Journal: Molecular Therapy

Article Title: Host-based Prophylaxis Successfully Targets Liver Stage Malaria Parasites

doi: 10.1038/mt.2015.18

Figure Lengend Snippet: Plasmodium falciparum is cleared from the liver of humanized mice treated with Serdemetan and Obatoclax. (a,b) FRG-HuHep mice were treated with either vehicle control or both 5 mg/kg of Obatoclax and 20 mg/kg Serdemetan by oral gavage once daily for 8 days. On the second day of treatment, mice were injected intravenously with 106 P. falciparum GFP-luc transgenic parasites. Parasite load was assessed by IVIS. Mice with undetected parasite burdens are depicted in red.

Article Snippet: Where indicated, cells were treated with ABT-737 (Selleck Chemicals, Houston, TX), Obatoclax mesylate (Selleck Chemicals), Nutlin-3 (Selleck Chemicals), Serdemetan (JNJ-26854165, Selleck Chemicals) and/or the pan-caspase inhibitor Q-VD-OPh ( N -(2-Quinolyl)-L-valyl-L-aspartyl-(2,6-difluorophenoxy) methylketone, SM Biochemicals LLC, Anaheim, CA at indicated concentrations.

Techniques: Control, Injection, Transgenic Assay

Journal: Molecular Therapy

Article Title: Host-based Prophylaxis Successfully Targets Liver Stage Malaria Parasites

doi: 10.1038/mt.2015.18

Figure Lengend Snippet: Serdemetan treatment decreases P. yoelii LS burden in Hepa 1–6 cells in a dose-dependent manner. (a) Hepa 1–6 cells were infected with P. yoelii sporozoites in chamber slides and treated with the indicated concentration of Serdemetan for 48 hours. Parasites were quantified microscopically by staining for UIS4 and HSP70. (b) Hepa 1–6 cells were treated with Serdemetan (10 µmol/l) for 48 hours and analyzed for P53 expression by immunoblot. (c) Hepa 1–6 cells were infected with P. yoelii and treated with Serdemetan (10 µmol/l) with or without the total caspase inhibitor qVD-OPh (20 µmol/l) for 24 hours. LS were quantified as in part (a). (d) Hepa 1–6 cells were infected with P. yoelii parasites and LS burden was quantified at 24 hours postinfection by microscopy as described in part a. Parasites were either treated with Serdemetan 24 hours before infection (-24 hours), 24 hours after infection (+24 hours) or both (-24 hours to +24 hours). NS (not significant), *P ≤ 0.05, **P ≤ 0.01 when compared with nontreated controls.

Article Snippet: Where indicated, cells were treated with ABT-737 (Selleck Chemicals, Houston, TX), Obatoclax mesylate (Selleck Chemicals), Nutlin-3 (Selleck Chemicals), Serdemetan (JNJ-26854165, Selleck Chemicals) and/or the pan-caspase inhibitor Q-VD-OPh ( N -(2-Quinolyl)-L-valyl-L-aspartyl-(2,6-difluorophenoxy) methylketone, SM Biochemicals LLC, Anaheim, CA at indicated concentrations.

Techniques: Infection, Concentration Assay, Staining, Expressing, Western Blot, Microscopy

Journal: Molecular Therapy

Article Title: Host-based Prophylaxis Successfully Targets Liver Stage Malaria Parasites

doi: 10.1038/mt.2015.18

Figure Lengend Snippet: Combination treatment of Serdemetan and Obatoclax completely eliminates LS burden. (a) Hepa 1–6 cells were infected with P. yoelii sporozoites in chamber slides and treated with Serdemetan (10 µmol/l), Obatoclax (100 nmol/l), Serdemetan and Obatoclax, or media only (NT) for 48 hours. LS parasites were identified by UIS4 and HSP70 expression using fluorescence microscopy and quantified. NS (not significant), *P ≤ 0.05, **P ≤ 0.01 when compared with nontreated controls. (b) BALB/cJ mice were treated 24 hours prior to infection, the day of infection, and for 3 days following infection with vehicle only, Serdemetan (20 mg/kg/day) only, Serdemetan (20 mg/kg/day) and Obatoclax (5 mg/kg/day), or double Serdemetan (40 mg/kg/day) and Obatoclax (5 mg/kg/day). There was an additional condition where mice were treated for 24 hours prior to infection, the day of infection, and for 8 days following infection with Serdemetan (20 mg/kg/day) and Obatoclax (5 mg/kg/day). Patency was monitored for all conditions by thin blood smear and Giemsa stain.

