Journal: Xenobiotica; the fate of foreign compounds in biological systems

Article Title: A metabolomic perspective of pazopanib-induced acute hepatotoxicity in mice

doi: 10.1080/00498254.2018.1489167

Figure Lengend Snippet: Metabolomic analysis of pazopanib metabolites in mouse feces. (A) Scores plot of an OPLS-DA model from pazopanib treatment without drug (control) and with 300 mg/kg pazopanib. (•, control-treated pazopanib; ▲, pazopanib-treated pazopanib) (B) S-plot obtained from OPLS-DA analysis. (C) Trend plot of M2 in feces of mice treated with vehicle and pazopanib. (D) Trend plot of M7 in feces of mice treated with vehicle and pazopanib. Metabolite codes correspond to those in Table 1.

Article Snippet: Chemicals and reagents Pazopanib was provided by Medchem Express (Shanghai, China).

Techniques: Metabolomic, Control

Journal: Xenobiotica; the fate of foreign compounds in biological systems

Article Title: A metabolomic perspective of pazopanib-induced acute hepatotoxicity in mice

doi: 10.1080/00498254.2018.1489167

Figure Lengend Snippet: Summary of pazopanib metabolites produced in vivo and in vitro metabolism.

Article Snippet: Chemicals and reagents Pazopanib was provided by Medchem Express (Shanghai, China).

Techniques: Produced, In Vivo, In Vitro, Clinical Proteomics

Journal: Xenobiotica; the fate of foreign compounds in biological systems

Article Title: A metabolomic perspective of pazopanib-induced acute hepatotoxicity in mice

doi: 10.1080/00498254.2018.1489167

Figure Lengend Snippet: Abundance of pazopanib and its metabolites in mouse feces, urine, serum, MLM and HLM after treatment with pazopanib or vehicle. (A) Percentage of whole metabolites (%) in feces. (B) Percentage of whole metabolites (%) in urine. (C) Percentage of whole metabolites (%) in serum. (D) Percentage of whole metabolites (%) in MLM and HLM.

Article Snippet: Chemicals and reagents Pazopanib was provided by Medchem Express (Shanghai, China).

Techniques:

Journal: Xenobiotica; the fate of foreign compounds in biological systems

Article Title: A metabolomic perspective of pazopanib-induced acute hepatotoxicity in mice

doi: 10.1080/00498254.2018.1489167

Figure Lengend Snippet: Tandem MS spectra and fragmentation pattern of pazopanib and its three isomeric metabolites. (A) Chemical structure of pazopanib. (B) MS/MS pattern of pazopanib. (C) Chromatogram of M1, M2 and M3. (D) MS/MS fragments and chemical structures of M1. (E) MS/MS fragments and chemical structure of M2. (F) MS/MS fragments and chemical structure of M3.

Article Snippet: Chemicals and reagents Pazopanib was provided by Medchem Express (Shanghai, China).

Techniques: Tandem Mass Spectroscopy

Journal: Xenobiotica; the fate of foreign compounds in biological systems

Article Title: A metabolomic perspective of pazopanib-induced acute hepatotoxicity in mice

doi: 10.1080/00498254.2018.1489167

Figure Lengend Snippet: Tandem MS spectra and fragmentation pattern of aldehyde metabolites and cysteine adducts of pazopanib. (A) MS/MS fragments and chemical structure of M14. (B) MS/MS fragments and proposed structure of M18. (C) MS/MS fragments and proposed structure of M19. (D) MS/MS fragments and proposed structure of M20.

Article Snippet: Chemicals and reagents Pazopanib was provided by Medchem Express (Shanghai, China).

Techniques: Tandem Mass Spectroscopy

Journal: Xenobiotica; the fate of foreign compounds in biological systems

Article Title: A metabolomic perspective of pazopanib-induced acute hepatotoxicity in mice

doi: 10.1080/00498254.2018.1489167

Figure Lengend Snippet: Roles of CYPs in the formation of pazopanib metabolites.

Article Snippet: Chemicals and reagents Pazopanib was provided by Medchem Express (Shanghai, China).

