-24-1421

Figure Lengend Snippet: 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 the NUGC-3 xenograft model. n = 4/group. Error bars show the SEM. The red symbols show plasma concentrations (µmol/L) and are designated on the right y -axis. B, Assessment of a panel of 84 p53 pathway genes measured by qRT-PCR. A representative number of upregulated and downregulated p53 target genes are shown across 6 days of 100 mg/kg PC14586 administration, with the mean value of log 2 (fold change) at each time point shown on the heatmap. See Supplementary File S12 for details. RNA samples extracted from tumor samples, as in A , were profiled by the Qiagen RT 2 p53 pathway qRT-PCR panel as described in the Methods section. Symbols represent the mean log 2 (fold change) for each. C, Volcano plots from RNA-seq analysis of expressed genes from NUGC-3 xenograft tumors following PC14586 (100 mg/kg) and vehicle treatment as indicated. Graphs were plotted as in , except that the p53-targeted lncRNA (upregulated) gene set was overlaid on top of the others. See Supplementary Fig. S5B for the corresponding scatter plots. In B and C, vehicle (consolidated), n = 12 and PC14586, n = 4 for each group, as in and and . D, Top enriched gene sets from GSEA of the Molecular Signatures Database C2 collection curated gene sets supplemented with Fischer p53-targeted lncRNA (86 genes; C2+) in the indicated RNA-seq data [rezatapopt (PC14586) for once daily (QD) ×6 at 24 hours] from DEGs. See Supplementary File S14 for details. Gene sets with a normalized enrichment score (NES) and an FDR q value ( q ) < 0.001 are highlighted in green, 0.001 to 0.05 are highlighted in orange, and 0.05 to 0.06 are highlighted in gray. Graphs were plotted as in . E, Updated schematic representation of p53 in regulating the cell cycle via retinoblastoma-E2F and DREAM complexes. Updated from , the lncRNA component was added to complement p21 in regulating the cell cycle. PINCR, p53-induced noncoding RNA.

Article Snippet: The 96-well ELISA plates were coated with WT p53 (150 ng/well; PAb1620; Caprico Biotechnologies, Cat. # 102201, RRID: AB_3662135), mutant p53 (100 ng/well; PAb240; Novus Biologicals, Cat. # NB200-103, RRID: AB_10001083), or total p53 (3.13 ng/well; PAb1801; Novus Biologicals, Cat. # NB200-104, RRID: AB_10001307) antibodies and incubated overnight at 4°C.

Techniques: In Vivo, Gene Expression, Clinical Proteomics, Quantitative RT-PCR, RNA Sequencing

Journal: Cancer Discovery

Article Title: Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator

doi: 10.1158/2159-8290.CD-24-1421

Figure Lengend Snippet: Pharmacologic activation of WT p53 inhibited tumor growth and induced immunologic cell changes in tumors. A, Average tumor volume (mm 3 ; left), AUC analysis of tumor growth (middle), and percentage of body weight change (right) in C57Bl/6 mice bearing subcutaneous MT373 tumors treated with vehicle (V) or PC14374 at 150 or 300 mg/kg (2Q7D: two doses on day 1 only on a weekly dosing cycle). n =10/group. Data shown are mean ± SEM. Percentage of TGI (% TGI) or tumor regression is relative to tumor volume at study start. Statistical significance relative to the vehicle was determined using one-way ANOVA with Dunnett’s multiple comparisons tests (adjusted P value: **** <0.0001). B and C, Six days after inoculation with MT373 cells, mice were administered PC14374 orally at 150 or 300 mg/kg (2Q7D × 2 or 2Q7D × 3: two doses on day 1 only of a weekly dosing cycle for 2 or 3 weeks, respectively). B, Tumors were harvested 72 hours after last dose to analyze tumor-infiltrating lymphocytes by flow cytometry. Percentage of cell population change is normalized to CD45 + cells. Vehicle, n = 3/group; PC14374, n = 4/group. Error bars show SEM. Statistical significance relative to the vehicle was determined using one-way ANOVA with Dunnett’s multiple comparisons tests (adjusted P value: * ≤0.01; *** ≤0.001; **** ≤0.0001). C, Tumors harvested 72 hours after last dose were analyzed on the NanoString IO 360 panel for gene expression. Box plots represent fold change in the signature scores and the raw P value for the comparison between treatments for each cell signature (*, P ≤0.01; **, P ≤0.001). Vehicle control is treated as the baseline of the comparison. Vehicle, n = 3/group; PC14374, n = 4/group. Error bars show SEM. D, Mice bearing MT373 tumors were administered 75 mg/kg or 150 mg/kg PC14374 (2Q7D: two doses on day 1 only of a weekly dosing cycle), 200 µg anti–PD-1 (Q3D: dose every three days), or a combination of PC14374 and anti–PD-1 starting on day 6 after cell implantation. Tumor volume (mm 3 ) measurements started on day 1 of dosing. Kaplan–Meier curves are shown as percentage of survival with n = 10/group. The dashed vertical line represents dosing discontinuation at day 102. E, Mice bearing MT373 tumors were administered 150 mg/kg of PC14374 (2Q7D), 200 µg of anti–PD-1 (Bio X Cell Clone RMPI-14; Q3D), or 250 µg of anti-CD8 (Bio X Cell Clone 2.43) as single agents or in combination starting on day 6 after cell implantation. Groups dosed with anti-CD8 were pretreated 3 days prior to the study start. Tumor volume (mm 3 ) measurements started on day 1 of dosing. Kaplan–Meier curves are shown as percentage of survival with n = 10/group. The dashed vertical line represents dosing discontinuation on day 19. Statistical significance across all groups was determined using the log-rank (Mantel–Cox) test.

Article Snippet: The 96-well ELISA plates were coated with WT p53 (150 ng/well; PAb1620; Caprico Biotechnologies, Cat. # 102201, RRID: AB_3662135), mutant p53 (100 ng/well; PAb240; Novus Biologicals, Cat. # NB200-103, RRID: AB_10001083), or total p53 (3.13 ng/well; PAb1801; Novus Biologicals, Cat. # NB200-104, RRID: AB_10001307) antibodies and incubated overnight at 4°C.

Techniques: Activation Assay, Flow Cytometry, Gene Expression, Comparison, Control

Journal: Cancer Discovery

Article Title: Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator

doi: 10.1158/2159-8290.CD-24-1421

Figure Lengend Snippet: 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 in target lesions. B, TP53 Y220C VAF over time. C, Reduction in the sum diameter of target lesions over time (the dotted line represents the value that would constitute a PR; 54.6 mm). D–F Patient with advanced endometrial cancer from the PYNNACLE phase I study. D, CT scans at baseline and 11 weeks showing a reduction in target lesions. E, Cancer antigen 125 (CA-125) levels over time. F, Reduction in the sum diameter of target lesions over time (the dotted line represents the value that would constitute a PR; 39.9 mm). VAF, variant allele frequency; EOT, end of treatment.

Article Snippet: The 96-well ELISA plates were coated with WT p53 (150 ng/well; PAb1620; Caprico Biotechnologies, Cat. # 102201, RRID: AB_3662135), mutant p53 (100 ng/well; PAb240; Novus Biologicals, Cat. # NB200-103, RRID: AB_10001083), or total p53 (3.13 ng/well; PAb1801; Novus Biologicals, Cat. # NB200-104, RRID: AB_10001307) antibodies and incubated overnight at 4°C.

Techniques: Variant Assay