Article Snippet: Where indicated, cells were treated with ABT-737 (Selleck Chemicals, Houston, TX), Obatoclax mesylate (Selleck Chemicals), Nutlin-3 (Selleck Chemicals), Serdemetan (JNJ-26854165, Selleck Chemicals) and/or the pan-caspase inhibitor Q-VD-OPh ( N -(2-Quinolyl)-L-valyl-L-aspartyl-(2,6-difluorophenoxy) methylketone, SM Biochemicals LLC, Anaheim, CA at indicated concentrations.

Techniques: Infection, Expressing, Fluorescence, Microscopy, Giemsa Stain

Journal: NPJ Precision Oncology

Article Title: Leveraging patient derived models of FGFR2 fusion positive intrahepatic cholangiocarcinoma to identify synergistic therapies

doi: 10.1038/s41698-022-00320-5

Figure Lengend Snippet: A High-throughput small molecule screen inclusive of >2100 clinically relevant anticancer drugs suggest targets synergistic with pemigatinib. Each dot represents a compound plotted against that drug’s synergy score on the y -axis. Smaller differential viability is synonymous with increased synergy. Targets of commonly synergistic pathways are specifically highlighted. B Quisinostat and pemigatinib have synergistic effects on viability in the PDC-DUC18828 model based on MacSynergy II calculation (95% confidence interval). Results are color-coded from purple (most antagonistic) to dark red (most synergistic). C Dose–response curves in the PDC-DUC18828 model shift left with increasing concentrations of pemigatinib, resulting in significant reduction in the IC 50 value of quisinostat, concordant with synergy observed in B . All curves are normalized to 0 nM quisinostat under the corresponding concentrations of pemigatinib. D Quisinostat and pemigatinib have synergistic effects on viability in the PDO-DUC18828 model based on MacSynergy II calculation (95% confidence interval). Data are represented as in B . E Dose–response curves in the PDO model shift left with increasing concentrations of pemigatinib, resulting in significant reduction in the IC 50 value of quisinostat, concordant with synergy observed in D (normalized as per C ). Viability results are normalized to DMSO control and presented as the mean +/− standard deviation (error bars) for three biologically independent replicates. F Quisinostat and pemigatinib have synergistic effects on tumor growth in vivo. Mice bearing subcutaneous xenografts (~125 mm 3 ) were randomized to control (sham/sham gavage with Ora-plus suspension) vs pemigatinib (3 mg/kg oral gavage + sham gavage with Ora-plus suspension) vs quisinostat (16 mg/kg oral gavage + sham gavage with Ora-plus suspension) vs combination treatment (pemigatinib 3 mg/kg oral gavage + quisinostat 16 mg/kg oral gavage) and were treated 5 days per week. Tumor volume was measured 3×/week until study endpoints were reached. Compared to the control cohort (sham/sham), combined treatment with pemigatinib and quisinostat impaired tumor growth by 59.4%, compared to 23.8% with pemigatinib alone and 15.1% with quisinostat alone. Solid brackets (also recognized by arrows) indicate p < 0.05 between treatment arms starting on day 10 of treatment, indicated by the asterisk (*), whereas dashed brackets were not significant. Data are represented as mean +/− standard error of the mean for each experimental condition, consisting of 12 mice each and compared using the Student’s t test.

Article Snippet: Pemigatinib (Cat# T12401), BGJ398 (infigratinib, Cat# T1975) and quisinostat (Cat# T6055) were purchased from TargetMol Chemicals (Boston, MA).