Techniques: Control

Journal: Xenobiotica; the fate of foreign compounds in biological systems

Article Title: A metabolomic perspective of pazopanib-induced acute hepatotoxicity in mice

doi: 10.1080/00498254.2018.1489167

Figure Lengend Snippet: Examination of hepatic function after exposure to pazopanib. (A) Scores plot of an OPLS-DA model from pazopanib treatment without drug (control) and with 300 mg/kg pazopanib. (•, control-treated pazopanib; ▲, pazopanib-treated pazopanib) (B) S-plot obtained from OPLS-DA analysis. (C) The relative content of unchanged pazopanib in liver after administration of 150 and 300 mg/kg. (D) The change of representative endogenous metabolites in mouse liver by pazopanib. (E) The change of serum ALT by pazopanib. (F) The change of serum AST by pazopanib. (G) Histological examination of liver from control and 150 mg/kg, 300 mg/kg pazopanib using H&E staining. Arrow represents inflammatory cell infiltration. Statistical analysis was performed using one-way ANOVA (n = 4 in each group). *p < 0.05, compared with control group.

Article Snippet: Chemicals and reagents Pazopanib was provided by Medchem Express (Shanghai, China).

Techniques: Control, Staining

Journal: Xenobiotica; the fate of foreign compounds in biological systems

Article Title: A metabolomic perspective of pazopanib-induced acute hepatotoxicity in mice

doi: 10.1080/00498254.2018.1489167

Figure Lengend Snippet: Unchanged pazopanib and GSH in serum and liver. (A) The content of unchanged pazopanib in serum at 3 and 24 h after administration of 150 and 300 mg/kg. (B) The level of GSH in liver. (C) The activity of SOD in liver. (D) The content of MDA in liver. (E) Effects of pazopanib administration on the expression levels of drug metabolic enzymes and transporters. Statistical analysis was performed using one-way ANOVA (n = 4 in each group). *p < 0.05, compared with control group.

Article Snippet: Chemicals and reagents Pazopanib was provided by Medchem Express (Shanghai, China).

Techniques: Activity Assay, Expressing, Control

Journal: Xenobiotica; the fate of foreign compounds in biological systems

Article Title: A metabolomic perspective of pazopanib-induced acute hepatotoxicity in mice

doi: 10.1080/00498254.2018.1489167

Figure Lengend Snippet: The relationship between reactive metabolites with pazopanib-induced hepatotoxicity. (A) The correlation between the abundance of M3 in urine with ALT activity. (B) The correlation between the abundance of M3 in urine with AST activity. (C) The correlation between the abundance of M18 in urine with ALT activity. (D) The correlation between the abundance of M18 in urine with AST activity. (E) The change of serum ALT by pazopanib (300 mg/kg) in pre-administration with ABT (100 mg/kg). (F) The change of serum ALT by pazopanib (300 mg/kg) in pre-administration with ABT. (G) The changes of reactive metabolites following the ABT pretreatment. Correlation factor (r) and p value were calculated with Pearson’s correlation analysis. Statistical analysis was performed using two-tailed Student’s t-test (n = 4 in each group). *p < 0.05, **p < 0.01, ***p < 0.001, compared with control group. #p < 0.05, compared with pazopanib group.

Article Snippet: Chemicals and reagents Pazopanib was provided by Medchem Express (Shanghai, China).

Techniques: Activity Assay, Two Tailed Test, Control

Journal: Xenobiotica; the fate of foreign compounds in biological systems

Article Title: A metabolomic perspective of pazopanib-induced acute hepatotoxicity in mice

doi: 10.1080/00498254.2018.1489167

Figure Lengend Snippet: Summary of the major in vivo metabolism pathway of pazopanib. Pazopanib (M0) can be conjugated with the group of cysteine, N-acetylcysteine and glycylcysteine to generate three conjugates M18, M19 and M20. Pazopanib also can be transformed into three aldehyde derivatives M14 and M15 by hydroformylation. Additionally, pazopanib can be converted two N-oxides M3 and M12 under the effect of oxidation.

Article Snippet: Chemicals and reagents Pazopanib was provided by Medchem Express (Shanghai, China).

Techniques: In Vivo, Transformation Assay

Journal: Clinical Oncology (Royal College of Radiologists (Great Britain)

Article Title: The Dandelion Dilemma Revisited for Oligoprogression: Treat the Whole Lawn or Weed Selectively?

doi: 10.1016/j.clon.2019.05.015

Figure Lengend Snippet: Retrospective studies of local ablative therapy for oligoprogression

Article Snippet: Multicentre 2007–2015 , RCC , ≤3 EC or CNS , n = 55 , n = 51 , Sunitinib, pazopanib, sorafenib , XRT: 25 Surgery: 25 Cryo/thermo-ablation: 5 , 14 (95% CI 6.9–21) (EC-OPD and CNS) , , No toxicity data reported.

