dasatinib Search Results


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  • 97
    Millipore dasatinib
    The effects of SDCBP overexpression and <t>dasatinib</t> treatment on cell proliferation, viability, the cell cycle, and its important regulatory molecules in MDA-MB-231 cells. (A) MTT assays were used to evaluate the effects of SDCBP overexpression on the proliferation of MDA-MD-231 cells. (B) Trypan blue staining was used to evaluate the effects of SDCBP overexpression and/or 100 nM dasatinib administration, as well as 100 nM dasatinib together with p27 siRNA on cell viability (#P > 0.05; ***P
    Dasatinib, supplied by Millipore, used in various techniques. Bioz Stars score: 97/100, based on 274 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/dasatinib/product/Millipore
    Average 97 stars, based on 274 article reviews
    Price from $9.99 to $1999.99
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    93
    BioVision dasatinib
    Co-inhibition of RELA and STAT5B pathways by small molecule inhibitors synergistically sensitizes chemoresistant ovarian cancer cells to cytotoxic effect of carboplatin. A) SKOV3-CR (left panel) and A2780-CR cells (right panel) were treated with a series of concentrations of carboplatin and BMS-345541 for 4 days before IC 50 curves were obtained. B) SKOV3-CR (left panel) and A2780-CR cells (right panel) were treated with a series of <t>dasatinib</t> concentrations, or a series of carboplatin concentrations, or 5 µM BMS-345541 in combination with a series of dasatinib concentrations, or a series of concentrations of dasatinib and carboplatin, or 5 µM BMS-345541 in combination with a series of concentrations of dasatinib and carboplatin for 4 days before IC 50 curves were measured. C) SKOV3-CR (left panel) and A2780-CR cells (right panel) were either transfected with STAT5B- or control shRNAs, with or without 5 µM BMS-345541 treatment, and subjected to a series of concentrations of carboplatin for 4 days before IC 50 curves were determined. D) Annexin V assay to measure apoptosis of chemoresistant cells and their naïve counterparts after treatment with carboplatin (6 µg/ml) and/or BMS-345541 (5 µM) and/or dasatinib (100 nM) for 48 hours. Annexin V positive cells were quantified using flow cytometry. Left panel: SKOV3-CR; right panel: A2780-CR.
    Dasatinib, supplied by BioVision, used in various techniques. Bioz Stars score: 93/100, based on 33 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/dasatinib/product/BioVision
    Average 93 stars, based on 33 article reviews
    Price from $9.99 to $1999.99
    dasatinib - by Bioz Stars, 2020-08
    93/100 stars
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    94
    Cell Signaling Technology Inc dasatinib
    GDC-0941 inhibits phosphorylation of PI3K substrates in the dual-resistant cells. Responsiveness of phospho-c-ABL Y245, phospho-Akt T308, phospho-PRAS40 T246, phospho-p70 S6 kinase T389, FOXO1 and BCL-2 to vehicle (DMSO, V), 100 n m <t>dasatinib</t> (D), 300 n m GDC-0941 (0941) or 300 n m GDC-0973 (0973) treatment for 1 h in parental K562 (Pa) or dual-resistant K562 cells (DR) by reverse-phase protein array. The data were normalized to total protein and log2-transformed. The error bars represent standard deviation. * P
    Dasatinib, supplied by Cell Signaling Technology Inc, used in various techniques. Bioz Stars score: 94/100, based on 64 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Average 94 stars, based on 64 article reviews
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    88
    LC Laboratories dasatinib sprycel
    <t>Dasatinib</t> increases MK ploidy in vitro. Progenitor cells isolated from murine BM were treated with 10μM dasatinib along with TPO at the beginning of the differentiation process and 24 hours later. Four days after the addition of TPO, DNA ploidy
    Dasatinib Sprycel, supplied by LC Laboratories, used in various techniques. Bioz Stars score: 88/100, based on 2 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/dasatinib sprycel/product/LC Laboratories
    Average 88 stars, based on 2 article reviews
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    85
    Bristol Myers dasatinib sprycel dasatinib
    Chemical structures of Bruton’s tyrosine kinase inhibitors. Ibrutinib (PCI-32765) is a covalent inhibitor currently under phase II and III clinical development for B-cell malignancies. Note: LFM-AI3, GDC-0834, and <t>dasatinib</t> are noncovalent adenosine triphosphate-competitive Bruton’s tyrosine kinase inhibitors.
    Dasatinib Sprycel Dasatinib, supplied by Bristol Myers, used in various techniques. Bioz Stars score: 85/100, based on 9 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/dasatinib sprycel dasatinib/product/Bristol Myers
    Average 85 stars, based on 9 article reviews
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    99
    Selleck Chemicals dasatinib sprycel
    Effect of <t>Dasatinib</t> and Dasatinib/PLX4720 combination on BRAF V600E EGFR HIGH /ERBB3 LOW -Invasive melanoma cell lines (A) Dose-response curves to Dasatinib, PLX4720 and their combination. Dasatinib IC50 was 8.54 μM for Me23, 0.6 μM for Me27 and 0.41 μM for Me36. Data shown are means and standard deviations of three replicates. (B) Drug interaction analysis by Chou and Talalay method. Shown are color-coded fraction affected values (effect, E) and combination indexes (CI) for Me23 and Me27 at the indicated drug combination doses. The color-code is shown at the bottom of the panel. (C) Effects of a 24 h treatment with PLX4720 (PLX, 1 μM), Dasatinib (Das, 0.25 μM) and their combination (PLX+Das) on phosphorylation of signaling molecules in Me23, Me27 and Me36. The combination between PLX4720 and Dasatinib reduced phosphorylation of S6 (S235–236 and S240–244) in comparison to single drugs when growth inhibitory effect was synergistic (Me23 and Me27). Controls are vehicle (DMSO) treated cells.
    Dasatinib Sprycel, supplied by Selleck Chemicals, used in various techniques. Bioz Stars score: 99/100, based on 18 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/dasatinib sprycel/product/Selleck Chemicals
    Average 99 stars, based on 18 article reviews
    Price from $9.99 to $1999.99
    dasatinib sprycel - by Bioz Stars, 2020-08
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    94
    Tocris dasatinib
    Effect of <t>Dasatinib</t> and Dasatinib/PLX4720 combination on BRAF V600E EGFR HIGH /ERBB3 LOW -Invasive melanoma cell lines (A) Dose-response curves to Dasatinib, PLX4720 and their combination. Dasatinib IC50 was 8.54 μM for Me23, 0.6 μM for Me27 and 0.41 μM for Me36. Data shown are means and standard deviations of three replicates. (B) Drug interaction analysis by Chou and Talalay method. Shown are color-coded fraction affected values (effect, E) and combination indexes (CI) for Me23 and Me27 at the indicated drug combination doses. The color-code is shown at the bottom of the panel. (C) Effects of a 24 h treatment with PLX4720 (PLX, 1 μM), Dasatinib (Das, 0.25 μM) and their combination (PLX+Das) on phosphorylation of signaling molecules in Me23, Me27 and Me36. The combination between PLX4720 and Dasatinib reduced phosphorylation of S6 (S235–236 and S240–244) in comparison to single drugs when growth inhibitory effect was synergistic (Me23 and Me27). Controls are vehicle (DMSO) treated cells.
    Dasatinib, supplied by Tocris, used in various techniques. Bioz Stars score: 94/100, based on 8 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/dasatinib/product/Tocris
    Average 94 stars, based on 8 article reviews
    Price from $9.99 to $1999.99
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    Image Search Results


    The effects of SDCBP overexpression and dasatinib treatment on cell proliferation, viability, the cell cycle, and its important regulatory molecules in MDA-MB-231 cells. (A) MTT assays were used to evaluate the effects of SDCBP overexpression on the proliferation of MDA-MD-231 cells. (B) Trypan blue staining was used to evaluate the effects of SDCBP overexpression and/or 100 nM dasatinib administration, as well as 100 nM dasatinib together with p27 siRNA on cell viability (#P > 0.05; ***P

    Journal: PLoS ONE

    Article Title: Dasatinib inhibits c-src phosphorylation and prevents the proliferation of Triple-Negative Breast Cancer (TNBC) cells which overexpress Syndecan-Binding Protein (SDCBP)

    doi: 10.1371/journal.pone.0171169

    Figure Lengend Snippet: The effects of SDCBP overexpression and dasatinib treatment on cell proliferation, viability, the cell cycle, and its important regulatory molecules in MDA-MB-231 cells. (A) MTT assays were used to evaluate the effects of SDCBP overexpression on the proliferation of MDA-MD-231 cells. (B) Trypan blue staining was used to evaluate the effects of SDCBP overexpression and/or 100 nM dasatinib administration, as well as 100 nM dasatinib together with p27 siRNA on cell viability (#P > 0.05; ***P

    Article Snippet: To prepare the working solution for the oral gavage administration, dasatinib was dissolved in a 50:50 mixture of polypropylene glycol (Sigma-Aldrich, St. Louis, MO, U.S.A) and water.

    Techniques: Over Expression, Multiple Displacement Amplification, MTT Assay, Staining

    Interaction between SDCBP and c-src in TNBC cell lines. (A) The c-src-specific antibody was used to immunoprecipitate from the cell lyastes of MDA-MB-231-SDCBP shRNA or BT-549 SDCBP shRNA and from the cell lysates of their corresponding control shRNA cells; the precipitated product were then analyzed using the SDCBP-specific antibody. (B) The SDCBP-specific antibody (or IgG as a control) was used to immunoprecipitate from MDA-MB-231 cell lysates; samples were then analyzed using the specific c-src antibody. (C) The c-src-specific antibody was used to immunoprecipitate wild-type SDCBP and SDCBP lacking the PDZ domains from their corresponding stably transfected MDA-MB-231 cell lysates. The precipitated products were then analyzed using the SDCBP-specific and FLAG antibodies. (D) Immunoblotting was used to evaluate the effects of SDCBP or its mutant protein lacking the PDZ domains overexpression on the tyrosine phosphorylation of c-src at residue 419. (E) Immunoblotting was used to evaluate the effects of SDCBP overexpression on c-src and p-c-src-Y419 levels in the presence or absence of 100 nM dasatinib treatment. WT represents wild-type MDA-MB-231 cells.

    Journal: PLoS ONE

    Article Title: Dasatinib inhibits c-src phosphorylation and prevents the proliferation of Triple-Negative Breast Cancer (TNBC) cells which overexpress Syndecan-Binding Protein (SDCBP)

    doi: 10.1371/journal.pone.0171169

    Figure Lengend Snippet: Interaction between SDCBP and c-src in TNBC cell lines. (A) The c-src-specific antibody was used to immunoprecipitate from the cell lyastes of MDA-MB-231-SDCBP shRNA or BT-549 SDCBP shRNA and from the cell lysates of their corresponding control shRNA cells; the precipitated product were then analyzed using the SDCBP-specific antibody. (B) The SDCBP-specific antibody (or IgG as a control) was used to immunoprecipitate from MDA-MB-231 cell lysates; samples were then analyzed using the specific c-src antibody. (C) The c-src-specific antibody was used to immunoprecipitate wild-type SDCBP and SDCBP lacking the PDZ domains from their corresponding stably transfected MDA-MB-231 cell lysates. The precipitated products were then analyzed using the SDCBP-specific and FLAG antibodies. (D) Immunoblotting was used to evaluate the effects of SDCBP or its mutant protein lacking the PDZ domains overexpression on the tyrosine phosphorylation of c-src at residue 419. (E) Immunoblotting was used to evaluate the effects of SDCBP overexpression on c-src and p-c-src-Y419 levels in the presence or absence of 100 nM dasatinib treatment. WT represents wild-type MDA-MB-231 cells.

    Article Snippet: To prepare the working solution for the oral gavage administration, dasatinib was dissolved in a 50:50 mixture of polypropylene glycol (Sigma-Aldrich, St. Louis, MO, U.S.A) and water.