Techniques: High Throughput Screening Assay, Standard Deviation, In Vivo

Journal: NPJ Precision Oncology

Article Title: Leveraging patient derived models of FGFR2 fusion positive intrahepatic cholangiocarcinoma to identify synergistic therapies

doi: 10.1038/s41698-022-00320-5

Figure Lengend Snippet: A Quisinostat and pemigatinib synergistically lower the proliferative index (Ki-67) in the PDC-DUC18828 model. The percentage of Ki-67-positive cells was determined and flow cytometry data are shown on the left with corresponding Ki-67 index for each condition shown in the bar graph on the right. Compared to DMSO control, 50 nM pemigatinib decreases the Ki-67 index by ~30%, 100 nM quisinostat decreases the Ki-67 index by ~24%, while 50 nM pemigatinib + 100 nM quisinostat (Pemi + Qui) synergistically decrease the Ki-67 index by ~53% (** p < 0.01 and *** p < 0.001). B Quisinostat and pemigatinib synergistically lower the Ki-67 in the PDO-DUC18828 model. Data are presented as in A . Compared to DMSO control, 10 nM pemigatinib decreases the Ki-67 by ~36%, 25 nM quisinostat decreases the Ki-67 by ~24%, while 10 nM pemigatinib + 25 nM quisinostat (Pemi + Qui) synergistically decreases the Ki-67 index by ~50% (* p < 0.05 and ** p < 0.01). C , D Quisinostat and pemigatinib synergistically enhance apoptosis in the PDC- and PDO-DUC18828 models, respectively. In both models, under the conditions indicated, combined inhibition of HDAC and FGFR increases the proportion of apoptotic cells, especially late-stage apoptosis, but also the early apoptotic population, compared to monotherapy or DMSO control. Q1, dead cells; Q2, late apoptotic/dead cells; Q3, early-apoptotic cells; Q4, healthy cells. E Western blot analysis of PDC-DUC18828 with pemigatinib (2P = 2 nM) monotherapy, quisinostat (50Q = 50 nM) monotherapy, and combination therapy (P + Q = 2 nM pemigatinib + 50 nM quisinostat). Compared to DMSO control, quisinostat monotherapy increases FGFR2, FRS2, MEK, and ERK activation, while pemigatinib monotherapy inhibits FGFR2 signaling, including downstream nodes, FRS2, MEK, and ERK. Combination therapy similarly impairs FGFR2, FRS2, MEK, and ERK activity. Neither monotherapy nor combination therapy alter AKT activity.

Article Snippet: Pemigatinib (Cat# T12401), BGJ398 (infigratinib, Cat# T1975) and quisinostat (Cat# T6055) were purchased from TargetMol Chemicals (Boston, MA).

Techniques: Flow Cytometry, Inhibition, Western Blot, Activation Assay, Activity Assay

Journal: Clinical and Experimental Pharmacology & Physiology

Article Title: Histamine via histamine H1 receptor enhances the muscarinic receptor‐induced calcium response to acetylcholine in an enterochromaffin cell model

doi: 10.1111/1440-1681.13682

Figure Lengend Snippet: H4R mRNA expression and effects of H4R ligands on the [Ca 2+ ] I response of P‐STS and HEK‐293 T cells to ACh. * P ≤ .05, PI: pre‐incubation (10 min), PPI: pre‐pre‐incubation, for example, pre‐incubation (2 min) before pre‐incubation with histamine). A, Expression of H4R mRNA in P‐STS and HEK‐293 T cells evaluated by amplification from the same cDNA used for H1R mRNA detection in Figure . The results were confirmed with an independent amplification from the same cDNA. Control: PCR with HEK‐293 T RNA without reverse transcription. B, Published pEC 50 and pK i or pA 2 values of the H4R ligands used in this study (an ³⁷ , b, ²⁰ c, ³⁸ d ¹⁹ ). D, [Ca 2+ ] i response of P‐STS cells to 10 μM 4‐methylhistamine (4mHA, left panel, 12 experiments) and to ACh with or without pre‐incubation with 10 μM 4mHA (right panel, 8 experiments). D, [Ca 2+ ] i response of P‐STS cells to VUF8430 alone or added simultaneously with ACh (8 experiments). E, [Ca 2+ ] i response of HEK‐293 T cells to 10 μM 4‐methylhistamine (8 experiments). F, Pre‐incubation with the H4R antagonist JNJ7777120 (1 μM) inhibits the [Ca 2+ ] i response to ACh in P‐STS cells (left panel, 7 experiments), whereas pre‐incubation with JNJ39758979 (1 μM), another H4R antagonist, is not inhibitory (right panel, 15 experiments). G, Pre‐incubation with JNJ39758979 (1 μM) does not inhibit the [Ca 2+ ] i response to ACh in HEK‐293 T cells (8 experiments). H, Effect of pre‐incubation with JNJ39758979 (1 μM) on the synergism of ACh with histamine in P‐STS cells (8 experiments). I, Effect of pre‐incubation with JNJ39758979 (1 μM) on the synergism of ACh with histamine in HEK‐293 T cells (18 experiments). J, JNJ39758979 (1 μM) does not inhibit the [Ca 2+ ] i response to ACh after pre‐incubation with the H4R agonist 4‐methylhistamine in HEK‐293 T cells (8 experiments). K, JNJ39758979 (1 μM) does not inhibit the [Ca 2+ ] i response to ACh after pre‐incubation with the H4R agonist 4‐methylhistamine in P‐STS cells (8 experiments). H4R, histamine H4 receptor; mRNA, messenger RNA; ACh, acetylcholine

