Journal: Oncotarget

Article Title: Combinatorial high-throughput experimental and bioinformatic approach identifies molecular pathways linked with the sensitivity to anticancer target drugs

doi:

Figure Lengend Snippet: Molecular pathways correlating with drug response, overlapping for the experimental and GDS datasets

Article Snippet: The following drugs were tested (purchased at Selleckchem, USA): Pazopanib, Sunitinib, Sorafenib and Temsirolimus.

Techniques:

Journal: Oncotarget

Article Title: Combinatorial high-throughput experimental and bioinformatic approach identifies molecular pathways linked with the sensitivity to anticancer target drugs

doi:

Figure Lengend Snippet: Schematic representation of the respective drug targets in the overall architecture of molecular interactions for the top pathways correlating with response to Pazopanib A. Sorafenib B. Sunitinib C. and Temsirolimus D. Protein targets of the respective drugs are shown in orange, intermediate molecules between pathway members and drug targets (in grey) and pathway members (in blue).

Article Snippet: The following drugs were tested (purchased at Selleckchem, USA): Pazopanib, Sunitinib, Sorafenib and Temsirolimus.

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: 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 Cancer Research and Clinical Oncology

Article Title: Belinostat and panobinostat (HDACI): in vitro and in vivo studies in thyroid cancer

doi: 10.1007/s00432-013-1465-6

Figure Lengend Snippet: Dose of drug that inhibited 50 % growth of human thyroid cancer cell line in vitro

Article Snippet: Pazopanib, motesanib, sorafenib and dasatinib (TKIs) (LC Laboratories) were dissolved in DMSO and stored in aliquots at −20 °C until use.

Techniques: Mutagenesis

Journal: Journal of Cancer Research and Clinical Oncology

Article Title: Belinostat and panobinostat (HDACI): in vitro and in vivo studies in thyroid cancer

doi: 10.1007/s00432-013-1465-6

Figure Lengend Snippet: Combination index of (a) belinostat/panobinostat and dasatinib on SW1736 cells, (b) belinostat/panobinostat and dasatinib on Cal 62 cells, (c) belinostat/panobinostat and pazopanib on BHP 2-7 cells

Article Snippet: Pazopanib, motesanib, sorafenib and dasatinib (TKIs) (LC Laboratories) were dissolved in DMSO and stored in aliquots at −20 °C until use.

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: 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

Journal: Metabolites

Article Title: Biological Role of Pazopanib and Sunitinib Aldehyde Derivatives in Drug-Induced Liver Injury

doi: 10.3390/metabo12090852

Figure Lengend Snippet: Chemical structures of pazopanib, sunitinib, and aldehyde derivatives (P-CHO and S-CHO, respectively).

Article Snippet: Sunitinib L-malate and pazopanib hydrochloride (HCl) were purchased from Alsachim (Illkirch Graffenstaden, France, purity > 98%).

Techniques:

Journal: Metabolites

Article Title: Biological Role of Pazopanib and Sunitinib Aldehyde Derivatives in Drug-Induced Liver Injury

doi: 10.3390/metabo12090852

Figure Lengend Snippet: Cytotoxicity on hepatocytes exposed to pazopanib, sunitinib, and their respective aldehydes. Drug cytotoxicity was assessed by measuring lactate dehydrogenase release after 24-h exposure to increasing concentrations of compounds in HepG2 cells ( A , B ) and HepaRG cells ( C , D ). Results are given as mean and standard deviation (s.d.). * p < 0.05 in comparing the parent molecule versus the aldehyde metabolite.

Article Snippet: Sunitinib L-malate and pazopanib hydrochloride (HCl) were purchased from Alsachim (Illkirch Graffenstaden, France, purity > 98%).

Techniques: Standard Deviation

Journal: Metabolites

Article Title: Biological Role of Pazopanib and Sunitinib Aldehyde Derivatives in Drug-Induced Liver Injury

doi: 10.3390/metabo12090852

Figure Lengend Snippet: Activation of apoptosis in HepG2 cells exposed to pazopanib, sunitinib, and their respective aldehydes. Apoptosis was evaluated in HepG2 cells by measuring caspases 3 and 7 activity in the presence of pazopanib or P-CHO ( A ) and sunitinib or S-CHO ( B ). Results are given as mean and standard deviation (s.d.) of fold-change of caspases activation compared to control. * p < 0.05 in comparing the parent molecule versus the aldehyde metabolite.