Techniques: Control

Journal: The Journal of pharmacology and experimental therapeutics

Article Title: Novel Bile Acid-Dependent Mechanisms of Hepatotoxicity Associated with Tyrosine Kinase Inhibitors.

doi: 10.1124/jpet.121.000828

Figure Lengend Snippet: Fig. 1. Bile acid-dependent toxicity from tyrosine kinase inhibitors in sandwich-cultured human hepatocytes (SCHH). Bile acid-dependent toxicity was measured in SCHH (lots EGO and WID) in Sensitization Medium (black bars, closed circles) and Standard Medium (white bars, open circles). SCHH were treated with (A) controls including 0.1% DMSO control, cyclosporine A (CsA; 10 lM), imatinib (40 lM) or troglitazone (TGZ; 75 lM) or (B) dasatinib, pazopanib, or sorafenib for 24 hours. ATP content and LDH release were normalized to 0.1% DMSO control. Data are shown as mean and standard deviation (n = 3). Statistically significant differences were determined by a repeated measures two-way ANOVA, with multi- ple comparisons corrected using the Sidak test (* P value < 0.05, **<0.0001, standard versus sensitization medium). #Precipitation was observed at 66.4 lM pazopanib, and therefore, the highest concentration was decreased to 33.2 lM for lot EGO. Imatinib and TGZ ATP values <2% of con- trol are not visible in Fig. 1A.

Article Snippet: Dasatinib (catalog #D-3307) and pazopanib (#S3012) were obtained from LC Laboratories (Woburn, MA) and Selleckchem (ThermoFisher Scientific, Pittsburgh, PA), respectively.

Techniques: Cell Culture, Control, Standard Deviation, Concentration Assay

Journal: The Journal of pharmacology and experimental therapeutics

Article Title: Novel Bile Acid-Dependent Mechanisms of Hepatotoxicity Associated with Tyrosine Kinase Inhibitors.

doi: 10.1124/jpet.121.000828

Figure Lengend Snippet: Fig. 2. Cellular concentration of tyrosine kinase inhibitors (TKIs) in sandwich-cultured human hepatocytes (SCHH) treated for 24 hours. TKI concentrations were measured in SCHH (lots EGO, RVQ, and WID) treated with dasatinib (1.8 mM), pazopanib (6.6 mM), or sorafenib (4.3 mM) using liquid chromatography with tandem mass spectrometry. Concentrations of each TKI were calculated, normalized to total protein and hepatocellular volume, and plotted as mean ± standard deviation (n = 3 or 4).

Article Snippet: Dasatinib (catalog #D-3307) and pazopanib (#S3012) were obtained from LC Laboratories (Woburn, MA) and Selleckchem (ThermoFisher Scientific, Pittsburgh, PA), respectively.

Techniques: Concentration Assay, Cell Culture, Liquid Chromatography, Mass Spectrometry, Standard Deviation

Journal: The Journal of pharmacology and experimental therapeutics

Article Title: Novel Bile Acid-Dependent Mechanisms of Hepatotoxicity Associated with Tyrosine Kinase Inhibitors.

doi: 10.1124/jpet.121.000828

Figure Lengend Snippet: Fig. 3. Gene expression analysis by RT-qPCR and quantitative analysis of bile acid concentrations in sandwich-cultured human hep- atocytes (SCHH) treated with tyrosine kinase inhibitors (TKIs). (A) mRNA was measured in SCHH (lots EGO and WID) after an 8-hour incubation with 0.1% DMSO control (DMSO Ctrl), dasa- tinib (1.8 lM), pazopanib (6.6 lM), or sorafenib (4.3 lM). Threshold cycle (CT) values of each gene of interest (SLC10A1, ABCB11, CYP7A1, CYP8B1, CYP27A1, BAAT, BACS, and CYP3A4) were normalized to the housekeeping gene b-actin (ACTB) and compared with 0.1% DMSO control. Data are plotted as mean ± standard deviation (n = 3). Sta- tistically significant differences were determined by a repeated measures two-way ANOVA with Dunnett’s multiple comparison test (*P value < 0.05, **<0.0001, TKI versus control). (B) Bile acid concentrations were quantified in SCHH (lots EGO, RVQ and WID) treated with 0.1% DMSO control, dasatinib (1.8 mM), pazopanib (6.6 mM) or sorafenib (4.3 mM) for 24 hours and in medium from each well using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Bile acid concentra- tions in “Cells1Bile” were normal- ized to total protein. Average fold change (n = 3 or 4) of each bile acid species [glycocholic acid (GCA), glycochenodeoxycholic acid (GCDCA), GCDCA-3-O-b-glucuro- nide (GCDCA-3G), GCDCA 3- sulfate (GCDCA-S), taurocheno- deoxycholic acid (TCDCA), and taurocholic acid (TCA)] was cal- culated, compared with 0.1% DMSO control in SCHH and medium, and plotted as a heat map (red = increase, blue = decrease). (C) Average total bile acid species in “Cells1Bile” and medium were plotted based on SCHH lot and treatment. BA, bile acids.