Article Snippet: Mepyramine maleate, ranitidine hydrochloride, JNJ7777120 dihydrobromid and JNJ39758979 dihydrochloride were from Tocris; ACh chloride, histamine dihydrochloride, VUF8430 dihydrobromid, cetirizine dihydrochloride, J104129 fumarate and L‐adrenaline were from Sigma Aldrich; VU0119498 was from Abcam, forskolin was from Cayman Chemical, Fluo‐4 AM and poly‐D‐lysine were from Thermo Fisher Scientific, and goat anti‐chromogranin A as well as mouse anti‐human monoclonal H1R antibody (G11) were from Santa Cruz Biotechnology.

Techniques: Expressing, Incubation, Amplification, Control, Reverse Transcription

Journal: NPJ Precision Oncology

Article Title: Tackling FGFR3-driven bladder cancer with a promising synergistic FGFR/HDAC targeted therapy

doi: 10.1038/s41698-023-00417-5

Figure Lengend Snippet: a Schematic diagram of FGFR3 fusions in SW780, RT112, and RT4 cells. All three FGFR3 fusions share a common construct, where the intact extracellular region, transmembrane helix, and intracellular kinase domain of FGFR3 are well-maintained, with only the C terminal tail of FGFR3 replaced by a fusion partner. Red arrowheads represent the breakpoints of FGFR3 fusions in each cell line. FGFR3-BAIBP2L1 fusion is indicated by blue dashed line. FGFR3-TACC3 fusion in RT4 cells is indicated by green dashed line. The alternative breakpoint in TACC3 for FGFR3-TACC3 fusion in RT112 cells is indicated by light green dashed line. I/II/III, immunoglobulin-like domain (Ig) I/II/III; TM, transmembrane domain; IMD, IRSp53/MIM homology domain; TACC, transforming acidic coiled-coil domain. b Western blots showing FGFR3 fusions in SW780 (FGFR3-BAIBP2L1), RT112 (FGFR3-TACC3), and RT4 (FGFR3-TACC3) cells. HEK293T cells were used as FGFR3 WT control. GAPDH was used as standard loading control. Positions for FGFR3 fusions and FGFR3 WT are indicated on the right. c – e MacSynergy II calculation (95% confidence interval) of the synergy between erdafitinib and quisinostat in SW780 cells ( c ), RT112 cells ( d ), and RT4 cells ( e ). Cells were treated by different concentrations of erdafitinib and/or quisinostat for 3 days. And cell viabilities were determined by WST-1 assay and normalized to DMSO control. Synergistic inhibition was calculated by MacSynergy II. Synergistic inhibition above 0 means synergy, equal to 0 indicates additivity, and below 0 suggests antagonism. f – h Cell viability of SW780 cells ( f ), RT112 cells ( g ), and RT4 cells ( h ) by the treatment of erdafitinib and/or quisinostat. Cells were treated by erdafitinib and/or quisinostat for 3 days. And cell viabilities were determined by WST-1 assay and normalized to DMSO control. Data were plotted as mean ± standard deviation from three biological replicates and statistics were calculated by one-way ANOVA (** p < 0.01; **** p < 0.0001). i Clonogenic assays of SW780, RT112, and RT4 cells, under the treatment of erdafitinib, quisinostat, or the combination. Cells were seeded in 6-well plates with DMSO control, erdafitinib, quisisnostat, or the combination and cultured for 9 days. j Quantification of ( i ). Colony area was quantified by ImageJ and normalized to DMSO control. Data were plotted as mean ± standard deviation from three biological replicates and statistics were calculated by one-way ANOVA (* p < 0.05; *** p < 0.001; **** p < 0.0001).