Article Snippet: Sunitinib L-malate and pazopanib hydrochloride (HCl) were purchased from Alsachim (Illkirch Graffenstaden, France, purity > 98%).

Techniques: Activation Assay, Activity Assay, Standard Deviation, Control

Journal: Metabolites

Article Title: Biological Role of Pazopanib and Sunitinib Aldehyde Derivatives in Drug-Induced Liver Injury

doi: 10.3390/metabo12090852

Figure Lengend Snippet: Pazopanib and sunitinib aldehydes impair mitochondrial function. Mitochondrial function was assessed in HepG2 cells by detecting intracellular ATP in cells cultured in a glucose (solid line) or a galactose (dotted line) medium and exposed to increasing concentrations of P-CHO ( A ) or S-CHO ( B ). Relative oxygen consumption rate (OCR) was measured by Seahorse assay in HepG2 cells cultured in a glucose medium. ATP production and Maximal Respiratory Capacity were evaluated for P-CHO ( C , E ) and S-CHO ( D , F ) and were expressed as the fold-change of OCR measured in non-treated cells. * p value < 0.05 compared to non-treated cells.

Article Snippet: Sunitinib L-malate and pazopanib hydrochloride (HCl) were purchased from Alsachim (Illkirch Graffenstaden, France, purity > 98%).

Techniques: Cell Culture

Journal: Metabolites

Article Title: Biological Role of Pazopanib and Sunitinib Aldehyde Derivatives in Drug-Induced Liver Injury

doi: 10.3390/metabo12090852

Figure Lengend Snippet: Production of mitochondrial superoxide and superoxide dismutase expression (SOD) in response to the accumulation of oxidative stress in HepG2 cells. Mitochondrial superoxide was measured after exposure to increasing concentrations of pazopanib ( A ), sunitinib ( B ), P-CHO ( C ), or S-CHO ( D ) with or without BSO that depleted intracellular glutathione. Response to the oxidative stress accumulation after 20 µM of P-CHO and S-CHO was evaluated by means of the relative gene expression of SOD1 ( E , F , respectively) and SOD2 ( G , H , respectively) measured in HepG2 cells cultured in either glucose or galactose media and incubated for either two or six hours. Expression levels are expressed as a fold-change compared with controls and results from two or three independent experiments (mean ± s.d.). * p value < 0.05 for BSO vs. non-BSO comparison. # p value < 0.05 for comparison with non-treated cells.

Article Snippet: Sunitinib L-malate and pazopanib hydrochloride (HCl) were purchased from Alsachim (Illkirch Graffenstaden, France, purity > 98%).

Techniques: Expressing, Gene Expression, Cell Culture, Incubation, Comparison

Journal: Metabolites

Article Title: Biological Role of Pazopanib and Sunitinib Aldehyde Derivatives in Drug-Induced Liver Injury

doi: 10.3390/metabo12090852

Figure Lengend Snippet: Pazopanib aldehyde interaction with NADPH-cytochrome P450 oxidoreductase. The structure of the POR enzyme (PDB reference: 3QFS ) is depicted here with the major cofactors NADP and FAD. The enlarged view focuses on His583 modified by P-CHO after incubation with microsomes.

Article Snippet: Sunitinib L-malate and pazopanib hydrochloride (HCl) were purchased from Alsachim (Illkirch Graffenstaden, France, purity > 98%).

Techniques: Modification, Incubation

Journal: Oncology Reports

Article Title: Development of patient-derived tumor organoids and a drug testing model for renal cell carcinoma

doi: 10.3892/or.2021.8177

Figure Lengend Snippet: Analysis of the antitumor effects of TKIs in RCC tumor organoids. (A) Analysis of cancer cell viability using colorimetric CellTiter assay in OR009, OR011, OR013 and OR024 tumor organoids treated with the TKIs, sunitinib, axitinib, pazopanib, sorafenib and cabozantinib, for 72 h. (B) GI 50 for each TKI in RCC TO models using GraphPrism 8.0. TKI, tyrosine kinase inhibitor; RCC, renal cell carcinoma; TO, tumor organoid; GI 50 , drug concentration that inhibited the growth of cancer cells by 50%.