    Techniques: Multiple Displacement Amplification, shRNA, Stable Transfection, Transfection, Mutagenesis, Over Expression

    The effects of SDCBP overexpression and the intragastric administration of dasatinib on tumor growth in nude mice inoculated with MDA-MB-231 cells. (A) Comparison of the tumor volumes at the end of each week after inoculation in different groups of nude mice inoculated with MDA-MB-231 cells that received SDCBP overexpression and/or the intragastric administration of dasatinib (#P > 0.05; *P

    Journal: PLoS ONE

    Article Title: Dasatinib inhibits c-src phosphorylation and prevents the proliferation of Triple-Negative Breast Cancer (TNBC) cells which overexpress Syndecan-Binding Protein (SDCBP)

    doi: 10.1371/journal.pone.0171169

    Figure Lengend Snippet: The effects of SDCBP overexpression and the intragastric administration of dasatinib on tumor growth in nude mice inoculated with MDA-MB-231 cells. (A) Comparison of the tumor volumes at the end of each week after inoculation in different groups of nude mice inoculated with MDA-MB-231 cells that received SDCBP overexpression and/or the intragastric administration of dasatinib (#P > 0.05; *P

    Article Snippet: To prepare the working solution for the oral gavage administration, dasatinib was dissolved in a 50:50 mixture of polypropylene glycol (Sigma-Aldrich, St. Louis, MO, U.S.A) and water.

    Techniques: Over Expression, Mouse Assay, Multiple Displacement Amplification

    Co-inhibition of RELA and STAT5B pathways by small molecule inhibitors synergistically sensitizes chemoresistant ovarian cancer cells to cytotoxic effect of carboplatin. A) SKOV3-CR (left panel) and A2780-CR cells (right panel) were treated with a series of concentrations of carboplatin and BMS-345541 for 4 days before IC 50 curves were obtained. B) SKOV3-CR (left panel) and A2780-CR cells (right panel) were treated with a series of dasatinib concentrations, or a series of carboplatin concentrations, or 5 µM BMS-345541 in combination with a series of dasatinib concentrations, or a series of concentrations of dasatinib and carboplatin, or 5 µM BMS-345541 in combination with a series of concentrations of dasatinib and carboplatin for 4 days before IC 50 curves were measured. C) SKOV3-CR (left panel) and A2780-CR cells (right panel) were either transfected with STAT5B- or control shRNAs, with or without 5 µM BMS-345541 treatment, and subjected to a series of concentrations of carboplatin for 4 days before IC 50 curves were determined. D) Annexin V assay to measure apoptosis of chemoresistant cells and their naïve counterparts after treatment with carboplatin (6 µg/ml) and/or BMS-345541 (5 µM) and/or dasatinib (100 nM) for 48 hours. Annexin V positive cells were quantified using flow cytometry. Left panel: SKOV3-CR; right panel: A2780-CR.

    Journal: PLoS ONE

    Article Title: Oncoproteomic Analysis Reveals Co-Upregulation of RELA and STAT5 in Carboplatin Resistant Ovarian Carcinoma

    doi: 10.1371/journal.pone.0011198

    Figure Lengend Snippet: Co-inhibition of RELA and STAT5B pathways by small molecule inhibitors synergistically sensitizes chemoresistant ovarian cancer cells to cytotoxic effect of carboplatin. A) SKOV3-CR (left panel) and A2780-CR cells (right panel) were treated with a series of concentrations of carboplatin and BMS-345541 for 4 days before IC 50 curves were obtained. B) SKOV3-CR (left panel) and A2780-CR cells (right panel) were treated with a series of dasatinib concentrations, or a series of carboplatin concentrations, or 5 µM BMS-345541 in combination with a series of dasatinib concentrations, or a series of concentrations of dasatinib and carboplatin, or 5 µM BMS-345541 in combination with a series of concentrations of dasatinib and carboplatin for 4 days before IC 50 curves were measured. C) SKOV3-CR (left panel) and A2780-CR cells (right panel) were either transfected with STAT5B- or control shRNAs, with or without 5 µM BMS-345541 treatment, and subjected to a series of concentrations of carboplatin for 4 days before IC 50 curves were determined. D) Annexin V assay to measure apoptosis of chemoresistant cells and their naïve counterparts after treatment with carboplatin (6 µg/ml) and/or BMS-345541 (5 µM) and/or dasatinib (100 nM) for 48 hours. Annexin V positive cells were quantified using flow cytometry. Left panel: SKOV3-CR; right panel: A2780-CR.

    Article Snippet: Apoptosis assay Cells were treated with DMSO, and/or carboplatin (6 µg/ml), and/or BMS-345541 (5 µM), and/or Dasatinib (100 nM) for 48 hours, and then analyzed using an Annexin V-FITC apoptosis detection kit (BioVision) according to the manufacturer's protocol.

    Techniques: Inhibition, Transfection, Annexin V Assay, Flow Cytometry, Cytometry

    Co-induction of RELA and STAT5 in chemoresistant cells results in upregulated Bcl-xL transcription. A) Schematic illustration of the six Bcl-X reporter constructs used in this study. The name of CAT constructs reflects their length relative to the first nucleotide in the Bcl-xL cDNA. STAT5-mut contains a point mutation in the Stat5 consensus binding site, while -298/22κB mut has three base substitutions in the RELA/p50 consensus binding site. B) Bcl-X promoter assay using 293T cells transfected with STAT5-wt or STAT5-mut or control reporter plasmid, plus pCMV-RELA and/or pCMV-STAT5B. Luciferase activity was measured 24 hours after transfection (right panel); exogenous RELA and STAT5B expression level at 24 hours after transfection of pCMV-RELA or pCMV-STAT5B or control plasmid (left panel). C) Bcl-X reporter assay in chemoresistant cells and their naïve counterparts transfected with STAT5-wt or STAT5-mut or control reporter plasmid (top panel: SKOV3; bottom panel: A2780). Luciferase activity was measured 24 hours after treatment with 5 µM BMS-345541 and/or 100 nM dasatinib and/or DMSO. D) CAT ELISA assay of chemoresistant cells and their naïve counterparts. CAT activity was measured 48 hours after transfection with the CAT-reporter plasmids (top panel: SKOV3; bottom panel: A2780)

    Journal: PLoS ONE

    Article Title: Oncoproteomic Analysis Reveals Co-Upregulation of RELA and STAT5 in Carboplatin Resistant Ovarian Carcinoma

    doi: 10.1371/journal.pone.0011198

    Figure Lengend Snippet: Co-induction of RELA and STAT5 in chemoresistant cells results in upregulated Bcl-xL transcription. A) Schematic illustration of the six Bcl-X reporter constructs used in this study. The name of CAT constructs reflects their length relative to the first nucleotide in the Bcl-xL cDNA. STAT5-mut contains a point mutation in the Stat5 consensus binding site, while -298/22κB mut has three base substitutions in the RELA/p50 consensus binding site. B) Bcl-X promoter assay using 293T cells transfected with STAT5-wt or STAT5-mut or control reporter plasmid, plus pCMV-RELA and/or pCMV-STAT5B. Luciferase activity was measured 24 hours after transfection (right panel); exogenous RELA and STAT5B expression level at 24 hours after transfection of pCMV-RELA or pCMV-STAT5B or control plasmid (left panel). C) Bcl-X reporter assay in chemoresistant cells and their naïve counterparts transfected with STAT5-wt or STAT5-mut or control reporter plasmid (top panel: SKOV3; bottom panel: A2780). Luciferase activity was measured 24 hours after treatment with 5 µM BMS-345541 and/or 100 nM dasatinib and/or DMSO. D) CAT ELISA assay of chemoresistant cells and their naïve counterparts. CAT activity was measured 48 hours after transfection with the CAT-reporter plasmids (top panel: SKOV3; bottom panel: A2780)

    Article Snippet: Apoptosis assay Cells were treated with DMSO, and/or carboplatin (6 µg/ml), and/or BMS-345541 (5 µM), and/or Dasatinib (100 nM) for 48 hours, and then analyzed using an Annexin V-FITC apoptosis detection kit (BioVision) according to the manufacturer's protocol.

    Techniques: Construct, Mutagenesis, Binding Assay, Promoter Assay, Transfection, Plasmid Preparation, Luciferase, Activity Assay, Expressing, Reporter Assay, Enzyme-linked Immunosorbent Assay

    Phosphorylation and activation of PKCδ by Src is important for the scatter of MDCK cells upon HGF stimulation A. MDCK cells were serum-starved for 24 h and were then treated with (+) or without (−) the Src inhibitor dasatinib at 100 nM for 1 h before they were stimulated with HGF (20 ng/ml) for 15 min. Endogenous PKCδ was immunoprecipitated using an anti-PKCδ antibody, and the immunocomplexes were analyzed by immunoblotting with antibodies to PKCδ or PKCδ pY311. To measure the PKCδ activity, the immuoncomplexes were subjected to an in vitro kinase assay in the presence of [γ- 32 P]ATP and myelin basic protein (MBP) as the substrate. The 32 P-incorporated MBP were fractionated by SDS-polyacrylamide gel electrophoresis and visualized by autoradiography. The radioisotope activity was quantified using a phosphoimager system. The data are expressed as fold relative to the level of the control. Values (mean ± SD) are from three experiments. *, P

    Journal: Oncotarget

    Article Title: Phosphorylation of E-cadherin at threonine 790 by protein kinase Cδ reduces β-catenin binding and suppresses the function of E-cadherin

    doi: 10.18632/oncotarget.9403

    Figure Lengend Snippet: Phosphorylation and activation of PKCδ by Src is important for the scatter of MDCK cells upon HGF stimulation A. MDCK cells were serum-starved for 24 h and were then treated with (+) or without (−) the Src inhibitor dasatinib at 100 nM for 1 h before they were stimulated with HGF (20 ng/ml) for 15 min. Endogenous PKCδ was immunoprecipitated using an anti-PKCδ antibody, and the immunocomplexes were analyzed by immunoblotting with antibodies to PKCδ or PKCδ pY311. To measure the PKCδ activity, the immuoncomplexes were subjected to an in vitro kinase assay in the presence of [γ- 32 P]ATP and myelin basic protein (MBP) as the substrate. The 32 P-incorporated MBP were fractionated by SDS-polyacrylamide gel electrophoresis and visualized by autoradiography. The radioisotope activity was quantified using a phosphoimager system. The data are expressed as fold relative to the level of the control. Values (mean ± SD) are from three experiments. *, P

    Article Snippet: Src inhibitor Dasatinib was purchased from BioVision (Milpitas, USA).

    Techniques: Activation Assay, Immunoprecipitation, Activity Assay, In Vitro, Kinase Assay, Polyacrylamide Gel Electrophoresis, Autoradiography

    Dietary fat accelerates Src-induced prostate tumor progression. A , schematic of the in vivo prostate regeneration assay. Host SCID mice carrying Src(Y529F)-transduced regeneration tissues were placed on a 10% or 60% fat diet for 8 weeks and treated with vehicle or dasatinib from week 5 to week 8 ( n = 4/group). UGSM , urogenital sinus mesenchyme. B , total calorie intake was not significantly different between the diet groups. C , representative images of regenerated prostate tumors. The dashed lines show the regenerated prostate grafts on the kidney ( scale bar = 4 mm). D , prostate tumor weight from A represented as mean ± S.E. ( n = 4/group). Asterisks indicate unpaired, two-tailed t test. E , representative H E (panoramic view, scale bars = 400 μm) and IHC staining (selected tumorigenic region, scale bars = 100 μm) of total Src, pSrc(Tyr-416), and pErk1/2 and co-staining of CK5, a basal epithelial cell marker, CK8, a luminal epithelial cell marker, and DAPI of tumors from C. F , the expression levels of pSrc and pErk were analyzed in IHC samples based on image analysis. #, p

    Journal: The Journal of Biological Chemistry

    Article Title: Myristoylation of Src kinase mediates Src-induced and high-fat diet–accelerated prostate tumor progression in mice

    doi: 10.1074/jbc.M117.798827

    Figure Lengend Snippet: Dietary fat accelerates Src-induced prostate tumor progression. A , schematic of the in vivo prostate regeneration assay. Host SCID mice carrying Src(Y529F)-transduced regeneration tissues were placed on a 10% or 60% fat diet for 8 weeks and treated with vehicle or dasatinib from week 5 to week 8 ( n = 4/group). UGSM , urogenital sinus mesenchyme. B , total calorie intake was not significantly different between the diet groups. C , representative images of regenerated prostate tumors. The dashed lines show the regenerated prostate grafts on the kidney ( scale bar = 4 mm). D , prostate tumor weight from A represented as mean ± S.E. ( n = 4/group). Asterisks indicate unpaired, two-tailed t test. E , representative H E (panoramic view, scale bars = 400 μm) and IHC staining (selected tumorigenic region, scale bars = 100 μm) of total Src, pSrc(Tyr-416), and pErk1/2 and co-staining of CK5, a basal epithelial cell marker, CK8, a luminal epithelial cell marker, and DAPI of tumors from C. F , the expression levels of pSrc and pErk were analyzed in IHC samples based on image analysis. #, p

    Article Snippet: SCID mice carrying the Src(Y529F) transduced grafts were also administrated dasatinib (BioVision, Milpitas, CA) or vehicle by gavage (75 mg/kg body weight) per day for 4 weeks.

