Journal: Toxicology letters

Article Title: A new strategy for the rapid identification and validation of direct toxicity targets of psoralen-induced hepatotoxicity.

doi: 10.1016/j.toxlet.2022.05.002

Figure Lengend Snippet: Fig. 3. Direct interaction of psoralen with ABL1. (A) Kinetics of psoralen binding to ABL1 determined by SPR, the kinetic parameters of KD were measured with BIAcore valuation software using a 1:1 binding model. (B) Three-dimensional molecular docking model of psoralen with the direct target protein ABL1 (PDB:2HYY).

Article Snippet: After stimulation for 24 h with a psoralen solution and specific concentrations of the ABL1 inhibitor imatinib (HY15463, MCE, USA), and an ABL1 agonist, DPH (HY12070, MCE, USA), the cells were digested with trypsin that did not contain EDTA and collected into a 1.5 mL centrifuge tube.

Techniques: Binding Assay, Software

Journal: Toxicology letters

Article Title: A new strategy for the rapid identification and validation of direct toxicity targets of psoralen-induced hepatotoxicity.

doi: 10.1016/j.toxlet.2022.05.002

Figure Lengend Snippet: Fig. 8. To investigate the expression changes of Nrf2 and mTOR in HepG2 cells under the influence of an ABL1 inhibitor and agonist. (A) The effect of imatinib/DPH on the viability of HepG2 cells; (B) Western blot analysis of mTOR and Nrf2 in each group in HepG2 cells; (C) After 24 h exposure to imatinib/DPH in HepG2 cells, immunofluorescence staining was performed with Nrf2, mTOR antibody to assess the distribution of Nrf2, mTOR. Green fluorescence indicates Nrf2 expression, red fluorescence indicates mTOR expression, and blue fluorescence (DAPI) stained nuclei as a control. Scale bars: 50 µm. Normalized to ± β-action, All Data are shown as mean ± SD (n = 3). “* ” indicates statistically significant difference with the control group. * and # P < 0.05, * * and ## P < 0.01, * ** and ### P < 0.001 versus the psoralen alone group.

Article Snippet: After stimulation for 24 h with a psoralen solution and specific concentrations of the ABL1 inhibitor imatinib (HY15463, MCE, USA), and an ABL1 agonist, DPH (HY12070, MCE, USA), the cells were digested with trypsin that did not contain EDTA and collected into a 1.5 mL centrifuge tube.

Techniques: Expressing, Western Blot, Immunofluorescence, Staining, Fluorescence, Control

Journal: Toxicology letters

Article Title: A new strategy for the rapid identification and validation of direct toxicity targets of psoralen-induced hepatotoxicity.

doi: 10.1016/j.toxlet.2022.05.002

Figure Lengend Snippet: Fig. 9. To investigate the expression changes of Nrf2 and mTOR in L02 cells under the influence of ABL1 inhibitor and agonist. (A) The effect of imatinib/DPH on the viability of L02 cells; (B) Western blot analysis of mTOR and Nrf2 in each group in L02 cells; (C) After 24 h of exposure to imatinib/DPH in L02 cells, immuno fluorescence staining was performed with Nrf2, mTOR antibodies to evaluate the distribution of Nrf2, mTOR. Green fluorescence indicates Nrf2 expression, red fluorescence indicates mTOR expression, and blue fluorescence (DAPI) stained nuclei as a control. Scale bars: 50 µm. Normalized to ± β-action, All Data are shown as mean ± SD (n = 3). “* ” indicates statistically significant difference with the control group. * and # P < 0.05, * * and ## P < 0.01, * ** and ### P < 0.001 versus the psoralen alone group.

Article Snippet: After stimulation for 24 h with a psoralen solution and specific concentrations of the ABL1 inhibitor imatinib (HY15463, MCE, USA), and an ABL1 agonist, DPH (HY12070, MCE, USA), the cells were digested with trypsin that did not contain EDTA and collected into a 1.5 mL centrifuge tube.