Article Snippet: Dasatinib (catalog #D-3307) and pazopanib (#S3012) were obtained from LC Laboratories (Woburn, MA) and Selleckchem (ThermoFisher Scientific, Pittsburgh, PA), respectively.

Techniques: Gene Expression, Quantitative RT-PCR, Cell Culture, Incubation, Control, Standard Deviation, Comparison, Liquid Chromatography, Mass Spectrometry, Liquid Chromatography with Mass Spectroscopy

Journal: The Journal of pharmacology and experimental therapeutics

Article Title: Novel Bile Acid-Dependent Mechanisms of Hepatotoxicity Associated with Tyrosine Kinase Inhibitors.

doi: 10.1124/jpet.121.000828

Figure Lengend Snippet: Fig. 4. Effect of tyrosine kinase inhibitors (TKIs) on the membrane protein abundance of hepatic bile acid transporters in sandwich-cul- tured human hepatocytes (SCHH). SCHH were treated with 0.1% DMSO control (Ctrl), dasatinib (1.8 lM), pazopanib (6.6 lM) or sorafe- nib (4.3 lM) for 24 hours. Abundance of bile salt export pump (BSEP), sodium taurocholate co-transporting polypeptide (NTCP), epidermal growth factor receptor (EGFR), and Na1/K1 ATPase (loading control) was evaluated using immunostaining of membrane fractions harvested from SCHH lots EGO, RVQ, and WID. Densitometry was performed using ImageJ and BSEP, NTCP, and EGFR signals were normalized to Na1/K1 ATPase. All treatments were performed in triplicate except in lot WID (n = 2). Statistically significant differences in lots EGO and RVQ were assessed using repeated measures two-way ANOVA with Dunnett’s multiple comparison test (*, P < 0.05, **, P < 0.0001, TKI versus control).

Article Snippet: Dasatinib (catalog #D-3307) and pazopanib (#S3012) were obtained from LC Laboratories (Woburn, MA) and Selleckchem (ThermoFisher Scientific, Pittsburgh, PA), respectively.

Techniques: Membrane, Quantitative Proteomics, Control, Immunostaining, Comparison

Journal: The Journal of pharmacology and experimental therapeutics

Article Title: Novel Bile Acid-Dependent Mechanisms of Hepatotoxicity Associated with Tyrosine Kinase Inhibitors.

doi: 10.1124/jpet.121.000828

Figure Lengend Snippet: Fig. 5. Effect of tyrosine kinase inhibitors (TKIs) on the function of hepatic bile acid transporters in sandwich-cultured human hepatocytes (SCHH). The function of bile acid transporters was measured using B-CLEAR technology in SCHH (lots EGO, RVQ, and WID); [3H]-taurocholate (TCA) biliary excretion index (BEI; %) and uptake clearance (CLuptake; ll/min/mg protein) values (Table 4) were calculated using Eqs. 4 and 5, respectively. SCHH were pretreated with 0.1% DMSO control (DMSO Ctrl), dasatinib (1.8 lM), pazopanib (6.6 lM), or sorafenib (4.3 lM) for 24 hours. Accumulation of 2 lM [3H]-TCA (200 nCi/ml) was measured in “Cells1Bile” and “Cells” using standard (1 Ca21; black bars) and Ca21-free ( Ca21; white bars) Hank’s balanced salt solution (HBSS) buffer. Data are plotted as mean ± standard deviation (n = 3). Statistically significant differences were assessed using an ordinary two-way ANOVA with Dunnett’s multiple comparison test (*, P < 0.05, **, P < 0.0001, TKI versus DMSO control).