    Techniques: In Vivo, Mouse Assay, Two Tailed Test, Immunohistochemistry, Staining, Marker, Expressing

    Constitutive levels of phosphorylated proteins including pJAK 1, pJAK 2, pSTAT 1, pSTAT 3, pERK , pJNK , pp38, and pAKT in natural killer ( NK ) cells (A) and cytotoxic T lymphocytes ( CTL s) (B) grouped according to treatment (dasatinib [ n = 18] or other TKI [ n = 12]) are shown. The values for phosphorylated proteins in each fraction are shown as the median fluorescence intensity (MFI).

    Journal: Cancer Medicine

    Article Title: Direct effect of dasatinib on signal transduction pathways associated with a rapid mobilization of cytotoxic lymphocytes

    doi: 10.1002/cam4.925

    Figure Lengend Snippet: Constitutive levels of phosphorylated proteins including pJAK 1, pJAK 2, pSTAT 1, pSTAT 3, pERK , pJNK , pp38, and pAKT in natural killer ( NK ) cells (A) and cytotoxic T lymphocytes ( CTL s) (B) grouped according to treatment (dasatinib [ n = 18] or other TKI [ n = 12]) are shown. The values for phosphorylated proteins in each fraction are shown as the median fluorescence intensity (MFI).

    Article Snippet: Reagents Dasatinib was purchased from BioVision (Mountain View, CA) and dissolved in dimethyl sulfoxide (DMSO) at a concentration of 300 μ mol/L.

    Techniques: CTL Assay, Fluorescence

    Direct effect of dasatinib on cytotoxic lymphocytes. Mononuclear cells obtained from peripheral blood before taking dasatinib were incubated with dimethylsulfoxide ( DMSO ) vehicle, 100 nmol/L or 300 nmol/L dasatinib, 2 μ mol/L imatinib, or 2 μ mol/L nilotinib, for 1 h, fixed with 1.5% paraformaldehyde, and permeabilized with 90% methanol, followed by surface and intracellular staining. The staining was evaluated by flow cytometry. Changes in the expression of phosphorylated proteins, including pERK and pAKT , were evaluated in five samples derived from patients who responded to dasatinib. Levels of each phosphorylated protein were evaluated as the median fluorescence intensity ( MFI ), and the ratio compared to the control was shown as log2 (fold change [ FC ]). Results are shown as the mean ± standard error of the mean. * P

    Journal: Cancer Medicine

    Article Title: Direct effect of dasatinib on signal transduction pathways associated with a rapid mobilization of cytotoxic lymphocytes

    doi: 10.1002/cam4.925

    Figure Lengend Snippet: Direct effect of dasatinib on cytotoxic lymphocytes. Mononuclear cells obtained from peripheral blood before taking dasatinib were incubated with dimethylsulfoxide ( DMSO ) vehicle, 100 nmol/L or 300 nmol/L dasatinib, 2 μ mol/L imatinib, or 2 μ mol/L nilotinib, for 1 h, fixed with 1.5% paraformaldehyde, and permeabilized with 90% methanol, followed by surface and intracellular staining. The staining was evaluated by flow cytometry. Changes in the expression of phosphorylated proteins, including pERK and pAKT , were evaluated in five samples derived from patients who responded to dasatinib. Levels of each phosphorylated protein were evaluated as the median fluorescence intensity ( MFI ), and the ratio compared to the control was shown as log2 (fold change [ FC ]). Results are shown as the mean ± standard error of the mean. * P

    Article Snippet: Reagents Dasatinib was purchased from BioVision (Mountain View, CA) and dissolved in dimethyl sulfoxide (DMSO) at a concentration of 300 μ mol/L.

    Techniques: Incubation, Staining, Flow Cytometry, Cytometry, Expressing, Derivative Assay, Fluorescence

    Heat map analysis showing changes in the values in natural killer ( NK ) cell (A) and cytotoxic T lymphocyte ( CTL ) (B) fractions ( n = 28). Changes in the median fluorescence intensity ( MFI ) values of phosphorylated proteins in each fraction were compared before and after treatment (1 h for dasatinib [patient no. 1–15, 17, 18] and 2 h for imatinib or nilotinib [patient no. 19–29]) and expressed as log2 (fold change [ FC ]).

    Journal: Cancer Medicine

    Article Title: Direct effect of dasatinib on signal transduction pathways associated with a rapid mobilization of cytotoxic lymphocytes

    doi: 10.1002/cam4.925

    Figure Lengend Snippet: Heat map analysis showing changes in the values in natural killer ( NK ) cell (A) and cytotoxic T lymphocyte ( CTL ) (B) fractions ( n = 28). Changes in the median fluorescence intensity ( MFI ) values of phosphorylated proteins in each fraction were compared before and after treatment (1 h for dasatinib [patient no. 1–15, 17, 18] and 2 h for imatinib or nilotinib [patient no. 19–29]) and expressed as log2 (fold change [ FC ]).

    Article Snippet: Reagents Dasatinib was purchased from BioVision (Mountain View, CA) and dissolved in dimethyl sulfoxide (DMSO) at a concentration of 300 μ mol/L.

    Techniques: CTL Assay, Fluorescence

    Changes in the number of lymphocytes, natural killer ( NK ) cells, and cytotoxic T lymphocytes ( CTL ) are shown. The values were compared before and after treatment (1 h for dasatinib and 2 h for imatinib or nilotinib) or according to treatment (A). The relative changes in the number of lymphocytes, NK cells, and CTL s are also shown and are expressed as log2 (fold change [ FC ]) (B).

    Journal: Cancer Medicine

    Article Title: Direct effect of dasatinib on signal transduction pathways associated with a rapid mobilization of cytotoxic lymphocytes

    doi: 10.1002/cam4.925

    Figure Lengend Snippet: Changes in the number of lymphocytes, natural killer ( NK ) cells, and cytotoxic T lymphocytes ( CTL ) are shown. The values were compared before and after treatment (1 h for dasatinib and 2 h for imatinib or nilotinib) or according to treatment (A). The relative changes in the number of lymphocytes, NK cells, and CTL s are also shown and are expressed as log2 (fold change [ FC ]) (B).

    Article Snippet: Reagents Dasatinib was purchased from BioVision (Mountain View, CA) and dissolved in dimethyl sulfoxide (DMSO) at a concentration of 300 μ mol/L.

    Techniques: CTL Assay

    Influence of prior history of cytomegalovirus ( CMV ) infection on the change of signal transduction pathways. CMV IgG status was examined in patients receiving dasatinib treatment, with positivity in 13 and negativity in five. Eleven patients were treated with other tyrosine kinase inhibitors ( TKI s). Changes of pERK and pAKT expression in natural killer ( NK ) cells and cytotoxic T lymphocytes ( CTL s) according to CMV IgG status are shown as log2 (fold change [FC]).

    Journal: Cancer Medicine

    Article Title: Direct effect of dasatinib on signal transduction pathways associated with a rapid mobilization of cytotoxic lymphocytes

    doi: 10.1002/cam4.925

    Figure Lengend Snippet: Influence of prior history of cytomegalovirus ( CMV ) infection on the change of signal transduction pathways. CMV IgG status was examined in patients receiving dasatinib treatment, with positivity in 13 and negativity in five. Eleven patients were treated with other tyrosine kinase inhibitors ( TKI s). Changes of pERK and pAKT expression in natural killer ( NK ) cells and cytotoxic T lymphocytes ( CTL s) according to CMV IgG status are shown as log2 (fold change [FC]).

    Article Snippet: Reagents Dasatinib was purchased from BioVision (Mountain View, CA) and dissolved in dimethyl sulfoxide (DMSO) at a concentration of 300 μ mol/L.

    Techniques: Infection, Transduction, Expressing, CTL Assay

    GDC-0941 inhibits phosphorylation of PI3K substrates in the dual-resistant cells. Responsiveness of phospho-c-ABL Y245, phospho-Akt T308, phospho-PRAS40 T246, phospho-p70 S6 kinase T389, FOXO1 and BCL-2 to vehicle (DMSO, V), 100 n m dasatinib (D), 300 n m GDC-0941 (0941) or 300 n m GDC-0973 (0973) treatment for 1 h in parental K562 (Pa) or dual-resistant K562 cells (DR) by reverse-phase protein array. The data were normalized to total protein and log2-transformed. The error bars represent standard deviation. * P

    Journal: Leukemia

    Article Title: A role for FOXO1 in BCR–ABL1-independent tyrosine kinase inhibitor resistance in chronic myeloid leukemia

    doi: 10.1038/leu.2016.51

    Figure Lengend Snippet: GDC-0941 inhibits phosphorylation of PI3K substrates in the dual-resistant cells. Responsiveness of phospho-c-ABL Y245, phospho-Akt T308, phospho-PRAS40 T246, phospho-p70 S6 kinase T389, FOXO1 and BCL-2 to vehicle (DMSO, V), 100 n m dasatinib (D), 300 n m GDC-0941 (0941) or 300 n m GDC-0973 (0973) treatment for 1 h in parental K562 (Pa) or dual-resistant K562 cells (DR) by reverse-phase protein array. The data were normalized to total protein and log2-transformed. The error bars represent standard deviation. * P

    Article Snippet: FOXO1 immunofluorescence Parental and dual-resistant K562 cells were treated with either DMSO, 100 nm dasatinib or 1 μm GDC-0941 for 1 h, fixed in 4% paraformaldehyde, blocked in 0.3% Triton/5% goat serum and stained with a FOXO1-specific antibody (Cell Signaling Technology, Danvers, MA, USA) or goat IgG overnight at 4 °C.

    Techniques: Protein Array, Transformation Assay, Standard Deviation

    The BCL-2 inhibitor, ABT-737, in combination with GDC-0941, inhibits growth of the dual-resistant but not parental K562 cells. Parental and dual-resistant K562 cells were treated with 0–10 μ m of the BCL-2 inhibitor, ABT-737, alone or in combination with 0–10 μ m dasatinib or GDC-0941. The cell viability after 72 h was measured using a CellTiter-Glo assay and mean percentage growth inhibition derived from quadruplicates at each dose or combination is shown.

    Journal: Leukemia

    Article Title: A role for FOXO1 in BCR–ABL1-independent tyrosine kinase inhibitor resistance in chronic myeloid leukemia

    doi: 10.1038/leu.2016.51

    Figure Lengend Snippet: The BCL-2 inhibitor, ABT-737, in combination with GDC-0941, inhibits growth of the dual-resistant but not parental K562 cells. Parental and dual-resistant K562 cells were treated with 0–10 μ m of the BCL-2 inhibitor, ABT-737, alone or in combination with 0–10 μ m dasatinib or GDC-0941. The cell viability after 72 h was measured using a CellTiter-Glo assay and mean percentage growth inhibition derived from quadruplicates at each dose or combination is shown.

    Article Snippet: FOXO1 immunofluorescence Parental and dual-resistant K562 cells were treated with either DMSO, 100 nm dasatinib or 1 μm GDC-0941 for 1 h, fixed in 4% paraformaldehyde, blocked in 0.3% Triton/5% goat serum and stained with a FOXO1-specific antibody (Cell Signaling Technology, Danvers, MA, USA) or goat IgG overnight at 4 °C.