Techniques: Expressing, Western Blot, Fluorescence, Staining, Control

Journal: Frontiers in Pharmacology

Article Title: c-Abl Inhibition Exerts Symptomatic Antiparkinsonian Effects Through a Striatal Postsynaptic Mechanism

doi: 10.3389/fphar.2018.01311

Figure Lengend Snippet: Effects of imatinib and levodopa on striatal motor behaviors and c-Abl/Cdk5/DARPP-32 signaling cascades. (A) Striatal penetration of intraperitoneally injected imatinib in mice. HPLC analysis were done to quantify concentrations of imatinib in the striatum ( n = 4), cortex ( n = 5), hippocampus ( n = 4), thalamus ( n = 4), and blood plasma ( n = 5) of naïve mice that received single i.p. injections of imatinib mesylate (25 mg/kg) 30 min before sacrifice. Values are expressed as means ± SEM. (B) Symptomatic antiparkinsonian effects of imatinib and levodopa in MPTP-treated mice. Behavioral tests were carried out in vehicle or MPTP-treated mice 30 min after a single i.p. injection of imatinib and/or levodopa. ( left-upper panel ) The beam-walking test for examining the effects of administration of imatinib mesylate (25 mg/kg) or levodopa (15 mg/kg). Values are means ± SEM ( n = 5–21). ∗ P < 0.05 versus vehicle-treated mice; one-way ANOVA [ F (5,77) = 11.265] followed by the Scheffe post hoc test. ( right-upper panel ) The rota-rod test for examining the effects of imatinib mesylate (25 mg/kg) or levodopa (15 mg/kg) administration. Values are means ± SEM ( n = 8–21). ∗ P < 0.05 versus vehicle-treated mice; one-way ANOVA [ F (5,80) = 7.710] followed by the Scheffe post hoc test. ( left-lower panel ) The beam-walking test for examining the effects of imatinib mesylate (10 mg/kg) and/or levodopa (2.5 or 5 mg/kg) administration. Values are means ± SEM ( n = 10–11). # P < 0.05 versus MPTP-treated mice; one-way ANOVA [ F (5,55) = 4.177] followed by the Scheffe post hoc test. ( right-lower panel ) The rota-rod test for examining the effects of imatinib mesylate (10 mg/kg) and/or levodopa (2.5 or 5 mg/kg) administration. Values are means ± SEM ( n = 10–11). ### P < 0.001 versus MPTP-treated mice; one-way ANOVA [ F (5,55) = 8.283] followed by the Scheffe post hoc test. (C) Western-blot analysis of striatal levels of Cdk5-pTyr15 and Cdk5 in vehicle or MPTP-treated mice 30 min after single i.p. injections of imatinib. Values are means ± SEM ( n = 4–5). ∗ P < 0.05 versus vehicle-treated mice, # P < 0.05 versus MPTP-treated mice; one-way ANOVA [ F Cdk5-pTyr15(4,19) = 50.391, F Cdk5(4,19) = 1.413] followed by the Scheffe post hoc test. IMB (10), imatinib mesylate (10 mg/kg); IMB (25), imatinib mesylate (25 mg/kg). (D) Western-blot analysis of striatal levels of DARPP-32-pThr75, DARPP-32-pThr34, and DARPP-32 in vehicle or MPTP-treated mice 30 min after a single i.p. injection of imatinib. Values are means ± SEM ( n = 4–5). ∗ P < 0.05 versus vehicle-treated mice, # P < 0.05 versus MPTP-treated mice; one-way ANOVA [ F DARPP-32-pThr75(4,19) = 35.089, F DARPP-32-pThr34(4,19) = 0.711, F DARPP-32(4,19) = 0.293] followed by the Scheffe post hoc test. IMB (10), imatinib mesylate (10 mg/kg); IMB (25), imatinib mesylate (25 mg/kg). (E) Western-blot analysis of striatal levels of Cdk5-pTyr15 and Cdk5 in MPTP-treated mice 30 min after a single i.p. injection of levodopa and/or imatinib. Values are expressed as means ± SEM ( n = 5–10). # P < 0.05, ## P < 0.01 versus MPTP-treated mice. One-way ANOVA [ F Cdk5-pTyr15(3,31) = 6.039, F Cdk5(3,17) = 0.258] followed by the Scheffe post hoc test. Levodopa (5), levodopa (5 mg/kg); IMB (10), imatinib mesylate (10 mg/kg). (F) Western-blot analysis of striatal levels of DARPP-32-pThr75, DARPP-32-pThr34, and DARPP-32 in MPTP-treated mice 30 min after a single i.p. injection of imatinib and/or levodopa. Values are expressed as means ± SEM ( n = 4-10). # P < 0.05, ## P < 0.01 versus MPTP-treated mice. One-way ANOVA [ F DARPP-32-pThr75(3,29) = 5.529, F DARPP-32-pThr34(3,16) = 1.257, F DARPP-32(3,16) = 2.886] followed by the Scheffe post hoc test. Levodopa (5), levodopa (5 mg/kg); IMB (10), imatinib mesylate (10 mg/kg). (G) Western-blot analysis of striatal levels of c-Abl-pTyr412, and c-Abl in MPTP-treated mice 30 min after a single i.p. injection of imatinib and/or levodopa. Values are expressed as means ± SEM ( n = 8–11). # P < 0.05 versus MPTP-treated mice; One-way ANOVA [ F c-Abl-pTyr412(3,34) = 5.820, F c-Abl(3,29) = 0.240] followed by Scheffe post hoc test. Levodopa (5), levodopa (5 mg/kg); IMB (10), imatinib mesylate (10 mg/kg).