Article Snippet: Dasatinib (catalog #D-3307) and pazopanib (#S3012) were obtained from LC Laboratories (Woburn, MA) and Selleckchem (ThermoFisher Scientific, Pittsburgh, PA), respectively.

Techniques: Cell Culture, Control, Standard Deviation, Comparison

Journal: The Journal of pharmacology and experimental therapeutics

Article Title: Novel Bile Acid-Dependent Mechanisms of Hepatotoxicity Associated with Tyrosine Kinase Inhibitors.

doi: 10.1124/jpet.121.000828

Figure Lengend Snippet: Fig. 6. Novel mechanisms of tyrosine kinase inhibitor (TKI)-induced hepatic injury. Data presented herein demonstrate that dasatinib and pazo- panib increase sodium taurocholate co-transporting polypeptide (NTCP) membrane protein abundance and the uptake clearance (CLuptake) of bile acids (red circles) in addition to increasing bile acid synthesis via induction of CYP7A1 mRNA in human hepatocytes. While dasatinib promoted basolateral efflux of bile acids into medium, presumably via multidrug resistance-associated protein (MRP) 3 and/or MRP4, pazopanib increased bile acids in human hepatocytes. Dasatinib reduced the biliary excretion index and pazopanib promoted bile salt export pump (BSEP)-mediated biliary excretion. Sorafenib increased cellular levels of GCDCA-3-O-b-glucuronide (GCDCA-3G). These novel findings contribute to TKI-induced hepatic injury. BC, bile canaliculus; TJ, tight junctions.

Article Snippet: Dasatinib (catalog #D-3307) and pazopanib (#S3012) were obtained from LC Laboratories (Woburn, MA) and Selleckchem (ThermoFisher Scientific, Pittsburgh, PA), respectively.

Techniques: Membrane, Quantitative Proteomics

Journal: Medical Hypothesis, Discovery and Innovation in Ophthalmology

Article Title: Pazopanib Selectively Inhibits Choroidal Vascular Endothelial Cell Proliferation and Promotes Apoptosis

doi:

Figure Lengend Snippet: Proliferation of CVECs in response to different concentrations of pazopanib at various time points. The proliferation rates were assessed using WST-1 assay.

Article Snippet: Treatment of CVECs with Pazopanib CVECs were treated with increasing doses of pazopanib (Santa Cruz, The USA) at concentrations of 10, 50, 100 and 250 μM.

Techniques: Incubation, Concentration Assay

Journal: Medical Hypothesis, Discovery and Innovation in Ophthalmology

Article Title: Pazopanib Selectively Inhibits Choroidal Vascular Endothelial Cell Proliferation and Promotes Apoptosis

doi:

Figure Lengend Snippet: Effect of pazopanib (10, 50, 100, and 250 µM) on choroidal vascular endothelial cells (CVECs) enriched with vascular endothelial growth factor (VEGF: 50ng/mL). Cell proliferation was determined by WST-1 assay at different time intervals. Results expressed as percentage of cell proliferation compared to control. A. 48h, B. 72h, and, C. 1 Week. Abbreviations: µM: micromole; ng/mL: nanogram per millilitre; h: hour; %: percentage; Conc.: concentration.

Article Snippet: Treatment of CVECs with Pazopanib CVECs were treated with increasing doses of pazopanib (Santa Cruz, The USA) at concentrations of 10, 50, 100 and 250 μM.

Techniques: WST-1 Assay, Control, Concentration Assay

Journal: Medical Hypothesis, Discovery and Innovation in Ophthalmology

Article Title: Pazopanib Selectively Inhibits Choroidal Vascular Endothelial Cell Proliferation and Promotes Apoptosis

doi:

Figure Lengend Snippet: The percentage of viable cells of VEGF enriched CVECs in response to pazopanib treatment at different concentrations and various time points. The cells viability rates were assessed using trypan blue exclusion assay as described in methods.

Article Snippet: Treatment of CVECs with Pazopanib CVECs were treated with increasing doses of pazopanib (Santa Cruz, The USA) at concentrations of 10, 50, 100 and 250 μM.

