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Image Search Results
Journal: Cancers
Article Title: SAM-Competitive EZH2-Inhibitors Induce Platinum Resistance by EZH2-Independent Induction of ABC-Transporters.
doi: 10.3390/cancers15113043
Figure Lengend Snippet: Figure 1. EZH2 is overexpressed in tumor tissue which is associated with prognosis. (A) In a cohort of MTCL with 381 cases, EZH2 mRNA expression was compared to normal lymphoid tissue (n = 14) by one-way ANOVA testing. (B) In the same cohort, survival analysis was performed by log-rank test. (C) In a tissue micro array of 50 MTCL cases, EZH2 protein expression was compared to healthy lymphoid tissue (n = 10) by unpaired Student’s t-test. (D) In the tissue micro array cohort, survival analysis was applied using log-rank test. (E) Cell viability response to SAM-competitive EZH2 inhibitors GSK126 and EPZ6438 was assessed in the cell lines HH and Jurkat (* p ≤0.05; ** p ≤0.005; *** p ≤0.001). (F) In a screening approach, established chemotherapeutics were used in combinational incubation with GSK126 and changes in sensitivity compared to chemotherapeutic single therapy were assessed.
Article Snippet: Data Availability Statement: The raw
Techniques: Expressing, Microarray, Incubation
Journal: Cancers
Article Title: SAM-Competitive EZH2-Inhibitors Induce Platinum Resistance by EZH2-Independent Induction of ABC-Transporters.
doi: 10.3390/cancers15113043
Figure Lengend Snippet: Figure 2. SAM-competitive EZH2 inhibitors increase oxaliplatin resistance significantly. Oxaliplatin resistance was induced by pharmacological EZH2 inhibition after (A) 72 h and persisted after (B) 96 h and (C) 7 d. Significant differences between oxaliplatin monotherapy and in combination with GSK126 (red) EPZ6438 (blue), and DZNep (yellow) are indicated by the respective colored asterisks. Each point represents mean ± SEM, n = 3 except for the respective 72 h of incubation, untreated data points which represent mean ± SEM, n = 6. (D) Synergy matrices of oxaliplatin in combination with GSK126 (top) or EPZ6438 (bottom) in HH and Jurkat were composed using Synergy Finder [26]. The HSA model was used for calculation. (E) EZH2 knockdown was established using shRNAs and validated in the cell lines HH and Jurkat by Western blot with the respective quantitative analysis shown below. Each bar represents mean ± SD, n = 5. (F) EZH2 mRNA reduction was validated by qPCR. Quantitative Western blot and qPCR analyses were normed to the respective mock control. Each bar represents mean ± SEM, n = 3. Modulation of chemotherapy sensitivity was not found in either HH (G,I) or Jurkat (H,J) by EZH2 knockdown. The induction of resistance can be regained by additional GSK126. Each bar represents mean ± SEM, n = 3 (* p ≤0.05; ** p ≤0.005; *** p ≤0.001; # number).
Article Snippet: Data Availability Statement: The raw
Techniques: Inhibition, Incubation, Knockdown, Western Blot, Control
Journal: Cancers
Article Title: SAM-Competitive EZH2-Inhibitors Induce Platinum Resistance by EZH2-Independent Induction of ABC-Transporters.
doi: 10.3390/cancers15113043
Figure Lengend Snippet: Figure 4. Transcriptional changes under pharmacological EZH2 inhibition. (A) Experimental setup for mRNA-sequencing analysis from the cell lines HH, DERL2, Jurkat, and Loucy combined in- cluding Venn analysis. Differentially expressed genes compared to untreated are indicated in italic. Further analyses were conducted from genes regulated by GSK126 treatment (green background). (B) Differentially expressed genes by pharmacological EZH2 inhibition using GSK126 compared to oxaliplatin. (C) Enriched and depleted pathways by pharmacological EZH2 inhibition using GSK126 compared to oxaliplatin. Pathway IDs with adjusted p-value and enrichment score are described below. (D) The sequencing findings for GSK126, oxaliplatin, and oxaliplatin/GSK126 treatments in relation to untreated control were validated by qPCR and expanded for EPZ6438, oxaliplatin/EPZ6438,
Article Snippet: Data Availability Statement: The raw
Techniques: Inhibition, Sequencing, Control