Article Snippet: Mice received a single i.p. injection of imatinib mesylate (10 or 25 mg/kg; LKT Laboratories, St. Paul, MN, United States) dissolved in 0.9% saline containing 10% dimethyl sulfoxide 3 days after the administration of MPTP or saline.

Techniques: Injection, Clinical Proteomics, Western Blot

Journal: Frontiers in Pharmacology

Article Title: c-Abl Inhibition Exerts Symptomatic Antiparkinsonian Effects Through a Striatal Postsynaptic Mechanism

doi: 10.3389/fphar.2018.01311

Figure Lengend Snippet: Effects of imatinib on striatal presynaptic dopaminergic markers in MPTP-treated mice. Western-blot and HPLC analyses were carried out on the striatal extracts from vehicle or MPTP-treated mice 30 min after a single i.p. injection of imatinib mesylate (10 or 25 mg/kg). (A) Western-blot analysis of striatal levels of TH. Values are means ± SEM ( n = 4-5). ∗ P < 0.05 versus vehicle-treated mice; one-way ANOVA [ F (4,19) = 107.43] followed by the Scheffe post hoc test. IMB (10), imatinib mesylate (10 mg/kg); IMB (25), imatinib mesylate (25 mg/kg). (B) Western-blot analysis of striatal levels of DAT. Values are means ± SEM ( n = 4–5). ∗ P < 0.05 versus vehicle-treated mice; one-way ANOVA [ F (4,19) = 21.749] followed by the Scheffe post hoc test. IMB (10), imatinib mesylate (10 mg/kg); IMB (25), imatinib mesylate (25 mg/kg). (C) Western-blot analysis of striatal levels of VMAT2. Values are means ± SEM ( n = 4–5). ∗ P < 0.05 versus vehicle-treated mice; one-way ANOVA [ F (4,19) = 20.615] followed by the Scheffe post hoc test. IMB (10), imatinib mesylate (10 mg/kg); IMB (25), imatinib mesylate (25 mg/kg). (D–G) HPLC analysis of striatal levels of DA (D) , DOPAC (E) , HVA (F) , and DA-turnover, which represents a net dopamine usage in striatum with (DOPAC + HVA)/DA (G) . Values are expressed as means ± SEM ( n = 4–5). ∗ P < 0.05 versus vehicle-treated mice; one-way ANOVA [ F DA(4,19) = 34.526, F DOPAC(4,19) = 15.383, F HV A(4,19) = 16.078, F DA-turnover(4,19) = 10.355] followed by the Scheffe post hoc test. IMB (10), imatinib mesylate (10 mg/kg); IMB (25), imatinib mesylate (25 mg/kg).