    Techniques: Glo Assay, Inhibition, Derivative Assay

    FOXO1 levels are elevated in a subset of relapsed patient samples and are sensitive to GDC-0941-mediated survival inhibition. ( a ) The baseline proteomic signature of TKI-naive samples (samples 180, 266 and 300) compared with samples from TKI-relapsed patients (resistant) lacking BCR – ABL1 mutations (samples 109-197) or harboring a BCR – ABL1 kinase domain mutation (samples 077 and 252). Samples with elevated FOXO1 expression are denoted by a red asterisk. ( b ) TKI-naive samples (180, 266 and 300) and patient samples with high FOXO1 (077, 109, 142, 185, 197 and 252) or low FOXO1 (123 and 186) were treated with dasatinib (50 n m ) and/or GDC-0941 (300 n m ) in colony-formation assays. The data represents percent of vehicle-treated controls. The error bars represent standard deviation. * P

    Journal: Leukemia

    Article Title: A role for FOXO1 in BCR–ABL1-independent tyrosine kinase inhibitor resistance in chronic myeloid leukemia

    doi: 10.1038/leu.2016.51

    Figure Lengend Snippet: FOXO1 levels are elevated in a subset of relapsed patient samples and are sensitive to GDC-0941-mediated survival inhibition. ( a ) The baseline proteomic signature of TKI-naive samples (samples 180, 266 and 300) compared with samples from TKI-relapsed patients (resistant) lacking BCR – ABL1 mutations (samples 109-197) or harboring a BCR – ABL1 kinase domain mutation (samples 077 and 252). Samples with elevated FOXO1 expression are denoted by a red asterisk. ( b ) TKI-naive samples (180, 266 and 300) and patient samples with high FOXO1 (077, 109, 142, 185, 197 and 252) or low FOXO1 (123 and 186) were treated with dasatinib (50 n m ) and/or GDC-0941 (300 n m ) in colony-formation assays. The data represents percent of vehicle-treated controls. The error bars represent standard deviation. * P

    Article Snippet: FOXO1 immunofluorescence Parental and dual-resistant K562 cells were treated with either DMSO, 100 nm dasatinib or 1 μm GDC-0941 for 1 h, fixed in 4% paraformaldehyde, blocked in 0.3% Triton/5% goat serum and stained with a FOXO1-specific antibody (Cell Signaling Technology, Danvers, MA, USA) or goat IgG overnight at 4 °C.

    Techniques: Inhibition, Mutagenesis, Expressing, Standard Deviation

    Dual-resistant cells and clones are sensitive to GDC-0941-mediated growth inhibition ( a ) Sensitivity of the dual-resistant K562 cells and resistant KCL-22 cells to 0–10 μ m GDC-0941 or 0–10 μ m GDC-0973 after 72 h treatment. The cells were treated for 72 h with the indicated drug and cell viability was measured and corrected relative to time zero (time of treatment). The data shows % control 0.001–10 μ m TKI-treated cells relative to vehicle (DMSO)-treated cells, which is set to 100% (upper dotted line). The data represent the average of three independent experiments. The error bars represent standard deviation. ( b ) The percentage of cells undergoing early apoptosis induced by 50 n m dasatinib or 300 n m GDC-0941 in the dual-resistant and parental K562 cells 48 h after treatment using AnnexinV/PI FACS analysis. The error bars represent standard deviation. * P

    Journal: Leukemia

    Article Title: A role for FOXO1 in BCR–ABL1-independent tyrosine kinase inhibitor resistance in chronic myeloid leukemia

    doi: 10.1038/leu.2016.51

    Figure Lengend Snippet: Dual-resistant cells and clones are sensitive to GDC-0941-mediated growth inhibition ( a ) Sensitivity of the dual-resistant K562 cells and resistant KCL-22 cells to 0–10 μ m GDC-0941 or 0–10 μ m GDC-0973 after 72 h treatment. The cells were treated for 72 h with the indicated drug and cell viability was measured and corrected relative to time zero (time of treatment). The data shows % control 0.001–10 μ m TKI-treated cells relative to vehicle (DMSO)-treated cells, which is set to 100% (upper dotted line). The data represent the average of three independent experiments. The error bars represent standard deviation. ( b ) The percentage of cells undergoing early apoptosis induced by 50 n m dasatinib or 300 n m GDC-0941 in the dual-resistant and parental K562 cells 48 h after treatment using AnnexinV/PI FACS analysis. The error bars represent standard deviation. * P

    Article Snippet: FOXO1 immunofluorescence Parental and dual-resistant K562 cells were treated with either DMSO, 100 nm dasatinib or 1 μm GDC-0941 for 1 h, fixed in 4% paraformaldehyde, blocked in 0.3% Triton/5% goat serum and stained with a FOXO1-specific antibody (Cell Signaling Technology, Danvers, MA, USA) or goat IgG overnight at 4 °C.

    Techniques: Clone Assay, Inhibition, Standard Deviation, FACS

    Imatinib and dual-resistant K562 cells are resistant to all three ABL-TKI therapies, whereas the KCL-22 cells are highly sensitive to ponatinib. ( a ) Sensitivity of the K562 parental, imatinib- and dual-resistant cell lines to 0–10 μ m imatinib, dasatinib or ponatinib after treatment for 72 h as measured by CellTiter-Glo assays. ( b ) Sensitivity of the KCL-22 parental and resistant cells to 0–10 μ m imatinib, dasatinib or ponatinib after treatment for 72 h as measured by CellTiter-Glo assays. The cell viability was measured and corrected relative to time zero (time of treatment). The data shows % control 0.001–10 μ m ABL-TKI-treated cells relative to vehicle (DMSO)-treated cells, which is set to 100% growth (upper dotted line). The data represent the average of three independent experiments. The error bars represent standard deviation.

    Journal: Leukemia

    Article Title: A role for FOXO1 in BCR–ABL1-independent tyrosine kinase inhibitor resistance in chronic myeloid leukemia

    doi: 10.1038/leu.2016.51

    Figure Lengend Snippet: Imatinib and dual-resistant K562 cells are resistant to all three ABL-TKI therapies, whereas the KCL-22 cells are highly sensitive to ponatinib. ( a ) Sensitivity of the K562 parental, imatinib- and dual-resistant cell lines to 0–10 μ m imatinib, dasatinib or ponatinib after treatment for 72 h as measured by CellTiter-Glo assays. ( b ) Sensitivity of the KCL-22 parental and resistant cells to 0–10 μ m imatinib, dasatinib or ponatinib after treatment for 72 h as measured by CellTiter-Glo assays. The cell viability was measured and corrected relative to time zero (time of treatment). The data shows % control 0.001–10 μ m ABL-TKI-treated cells relative to vehicle (DMSO)-treated cells, which is set to 100% growth (upper dotted line). The data represent the average of three independent experiments. The error bars represent standard deviation.

    Article Snippet: FOXO1 immunofluorescence Parental and dual-resistant K562 cells were treated with either DMSO, 100 nm dasatinib or 1 μm GDC-0941 for 1 h, fixed in 4% paraformaldehyde, blocked in 0.3% Triton/5% goat serum and stained with a FOXO1-specific antibody (Cell Signaling Technology, Danvers, MA, USA) or goat IgG overnight at 4 °C.

    Techniques: Standard Deviation

    Elevated FOXO1 accumulates in the cytoplasm of the dual-resistant K562 cells and translocates into the nucleus upon GDC-0941 treatment. Immunofluorescence cytochemistry revealed that FOXO1 was localized primarily within the cytoplasm of dual-resistant K562 cells treated with DMSO or 100 n m dasatinib, whereas it was low to undetectable in the parental TKI-sensitive controls. The treatment of dual-resistant K562 cells with 1 μ m GDC-0941 resulted in a translocation of FOXO1 to the nucleus. Representative images of the treatment groups are shown under × 40 magnification using confocal microscopy. For clarity, single-cell images are shown for the dual-resistant cells.

    Journal: Leukemia

    Article Title: A role for FOXO1 in BCR–ABL1-independent tyrosine kinase inhibitor resistance in chronic myeloid leukemia

    doi: 10.1038/leu.2016.51

    Figure Lengend Snippet: Elevated FOXO1 accumulates in the cytoplasm of the dual-resistant K562 cells and translocates into the nucleus upon GDC-0941 treatment. Immunofluorescence cytochemistry revealed that FOXO1 was localized primarily within the cytoplasm of dual-resistant K562 cells treated with DMSO or 100 n m dasatinib, whereas it was low to undetectable in the parental TKI-sensitive controls. The treatment of dual-resistant K562 cells with 1 μ m GDC-0941 resulted in a translocation of FOXO1 to the nucleus. Representative images of the treatment groups are shown under × 40 magnification using confocal microscopy. For clarity, single-cell images are shown for the dual-resistant cells.

    Article Snippet: FOXO1 immunofluorescence Parental and dual-resistant K562 cells were treated with either DMSO, 100 nm dasatinib or 1 μm GDC-0941 for 1 h, fixed in 4% paraformaldehyde, blocked in 0.3% Triton/5% goat serum and stained with a FOXO1-specific antibody (Cell Signaling Technology, Danvers, MA, USA) or goat IgG overnight at 4 °C.

    Techniques: Immunofluorescence, Translocation Assay, Confocal Microscopy

    Small molecule EphA2 inhibitor dasatinib affects Ctr infection. (A) HUVEC cells were pretreated with DMSO(1) control or with 2.5 μM, 5 μM and 10 μM of DA, respectively, for 1 h at 37°C and were infected with Ctr (MOI-1) for 24 h. Or the cells were first infected with Ctr for 14 h and then treated with DMSO(2) control or with 5 μM, 10 μM and 20 μM DA, respectively, for 10 h. Cells were harvested for WB analysis. (B, C, D) Experiments were performed as (A) and immunostained for Ctr inclusion (Hsp60, green) and DNA (Draq5, blue). (B) The size of the inclusion was measured by ImageJ software. Shown is the mean ± SD of two independent experiments normalized to control. **P

    Journal: PLoS Pathogens

    Article Title: EphrinA2 Receptor (EphA2) Is an Invasion and Intracellular Signaling Receptor for Chlamydia trachomatis

    doi: 10.1371/journal.ppat.1004846

    Figure Lengend Snippet: Small molecule EphA2 inhibitor dasatinib affects Ctr infection. (A) HUVEC cells were pretreated with DMSO(1) control or with 2.5 μM, 5 μM and 10 μM of DA, respectively, for 1 h at 37°C and were infected with Ctr (MOI-1) for 24 h. Or the cells were first infected with Ctr for 14 h and then treated with DMSO(2) control or with 5 μM, 10 μM and 20 μM DA, respectively, for 10 h. Cells were harvested for WB analysis. (B, C, D) Experiments were performed as (A) and immunostained for Ctr inclusion (Hsp60, green) and DNA (Draq5, blue). (B) The size of the inclusion was measured by ImageJ software. Shown is the mean ± SD of two independent experiments normalized to control. **P

    Article Snippet: Inhibitors for PI3 kinase (LY294002), MEK1/2 (UO126) and EphA2 (dasatinib) were bought from Cell Signaling.

    Techniques: Infection, Western Blot, Software

    Dasatinib increases MK ploidy in vitro. Progenitor cells isolated from murine BM were treated with 10μM dasatinib along with TPO at the beginning of the differentiation process and 24 hours later. Four days after the addition of TPO, DNA ploidy

    Journal: Blood

    Article Title: Dasatinib enhances megakaryocyte differentiation but inhibits platelet formation

    doi: 10.1182/blood-2010-12-326850

    Figure Lengend Snippet: Dasatinib increases MK ploidy in vitro. Progenitor cells isolated from murine BM were treated with 10μM dasatinib along with TPO at the beginning of the differentiation process and 24 hours later. Four days after the addition of TPO, DNA ploidy

    Article Snippet: Dasatinib (Sprycel) was purchased from LC Laboratories.

    Techniques: In Vitro, Isolation

    Localization of MKs in BM of dasatinib-treated mice. Localization of MKs in vivo was visualized by 2-photon intravital microscopy using mouse skull BM. The MKs (green) were identified using CD41-YFP ki/+ mice in which enhanced YFP was expressed as a targeted

    Journal: Blood

    Article Title: Dasatinib enhances megakaryocyte differentiation but inhibits platelet formation

    doi: 10.1182/blood-2010-12-326850

    Figure Lengend Snippet: Localization of MKs in BM of dasatinib-treated mice. Localization of MKs in vivo was visualized by 2-photon intravital microscopy using mouse skull BM. The MKs (green) were identified using CD41-YFP ki/+ mice in which enhanced YFP was expressed as a targeted

    Article Snippet: Dasatinib (Sprycel) was purchased from LC Laboratories.

    Techniques: Mouse Assay, In Vivo, Intravital Microscopy

    Dasatinib-treated mice exhibit a normal platelet life span. Control mice (solid line) and dasatinib-treated (5 mg/kg/d) mice (dashed line) were intravenously injected with biotin-NHS on day 0 and the percentage of biotinylated platelets was determined

    Journal: Blood

    Article Title: Dasatinib enhances megakaryocyte differentiation but inhibits platelet formation

    doi: 10.1182/blood-2010-12-326850

    Figure Lengend Snippet: Dasatinib-treated mice exhibit a normal platelet life span. Control mice (solid line) and dasatinib-treated (5 mg/kg/d) mice (dashed line) were intravenously injected with biotin-NHS on day 0 and the percentage of biotinylated platelets was determined

    Article Snippet: Dasatinib (Sprycel) was purchased from LC Laboratories.