Techniques: Trypan Blue Exclusion Assay, Incubation, Concentration Assay

Journal: Medical Hypothesis, Discovery and Innovation in Ophthalmology

Article Title: Pazopanib Selectively Inhibits Choroidal Vascular Endothelial Cell Proliferation and Promotes Apoptosis

doi:

Figure Lengend Snippet: Effect of pazopanib (10, 50, 100, 250 µM) on choroidal vascular endothelial cells (CVECs) enriched with vascular endothelial growth factor (VEGF: 50ng/mL). Cell viability was defined by trypan blue assay using ViCell XR Cell analyzer at different time intervals. Results expressed as percentage of cell proliferation compared to control. A. 48h, B. 72h, and, C. 1 Week. Abbreviations: µM: micromole; ng/mL: nanogram per millilitre; h: hour; %: percentage; Conc.: concentration.

Article Snippet: Treatment of CVECs with Pazopanib CVECs were treated with increasing doses of pazopanib (Santa Cruz, The USA) at concentrations of 10, 50, 100 and 250 μM.

Techniques: Control, Concentration Assay

Journal: Medical Hypothesis, Discovery and Innovation in Ophthalmology

Article Title: Pazopanib Selectively Inhibits Choroidal Vascular Endothelial Cell Proliferation and Promotes Apoptosis

doi:

Figure Lengend Snippet: Reactive oxygen species (ROS) levels measured using dihydrorhodamine 123 (DHR 123) after exposure to various concentrations of pazopanib at different time intervals. A. 48h, B. 72h, and, C. 1 Week.

Article Snippet: Treatment of CVECs with Pazopanib CVECs were treated with increasing doses of pazopanib (Santa Cruz, The USA) at concentrations of 10, 50, 100 and 250 μM.

Techniques:

Journal: Medical Hypothesis, Discovery and Innovation in Ophthalmology

Article Title: Pazopanib Selectively Inhibits Choroidal Vascular Endothelial Cell Proliferation and Promotes Apoptosis

doi:

Figure Lengend Snippet: Measurement of activated caspase-3 levels in CVECs enriched with VEGF treated with different concentrations of pazopanib at 72h showed a 5-fold increase in activated caspase 3 levels compared to control. Abbreviations: µM: micromole; h: hour; VEGF: vascular endothelial growth factor; CVECs: choroidal vascular endothelial cells; Conc.: concentration.

Article Snippet: Treatment of CVECs with Pazopanib CVECs were treated with increasing doses of pazopanib (Santa Cruz, The USA) at concentrations of 10, 50, 100 and 250 μM.

Techniques: Control, Concentration Assay

Journal: Medical Hypothesis, Discovery and Innovation in Ophthalmology

Article Title: Pazopanib Selectively Inhibits Choroidal Vascular Endothelial Cell Proliferation and Promotes Apoptosis

doi:

Figure Lengend Snippet: Effect of different concentrations of pazopanib on cell morphology of VEGF enriched choroidal vascular endothelial cells at 72 hrs; Decrease in cell size and irregular membrane was observed compared to controls. Bright field images were taken at 20X magnification (A‐E: Control, 10, 50, 100 and 250 micrometer).

Article Snippet: Treatment of CVECs with Pazopanib CVECs were treated with increasing doses of pazopanib (Santa Cruz, The USA) at concentrations of 10, 50, 100 and 250 μM.

Techniques: Membrane, Control

Journal: Journal of pharmaceutical and biomedical analysis

Article Title: Development and validation of a sensitive LC–MS/MS method for simultaneous determination of eight tyrosine kinase inhibitors and its application in mice pharmacokinetic studies

doi: 10.1016/j.jpba.2017.09.013

Figure Lengend Snippet: Compound-dependent parameters of eight tyrosine kinase inhibitors with testosterone as internal standard (IS) in UHPLC–MS/MS analysis.

Article Snippet: Chemicals and reagents Imatinib, gefitinib, erlotinib hydrochloride, sorafenib tosylate, sunitinib malate, dasatinib, lapatinib, nilotinib, pazopanib hydrochloride, axitinib, and afatinib were purchased from LC laboratories (Woburn, MA, USA).

Techniques:

Journal: Journal of pharmaceutical and biomedical analysis

Article Title: Development and validation of a sensitive LC–MS/MS method for simultaneous determination of eight tyrosine kinase inhibitors and its application in mice pharmacokinetic studies

doi: 10.1016/j.jpba.2017.09.013

Figure Lengend Snippet: A representative SRM chromatogram of a calibration standard spiked in blank blood containing 1) sunitinib, 2) pazopanib, 3) axitinib, 4) dasatinib, 5) erlotinib, 6) nilotinib, 7) lapatinib, 8) sorafenib, and 9) testosterone (IS).