Article Snippet: Mice received a single i.p. injection of imatinib mesylate (10 or 25 mg/kg; LKT Laboratories, St. Paul, MN, United States) dissolved in 0.9% saline containing 10% dimethyl sulfoxide 3 days after the administration of MPTP or saline.

Techniques: Western Blot, Injection

Journal: International Journal of Molecular Sciences

Article Title: Perturbation of p38α MAPK as a Novel Strategy to Effectively Sensitize Chronic Myeloid Leukemia Cells to Therapeutic BCR-ABL Inhibitors

doi: 10.3390/ijms222212573

Figure Lengend Snippet: Specific p38α inhibitor TAK715 greatly increased the therapeutic efficacy of imatinib and dasatinib toward CML cells. K562 leukemia cells were treated with imatinib (0.3 µM) ( A ) or dasatinib (1 nM) ( B ) in combination with p38α inhibitor TAK715 (5 or 10 µM). Alternatively, cells were treated with TAK715 (5 or 10 µM) alone ( C ). The viability of cells was examined by trypan blue exclusion. All results shown are representative of three independent experiments. Viable and dead cell numbers are presented as the mean ± SE of three repeats. * p < 0.05, ** p < 0.01, and *** p < 0.005.

Article Snippet: Imatinib (SC-202180, Santa Cruz Biotechnology, Dallas, TX, USA) and dasatinib (SC-358114, Santa Cruz Biotechnology, Dallas, TX, USA) were dissolved in sterile distilled water, diluted to the desired concentrations, and added directly into media.

Techniques:

Journal: eLife

Article Title: FGF2-FGFR1 signaling regulates release of Leukemia-Protective exosomes from bone marrow stromal cells

doi: 10.7554/elife.40033

Figure Lengend Snippet: Figure 1. Extracellular vesicles (ECVs) secreted by HS-5 cells are internalized by MOLM14 and K562 cells and protect from treatment with AC220 or imatinib, respectively. HS-5 conditioned media (CM) was collected and separated by ultracentrifugation at 100,000 g into a supernatant (S100) and pellet (P100) fraction containing ECVs. These fractions were incubated with (A) K562 cells ± 1 mM imatinib, or (B) MOLM14 cells ± 10 nM AC220, and Figure 1 continued on next page

Article Snippet: DOI: https://doi.org/10.7554/eLife.40033 14 of 23 Continued Reagent type (species) or resource Designation Source or reference Identifiers Additional information Genetic reagent (homo sapiens) FGF2-2 GenScript CRISPR/Cas nine guide RNA design Genetic reagent (homo sapiens) FGFR1-1 GenScript CRISPR/Cas nine guide RNA design Genetic reagent (homo sapiens) FGFR1-2 GenScript CRISPR/Cas nine guide RNA design Genetic reagent (mus musculus) pMIG with BCR-ABL and GFP murine retrovirus Cell line (homo sapiens) MOLM14 Dr. Yoshinobu Matsuo RRID:CVCL_7916 Cell line (homo sapiens) K562 American Type Culture Collection RRID:CVCL_0004 Cell line (homo sapiens) HS-5 Dr. Beverly Torok-Storb RRID:CVCL_3720 Cell line (homo sapiens) HS-27 Dr. Beverly Torok-Storb RRID:CVCL_0335 Antibody Mouse monoclonal anti-FGFR1 Cell Signaling 9740 Dilution 1:1000 Antibody Rabbit polyclonal anti-FGF2 Santa Cruz Sc-79 Dilution 1:500 Antibody Rabbit monoclonal anti-CD63 ABCAM ab134045 Dilution 1:1000 Antibody Rabbit polyclonal anti-CD9 Santa Cruz Sc-9148 Dilution 1:200 Antibody Mouse monoclonal anti-tsg-101 Santa Cruz Sc-7964 Dilution 1:200 Antibody Mouse monoclonal anti-actin Millipore MAB1501 Dilution 1:5000 Peptide, recombinant protein FGF2 (human) Peprotech Commercial assay or kit Thermo Scientific lentiviral transfection kit Chemical compound, drug quizartinib (AC220) LC labs Chemical compound, drug imatinib LC labs Chemical compound, drug nilotinib SelleckChem Chemical compound, drug PD173074 SelleckChem Chemical compound, drug BGJ-398 SelleckChem Chemical compound, drug doxycycline Fisher Software, algorithm CellProfiler Cell area