    Techniques: Mouse Assay, Injection

    Dasatinib-treated mice exhibit a delay in platelet recovery after immune-induced thrombocytopenia. Whole-blood platelet count from control mice (solid line) and dasatinib-treated (5 mg/kg/d) mice (dashed line) were obtained, and then thrombocytopenia

    Journal: Blood

    Article Title: Dasatinib enhances megakaryocyte differentiation but inhibits platelet formation

    doi: 10.1182/blood-2010-12-326850

    Figure Lengend Snippet: Dasatinib-treated mice exhibit a delay in platelet recovery after immune-induced thrombocytopenia. Whole-blood platelet count from control mice (solid line) and dasatinib-treated (5 mg/kg/d) mice (dashed line) were obtained, and then thrombocytopenia

    Article Snippet: Dasatinib (Sprycel) was purchased from LC Laboratories.

    Techniques: Mouse Assay

    Dasatinib induces an increased number of mature MKs in BM and spleen. (A) Representative longitudinal sections of whole murine femurs and spleens stained with H E from control mice and dasatinib-treated (5 mg/kg/d) mice for 7 days (scale bar =

    Journal: Blood

    Article Title: Dasatinib enhances megakaryocyte differentiation but inhibits platelet formation

    doi: 10.1182/blood-2010-12-326850

    Figure Lengend Snippet: Dasatinib induces an increased number of mature MKs in BM and spleen. (A) Representative longitudinal sections of whole murine femurs and spleens stained with H E from control mice and dasatinib-treated (5 mg/kg/d) mice for 7 days (scale bar =

    Article Snippet: Dasatinib (Sprycel) was purchased from LC Laboratories.

    Techniques: Staining, Mouse Assay

    Dasatinib impairs MK migration in response to a SDF1α gradient, spreading, proplatelet formation, and integrin-induced tyrosine phosphorylation. (A) Purified BM-derived mature MKs adherent on a fibronectin (20 μg/mL)–coated coverslip

    Journal: Blood

    Article Title: Dasatinib enhances megakaryocyte differentiation but inhibits platelet formation

    doi: 10.1182/blood-2010-12-326850

    Figure Lengend Snippet: Dasatinib impairs MK migration in response to a SDF1α gradient, spreading, proplatelet formation, and integrin-induced tyrosine phosphorylation. (A) Purified BM-derived mature MKs adherent on a fibronectin (20 μg/mL)–coated coverslip

    Article Snippet: Dasatinib (Sprycel) was purchased from LC Laboratories.

    Techniques: Migration, Purification, Derivative Assay

    Dasatinib induces reversible thrombocytopenia in mice. (A) Whole-blood platelet count from control mice (solid line) and dasatinib-treated (5 mg/kg/d) mice (dashed line) were monitored every day for 7 days. Error bars represent SEM; ** P

    Journal: Blood

    Article Title: Dasatinib enhances megakaryocyte differentiation but inhibits platelet formation

    doi: 10.1182/blood-2010-12-326850

    Figure Lengend Snippet: Dasatinib induces reversible thrombocytopenia in mice. (A) Whole-blood platelet count from control mice (solid line) and dasatinib-treated (5 mg/kg/d) mice (dashed line) were monitored every day for 7 days. Error bars represent SEM; ** P

    Article Snippet: Dasatinib (Sprycel) was purchased from LC Laboratories.

    Techniques: Mouse Assay

    Chemical structures of Bruton’s tyrosine kinase inhibitors. Ibrutinib (PCI-32765) is a covalent inhibitor currently under phase II and III clinical development for B-cell malignancies. Note: LFM-AI3, GDC-0834, and dasatinib are noncovalent adenosine triphosphate-competitive Bruton’s tyrosine kinase inhibitors.

    Journal: OncoTargets and therapy

    Article Title: Novel Bruton's tyrosine kinase inhibitors currently in development

    doi: 10.2147/OTT.S33732

    Figure Lengend Snippet: Chemical structures of Bruton’s tyrosine kinase inhibitors. Ibrutinib (PCI-32765) is a covalent inhibitor currently under phase II and III clinical development for B-cell malignancies. Note: LFM-AI3, GDC-0834, and dasatinib are noncovalent adenosine triphosphate-competitive Bruton’s tyrosine kinase inhibitors.

    Article Snippet: Dasatinib (Sprycel) Dasatinib (Sprycel/BMS-354825, Bristol-Myers Squibb) [N -(2-chloro-6-methylphenyl)-2-(6-(4-(2-hydroxyethyl) piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamide], is a potent, orally active, multikinase BCR/Abl and Src family TKI that is FDA-approved for treatment of CML and is a potent inhibitor of Btk., A chemical proteomics-profiling approach identified the Tec kinases Btk and Tec to be very prominent targets of dasatinib., Structure-based mutagenesis experiments by Hantschel et al identified the gatekeeper residue as a critical determinant for dasatinib sensitivity.

    Techniques:

    Differential Sensitivities of HNSCC Cells to Dasatinib

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

    Article Title: Degradation of Epidermal Growth Factor Receptor Mediates Dasatinib-Induced Apoptosis in Head and Neck Squamous Cell Carcinoma Cells 1Degradation of Epidermal Growth Factor Receptor Mediates Dasatinib-Induced Apoptosis in Head and Neck Squamous Cell Carcinoma Cells 1 2

    doi:

    Figure Lengend Snippet: Differential Sensitivities of HNSCC Cells to Dasatinib

    Article Snippet: Dasatinib (Sprycel) was kindly provided by Bristol Myers Squibb pharmaceuticals (Princeton, NJ).

    Techniques:

    Down-regulation of EGFR by dasatinib correlates with the sensitivity of dasatinib. (A, B) Expression of EGFR and downstream Akt and Erk in dasatinib-sensitive (A) and -resistant (B) cells treated with dasatinib 1 µ M for indicated intervals. Upper

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

    Article Title: Degradation of Epidermal Growth Factor Receptor Mediates Dasatinib-Induced Apoptosis in Head and Neck Squamous Cell Carcinoma Cells 1Degradation of Epidermal Growth Factor Receptor Mediates Dasatinib-Induced Apoptosis in Head and Neck Squamous Cell Carcinoma Cells 1 2

    doi:

    Figure Lengend Snippet: Down-regulation of EGFR by dasatinib correlates with the sensitivity of dasatinib. (A, B) Expression of EGFR and downstream Akt and Erk in dasatinib-sensitive (A) and -resistant (B) cells treated with dasatinib 1 µ M for indicated intervals. Upper

    Article Snippet: Dasatinib (Sprycel) was kindly provided by Bristol Myers Squibb pharmaceuticals (Princeton, NJ).

    Techniques: Expressing

    In vivo effect of dasatinib on xenograft nude mice. (A) Antitumor effect of dasatinib on HSC3 tumors. Line, mean ( n = 9); bars, SE; * P

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

    Article Title: Degradation of Epidermal Growth Factor Receptor Mediates Dasatinib-Induced Apoptosis in Head and Neck Squamous Cell Carcinoma Cells 1Degradation of Epidermal Growth Factor Receptor Mediates Dasatinib-Induced Apoptosis in Head and Neck Squamous Cell Carcinoma Cells 1 2

    doi:

    Figure Lengend Snippet: In vivo effect of dasatinib on xenograft nude mice. (A) Antitumor effect of dasatinib on HSC3 tumors. Line, mean ( n = 9); bars, SE; * P

    Article Snippet: Dasatinib (Sprycel) was kindly provided by Bristol Myers Squibb pharmaceuticals (Princeton, NJ).

    Techniques: In Vivo, Mouse Assay

    Effect of dasatinib on Src, Akt, Erk, and Bcl-2. Inactivation of Src, Akt, and Erk in dasatinib-sensitive and -resistant cells treated with dasatinib at the indicated doses for 24 hours. Upper panel, Western blot analysis of HNSCC cells. Representative

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

    Article Title: Degradation of Epidermal Growth Factor Receptor Mediates Dasatinib-Induced Apoptosis in Head and Neck Squamous Cell Carcinoma Cells 1Degradation of Epidermal Growth Factor Receptor Mediates Dasatinib-Induced Apoptosis in Head and Neck Squamous Cell Carcinoma Cells 1 2

    doi:

    Figure Lengend Snippet: Effect of dasatinib on Src, Akt, Erk, and Bcl-2. Inactivation of Src, Akt, and Erk in dasatinib-sensitive and -resistant cells treated with dasatinib at the indicated doses for 24 hours. Upper panel, Western blot analysis of HNSCC cells. Representative

    Article Snippet: Dasatinib (Sprycel) was kindly provided by Bristol Myers Squibb pharmaceuticals (Princeton, NJ).

    Techniques: Western Blot

    Role of EGFR in dasatinib-induced apoptosis. (A, B) Effect of EGF addition to dasatinib (1 µ M)-induced apoptosis and inactivation of Akt and Erk in sensitive HSC3 (A) and Ca9-22 (B) cells. Cells were treated with dasatinib (1 µ M, 0 hour)

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

    Article Title: Degradation of Epidermal Growth Factor Receptor Mediates Dasatinib-Induced Apoptosis in Head and Neck Squamous Cell Carcinoma Cells 1Degradation of Epidermal Growth Factor Receptor Mediates Dasatinib-Induced Apoptosis in Head and Neck Squamous Cell Carcinoma Cells 1 2

    doi:

    Figure Lengend Snippet: Role of EGFR in dasatinib-induced apoptosis. (A, B) Effect of EGF addition to dasatinib (1 µ M)-induced apoptosis and inactivation of Akt and Erk in sensitive HSC3 (A) and Ca9-22 (B) cells. Cells were treated with dasatinib (1 µ M, 0 hour)

    Article Snippet: Dasatinib (Sprycel) was kindly provided by Bristol Myers Squibb pharmaceuticals (Princeton, NJ).

    Techniques:

    Mechanism of dasatinib-induced EGFR down-regulation. (A) Effect of lysosome inhibitor (NH 4 Cl, 20 mM) and proteasome inhibitor (lactacystin, 10 µ M) on dasatinib-induced EGFR down-regulation in HSC3 and Ca9-22 cells. Lower panel, Western blot analysis

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

    Article Title: Degradation of Epidermal Growth Factor Receptor Mediates Dasatinib-Induced Apoptosis in Head and Neck Squamous Cell Carcinoma Cells 1Degradation of Epidermal Growth Factor Receptor Mediates Dasatinib-Induced Apoptosis in Head and Neck Squamous Cell Carcinoma Cells 1 2

    doi:

    Figure Lengend Snippet: Mechanism of dasatinib-induced EGFR down-regulation. (A) Effect of lysosome inhibitor (NH 4 Cl, 20 mM) and proteasome inhibitor (lactacystin, 10 µ M) on dasatinib-induced EGFR down-regulation in HSC3 and Ca9-22 cells. Lower panel, Western blot analysis

    Article Snippet: Dasatinib (Sprycel) was kindly provided by Bristol Myers Squibb pharmaceuticals (Princeton, NJ).

    Techniques: Western Blot

    Correlation of ERα and EGFR in dasatinib-treated HNSCC cells. (A) Expression of ERα in HNSCC cells treated with dasatinib at 1 µ M for designated intervals. (B) Protein stability of ERα. Left, Expression of ERα in

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

    Article Title: Degradation of Epidermal Growth Factor Receptor Mediates Dasatinib-Induced Apoptosis in Head and Neck Squamous Cell Carcinoma Cells 1Degradation of Epidermal Growth Factor Receptor Mediates Dasatinib-Induced Apoptosis in Head and Neck Squamous Cell Carcinoma Cells 1 2

    doi:

    Figure Lengend Snippet: Correlation of ERα and EGFR in dasatinib-treated HNSCC cells. (A) Expression of ERα in HNSCC cells treated with dasatinib at 1 µ M for designated intervals. (B) Protein stability of ERα. Left, Expression of ERα in

    Article Snippet: Dasatinib (Sprycel) was kindly provided by Bristol Myers Squibb pharmaceuticals (Princeton, NJ).