Article Snippet: The TOs were grown in flat-bottom 96-well plates (Corning, Inc.) at 37°C in a 5% CO 2 atmosphere and treated with various concentrations (0.1, 0.5, 1, 5, 10, 50, 100 and 500 μM) sunitinib (#PZ0012, Sigma-Aldrich; Merck KGaA), pazopanib (#12097, Cayman Chemical Company), cabozantinib (#C8999, LC Laboratories), axitinib (#PZ0193, Sigma-Aldrich; Merck KGaA) and sorafenib (#CS0164, Chemscene) for 72 h. TO proliferation was measured using a CellTiter 96 ® AQueous One Solution Cell Proliferation assay (#93582, Promega Corporation).

Techniques: Concentration Assay

Journal: British Journal of Pharmacology

Article Title: Effects of receptor tyrosine kinase inhibitors on VEGF 165 a- and VEGF 165 b-stimulated gene transcription in HEK-293 cells expressing human VEGFR2

doi: 10.1111/bph.13116

Figure Lengend Snippet: The effect of selected RTKIs on VEGF-stimulated firefly luciferase production in VEGFR2 NFAT cells

Article Snippet: Vandetanib, pazopanib, cediranib and sorafenib were supplied by Sequoia Research Products (Pangbourne, UK).

Techniques: Luciferase, Inhibition, Binding Assay, Purification

Journal: British Journal of Pharmacology

Article Title: Effects of receptor tyrosine kinase inhibitors on VEGF 165 a- and VEGF 165 b-stimulated gene transcription in HEK-293 cells expressing human VEGFR2

doi: 10.1111/bph.13116

Figure Lengend Snippet: The effect of selected RTKIs on NFAT gene transcription stimulated by 1 nM VEGF 165 a. VEGFR2 NFAT cells were treated with (A) cediranib, (B) pazopanib, (C) vandetanib or (D) sorafenib. Data are mean ± SEM of five separate experiments. Data are expressed as a percentage of the response to 1 nM VEGF 165 a in the absence of RTKIs. Each individual experiment was performed in quadruplicate.

Article Snippet: Vandetanib, pazopanib, cediranib and sorafenib were supplied by Sequoia Research Products (Pangbourne, UK).

Techniques:

Journal: British Journal of Pharmacology

Article Title: Effects of receptor tyrosine kinase inhibitors on VEGF 165 a- and VEGF 165 b-stimulated gene transcription in HEK-293 cells expressing human VEGFR2

doi: 10.1111/bph.13116

Figure Lengend Snippet: The effect of RTKIs on VEGF 165 a concentration–response curves. VEGFR2 NFAT cells were treated with (A) pazopanib, (B) vandetanib, (C) cediranib or (D) sorafenib for 1 h prior to the addition of increasing concentrations of VEGF 165 a. Data are mean ± SEM of five (A and B), six (C) or seven (D) replicate experiments. Each individual experiment was performed in quadruplicate. Global analysis of the combined data presented for each RTKI (A–D; extra sum of squares F -test) indicated that there was only a significant difference in the EC 50 values for cetiranib ( P < 0.05). In contrast, there was a significant decrease in E max with all four RTKIs ( P < 0001; Figure 3; extra sum of squares F -test).

Article Snippet: Vandetanib, pazopanib, cediranib and sorafenib were supplied by Sequoia Research Products (Pangbourne, UK).

Techniques: Concentration Assay

Journal: British Journal of Pharmacology

Article Title: Effects of receptor tyrosine kinase inhibitors on VEGF 165 a- and VEGF 165 b-stimulated gene transcription in HEK-293 cells expressing human VEGFR2

doi: 10.1111/bph.13116

Figure Lengend Snippet:

Article Snippet: Vandetanib, pazopanib, cediranib and sorafenib were supplied by Sequoia Research Products (Pangbourne, UK).

Techniques:

Journal: British Journal of Pharmacology

Article Title: Effects of receptor tyrosine kinase inhibitors on VEGF 165 a- and VEGF 165 b-stimulated gene transcription in HEK-293 cells expressing human VEGFR2

doi: 10.1111/bph.13116

Figure Lengend Snippet: Effect of RTKIs on VEGF 165 a concentration–response parameters

Article Snippet: Vandetanib, pazopanib, cediranib and sorafenib were supplied by Sequoia Research Products (Pangbourne, UK).

Techniques: Concentration Assay