Techniques: Incubation

Journal: eLife

Article Title: FGF2-FGFR1 signaling regulates release of Leukemia-Protective exosomes from bone marrow stromal cells

doi: 10.7554/elife.40033

Figure Lengend Snippet: Figure 7. Fgf2 -/- mice survive significantly longer with TKI therapy in a murine BCR-ABL leukemia model. Fgf2 +/+ bone marrow was removed from donor mice and spinoculated with pMIG BCR-ABL retrovirus containing an IRES-GFP marker. The transfected bone marrow was then transplanted into lethally irradiated Fgf2 +/+ or -/- recipients. Mice were treated with 75 mg/kg/day nilotinib by oral gavage starting on day 11 of transplant. (A) Survival curves of untreated and nilotinib-treated Fgf2 +/+ and -/- mice. (B) GFP in peripheral blood was evaluated weekly and at time of euthanasia to quantify disease burden. The average GFP (percent of nucleated cells) is shown and did not differ significantly between groups indicating that all animals developed similar disease burden. Error bars indicate standard deviation. (C) Bone marrow cells from Fgf2 +/+ mice were spinoculated with pMIG BCR- ABL retrovirus containing GFP-IRES. The cells were then incubated with ECVs obtained from Fgf2 +/+ and -/- primary stroma cultured alone or with 500 nM PD173074. The next day the incubated cells were washed three times to remove cytokines and exosomes and plated in cytokine-free methylcellulose ± imatinib. After 8 days, colonies were counted and normalized to untreated condition. Graph shown on right. Error bars indicate standard error of the mean. *p<0.05 and **p<0.005. (D) Lineage-negative bone marrow cells were isolated from Fgf2 +/+ mice and cells were stained with DiO (green) tracer, washed, and immobilized on Poly-D-lysine coated chamber slides. ECVs from bone marrow stroma of Fgf2 +/+ or -/- mice were stained with DiI (red) tracer and added to the cells for a 24 hr incubation. Slides were stained with DAPI (blue) and imaged by confocal fluorescent microscopy. Movie of the z-stack images are included as Figure 7—video 1 and 2. (E) Model of bone marrow stromal FGF2 autocrine signaling and paracrine protection of leukemia cells by FGF2-containing exosomes. Figure 7 continued on next page

Article Snippet: DOI: https://doi.org/10.7554/eLife.40033 14 of 23 Continued Reagent type (species) or resource Designation Source or reference Identifiers Additional information Genetic reagent (homo sapiens) FGF2-2 GenScript CRISPR/Cas nine guide RNA design Genetic reagent (homo sapiens) FGFR1-1 GenScript CRISPR/Cas nine guide RNA design Genetic reagent (homo sapiens) FGFR1-2 GenScript CRISPR/Cas nine guide RNA design Genetic reagent (mus musculus) pMIG with BCR-ABL and GFP murine retrovirus Cell line (homo sapiens) MOLM14 Dr. Yoshinobu Matsuo RRID:CVCL_7916 Cell line (homo sapiens) K562 American Type Culture Collection RRID:CVCL_0004 Cell line (homo sapiens) HS-5 Dr. Beverly Torok-Storb RRID:CVCL_3720 Cell line (homo sapiens) HS-27 Dr. Beverly Torok-Storb RRID:CVCL_0335 Antibody Mouse monoclonal anti-FGFR1 Cell Signaling 9740 Dilution 1:1000 Antibody Rabbit polyclonal anti-FGF2 Santa Cruz Sc-79 Dilution 1:500 Antibody Rabbit monoclonal anti-CD63 ABCAM ab134045 Dilution 1:1000 Antibody Rabbit polyclonal anti-CD9 Santa Cruz Sc-9148 Dilution 1:200 Antibody Mouse monoclonal anti-tsg-101 Santa Cruz Sc-7964 Dilution 1:200 Antibody Mouse monoclonal anti-actin Millipore MAB1501 Dilution 1:5000 Peptide, recombinant protein FGF2 (human) Peprotech Commercial assay or kit Thermo Scientific lentiviral transfection kit Chemical compound, drug quizartinib (AC220) LC labs Chemical compound, drug imatinib LC labs Chemical compound, drug nilotinib SelleckChem Chemical compound, drug PD173074 SelleckChem Chemical compound, drug BGJ-398 SelleckChem Chemical compound, drug doxycycline Fisher Software, algorithm CellProfiler Cell area

