Journal: Molecular Therapy. Nucleic Acids

Article Title: Combining anti-gene γPNA with small molecules and RNA inhibitors: A strategy to enhance anti-tumor efficacy

doi: 10.1016/j.omtn.2025.102804

Figure Lengend Snippet: Design of anti-transcription γPNA and combination treatments to target the c-Myc oncogene (A) Schematic representation of gamma peptide nucleic (γPNA)-mediated inhibition of human c-Myc transcription and target site (NCBI database RefSeq: NG_007161.2 ). (B) Design of γPNA conjugated with nuclear localization signal (NLS) to target the indicated sites. ScR-γPNA2 is the scramble control. (C) Graphic representation of combination treatments with anti-transcription, γPNA1. The combination treatments include histone deacetylase inhibitors (HDACis), MYC/MAX inhibitors, small interfering RNA (siRNA), and small molecules targeting other pathways. (D) Polymerase chain reaction (PCR)-based amplicon assay to confirm binding of γPNA1 to the target site in U2932 cells. Amplicon assay after treatment of γPNA1 and ScR-γPNA2 with HDACi. (E) The graph represents quantification of γPNA1 and ScR-γPNA2 amplicon in combination with HDACi. (F) The graph represents the quantification of amplicon assay from class I HDACi with γPNA1. Results are presented as mean ± SEM. One-way ANOVA was used to determine the statistically significant difference between groups.

Article Snippet: U2932 cells were treated with HDACi: panobinostat (MedchemExpress, #HY-10224; 30 nM), belinostat (MedchemExpress, #HY-10225; 2.5 μM), entinostat (MedchemExpress, #HY-12163; 10 μM, romidepsin (Sigma-Aldrich, #SML1175; 10 nM), and vorinostat (Selleckchem, #S1047; 2.5 μM) for 24 h followed by PBS, γPNA1, and ScR-γPNA2 at 3 μM for 48 h cotreatment.

Techniques: Inhibition, Control, Histone Deacetylase Assay, Small Interfering RNA, Polymerase Chain Reaction, Amplification, Binding Assay

Journal: Molecular Therapy. Nucleic Acids

Article Title: Combining anti-gene γPNA with small molecules and RNA inhibitors: A strategy to enhance anti-tumor efficacy

doi: 10.1016/j.omtn.2025.102804

Figure Lengend Snippet: Anti-transcription activity of γPNA1 with HDACi in lymphoma cells Relative fold change of c-Myc levels in U2932 cells measured by real-time PCR on day 2 after treatment with (A) γPNA1 and (B) ScR-γPNA2 in combination with romidepsin, entinostat, vorinostat, panobinostat, and belinostat. Results are presented as mean ± SEM and two-way ANOVA was used to determine the statistically significant difference between groups. Western blot analysis representing the change in c-MYC protein on day 2 after treatment with γPNA1 and ScR-γPNA2 in combination with (C) romidepsin, (D) entinostat, (E) vorinostat, (F) panobinostat, and (G) belinostat. ∗∗(C–F) Cyclophilin B was used as an endogenous control, and the same blots are presented in C–S3G. c-MYC, EZH2, and cyclophilin B were probed from the same blot. Results are presented as mean ± SEM, and the p value between groups was determined using one-way ANOVA.

Article Snippet: U2932 cells were treated with HDACi: panobinostat (MedchemExpress, #HY-10224; 30 nM), belinostat (MedchemExpress, #HY-10225; 2.5 μM), entinostat (MedchemExpress, #HY-12163; 10 μM, romidepsin (Sigma-Aldrich, #SML1175; 10 nM), and vorinostat (Selleckchem, #S1047; 2.5 μM) for 24 h followed by PBS, γPNA1, and ScR-γPNA2 at 3 μM for 48 h cotreatment.

Techniques: Activity Assay, Real-time Polymerase Chain Reaction, Western Blot, Control

Journal: Molecular Therapy. Nucleic Acids

Article Title: Combining anti-gene γPNA with small molecules and RNA inhibitors: A strategy to enhance anti-tumor efficacy

doi: 10.1016/j.omtn.2025.102804

Figure Lengend Snippet: Cell viability of Histone deacetylase inhibitors in combination with γPNA1 (A) Cell viability of U2932 cells treated with increasing doses of HDACi (romidepsin, entinostat, vorinostat, panobinostat, and belinostat) alone and in combination with γPNA1 and ScR-γPNA2 (8 μM) for 48 h. Results are presented as mean ± SEM. (B) The IC 50 ± SEM values of HDACi and combination treatment of HDACi with γPNA1 in U2932 cells. (C) Cell viability of Raji cells treated with increasing doses of HDACi (romidepsin, entinostat, vorinostat, panobinostat, and belinostat) alone and in combination with γPNA1 and ScR-γPNA2 (8 μM) for 48 h. Results are presented as mean ± SEM. (D) The IC 50 ± SEM values of HDACi and combination treatment of HDACi with γPNA1 in Raji cells.