Article Snippet: Chemicals and reagents Imatinib, gefitinib, erlotinib hydrochloride, sorafenib tosylate, sunitinib malate, dasatinib, lapatinib, nilotinib, pazopanib hydrochloride, axitinib, and afatinib were purchased from LC laboratories (Woburn, MA, USA).

Techniques:

Journal: Journal of pharmaceutical and biomedical analysis

Article Title: Development and validation of a sensitive LC–MS/MS method for simultaneous determination of eight tyrosine kinase inhibitors and its application in mice pharmacokinetic studies

doi: 10.1016/j.jpba.2017.09.013

Figure Lengend Snippet: Intra-day and inter-day accuracy and precision of eight TKIs from the assay samples.

Article Snippet: Chemicals and reagents Imatinib, gefitinib, erlotinib hydrochloride, sorafenib tosylate, sunitinib malate, dasatinib, lapatinib, nilotinib, pazopanib hydrochloride, axitinib, and afatinib were purchased from LC laboratories (Woburn, MA, USA).

Techniques: Concentration Assay

Journal: Journal of pharmaceutical and biomedical analysis

Article Title: Development and validation of a sensitive LC–MS/MS method for simultaneous determination of eight tyrosine kinase inhibitors and its application in mice pharmacokinetic studies

doi: 10.1016/j.jpba.2017.09.013

Figure Lengend Snippet: Extraction recovery and matrix effect of eight TKIs.

Article Snippet: Chemicals and reagents Imatinib, gefitinib, erlotinib hydrochloride, sorafenib tosylate, sunitinib malate, dasatinib, lapatinib, nilotinib, pazopanib hydrochloride, axitinib, and afatinib were purchased from LC laboratories (Woburn, MA, USA).

Techniques: Extraction, Concentration Assay

Journal: Journal of pharmaceutical and biomedical analysis

Article Title: Development and validation of a sensitive LC–MS/MS method for simultaneous determination of eight tyrosine kinase inhibitors and its application in mice pharmacokinetic studies

doi: 10.1016/j.jpba.2017.09.013

Figure Lengend Snippet: The concentration (mean ± SD, n = 4, ng/ml) of those compounds only detected at certain time points in the PK study.

Article Snippet: Chemicals and reagents Imatinib, gefitinib, erlotinib hydrochloride, sorafenib tosylate, sunitinib malate, dasatinib, lapatinib, nilotinib, pazopanib hydrochloride, axitinib, and afatinib were purchased from LC laboratories (Woburn, MA, USA).

Techniques: Concentration Assay

Journal: Oncotarget

Article Title: In comparative analysis of multi-kinase inhibitors for targeted medulloblastoma therapy pazopanib exhibits promising in vitro and in vivo efficacy

doi:

Figure Lengend Snippet: The cell lines MEB-Med-8A, D283 Med, Daoy and D341 Med were treated with increasing concentrations of Pazopanib and Sorafenib. Areas shaded in grey indicate the range of the respective MKI concentrations detectable in patient's plasma. The vehicle DMSO served as control. After 48h of drug exposure the cell viability was assessed by MTS assay. Values below an asterisk are significantly different from the control (*p<0,05). Each experiment was performed in triplicates and repeated four times.

Article Snippet: Pazopanib (GW786034B) and Sorafenib (BAY 43-9006) were obtained from LC Laboratories.

Techniques: Clinical Proteomics, Control, MTS Assay

Journal: Oncotarget

Article Title: In comparative analysis of multi-kinase inhibitors for targeted medulloblastoma therapy pazopanib exhibits promising in vitro and in vivo efficacy

doi:

Figure Lengend Snippet: In a combined proliferation-apoptosis assay based on a CFSE-7AAD-Annexin-V staining the capacity of Pazopanib and Sorafenib to inhibit proliferation (a) and induce apoptosis (b) in medulloblastoma cell lines was determined. The cells were treated for 24, 48 and 72h with MKI concentrations corresponding to patient's plasma levels (Pazopanib 15 μM and Sorafenib 10 μM). The vehicle DMSO served as control. The proliferation were normalized with the DMSO control. Statistically significant differences compared to control are marked by an asterisk (*p<0,05). The data represent four independent experiments.

Article Snippet: Pazopanib (GW786034B) and Sorafenib (BAY 43-9006) were obtained from LC Laboratories.