Techniques: Marker, Transfection, Irradiation, Standard Deviation, Incubation, Cell Culture, Isolation, Staining, Microscopy

Journal: BioMed Research International

Article Title: SEA Antagonizes the Imatinib-Meditated Inhibitory Effects on T Cell Activation via the TCR Signaling Pathway

doi: 10.1155/2014/682010

Figure Lengend Snippet: The cell proliferation and IL-2 production of Jurkat cells and PBMCs following TCR stimulation. (Control) Untreated Jurkat cells or PBMCs. (SEA) Cells were pretreated with SEA (20 ng/mL). (IM) Cells were pretreated with 40 nM imatinib. (SEA + IM) Cells were pretreated with SEA (20 ng/mL) for 24 h followed by 40 nM imatinib treatment for 15 min. Each group was stimulated with anti-CD3/CD28 coated beads at a cell : bead ratio of 5 : 1 for 24 h. Cell proliferation was assayed with the CCK-8 kit (a) and (b). The IL-2 level was assayed using a human IL-2 ELISA kit (c) and (d). The mean value and standard deviation of 3 independent experiments are shown.

Article Snippet: Imatinib mesylate (Glivec, STI571) was purchased from Selleck Chemicals (USA), and SEA was obtained from Sigma (USA).

Techniques: Control, CCK-8 Assay, Enzyme-linked Immunosorbent Assay, Standard Deviation

Journal: BioMed Research International

Article Title: SEA Antagonizes the Imatinib-Meditated Inhibitory Effects on T Cell Activation via the TCR Signaling Pathway

doi: 10.1155/2014/682010

Figure Lengend Snippet: SEA pretreatment inhibited the reduction in imatinib-induced phosphorylation of Lck, ZAP70, and PLC γ 1 in Jurkat cells (a) and PBMCs (b). Densitometry (target protein : GAPDH ratio normalized to control) was conducted on three independent experiments in Jurkat cells (c) and PBMCs (d). Jurkat cells or PBMCs were pretreated in the absence or presence of SEA (20 ng/mL) followed by treatment with or without imatinib (40 nM), and cells were then stimulated with anti-CD3/CD28 coated beads for 15 min. Total cell extracts were resolved by SDS-PAGE and subjected to immunoblot analysis using phosphospecific antibodies as indicated.

Article Snippet: Imatinib mesylate (Glivec, STI571) was purchased from Selleck Chemicals (USA), and SEA was obtained from Sigma (USA).

Techniques: Phospho-proteomics, Control, SDS Page, Western Blot

Journal: Gastric Cancer

Article Title: Targeting yes-associated protein to overcome imatinib resistance in gastrointestinal stromal tumor drug-tolerant persister cells

doi: 10.1007/s10120-025-01657-z

Figure Lengend Snippet: Characterization of imatinib-derived gastrointestinal stromal tumor (GIST) drug-tolerant persister cells (DTPs). A Schematic explanation of DTP generation. B Cell proliferation measured by WST-8 assays at 72 h after imatinib treatment in GIST-T1 parental cells and DTPs. Each value is presented as mean ± SD (n = 6). Two-sided t-test (*** p < 0.001). C Western blot analysis of cKIT, pKIT, YAP and pYAP in nuclear and whole cell lysates of parental cells, DTPs, and regrown cells. D Cell cycle analysis of parental cells and DTPs. E Immunofluorescence staining of YAP/TAZ in parental cells, DTPs, and regrown cells. Scale bar:20 μm