Article Snippet: U2932 cells were treated with HDACi: panobinostat (MedchemExpress, #HY-10224; 30 nM), belinostat (MedchemExpress, #HY-10225; 2.5 μM), entinostat (MedchemExpress, #HY-12163; 10 μM, romidepsin (Sigma-Aldrich, #SML1175; 10 nM), and vorinostat (Selleckchem, #S1047; 2.5 μM) for 24 h followed by PBS, γPNA1, and ScR-γPNA2 at 3 μM for 48 h cotreatment.

Techniques: Histone Deacetylase Assay

Journal: Molecular Therapy. Nucleic Acids

Article Title: Combining anti-gene γPNA with small molecules and RNA inhibitors: A strategy to enhance anti-tumor efficacy

doi: 10.1016/j.omtn.2025.102804

Figure Lengend Snippet: MYC/MAX inhibitors in combination with anti-transcription γPNA1 Cell viability of (A) U2932 and (B) Raji cells treated with increasing doses of MYC/MAX inhibitors (Myci975, EN4, 10058-F4, and sAJM589) alone and in combination with γPNA1 and ScR-γPNA2 (8 μM) for 72 h. Results are presented as mean ± SEM. The IC 50 (95% CI) values of MYC/MAX inhibitors alone and combination treatment of MYC/MAX with γPNA1 in (C) U2932 and (D) Raji cells. (E) Cell viability of γPNA1-treated U2932 and Raji cells at 8 μM concentration. Western blot analysis representing the change in c-MYC protein 72 h after treatment with γPNA1 and ScR-γPNA2 in combination with (F) Myci975, (G) EN4, (H) 10058-F4, and (I) sAJM589. ∗∗(F–I) Cyclophilin B was used as an endogenous control, and the same blots are presented in A–S7D. c-MYC, EZH2, and cyclophilin B were probed from the same blot. Results are presented as mean ± SEM, p value for one-way ANOVA.

Article Snippet: U2932 cells were treated with HDACi: panobinostat (MedchemExpress, #HY-10224; 30 nM), belinostat (MedchemExpress, #HY-10225; 2.5 μM), entinostat (MedchemExpress, #HY-12163; 10 μM, romidepsin (Sigma-Aldrich, #SML1175; 10 nM), and vorinostat (Selleckchem, #S1047; 2.5 μM) for 24 h followed by PBS, γPNA1, and ScR-γPNA2 at 3 μM for 48 h cotreatment.

Techniques: Concentration Assay, Western Blot, Control

Journal: Molecular Therapy. Nucleic Acids

Article Title: Combining anti-gene γPNA with small molecules and RNA inhibitors: A strategy to enhance anti-tumor efficacy

doi: 10.1016/j.omtn.2025.102804

Figure Lengend Snippet: Efficacy of small molecules targeting other pathways with anti-transcription γPNA1 (A) Cell viability of U2932 and Raji cells treated with increasing doses JQ1 (BRD4 inhibitor) alone and with γPNA1 and ScR-γPNA2 for 48 h. (B) Cell viability of U2932 and Raji cells treated with increasing doses of sapnisertid (mTOR inhibitor) alone and with γPNA1 and ScR-γPNA2 for 48 h. (C) Cell viability of MDA-MB-231 cells treated with increasing doses of dinaciclib (CDK inhibitor) alone and with γPNA1 and ScR-γPNA2 for 48 h. (D) The IC 50 (95% CI) values of small molecule inhibitors alone and in combination with γPNA1. (A–C) Results are presented as mean ± SEM.

Article Snippet: U2932 cells were treated with HDACi: panobinostat (MedchemExpress, #HY-10224; 30 nM), belinostat (MedchemExpress, #HY-10225; 2.5 μM), entinostat (MedchemExpress, #HY-12163; 10 μM, romidepsin (Sigma-Aldrich, #SML1175; 10 nM), and vorinostat (Selleckchem, #S1047; 2.5 μM) for 24 h followed by PBS, γPNA1, and ScR-γPNA2 at 3 μM for 48 h cotreatment.