Article Snippet: Erdafitinib (#HY-18708) and quisinostat (#HY-15433) were purchased from MedChemExpress.

Techniques: Construct, Western Blot, Control, WST-1 Assay, Inhibition, Standard Deviation, Cell Culture

Journal: NPJ Precision Oncology

Article Title: Tackling FGFR3-driven bladder cancer with a promising synergistic FGFR/HDAC targeted therapy

doi: 10.1038/s41698-023-00417-5

Figure Lengend Snippet: Effects of erdafitinib on quisinostat IC 50 .

Article Snippet: Erdafitinib (#HY-18708) and quisinostat (#HY-15433) were purchased from MedChemExpress.

Techniques:

Journal: NPJ Precision Oncology

Article Title: Tackling FGFR3-driven bladder cancer with a promising synergistic FGFR/HDAC targeted therapy

doi: 10.1038/s41698-023-00417-5

Figure Lengend Snippet: a , b Tumor volumes of SW780 xenografts ( a ) under the treatment of vehicle, 10 mg/kg erdafitinib, 10 mg/kg quisinostat, or the combination. And tumor volumes of RT112 xenografts ( b ) under the treatment of vehicle, 10 mg/kg erdafitinib, 5 mg/kg quisinostat, or the combination. Data were plotted as mean ± SEM ( n = 5). Statistics were calculated by one-way ANOVA based on the tumor volume at Day 21 for SW780 xenografts and Day 22 for RT112 xenograft (* p < 0.05; ** p < 0.01; **** p < 0.0001). c , d Overall survival of SW780 xenografts ( c ) under the treatment of vehicle, 10 mg/kg erdafitinib, 10 mg/kg quisinostat, or the combination ( n = 10). And overall survival of RT112 xenografts ( d ) under the treatment of vehicle, 10 mg/kg erdafitinib, 5 mg/kg quisinostat, or the combination ( n = 10). Log-Rank (Mantel-Cox) test was used to test for significance, as indicated in the figure. n.s., non-significant.

Article Snippet: Erdafitinib (#HY-18708) and quisinostat (#HY-15433) were purchased from MedChemExpress.

Techniques:

Journal: NPJ Precision Oncology

Article Title: Tackling FGFR3-driven bladder cancer with a promising synergistic FGFR/HDAC targeted therapy