Article Snippet: Cells were treated with imatinib mesylate (Tocris, Bristol, UK), verteporfin (a YAP inhibitor (Selleck chemicals, Houston, TX), or XAV-939 (a tankyrase inhibitor that indirectly suppresses YAP activity; Selleck chemicals, Houston, TX) [ ].

Techniques: Derivative Assay, Western Blot, Cell Cycle Assay, Immunofluorescence, Staining

Journal: Gastric Cancer

Article Title: Targeting yes-associated protein to overcome imatinib resistance in gastrointestinal stromal tumor drug-tolerant persister cells

doi: 10.1007/s10120-025-01657-z

Figure Lengend Snippet: Evaluation of YAP in patient samples A immunohistochemistry (IHC) staining for YAP in GIST patient samples with or without preoperative imatinib treatment. Scale bar:50 μm. B Proportion of YAP-positive tumor cell nuclei in 26 untreated or imatinib-resistant cases and 17 imatinib-responsive cases. Each value is presented as mean ± SEM. Mann–Whitney U test (**p < 0.01)

Article Snippet: Cells were treated with imatinib mesylate (Tocris, Bristol, UK), verteporfin (a YAP inhibitor (Selleck chemicals, Houston, TX), or XAV-939 (a tankyrase inhibitor that indirectly suppresses YAP activity; Selleck chemicals, Houston, TX) [ ].

Techniques: Immunohistochemistry, MANN-WHITNEY

Journal: Gastric Cancer

Article Title: Targeting yes-associated protein to overcome imatinib resistance in gastrointestinal stromal tumor drug-tolerant persister cells

doi: 10.1007/s10120-025-01657-z

Figure Lengend Snippet: Effects of YAP inhibitors on DTPs. A Western blot analysis of YAP and pYAP in nuclear and whole-cell lysates of parental cells, DTPs, and DTPs treated with verteporfin or XAV-939. B Immunofluorescence staining of YAP/TAZ in DTPs treated with verteporfin or XAV-939. Scale bar:20 μm. C Cell proliferation measured by WST-8 assays at 72 h after verteporfin or XAV-939 treatment in parental cells and DTPs. Each value is presented as mean ± SD (n = 6). Two-sided t-test (* p < 0.05, ** p < 0.01, *** p < 0.001). ( D ) Caspase 3/7 assay of the DTPs at 8 h after treatment with DMSO, imatinib, verteporfin or XAV-939, respectively. Each value is presented as mean ± SD (n = 4). Two-sided t-test (* p < 0.05)

Article Snippet: Cells were treated with imatinib mesylate (Tocris, Bristol, UK), verteporfin (a YAP inhibitor (Selleck chemicals, Houston, TX), or XAV-939 (a tankyrase inhibitor that indirectly suppresses YAP activity; Selleck chemicals, Houston, TX) [ ].

Techniques: Western Blot, Immunofluorescence, Staining

Journal: Gastric Cancer

Article Title: Targeting yes-associated protein to overcome imatinib resistance in gastrointestinal stromal tumor drug-tolerant persister cells