Techniques:

Journal: Cancer letters

Article Title: WEE1 Stabilizes MYC to Promote Therapeutic Resistance in Esophageal Adenocarcinoma

doi: 10.1016/j.canlet.2026.218418

Figure Lengend Snippet: A. 21 positive hits (red), which synergized with MK-1775 in O19 cells during the first round of screening using an 892 FDA-approved drug screening library. B. Panobinostat (red arrow) was found to synergize with MK-1775 in FLO1 (blue) and SK-GT4 (red) cell lines during the second round of screening. C. Synergy Finder analysis results in FLO1, OE33, OE19, and SK-GT4 cell lines treated with MK-1775 and Panobinostat. *P<0.05, **P<0.01, ***P<0.001. D. Flow cytometric analysis of Annexin V & SYTOX red dual staining in OE33 cells treated with MK-1775/Panobinostat alone or a combination. E. Percentage of apoptotic cells from Fig D *P<0.05, **P<0.01, ***P<0.001. F. Western blot analysis of PARP, Cl-PARP, Caspase 3, Cl-Caspase 3, and β-ACTIN in OE33 cells treated with MK-1775/ Panobinostat alone or a combination. G. Flow cytometric analysis of Annexin V & SYTOX red dual staining in OE19 cells treated with MK-1775/Panobinostat alone or a combination. H. Percentage of apoptotic cells from Fig G *P<0.05, **P<0.01, ***P<0.001. I. Western blot analysis of PARP, Cl-PARP, Caspase 3, Cl-Caspase 3, and β-ACTIN in OE19 cells treated with MK-1775/ Panobinostat alone or a combination.

Article Snippet: Panobinostat (Selleckchem) was administered intraperitonially at a dose of 10 mg/kg, once a week for 4 weeks.

Techniques: Drug discovery, Staining, Western Blot

Journal: Cancer letters

Article Title: WEE1 Stabilizes MYC to Promote Therapeutic Resistance in Esophageal Adenocarcinoma

doi: 10.1016/j.canlet.2026.218418

Figure Lengend Snippet: A. Human EAC PDX-derived Organoids treated with MK-1775 / Panobinostat alone or in combination. B. Quantification of organoid diameter from A. C. Tumor growth curves in 4 experimental groups (Untreated control, MK-1775, Panobinostat, combination of MK-1775 & Panobinostat) at the end of the experiment. D. Western blot analysis of PARP, Cl-PARP, Caspase 3, CL-Caspase3, and β-ACTIN in Mouse Xenografts. E. Immunofluorescence staining for P-CDC2 Y15 (green), C-MYC (red), MRP1 (green), and Ki67 (red) in Mouse EAC PDXs, captured at 20X Magnification. F. Quantification data from E. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

Article Snippet: Panobinostat (Selleckchem) was administered intraperitonially at a dose of 10 mg/kg, once a week for 4 weeks.

Techniques: In Vivo, Derivative Assay, Control, Western Blot, Immunofluorescence, Staining

Journal: Molecular Therapy. Nucleic Acids

Article Title: Combining anti-gene γPNA with small molecules and RNA inhibitors: A strategy to enhance anti-tumor efficacy

doi: 10.1016/j.omtn.2025.102804

Figure Lengend Snippet: Design of anti-transcription γPNA and combination treatments to target the c-Myc oncogene (A) Schematic representation of gamma peptide nucleic (γPNA)-mediated inhibition of human c-Myc transcription and target site (NCBI database RefSeq: NG_007161.2 ). (B) Design of γPNA conjugated with nuclear localization signal (NLS) to target the indicated sites. ScR-γPNA2 is the scramble control. (C) Graphic representation of combination treatments with anti-transcription, γPNA1. The combination treatments include histone deacetylase inhibitors (HDACis), MYC/MAX inhibitors, small interfering RNA (siRNA), and small molecules targeting other pathways. (D) Polymerase chain reaction (PCR)-based amplicon assay to confirm binding of γPNA1 to the target site in U2932 cells. Amplicon assay after treatment of γPNA1 and ScR-γPNA2 with HDACi. (E) The graph represents quantification of γPNA1 and ScR-γPNA2 amplicon in combination with HDACi. (F) The graph represents the quantification of amplicon assay from class I HDACi with γPNA1. Results are presented as mean ± SEM. One-way ANOVA was used to determine the statistically significant difference between groups.