    Techniques: Expressing

    Differential sensitivity of dasatinib in HNSCC cells. (A) MTT cell viability in HNSCC cells treated with dasatinib at the indicated doses for 48 hours. Dot, mean ( n = 3); bar, SD. (B) Sub-G 1 analysis of HNSCC cells treated with dasatinib at the indicated

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

    Article Title: Degradation of Epidermal Growth Factor Receptor Mediates Dasatinib-Induced Apoptosis in Head and Neck Squamous Cell Carcinoma Cells 1Degradation of Epidermal Growth Factor Receptor Mediates Dasatinib-Induced Apoptosis in Head and Neck Squamous Cell Carcinoma Cells 1 2

    doi:

    Figure Lengend Snippet: Differential sensitivity of dasatinib in HNSCC cells. (A) MTT cell viability in HNSCC cells treated with dasatinib at the indicated doses for 48 hours. Dot, mean ( n = 3); bar, SD. (B) Sub-G 1 analysis of HNSCC cells treated with dasatinib at the indicated

    Article Snippet: Dasatinib (Sprycel) was kindly provided by Bristol Myers Squibb pharmaceuticals (Princeton, NJ).

    Techniques: MTT Assay

    A simplified Markov diagram of generic imatinib-first vs physician’s choice (the current standard of care) treatment strategies for treating chronic myeloid leukemia in chronic phase. Under physician’s choice, patients have equal probability of beginning on imatinib, dasatinib, or nilotinib and remain on a drug until they reach a chance node. The chance nodes depicted in the figure represent CCyR at 12 months (or, as noted in the Methods, EMR at 3 months). Patients have three possible outcomes prior to reaching the first chance node, whether at 12 months in the first CCyR model or three months in the second EMR model: remaining on TKI therapy, progressing to AP/BC, or death. Patients who respond positively to a TKI stay on it the remainder of time, and overall survival since progression to AP/BC or death is uncommon after that point. Patients who fail their initial TKI because of intolerance or lack of efficacy can switch once (*) at 12 months (or 3 months in the EMR model) to another TKI. Under generic imatinib-first, 100% of patients begin on imatinib and only switch to nilotinib or dasatinib because of intolerance or if a CCyR (or EMR) was not reached. Some patients who fail under TKI therapy transition to the AP/BC state, which includes the risk of death. *Indicates where one switch at 12 months (or 3 months) can take place. AP/BC = accelerated phase/blast crisis; CCyR = complete cytogenetic response; EMR = early molecular response; M = Markov node; TKI = tyrosine kinase inhibitor.

    Journal: JNCI Journal of the National Cancer Institute

    Article Title: Cost-effectiveness of Tyrosine Kinase Inhibitor Treatment Strategies for Chronic Myeloid Leukemia in Chronic Phase After Generic Entry of Imatinib in the United States

    doi: 10.1093/jnci/djw003

    Figure Lengend Snippet: A simplified Markov diagram of generic imatinib-first vs physician’s choice (the current standard of care) treatment strategies for treating chronic myeloid leukemia in chronic phase. Under physician’s choice, patients have equal probability of beginning on imatinib, dasatinib, or nilotinib and remain on a drug until they reach a chance node. The chance nodes depicted in the figure represent CCyR at 12 months (or, as noted in the Methods, EMR at 3 months). Patients have three possible outcomes prior to reaching the first chance node, whether at 12 months in the first CCyR model or three months in the second EMR model: remaining on TKI therapy, progressing to AP/BC, or death. Patients who respond positively to a TKI stay on it the remainder of time, and overall survival since progression to AP/BC or death is uncommon after that point. Patients who fail their initial TKI because of intolerance or lack of efficacy can switch once (*) at 12 months (or 3 months in the EMR model) to another TKI. Under generic imatinib-first, 100% of patients begin on imatinib and only switch to nilotinib or dasatinib because of intolerance or if a CCyR (or EMR) was not reached. Some patients who fail under TKI therapy transition to the AP/BC state, which includes the risk of death. *Indicates where one switch at 12 months (or 3 months) can take place. AP/BC = accelerated phase/blast crisis; CCyR = complete cytogenetic response; EMR = early molecular response; M = Markov node; TKI = tyrosine kinase inhibitor.

    Article Snippet: Dasatinib (Sprycel, Bristol-Myers Squibb) and nilotinib (Tasigna, Novartis Oncology) were granted first-line approval for the treatment of CML-CP by the FDA.

    Techniques:

    Effect of Dasatinib and Dasatinib/PLX4720 combination on BRAF V600E EGFR HIGH /ERBB3 LOW -Invasive melanoma cell lines (A) Dose-response curves to Dasatinib, PLX4720 and their combination. Dasatinib IC50 was 8.54 μM for Me23, 0.6 μM for Me27 and 0.41 μM for Me36. Data shown are means and standard deviations of three replicates. (B) Drug interaction analysis by Chou and Talalay method. Shown are color-coded fraction affected values (effect, E) and combination indexes (CI) for Me23 and Me27 at the indicated drug combination doses. The color-code is shown at the bottom of the panel. (C) Effects of a 24 h treatment with PLX4720 (PLX, 1 μM), Dasatinib (Das, 0.25 μM) and their combination (PLX+Das) on phosphorylation of signaling molecules in Me23, Me27 and Me36. The combination between PLX4720 and Dasatinib reduced phosphorylation of S6 (S235–236 and S240–244) in comparison to single drugs when growth inhibitory effect was synergistic (Me23 and Me27). Controls are vehicle (DMSO) treated cells.

    Journal: Oncotarget

    Article Title: A melanoma subtype with intrinsic resistance to BRAF inhibition identified by receptor tyrosine kinases gene-driven classification

    doi:

    Figure Lengend Snippet: Effect of Dasatinib and Dasatinib/PLX4720 combination on BRAF V600E EGFR HIGH /ERBB3 LOW -Invasive melanoma cell lines (A) Dose-response curves to Dasatinib, PLX4720 and their combination. Dasatinib IC50 was 8.54 μM for Me23, 0.6 μM for Me27 and 0.41 μM for Me36. Data shown are means and standard deviations of three replicates. (B) Drug interaction analysis by Chou and Talalay method. Shown are color-coded fraction affected values (effect, E) and combination indexes (CI) for Me23 and Me27 at the indicated drug combination doses. The color-code is shown at the bottom of the panel. (C) Effects of a 24 h treatment with PLX4720 (PLX, 1 μM), Dasatinib (Das, 0.25 μM) and their combination (PLX+Das) on phosphorylation of signaling molecules in Me23, Me27 and Me36. The combination between PLX4720 and Dasatinib reduced phosphorylation of S6 (S235–236 and S240–244) in comparison to single drugs when growth inhibitory effect was synergistic (Me23 and Me27). Controls are vehicle (DMSO) treated cells.

    Article Snippet: Inhibitors PLX4720, AZD8055, GDC0941, BEZ235, Canertinib, Erlotinib (Tarceva), Gefitinib (Iressa), Crenolanib, Lapatinib (Tykerb) and Dasatinib (Sprycel) (all from Selleck Chemicals, Houston, TX, USA) were diluted in DMSO at 10 mM/ml and stored at −20°C until use; when added to cell cultures, the final DMSO concentration was 0.25–0.5%.

    Techniques:

    The 2H7 monobody did not perturb the kinase activity of Lyn. The kinase assay was performed with a Beacon Tyrosine kinase assay kit (Invitrogen), according to the manufacturer’s instructions. The assay with wild-type FN3 (Lyn + WT-FN3) was a non-perturbed control and the assay with Dasatinib (Lyn + Dasatinib) was a kinase-inhibited control. The assay with the Lyn kinase protein without any inhibitor or monobodies present served as the non-treatment control. Two internal controls of the assay were also included: when an anti-phosphopeptide antibody was excluded in the assay, a maximum fluorescence signal was observed (i.e., positive control), and when the recombinant Lyn protein was excluded in the assay, the lowest fluorescence signal was observed (i.e., negative control). Error bars are the standard deviations of triplicate measurements.

    Journal: PLoS ONE

    Article Title: Directed Evolution of a Highly Specific FN3 Monobody to the SH3 Domain of Human Lyn Tyrosine Kinase

    doi: 10.1371/journal.pone.0145872

    Figure Lengend Snippet: The 2H7 monobody did not perturb the kinase activity of Lyn. The kinase assay was performed with a Beacon Tyrosine kinase assay kit (Invitrogen), according to the manufacturer’s instructions. The assay with wild-type FN3 (Lyn + WT-FN3) was a non-perturbed control and the assay with Dasatinib (Lyn + Dasatinib) was a kinase-inhibited control. The assay with the Lyn kinase protein without any inhibitor or monobodies present served as the non-treatment control. Two internal controls of the assay were also included: when an anti-phosphopeptide antibody was excluded in the assay, a maximum fluorescence signal was observed (i.e., positive control), and when the recombinant Lyn protein was excluded in the assay, the lowest fluorescence signal was observed (i.e., negative control). Error bars are the standard deviations of triplicate measurements.

    Article Snippet: In the kinase buffer, Dasatinib (Final concentration: 10 μM; Selleck Chemicals; Houston, TX, # S1021), 2H7 and wild-type FN3 (WT-FN3) (Final concentration for both: 7.5 μM) were mixed with Lyn kinase (final concentration: 105 nM; Invitrogen, # P2907).

    Techniques: Activity Assay, Kinase Assay, Tyrosine Kinase Assay, Fluorescence, Positive Control, Recombinant, Negative Control

    Dasatinib-induced senescence is mediated by Chk1, TAZ, and p21 A. H1666 cells were transfected with DNA vectors containing Chk1, TAZ, or both and sensitivity to dasatinib was measured using the MTT assay at the indicated drug concentrations after 72 hours of incubation. B. Senescence was estimated using β-galactosidase staining in transfected cells treated with 150nM dasatinib or vehicle control for 72 hours. C. Overexpression (OE) was confirmed by Western blot analysis. D. Non-small cell lung cancer cell lines with kinase-inactivating BRAF mutations (Cal12T, H1666) were transfected with siRNA targeting p21 or a scrambled control and incubated with 150nM dasatinib or vehicle control for 72 hours. Senescence was estimated using β-galactosidase staining. E. Knockdown (KD) was confirmed by Western blot analysis. Error bars represent standard deviation. * P

    Journal: Oncotarget

    Article Title: Dasatinib induces DNA damage and activates DNA repair pathways leading to senescence in non-small cell lung cancer cell lines with kinase-inactivating BRAF mutations

    doi:

    Figure Lengend Snippet: Dasatinib-induced senescence is mediated by Chk1, TAZ, and p21 A. H1666 cells were transfected with DNA vectors containing Chk1, TAZ, or both and sensitivity to dasatinib was measured using the MTT assay at the indicated drug concentrations after 72 hours of incubation. B. Senescence was estimated using β-galactosidase staining in transfected cells treated with 150nM dasatinib or vehicle control for 72 hours. C. Overexpression (OE) was confirmed by Western blot analysis. D. Non-small cell lung cancer cell lines with kinase-inactivating BRAF mutations (Cal12T, H1666) were transfected with siRNA targeting p21 or a scrambled control and incubated with 150nM dasatinib or vehicle control for 72 hours. Senescence was estimated using β-galactosidase staining. E. Knockdown (KD) was confirmed by Western blot analysis. Error bars represent standard deviation. * P

    Article Snippet: Materials Dasatinib, BIBW2992, PD0325091 and Etoposide were purchased from Selleck Chemicals (Houston, TX) and prepared as 20 mM stock solutions in DMSO.

    Techniques: Transfection, MTT Assay, Incubation, Staining, Over Expression, Western Blot, Standard Deviation

    Proteins involved in DNA repair and TAZ are differentially expressed and modulated between non-small cell lung cancer cells with kinase-inactivating BRAF mutations ( KI BRAF) and those with wild-type BRAF ( WT BRAF) A. Basal protein expression of 137 proteins and phosphoproteins was compared between KI BRAF and WT BRAF cells. To generate the heat map, we used Pearson correlation distance between proteins and Euclidean distance between samples. We used the Ward method for both genes' and the samples' linkage rule. A 2-sample t test was applied and 6 markers were identified at a false discovery rate of 0.45. B. The mean protein expression of all 137 measured proteins before and after 72 hours of incubation with 150 nM dasatinib was compared between KI BRAF and WT BRAF cells. Error bars represent standard deviation. P

    Journal: Oncotarget

    Article Title: Dasatinib induces DNA damage and activates DNA repair pathways leading to senescence in non-small cell lung cancer cell lines with kinase-inactivating BRAF mutations

    doi:

    Figure Lengend Snippet: Proteins involved in DNA repair and TAZ are differentially expressed and modulated between non-small cell lung cancer cells with kinase-inactivating BRAF mutations ( KI BRAF) and those with wild-type BRAF ( WT BRAF) A. Basal protein expression of 137 proteins and phosphoproteins was compared between KI BRAF and WT BRAF cells. To generate the heat map, we used Pearson correlation distance between proteins and Euclidean distance between samples. We used the Ward method for both genes' and the samples' linkage rule. A 2-sample t test was applied and 6 markers were identified at a false discovery rate of 0.45. B. The mean protein expression of all 137 measured proteins before and after 72 hours of incubation with 150 nM dasatinib was compared between KI BRAF and WT BRAF cells. Error bars represent standard deviation. P

    Article Snippet: Materials Dasatinib, BIBW2992, PD0325091 and Etoposide were purchased from Selleck Chemicals (Houston, TX) and prepared as 20 mM stock solutions in DMSO.

