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

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: 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: bioRxiv

Article Title: Targeting the translational machinery in gastrointestinal stromal tumors (GIST) – a new therapeutic vulnerability

doi: 10.1101/2021.09.01.458633

Figure Lengend Snippet: Homoharringtonine inhibits nascent protein synthesis and reduces KIT protein expression in GIST cells. (A) Nascent protein synthesis of GIST cells treated with homoharringtonine (HHT, 0.1 μM; green), cycloheximide (CHX, 100 μg/ml; blue), KIT inhibitor (IM, 1μM for GIST882 and GIST-T1; sunitinib, SU, 1μM for GIST430 and GIST48; orange) or 0.1% DMSO control (red) for 1 h or 8 h. Cells were labelled with HPG during the last 30 min of drug treatment and incorporated cellular HPG linked to azide-modified Alexa488 was quantitated by flow cytometry. Unstained control cells are shown in black in the histogram. A change in nascent protein synthesis is indicated as a relative mean fluorescence value to the DMSO control in the bar graphs. Columns, mean + SE; *, p<0.05 in comparison to DMSO control; **, p<0.01 in comparison to control; ***, p<0.001 in comparison to control (Student’s t-test, 2-tailed). (B) Immunoblot analysis for KIT protein expression of imatinib (IM)-sensitive (GIST882, GIST-T1) and IM-resistant (GIST430, GIST48) GIST cells after treatment with the protein translation inhibitor cycloheximide (CHX; 30 μg/ml for 3 h). (C) Immunoblotting for KIT protein expression in IM-sensitive (GIST882, GIST-T1) and IM-resistant (GIST430, GIST48) GIST cells after treatment with HHT for 72 h at the indicated concentrations. Abbreviations: 882 (GIST882), T1 (GIST-T1), 430 (GIST430), 48 (GIST48). (B, C) Grouped immunoblot images are either cropped from different parts of the same gel or from a separate gel run with another aliquot of the same protein lysate

Article Snippet: Homoharringtonine (HHT; Santa Cruz) treatments were performed at the indicated concentrations (in DMSO) compared to 0.1% DMSO for up to 72 h. Treatment with imatinib mesylate (1 µM in DMSO; LC Laboratories) or sunitinib (1 µM in DMSO; LC Laboratories) served as control.

Techniques: Expressing, Modification, Flow Cytometry, Fluorescence, Western Blot

Journal: Neoplasia (New York, N.Y.)

Article Title: The Abl/Abi signaling links WAVE regulatory complex to Cbl E3 ubiquitin ligase and is essential for breast cancer cell metastasis

doi: 10.1016/j.neo.2022.100819

Figure Lengend Snippet: Abl tyrosine kinases dependent degradation of Abi Proteins in Bcr-Abl-positive leukemic cells. A. Expression of p185 Bcr-Abl in Ba/F3 cells induces down regulation of Abi2. Total lysates from 1 × 10 6 Ba/F3 and Ba/F3 expressing p185 Bcr-Abl cells were analyzed by western blot using indicated antibodies. B. Abl tyrosine kinase inhibitor imatinib (IM) reverts Bcr-Abl-induced down-regulation of Abi and WAVE2 proteins. Ba/F3 p185 Bcr-Abl and K562 cells were treated with or without 5 μM Abl kinase inhibitor imatinib (IM) for 8 h. Total lysates of 1 × 10 6 cells were analyzed by western blot using indicated antibodies. C. Imatinib (IM) treatment increases Abi1 protein level in p185 Bcr-Abl -positive leukemic cells. The p185 Bcr-Abl cells expressing HA-tagged Abi1 were treated with or without 5 μM Abl kinase inhibitor imatinib (IM), as indicated, at the presence of 50 μM cycloheximide (CHX) for indicated hours. Total lysates of 1 × 10 6 cells were analyzed by western blot using indicated antibodies. D. Proteasome inhibitors revert Bcr-Abl-induced Abi2 down regulation. The p185 Bcr-Abl cells were treated with proteasome inhibitors MG132 (20 μM) and lactacystin (10 μM), lysosome inhibitors bafilomycin A1 (1 μM) and chloroquine (100> μM), and calpain inhibitor ALLN (25 μM), as indicated, for 5 >h. Total lysates from 1 × 10 6 cells were subjected to western blot analysis.

Article Snippet: The Abl inhibitor imatinib was purchased from LC Laboratories (Woburn, MA).

Techniques: Expressing, Western Blot