doi: 10.1038/s41698-023-00417-5

Figure Lengend Snippet: a Western blots showing the phospho-FGFR (pFGFR) level treated by erdafitinib in SW780, RT112, and RT4 cells. Cells were first treated by erdafitinib or DMSO in no serum media for 3 h. FGFR signaling was then stimulated by adding 50 ng/ml FGF1 and 10 ug/ml heparin and examined by western blotting. GAPDH was used as standard loading control. Red arrowheads represent the position of FGFR3 fusions. 2/10E, 2/10 nM erdafitinib. b Western blots showing the FGFR3 expression level treated by quisinostat in SW780, RT112, and RT4 cells. Cells were first treated by quisinostat or DMSO for 2 days and then harvested for western blotting. GAPDH was used as standard loading control. Red arrowheads represent the position of FGFR3 fusions. 10/25Q, 10/25 nM erdafitinib. c , e Western blots showing the FGFR3 expression level after siRNA knockdown by both siRNAs of FGFR3 (siFGFR3-1 and -2) in RT112 cells ( c ) and RT4 cells ( e ). β-actin (ACTB) was used as standard loading control. Red arrowheads represent the position of FGFR3 fusions. d , f Cell viabilities of RT112 cells ( d ) and RT4 cells ( f ) treated by erdafitinib with or without FGFR3 knockdown. Cells were treated by erdafitinib for 3 days. And cell viabilities were determined by WST-1 assay and normalized to DMSO control for each cell line. Data were plotted as mean ± standard deviation from three biological replicates and statistics were calculated by one-way ANOVA (** p < 0.01; *** p < 0.001; **** p < 0.0001). siControl, siRNA of non-targeting control; 0.5/1/2.5/5E, 0.5/1/2.5/5 nM erdafitinib. g Western blots showing the FGFR3-TACC3 overexpression in RT112 cells. β-actin (ACTB) was used as standard loading control. Red arrowhead represents the position of FGFR3 fusion. EV, empty vector; F3-T3, FGFR3-TACC3. h Cell viabilities of RT112 cells treated by erdafitinib and/or quisinostat with or without FGFR3-TACC3 overexpression. Cells were treated by erdafitinib and/or quisinostat for 3 days. And cell viabilities were determined by WST-1 assay and normalized to DMSO control for each cell line. Data were plotted as mean ± standard deviation from three biological replicates and statistics were calculated by t tests (**** p < 0.0001). EV, empty vector; 1E, 1 nM erdafitinib; 10Q, 10 nM quisinostat. i , j Cell viabilities of RT112 cells ( i ) and RT4 cells ( j ) treated by erdafitinib and/or quisinostat with or without adding FGF1. Cells were treated by erdafitinib and/or quisinostat for 3 days with or without adding 50 ng/ml FGF1 and 10 ug/ml heparin. And cell viabilities were determined by WST-1 assay and normalized to DMSO control for each condition. Data were plotted as mean ± standard deviation from three biological replicates and statistics were calculated by t tests (*** p < 0.001; **** p < 0.0001). 1/5E, 1/5 nM erdafitinib; 5/10Q, 5/10 nM quisinostat.

Article Snippet: Erdafitinib (#HY-18708) and quisinostat (#HY-15433) were purchased from MedChemExpress.

Techniques: Western Blot, Control, Expressing, Knockdown, WST-1 Assay, Standard Deviation, Over Expression, Plasmid Preparation

Journal: NPJ Precision Oncology

Article Title: Tackling FGFR3-driven bladder cancer with a promising synergistic FGFR/HDAC targeted therapy

doi: 10.1038/s41698-023-00417-5

Figure Lengend Snippet: Western blots showing the combinational effects of erdafitinib and quisinostat on FGFR signaling activation. Cells were first treated by quisinostat or DMSO control for 2 days, followed by the treatment by erdafitinib or DMSO control in no serum media for 3 h. Then FGFR signaling was stimulated by 50 ng/ml FGF1 + 10 µg/ml heparin and analyzed by western blotting. β-actin (ACTB) was used as standard loading control. Red arrowheads represent the position of FGFR3 fusions. Red boxes represent the signaling pathways that can be further inhibited by the combinational treatment, compared to each individual drug treatment alone. 1E, 1 nM erdafitinib; 2E, 2 nM erdafitinib; 25Q, 25 nM quisinostat; 50Q, 50 nM quisinostat; E + Q, the combination of erdafitinib and quisinostat.

Article Snippet: Erdafitinib (#HY-18708) and quisinostat (#HY-15433) were purchased from MedChemExpress.

Techniques: Western Blot, Activation Assay, Control

Journal: NPJ Precision Oncology

Article Title: Tackling FGFR3-driven bladder cancer with a promising synergistic FGFR/HDAC targeted therapy