Article Snippet: U2932 cells were treated with HDACi: panobinostat (MedchemExpress, #HY-10224; 30 nM), belinostat (MedchemExpress, #HY-10225; 2.5 μM), entinostat (MedchemExpress, #HY-12163; 10 μM, romidepsin (Sigma-Aldrich, #SML1175; 10 nM), and vorinostat (Selleckchem, #S1047; 2.5 μM) for 24 h followed by PBS, γPNA1, and ScR-γPNA2 at 3 μM for 48 h cotreatment.

Techniques: Inhibition, Control, Histone Deacetylase Assay, Small Interfering RNA, Polymerase Chain Reaction, Amplification, Binding Assay

Journal: Molecular Therapy. Nucleic Acids

Article Title: Combining anti-gene γPNA with small molecules and RNA inhibitors: A strategy to enhance anti-tumor efficacy

doi: 10.1016/j.omtn.2025.102804

Figure Lengend Snippet: Anti-transcription activity of γPNA1 with HDACi in lymphoma cells Relative fold change of c-Myc levels in U2932 cells measured by real-time PCR on day 2 after treatment with (A) γPNA1 and (B) ScR-γPNA2 in combination with romidepsin, entinostat, vorinostat, panobinostat, and belinostat. Results are presented as mean ± SEM and two-way ANOVA was used to determine the statistically significant difference between groups. Western blot analysis representing the change in c-MYC protein on day 2 after treatment with γPNA1 and ScR-γPNA2 in combination with (C) romidepsin, (D) entinostat, (E) vorinostat, (F) panobinostat, and (G) belinostat. ∗∗(C–F) Cyclophilin B was used as an endogenous control, and the same blots are presented in C–S3G. c-MYC, EZH2, and cyclophilin B were probed from the same blot. Results are presented as mean ± SEM, and the p value between groups was determined using one-way ANOVA.

Article Snippet: U2932 cells were treated with HDACi: panobinostat (MedchemExpress, #HY-10224; 30 nM), belinostat (MedchemExpress, #HY-10225; 2.5 μM), entinostat (MedchemExpress, #HY-12163; 10 μM, romidepsin (Sigma-Aldrich, #SML1175; 10 nM), and vorinostat (Selleckchem, #S1047; 2.5 μM) for 24 h followed by PBS, γPNA1, and ScR-γPNA2 at 3 μM for 48 h cotreatment.

Techniques: Activity Assay, Real-time Polymerase Chain Reaction, Western Blot, Control

Journal: Molecular Therapy. Nucleic Acids

Article Title: Combining anti-gene γPNA with small molecules and RNA inhibitors: A strategy to enhance anti-tumor efficacy

doi: 10.1016/j.omtn.2025.102804

Figure Lengend Snippet: Cell viability of Histone deacetylase inhibitors in combination with γPNA1 (A) Cell viability of U2932 cells treated with increasing doses of HDACi (romidepsin, entinostat, vorinostat, panobinostat, and belinostat) alone and in combination with γPNA1 and ScR-γPNA2 (8 μM) for 48 h. Results are presented as mean ± SEM. (B) The IC 50 ± SEM values of HDACi and combination treatment of HDACi with γPNA1 in U2932 cells. (C) Cell viability of Raji cells treated with increasing doses of HDACi (romidepsin, entinostat, vorinostat, panobinostat, and belinostat) alone and in combination with γPNA1 and ScR-γPNA2 (8 μM) for 48 h. Results are presented as mean ± SEM. (D) The IC 50 ± SEM values of HDACi and combination treatment of HDACi with γPNA1 in Raji cells.

Article Snippet: U2932 cells were treated with HDACi: panobinostat (MedchemExpress, #HY-10224; 30 nM), belinostat (MedchemExpress, #HY-10225; 2.5 μM), entinostat (MedchemExpress, #HY-12163; 10 μM, romidepsin (Sigma-Aldrich, #SML1175; 10 nM), and vorinostat (Selleckchem, #S1047; 2.5 μM) for 24 h followed by PBS, γPNA1, and ScR-γPNA2 at 3 μM for 48 h cotreatment.

Techniques: Histone Deacetylase Assay