doi: 10.1007/s10120-025-01657-z

Figure Lengend Snippet: Effects of combination therapies of imatinib and YAP inhibitors. A Proliferation of cells treated with the following therapies, followed by drug washout: (1) vehicle, (2) verteporfin for 3 d, (3) XAV-939 for 3 d, (4) imatinib for 12 d, (5) imatinib for 9 d followed by a combination of imatinib and verteporfin for 3 d, and (6) imatinib for 9 d followed by a combination of imatinib and XAV-939 for 3 d. Each value is presented as mean ± SD (n = 6). Tukey–Kramer honestly significant difference test (** p < 0.01, *** p < 0.001). B Cell cycle assay of DTPs treated with the indicated therapies and incubated for 8 d after drug washout: (1) imatinib for 3 d, (2) imatinib and verteporfin for 3 d, and (3) imatinib and XAV-939 for 3 d. Each value is presented as mean ± SD (n = 3). Two-sided t-test (*** p < 0.001). C Annexin V-FITC/DAPI apoptosis assay in parental cells and DTPs treated with the indicated therapies for 8 h. Parental cells: (1) vehicle, (2) imatinib, (3) verteporfin, (4) XAV-939. DTPs: (5) vehicle, (6) imatinib, (7) imatinib and verteporfin, and (8) imatinib and XAV-939

Article Snippet: Cells were treated with imatinib mesylate (Tocris, Bristol, UK), verteporfin (a YAP inhibitor (Selleck chemicals, Houston, TX), or XAV-939 (a tankyrase inhibitor that indirectly suppresses YAP activity; Selleck chemicals, Houston, TX) [ ].

Techniques: Cell Cycle Assay, Incubation, Apoptosis Assay

Journal: Gastric Cancer

Article Title: Targeting yes-associated protein to overcome imatinib resistance in gastrointestinal stromal tumor drug-tolerant persister cells

doi: 10.1007/s10120-025-01657-z

Figure Lengend Snippet: Antitumor effects of verteporfin in a GIST xenograft mouse model. A GIST-T1 cells were transplanted subcutaneously and treated with the following therapies: (1) vehicle (n = 4), (2) verteporfin for 3 d (n = 4), (3) imatinib for 12 d (n = 4), and (4) imatinib for 9 d followed by a combination of imatinib and verteporfin for 3 d (n = 4). Treatment was initiated when tumor volume reached approximately 500 mm 3 (day 0). B Body weight and ( C ) tumor volume were measured every day until day 35. Each value is presented as mean ± SD (n = 4). Two-sided t-test (* p < 0.05, ** p < 0.01, *** p < 0.001). D Representative YAP-stained tumor sections from each treatment group. Scale bar: 25 μm. E Proportion of YAP positive nuclei. Each value is presented as mean ± SEM (n = 3), Tukey–Kramer honestly significant difference test (* p < 0.05, ** p < 0.01). F Apoptosis analysis by TUNEL staining from each treatment group. Scale bar: 100 µm

Article Snippet: Cells were treated with imatinib mesylate (Tocris, Bristol, UK), verteporfin (a YAP inhibitor (Selleck chemicals, Houston, TX), or XAV-939 (a tankyrase inhibitor that indirectly suppresses YAP activity; Selleck chemicals, Houston, TX) [ ].

Techniques: Staining, TUNEL Assay

Journal: Cellular and Molecular Gastroenterology and Hepatology

Article Title: CMTM3 Promotes Colitis-associated Carcinogenesis via CLTC Stabilization and Modulation of VE-cadherin

doi: 10.1016/j.jcmgh.2025.101528

Figure Lengend Snippet: CMTM3 is a potential therapeutic target for UC. ( A ) A schematic overview of imatinib treatment. Starting from the first day of DSS, Imatinib mesylate (50 mg/kg) dissolved in PBS is administered intraperitoneally once a day until the final day of DSS treatment. The application of PBS served as a control. ( B ) Body weight was initially measured (day 0) and monitored daily thereafter throughout the experiment. ( C ) DAI scores of the 4 groups. ( D ) Representative images of hematoxylin and eosin staining of colon tissue. ( E ) Histologic scores. Scale bar = 100 μm. n = 3–5. Data is representative of 2 experiments with similar results. The data represents the mean ± SD, and statistical significance was determined by 1-way ANOVA with Tukey’s multiple comparisons test. ∗∗ P < .01 and ∗∗∗ P < .001; ns represents no significant difference.

Article Snippet: Starting from the first day of DSS, imatinib mesylate (50 mg/kg, HY-50946, MedChemExpress) dissolved in PBS was administered intraperitoneally once a day until the final day of DSS-induced colitis.

Techniques: Control, Staining