doi: 10.1038/s41698-023-00417-5

Figure Lengend Snippet: a RNA-seq results showing the representative genes that are downregulated by quisinostat in all three BC cells. b RT-qPCR results showing the HDGF mRNA level with or without quisinostat treatment. Cells were treated by quisisnostat for 2 days and then harvested for RT-qPCR. All results were first normalized to β-actin (ACTB) loading control and then normalized to DMSO control of each cell line. Data were plotted as mean ± SEM from four biological replicates and statistics were calculated by t tests (**** p < 0.0001). c Western blots showing the HDGF protein expression level with or without quisinostat treatment. Cells were treated by quisisnostat for 2 days and then harvested for western blotting. β-actin (ACTB) was used as standard loading control. d Quantification of ( c ) by ImageJ. Results were normalized to DMSO control for each cell line. Data were plotted as mean ± standard deviation from three biological replicates and statistics were calculated by t tests (**** p < 0.0001). e TCGA analysis of the bladder cancer cohort showing that HDGF expression is higher in bladder cancer patients than in healthy tissue. Statistics were calculated by one-way ANOVA (* p < 0.05). Center lines represent the median value, upper and lower bounds of the boxes denote the upper and lower quartiles, upper and lower whiskers represent the 1.5x interquartile range, and data points outside the upper and lower whiskers are considered outliers. f Western blots showing that both siRNAs of HDGF (siHDGFs) can successfully knock down HDGF without affecting the expression of FGFR3 fusions in SW780 and RT112 cells. β-actin (ACTB) was used as standard loading control. C, siRNA of non-targeting control. g , h Cell viabilities of SW780 cells ( g ) and RT112 cells ( h ) treated by erdafitinib with or without HDGF knockdown. Cells were treated by erdafitinib for 3 days. And cell viabilities were determined by WST-1 assay and normalized to DMSO control for each cell line. Data were plotted as mean ± standard deviation from three biological replicates and statistics were calculated by one-way ANOVA (** p < 0.01; **** p < 0.0001). siControl, siRNA of non-targeting control. 10/25/50E, 10/25/50 nM erdafitinib; 50Q, 50 nM quisinostat.

Article Snippet: Erdafitinib (#HY-18708) and quisinostat (#HY-15433) were purchased from MedChemExpress.

Techniques: RNA Sequencing Assay, Quantitative RT-PCR, Control, Western Blot, Expressing, Standard Deviation, Knockdown, WST-1 Assay

Journal: NPJ Precision Oncology

Article Title: Tackling FGFR3-driven bladder cancer with a promising synergistic FGFR/HDAC targeted therapy

doi: 10.1038/s41698-023-00417-5

Figure Lengend Snippet: a Schematic diagram of FGFR3 S249 mutation. Red arrowhead represents the position of S249C in FGFR3. b MacSynergy II calculation (95% confidence interval) of the synergy between erdafitinib and quisinostat in UM-UC-14 cells, which is a BC cell line with FGFR3 S249C mutation. Cells were treated by different concentrations of erdafitinib and/or quisinostat for 3 days. And cell viabilities were determined by WST-1 assay and normalized to DMSO control. Synergistic inhibition was calculated by MacSynergy II. Synergistic inhibition above 0 means synergy, equal to 0 indicates additivity, and below 0 suggests antagonism. c Cell viability of UM-UC-14 cells by the treatment of erdafitinib and/or quisinostat. Cells were treated by erdafitinib and/or quisinostat for 3 days. And cell viabilities were determined by WST-1 assay and normalized to DMSO control. Data were plotted as mean ± standard deviation from three biological replicates and statistics were calculated by one-way ANOVA (**** p < 0.0001). 2.5E, 2.5 nM erdafitinib; 2.5Q, 2.5 nM quisisnostat. d Western blots showing the FGFR3 and HDGF expression level with or without quisinostat treatment in UM-UC-14 cells. Cells were treated by quisisnostat for 2 days and then harvested for western blotting. β-actin (ACTB) was used as standard loading control. 10/25/50Q, 10/25/50 nM quisisnostat.

Article Snippet: Erdafitinib (#HY-18708) and quisinostat (#HY-15433) were purchased from MedChemExpress.

Techniques: Mutagenesis, WST-1 Assay, Control, Inhibition, Standard Deviation, Western Blot, Expressing

Journal: Cell systems

Article Title: Quantifying drug combination synergy along potency and efficacy axes.

doi: 10.1016/j.cels.2019.01.003

Figure Lengend Snippet: KEY RESOURCES TABLE

Article Snippet: Quisinostat (JNJ-26481585) , SelleckChem , S1096.

Techniques: Virus, Recombinant, Sample Prep, Reverse Transcription, SYBR Green Assay, Expressing, Derivative Assay, Plasmid Preparation, Software