    Techniques: Expressing, Incubation, Standard Deviation

    Chk1 and TAZ are differentially modulated between non-small cell lung cancer cells with BRAF mutations ( KI BRAF) and those with wild-type BRAF ( WT BRAF) A. Western blot analysis showing changes in protein expression for cells incubated with 150nM dasatinib for the indicated times. Bands were quantitated in the line graphs at the bottom. B. mRNA levels of Chk1 and TAZ were measured using quantitative polymerase chain reaction for the indicated times following incubation with 150nM dasatinib. C. mRNA levels of TAZ target genes were measured using quantitative polymerase chain reaction for the indicated times following incubation with 150nM dasatinib. Error bars represent standard deviation. * P

    Journal: Oncotarget

    Article Title: Dasatinib induces DNA damage and activates DNA repair pathways leading to senescence in non-small cell lung cancer cell lines with kinase-inactivating BRAF mutations

    doi:

    Figure Lengend Snippet: Chk1 and TAZ are differentially modulated between non-small cell lung cancer cells with BRAF mutations ( KI BRAF) and those with wild-type BRAF ( WT BRAF) A. Western blot analysis showing changes in protein expression for cells incubated with 150nM dasatinib for the indicated times. Bands were quantitated in the line graphs at the bottom. B. mRNA levels of Chk1 and TAZ were measured using quantitative polymerase chain reaction for the indicated times following incubation with 150nM dasatinib. C. mRNA levels of TAZ target genes were measured using quantitative polymerase chain reaction for the indicated times following incubation with 150nM dasatinib. Error bars represent standard deviation. * P

    Article Snippet: Materials Dasatinib, BIBW2992, PD0325091 and Etoposide were purchased from Selleck Chemicals (Houston, TX) and prepared as 20 mM stock solutions in DMSO.

    Techniques: Western Blot, Expressing, Incubation, Real-time Polymerase Chain Reaction, Standard Deviation

    Dasatinib induces DNA damage in non-small cell lung cancer cells with kinase-inactivating BRAF mutations ( KI BRAF) A. KI BRAF cells (Cal12T, H1666) and wild-type BRAF cells (H661, A549) were incubated with 150nM dasatinib for 72 hours and DNA damage was measured using the COMET assay. COMET-Assay IV software was used to estimate the tail length, head length, and tail moment. Error bars represent standard deviation. * P

    Journal: Oncotarget

    Article Title: Dasatinib induces DNA damage and activates DNA repair pathways leading to senescence in non-small cell lung cancer cell lines with kinase-inactivating BRAF mutations

    doi:

    Figure Lengend Snippet: Dasatinib induces DNA damage in non-small cell lung cancer cells with kinase-inactivating BRAF mutations ( KI BRAF) A. KI BRAF cells (Cal12T, H1666) and wild-type BRAF cells (H661, A549) were incubated with 150nM dasatinib for 72 hours and DNA damage was measured using the COMET assay. COMET-Assay IV software was used to estimate the tail length, head length, and tail moment. Error bars represent standard deviation. * P

    Article Snippet: Materials Dasatinib, BIBW2992, PD0325091 and Etoposide were purchased from Selleck Chemicals (Houston, TX) and prepared as 20 mM stock solutions in DMSO.

    Techniques: Incubation, Single Cell Gel Electrophoresis, Software, Standard Deviation

    Dasatinib does not induce oncogene-induced senescence Non-small cell lung cancer cell lines with kinase-inactivating BRAF mutations (Cal12T, H1666) or wild-type BRAF (H661, A549) were incubated with 150nM dasatinib for the indicated times (A, C) or for 72 hours (B) Activation of the MEK/ERK pathway was measured using Western blot analysis with the indicated antibodies A. or quantitative polymerase chain reaction for downstream transcriptional targets B. Error bars represent standard deviation. * P

    Journal: Oncotarget

    Article Title: Dasatinib induces DNA damage and activates DNA repair pathways leading to senescence in non-small cell lung cancer cell lines with kinase-inactivating BRAF mutations

    doi:

    Figure Lengend Snippet: Dasatinib does not induce oncogene-induced senescence Non-small cell lung cancer cell lines with kinase-inactivating BRAF mutations (Cal12T, H1666) or wild-type BRAF (H661, A549) were incubated with 150nM dasatinib for the indicated times (A, C) or for 72 hours (B) Activation of the MEK/ERK pathway was measured using Western blot analysis with the indicated antibodies A. or quantitative polymerase chain reaction for downstream transcriptional targets B. Error bars represent standard deviation. * P

    Article Snippet: Materials Dasatinib, BIBW2992, PD0325091 and Etoposide were purchased from Selleck Chemicals (Houston, TX) and prepared as 20 mM stock solutions in DMSO.

    Techniques: Incubation, Activation Assay, Western Blot, Real-time Polymerase Chain Reaction, Standard Deviation

    Comparison of gene expression changes following treatment with dasatinib in non-small cell lung cancer cells with and without kinase-inactivating BRAF mutations ( KI BRAF) A. Heat map of the 2061 gene features that were differentially modulated by dasatinib in KI BRAF cells compared to wild-type BRAF ( WT BRAF ; fold change ≥ 1.35, P

    Journal: Oncotarget

    Article Title: Dasatinib induces DNA damage and activates DNA repair pathways leading to senescence in non-small cell lung cancer cell lines with kinase-inactivating BRAF mutations

    doi:

    Figure Lengend Snippet: Comparison of gene expression changes following treatment with dasatinib in non-small cell lung cancer cells with and without kinase-inactivating BRAF mutations ( KI BRAF) A. Heat map of the 2061 gene features that were differentially modulated by dasatinib in KI BRAF cells compared to wild-type BRAF ( WT BRAF ; fold change ≥ 1.35, P

    Article Snippet: Materials Dasatinib, BIBW2992, PD0325091 and Etoposide were purchased from Selleck Chemicals (Houston, TX) and prepared as 20 mM stock solutions in DMSO.

    Techniques: Expressing

    Changes in the adhered cell fraction induced by dasatinib pretreatment. JURL-MK1 (A) or MOLM-7 (B) cells were pretreated for 30 min with dasatinib at the indicated concentrations, seeded into FN-coated wells and incubated for 1 h at 37°C. Thereafter, the plate was washed and the fraction of attached cells was determined fluorimetrically and normalized using the value found in the control sample. The graphs show the means and standard deviations from at least 4 experiments for each condition, the statistical significance of the observed differences was evaluated using Student's paired t-test. Results significantly differing from untreated controls are denoted by asterisks (* p

    Journal: PLoS ONE

    Article Title: Real-Time Analysis of Imatinib- and Dasatinib-Induced Effects on Chronic Myelogenous Leukemia Cell Interaction with Fibronectin

    doi: 10.1371/journal.pone.0107367

    Figure Lengend Snippet: Changes in the adhered cell fraction induced by dasatinib pretreatment. JURL-MK1 (A) or MOLM-7 (B) cells were pretreated for 30 min with dasatinib at the indicated concentrations, seeded into FN-coated wells and incubated for 1 h at 37°C. Thereafter, the plate was washed and the fraction of attached cells was determined fluorimetrically and normalized using the value found in the control sample. The graphs show the means and standard deviations from at least 4 experiments for each condition, the statistical significance of the observed differences was evaluated using Student's paired t-test. Results significantly differing from untreated controls are denoted by asterisks (* p

    Article Snippet: Chemicals Dasatinib was purchased from Selleckchem, 50 mM and 1 mM stock solutions were made in sterile dimethylsulfoxide.

    Techniques: Incubation

    Dasatinib-induced dephosphorylation of SFK and BCR-ABL. Phosphorylation status of SFK and BCR-ABL after 2 h incubation with dasatinib. Quantification summary from 3 independent experiments and representative western-blots are shown for each cell line. A: JURL-MK1, B: MOLM-7, C: HEL, D: JURKAT.

    Journal: PLoS ONE

    Article Title: Real-Time Analysis of Imatinib- and Dasatinib-Induced Effects on Chronic Myelogenous Leukemia Cell Interaction with Fibronectin

    doi: 10.1371/journal.pone.0107367

    Figure Lengend Snippet: Dasatinib-induced dephosphorylation of SFK and BCR-ABL. Phosphorylation status of SFK and BCR-ABL after 2 h incubation with dasatinib. Quantification summary from 3 independent experiments and representative western-blots are shown for each cell line. A: JURL-MK1, B: MOLM-7, C: HEL, D: JURKAT.

    Article Snippet: Chemicals Dasatinib was purchased from Selleckchem, 50 mM and 1 mM stock solutions were made in sterile dimethylsulfoxide.

    Techniques: De-Phosphorylation Assay, Incubation, Western Blot

    Changes in cell interaction with fibronectin after inhibitor treatment. The cells (6×10 4 per well) were seeded into fibronectin-coated E-plates. After the microimpedance signal stabilization, the appropriate inhibitor was added in triplets. Black circles: control cells. Time of inhibitor addition is indicated by an arrow. Microimpedance signal (cell index) was normalized to 1 at the time of inhibitor addition. The graphs show mean and standard deviation of well triplets. A,C,E: JURL-MK1 cells, B,D,F: MOLM-7 cells. A,B: imatinib was added at 1 µM (blue circles) or 10 µM (red squares) final concentration. C,D: dasatinib was added at 2 nM (blue circles) or 10 nM (red squares) final concentration. E,F: dasatinib was added at 100 nM final concentration (red circles).

    Journal: PLoS ONE

    Article Title: Real-Time Analysis of Imatinib- and Dasatinib-Induced Effects on Chronic Myelogenous Leukemia Cell Interaction with Fibronectin

    doi: 10.1371/journal.pone.0107367

    Figure Lengend Snippet: Changes in cell interaction with fibronectin after inhibitor treatment. The cells (6×10 4 per well) were seeded into fibronectin-coated E-plates. After the microimpedance signal stabilization, the appropriate inhibitor was added in triplets. Black circles: control cells. Time of inhibitor addition is indicated by an arrow. Microimpedance signal (cell index) was normalized to 1 at the time of inhibitor addition. The graphs show mean and standard deviation of well triplets. A,C,E: JURL-MK1 cells, B,D,F: MOLM-7 cells. A,B: imatinib was added at 1 µM (blue circles) or 10 µM (red squares) final concentration. C,D: dasatinib was added at 2 nM (blue circles) or 10 nM (red squares) final concentration. E,F: dasatinib was added at 100 nM final concentration (red circles).

    Article Snippet: Chemicals Dasatinib was purchased from Selleckchem, 50 mM and 1 mM stock solutions were made in sterile dimethylsulfoxide.

    Techniques: Standard Deviation, Concentration Assay

    Dasatinib-induced cell death in BCR-ABL-positive and -negative cell lines. JURL-MK1 (full squares) and JURKAT (empty squares) cells were treated with dasatinib at different concentrations as indicated. After 45–48 h incubation, the fraction of non-viable cells was determined by counting of trypan blue-stained samples. Summary of 3 independent experiments for each cell line is shown.

    Journal: PLoS ONE

    Article Title: Real-Time Analysis of Imatinib- and Dasatinib-Induced Effects on Chronic Myelogenous Leukemia Cell Interaction with Fibronectin

    doi: 10.1371/journal.pone.0107367

    Figure Lengend Snippet: Dasatinib-induced cell death in BCR-ABL-positive and -negative cell lines. JURL-MK1 (full squares) and JURKAT (empty squares) cells were treated with dasatinib at different concentrations as indicated. After 45–48 h incubation, the fraction of non-viable cells was determined by counting of trypan blue-stained samples. Summary of 3 independent experiments for each cell line is shown.

    Article Snippet: Chemicals Dasatinib was purchased from Selleckchem, 50 mM and 1 mM stock solutions were made in sterile dimethylsulfoxide.