Techniques: Apoptosis Assay, Staining, Clinical Proteomics, Control

Journal: Oncotarget

Article Title: In comparative analysis of multi-kinase inhibitors for targeted medulloblastoma therapy pazopanib exhibits promising in vitro and in vivo efficacy

doi:

Figure Lengend Snippet: Daoy and MEB-Med8A cells were treated for 48h with concentrations corresponding to patient's plasma levels (Pazopanib 15 μM and Sorafenib 10 μM). Subsequently cell cycle distribution was determined by Hoechst 33342 staining. The vehicle DMSO served as control. The lower panel depicts the reduction in cell density and changes in morphology for Daoy and MEB-Med-8a after drug exposure for 48h (scale bar 100 μm). Statistically significant differences from control are marked by an asterix (*p<0,05). The data shown represent five independent experiments.

Article Snippet: Pazopanib (GW786034B) and Sorafenib (BAY 43-9006) were obtained from LC Laboratories.

Techniques: Clinical Proteomics, Staining, Control

Journal: Oncotarget

Article Title: In comparative analysis of multi-kinase inhibitors for targeted medulloblastoma therapy pazopanib exhibits promising in vitro and in vivo efficacy

doi:

Figure Lengend Snippet: Daoy and MEB-Med-8A cells were exposed to 15 μM of Pazopanib and 10 μM of Sorafenib respectively for 48h. Subsequently the cells were maintained in standard growth medium for 7 days and colony formation and colony size were assessed. Statistically significant differences are marked by an asterisk (*p<0.05). The data shown represent five independent experiments.

Article Snippet: Pazopanib (GW786034B) and Sorafenib (BAY 43-9006) were obtained from LC Laboratories.

Techniques:

Journal: Oncotarget

Article Title: In comparative analysis of multi-kinase inhibitors for targeted medulloblastoma therapy pazopanib exhibits promising in vitro and in vivo efficacy

doi:

Figure Lengend Snippet: In Daoy, MEB-Med-8A, D283 Med and D341 Med cells were treated with Pazopanib and Sorafenib at concentrations corresponding to patient's plasma levels (Pazopanib 15 μM and Sorafenib 10 μM) for a 1, 12, 24 and 48h period. Total protein levels and the phosphorylation status of STAT3 were determined by westernblot. Beta-tubulin and ERGIC53 respectively served as loading controls. The data-set shown represents 1 of 3 independent experiments.

Article Snippet: Pazopanib (GW786034B) and Sorafenib (BAY 43-9006) were obtained from LC Laboratories.

Techniques: Clinical Proteomics, Phospho-proteomics

Journal: Oncotarget

Article Title: In comparative analysis of multi-kinase inhibitors for targeted medulloblastoma therapy pazopanib exhibits promising in vitro and in vivo efficacy

doi:

Figure Lengend Snippet: After a single scratch was made in a confluent monolayer of Daoy cells, these were exposed to Pazopanib and Sorafenib at concentrations corresponding to patient plasma levels (Pazopanib 15 μM and Sorafenib 10 μM) for 24h. Each scratch was photographed after 12 and 24h and its width determined. Statistically significant differences from control are marked by an asterisk (*p<0,05). The data shown represent four independent experiments.

Article Snippet: Pazopanib (GW786034B) and Sorafenib (BAY 43-9006) were obtained from LC Laboratories.

Techniques: Clinical Proteomics, Control

Journal: Oncotarget

Article Title: In comparative analysis of multi-kinase inhibitors for targeted medulloblastoma therapy pazopanib exhibits promising in vitro and in vivo efficacy

doi:

Figure Lengend Snippet: In a orthotopic xenograft mouse model we analysed whether Pazopanib and Sorafenib could inhibit medulloblastoma growth in vivo . For this purpose 2×10 4 MEB-Med-8A cells were transplanted into the cerebellum of mice to establish tumors. The tumor growth was analyzed by bioluminescent imagining after 1, 2, 3 and 4 weeks. One week after transplantation mice were treated with 60 mg/kg of Pazopanib and 30 mg/kg of Sorafenib once daily by gavage until they developed symptoms. Figure depicts the normalized tumor growth delay while figure shows the survival of treated and untreated animals via Kaplan-Meyer curve. Pazopanib and Sorafenib treatment prolonged the survival of medulloblastoma bearing mice significantly.

Article Snippet: Pazopanib (GW786034B) and Sorafenib (BAY 43-9006) were obtained from LC Laboratories.

Techniques: In Vivo, Transplantation Assay