    Techniques: Incubation, Staining

    In vivo administration of Src inhibitor dasatinib leads to more severe DSS-induced colitis with decrease of IL-10 expression. ( A , B ) Hematoxylin-eosin staining ( A ) and the histological score ( B ) of the colon from mice treated with DMSO or dasatinib and fed with 3% DSS in water for 7 days. Magnification: Left: ×50 Right: ×200. ( B ) Q-PCR of IL-10(left) and TNF-α (right) in the colon from mice treated with DMSO or dasatinib after fed with 3% DSS in water. Data are representative of three independent experiments with similar results and presented as means ± SD. * P

    Journal: Scientific Reports

    Article Title: Integrin CD11b attenuates colitis by strengthening Src-Akt pathway to polarize anti-inflammatory IL-10 expression

    doi: 10.1038/srep26252

    Figure Lengend Snippet: In vivo administration of Src inhibitor dasatinib leads to more severe DSS-induced colitis with decrease of IL-10 expression. ( A , B ) Hematoxylin-eosin staining ( A ) and the histological score ( B ) of the colon from mice treated with DMSO or dasatinib and fed with 3% DSS in water for 7 days. Magnification: Left: ×50 Right: ×200. ( B ) Q-PCR of IL-10(left) and TNF-α (right) in the colon from mice treated with DMSO or dasatinib after fed with 3% DSS in water. Data are representative of three independent experiments with similar results and presented as means ± SD. * P

    Article Snippet: DSS mice model with Dasatinib Dasatinib (Selleck) was dissolved in DMSO at 60 mg/ml and stored in aliquots at −20 °C.

    Techniques: In Vivo, Expressing, Staining, Mouse Assay, Polymerase Chain Reaction

    Activation of TRKA affected response of HMC-1 and HMC-1.2 cells to KIT inhibition ( A ) Flow cytometric analysis showing expression of TRKA and KIT in HMC-1 cells carrying only KIT V560G mutation (negative control shown as inset). ( B ) By flow cytometry, HMC-1 cells did not express NGF. Cells were stained with anti-NGF biotin antibody followed by staining with streptavidin APC antibody. 32D cells transduced with retroviral vector expressing NGF were served as a positive control. HMC-1 cells stained with streptavidin APC antibody were used as a negative control. ( C ) To analyze clonal growth of HMC-1 cells, colony forming assay was performed in the presence of kinase inhibitors. Note > 99% growth inhibition by dasatinib = dasa (100 nM, targeting KIT), efficient rescue of HMC-1 cells in the presence of NGF (100 ng/ml), and efficient block ( > 98%) of NGF-induced rescue by the new TRK inhibitor entrectinib = entrec ( p

    Journal: Oncotarget

    Article Title: Activation of TRKA receptor elicits mastocytosis in mice and is involved in the development of resistance to KIT-targeted therapy

    doi: 10.18632/oncotarget.18027

    Figure Lengend Snippet: Activation of TRKA affected response of HMC-1 and HMC-1.2 cells to KIT inhibition ( A ) Flow cytometric analysis showing expression of TRKA and KIT in HMC-1 cells carrying only KIT V560G mutation (negative control shown as inset). ( B ) By flow cytometry, HMC-1 cells did not express NGF. Cells were stained with anti-NGF biotin antibody followed by staining with streptavidin APC antibody. 32D cells transduced with retroviral vector expressing NGF were served as a positive control. HMC-1 cells stained with streptavidin APC antibody were used as a negative control. ( C ) To analyze clonal growth of HMC-1 cells, colony forming assay was performed in the presence of kinase inhibitors. Note > 99% growth inhibition by dasatinib = dasa (100 nM, targeting KIT), efficient rescue of HMC-1 cells in the presence of NGF (100 ng/ml), and efficient block ( > 98%) of NGF-induced rescue by the new TRK inhibitor entrectinib = entrec ( p

    Article Snippet: Inhibitors dasatinib and entrectinib were purchased from Selleckchem (Houston, TX).

    Techniques: Activation Assay, Inhibition, Flow Cytometry, Expressing, Mutagenesis, Negative Control, Cytometry, Staining, Transduction, Plasmid Preparation, Positive Control, Blocking Assay

    Targeting both TRK and KIT in primary mast cells from patients with SM and in xenotransplanted mice ( A ) Additional inhibition of TRK improved targeted treatment by KIT inhibition in malignant mast cells from patients T207 and T208 in vitro . Both patients had KIT D816V mutation and TRKA expression on mast cells. Mast cells were cultured in the presence of inhibitors for 48 hours before apoptosis analysis. Note the strong rescue effect of NGF in patient T207. ( B – E ) Immunohistochemical staining for tryptase (B, D, × 600) and bone marrow smears (C, E, × 1000) showing infiltration of mast cells in bone marrow in patients T207 (B, C) and T208 (D, E). T207 = Aggressive SM (the major criterion and at least 3 minor criteria for diagnosis of SM [ 5 ] were present), T208 = SM with associated clonal hematological non-mast cell lineage diseases ( SM-AHN, at least 3 minor criteria for diagnosis of SM were present). ( F ) Kaplan-Meier analysis of animal survival. In line with in vitro data, entrectinib alone did not affect the survival of animals compared with the placebo group. Both treatment regimens (dasatinib alone and dasatinib/entrectinib) showed a significantly prolonged survival of NSG animals transplanted with HMC-1 cells ( p

    Journal: Oncotarget

    Article Title: Activation of TRKA receptor elicits mastocytosis in mice and is involved in the development of resistance to KIT-targeted therapy

    doi: 10.18632/oncotarget.18027

    Figure Lengend Snippet: Targeting both TRK and KIT in primary mast cells from patients with SM and in xenotransplanted mice ( A ) Additional inhibition of TRK improved targeted treatment by KIT inhibition in malignant mast cells from patients T207 and T208 in vitro . Both patients had KIT D816V mutation and TRKA expression on mast cells. Mast cells were cultured in the presence of inhibitors for 48 hours before apoptosis analysis. Note the strong rescue effect of NGF in patient T207. ( B – E ) Immunohistochemical staining for tryptase (B, D, × 600) and bone marrow smears (C, E, × 1000) showing infiltration of mast cells in bone marrow in patients T207 (B, C) and T208 (D, E). T207 = Aggressive SM (the major criterion and at least 3 minor criteria for diagnosis of SM [ 5 ] were present), T208 = SM with associated clonal hematological non-mast cell lineage diseases ( SM-AHN, at least 3 minor criteria for diagnosis of SM were present). ( F ) Kaplan-Meier analysis of animal survival. In line with in vitro data, entrectinib alone did not affect the survival of animals compared with the placebo group. Both treatment regimens (dasatinib alone and dasatinib/entrectinib) showed a significantly prolonged survival of NSG animals transplanted with HMC-1 cells ( p

    Article Snippet: Inhibitors dasatinib and entrectinib were purchased from Selleckchem (Houston, TX).

    Techniques: Mouse Assay, Inhibition, In Vitro, Mutagenesis, Expressing, Cell Culture, Immunohistochemistry, Staining

    Yes inhibitors block NF2 -deficient PRCC cell cycle Quantification of UOK275 ( A ) and HEK293 ( B ) cell cycle phases by BrdU and propidium iodide (PI) staining. The panels display the position of gates used to quantify cells in G0-G1, S or G2-M phases after 18 hours of treatment with DMSO (control), or dasatinib (50 nM or 500 nM). ( C ) Quantification of cells in the different cell cycle phases in HEK293, UOK275, UOK342 and ACHN after DMSO or dasatinib treatment (average of 3 distinct experiments).

    Journal: Oncotarget

    Article Title: Targeting loss of the Hippo signaling pathway in NF2-deficient papillary kidney cancers

    doi: 10.18632/oncotarget.24112

    Figure Lengend Snippet: Yes inhibitors block NF2 -deficient PRCC cell cycle Quantification of UOK275 ( A ) and HEK293 ( B ) cell cycle phases by BrdU and propidium iodide (PI) staining. The panels display the position of gates used to quantify cells in G0-G1, S or G2-M phases after 18 hours of treatment with DMSO (control), or dasatinib (50 nM or 500 nM). ( C ) Quantification of cells in the different cell cycle phases in HEK293, UOK275, UOK342 and ACHN after DMSO or dasatinib treatment (average of 3 distinct experiments).

    Article Snippet: Reagents Dasatinib, sarcatinib, PP2 and WH-4-023 were purchased from Selleck Chemicals (Houston, TX, USA).

    Techniques: Blocking Assay, Staining

    Yes inhibitors lower YAP1-mediated transcriptional network ( A ) Dose concentration treatment of dasatinib (μM) on the viability of UOK275, UOK342 and ACHN. HEK293 were used as controls. Cells were treated as indicated for 48 hours then viability was assessed by Cell-Titer Glo assay. ( B ) Yes-dependent phosphorylation of YAP1 and protein expression of survivin, cyclin D1 and CTGF was evaluated following 24 hours of dasatinib treatment by immunoblotting. ( C ) Expression of BIRC5 (survivin), CTGF (CTGF) and CCND1 (cyclin D1) was assessed by TaqMan assay 24 hours after dasatinib treatment (100nM) in HEK293, UOK275, UOK342 and ACHN.

    Journal: Oncotarget

    Article Title: Targeting loss of the Hippo signaling pathway in NF2-deficient papillary kidney cancers

    doi: 10.18632/oncotarget.24112

    Figure Lengend Snippet: Yes inhibitors lower YAP1-mediated transcriptional network ( A ) Dose concentration treatment of dasatinib (μM) on the viability of UOK275, UOK342 and ACHN. HEK293 were used as controls. Cells were treated as indicated for 48 hours then viability was assessed by Cell-Titer Glo assay. ( B ) Yes-dependent phosphorylation of YAP1 and protein expression of survivin, cyclin D1 and CTGF was evaluated following 24 hours of dasatinib treatment by immunoblotting. ( C ) Expression of BIRC5 (survivin), CTGF (CTGF) and CCND1 (cyclin D1) was assessed by TaqMan assay 24 hours after dasatinib treatment (100nM) in HEK293, UOK275, UOK342 and ACHN.

    Article Snippet: Reagents Dasatinib, sarcatinib, PP2 and WH-4-023 were purchased from Selleck Chemicals (Houston, TX, USA).

    Techniques: Concentration Assay, Glo Assay, Expressing, TaqMan Assay

    Dasatinib inhibits NF2 -deficient tumor growth in two xenograft animal models ( A ) Twenty female athymic nude mice were injected subcutaneously with 2 million of UOK275 cells. When the tumor volumes reached > 80 mm 3 , mice were randomized into 2 groups. One group was treated with dasatinib (25 mg/kg week days by oral gavage) while the other group received the vehicle (water/PEG 1:1) in a similar manner. Tumor volumes were measured once a week using calipers. Tumor volume was estimated using the formula v = lxL 2 . ( B ) Twenty female athymic nude mice were injected with 2 million of UOK342 cells. When the tumor volumes reached > 100 mm 3 , mice were randomized into 2 groups treated either with dasatinib (25 mg/kg week days by oral gavage) or the vehicle (water/PEG 1:1). Tumor volumes were measured using calipers once a week. Tumor volume was estimated using the formula v = lxL 2 .

    Journal: Oncotarget

    Article Title: Targeting loss of the Hippo signaling pathway in NF2-deficient papillary kidney cancers

    doi: 10.18632/oncotarget.24112

    Figure Lengend Snippet: Dasatinib inhibits NF2 -deficient tumor growth in two xenograft animal models ( A ) Twenty female athymic nude mice were injected subcutaneously with 2 million of UOK275 cells. When the tumor volumes reached > 80 mm 3 , mice were randomized into 2 groups. One group was treated with dasatinib (25 mg/kg week days by oral gavage) while the other group received the vehicle (water/PEG 1:1) in a similar manner. Tumor volumes were measured once a week using calipers. Tumor volume was estimated using the formula v = lxL 2 . ( B ) Twenty female athymic nude mice were injected with 2 million of UOK342 cells. When the tumor volumes reached > 100 mm 3 , mice were randomized into 2 groups treated either with dasatinib (25 mg/kg week days by oral gavage) or the vehicle (water/PEG 1:1). Tumor volumes were measured using calipers once a week. Tumor volume was estimated using the formula v = lxL 2 .

    Article Snippet: Reagents Dasatinib, sarcatinib, PP2 and WH-4-023 were purchased from Selleck Chemicals (Houston, TX, USA).

    Techniques: Mouse Assay, Injection