Journal: Oncotarget

Article Title: The addition of abemaciclib to sunitinib induces regression of renal cell carcinoma xenograft tumors

doi: 10.18632/oncotarget.19618

Figure Lengend Snippet: 786-O (A) and Caki-1 (B) cells were treated with single agent therapy, or in combination with sunitinib. Cellular viability was determined by CellTiter-Glo ® .

Article Snippet: After 5 weeks of treatment, mice in the vehicle cohort and mice in the sunitinib cohort were treated with the combination of sunitinib 40 mg/kg and abemaciclib 100 mg/kg (HY-16297, Medchemexpress) for an additional 4 weeks.

Techniques:

Journal: Oncotarget

Article Title: The addition of abemaciclib to sunitinib induces regression of renal cell carcinoma xenograft tumors

doi: 10.18632/oncotarget.19618

Figure Lengend Snippet: 786-O cells were treated with DMSO (A) , sunitinib (B) , abemaciclib (C) , or abemaciclib + sunitinib (D) . Cells were stained for annexin V and positivity determined by flow cytometry.

Article Snippet: After 5 weeks of treatment, mice in the vehicle cohort and mice in the sunitinib cohort were treated with the combination of sunitinib 40 mg/kg and abemaciclib 100 mg/kg (HY-16297, Medchemexpress) for an additional 4 weeks.

Techniques: Staining, Flow Cytometry

Journal: Oncotarget

Article Title: The addition of abemaciclib to sunitinib induces regression of renal cell carcinoma xenograft tumors

doi: 10.18632/oncotarget.19618

Figure Lengend Snippet: In 786-O cells (A) and Caki-1 cells (B) abemaciclib exposure results in increased PARP cleavage. This effect is more rapid and pronounced when abemaciclib is combined with sunitinib.

Article Snippet: After 5 weeks of treatment, mice in the vehicle cohort and mice in the sunitinib cohort were treated with the combination of sunitinib 40 mg/kg and abemaciclib 100 mg/kg (HY-16297, Medchemexpress) for an additional 4 weeks.

Techniques:

Journal: Oncotarget

Article Title: The addition of abemaciclib to sunitinib induces regression of renal cell carcinoma xenograft tumors

doi: 10.18632/oncotarget.19618

Figure Lengend Snippet: 786-O cells were treated with DMSO (A) , sunitinib (B) , abemaciclib (C) , or abemaciclib + sunitinib (D) . Pictures were taken after 24 hours of treatment. Magnification factor is 20X.

Article Snippet: After 5 weeks of treatment, mice in the vehicle cohort and mice in the sunitinib cohort were treated with the combination of sunitinib 40 mg/kg and abemaciclib 100 mg/kg (HY-16297, Medchemexpress) for an additional 4 weeks.

Techniques:

Journal: Oncotarget

Article Title: The addition of abemaciclib to sunitinib induces regression of renal cell carcinoma xenograft tumors

doi: 10.18632/oncotarget.19618

Figure Lengend Snippet: Mice with xenograft RCC tumors were treated with sunitinib or vehicle. (A) Tumor size in individual mice. Mice were treated with vehicle or sunitinib as labelled and tumor size measured with calipers. (B) Mean tumor size in each treatment cohort. Error bars are standard deviation. The trend lines are shown within each group. P-value is for difference in slope over the course of the therapy.

Article Snippet: After 5 weeks of treatment, mice in the vehicle cohort and mice in the sunitinib cohort were treated with the combination of sunitinib 40 mg/kg and abemaciclib 100 mg/kg (HY-16297, Medchemexpress) for an additional 4 weeks.

Techniques: Standard Deviation

Journal: Oncotarget

Article Title: The addition of abemaciclib to sunitinib induces regression of renal cell carcinoma xenograft tumors

doi: 10.18632/oncotarget.19618

Figure Lengend Snippet: Mice with xenograft RCC tumors were first treated with sunitinib or vehicle. At the end of treatment, all mice were treated with combination abemaciclib/sunitinib. (A) Tumor size in individual mice. (B) Mean tumor size in each treatment cohort. Error bars represent standard deviation. The trend lines are shown within each group.

Article Snippet: After 5 weeks of treatment, mice in the vehicle cohort and mice in the sunitinib cohort were treated with the combination of sunitinib 40 mg/kg and abemaciclib 100 mg/kg (HY-16297, Medchemexpress) for an additional 4 weeks.

Techniques: Standard Deviation

Journal: Oncotarget

Article Title: The addition of abemaciclib to sunitinib induces regression of renal cell carcinoma xenograft tumors

doi: 10.18632/oncotarget.19618

Figure Lengend Snippet: After a course of sunitinib, mice were subsequently treated with combination abemaciclib/sunitinib and tumor response determined by measurement with calipers. (A) Individual responses, each line represents an individual mouse. (B) Mean response of cohort. Error bars represent standard error of the mean.

Article Snippet: After 5 weeks of treatment, mice in the vehicle cohort and mice in the sunitinib cohort were treated with the combination of sunitinib 40 mg/kg and abemaciclib 100 mg/kg (HY-16297, Medchemexpress) for an additional 4 weeks.

Techniques:

Journal: Human molecular genetics

Article Title: High-throughput screening uncovers miRNAs enhancing glioblastoma cell susceptibility to tyrosine kinase inhibitors.

doi: 10.1093/hmg/ddx323

Figure Lengend Snippet: Figure 1. MiR-302/520 miRNA family increases susceptibility of GBM cells to sunitinib treatment. a) Overview

Article Snippet: Temozolomide and the multitargeted tyrosine kinase inhibitors sunitinib malate and axitinib were acquired from Selleckchem (Houston, USA) and stored at 20 C in DMSO.

Techniques:

Journal: Human molecular genetics

Article Title: High-throughput screening uncovers miRNAs enhancing glioblastoma cell susceptibility to tyrosine kinase inhibitors.

doi: 10.1093/hmg/ddx323

Figure Lengend Snippet: Figure 3. Combination of miRNA-302a/520b expression with multitargeted tyrosine kinase inhibitors decreases GBM cell viability. U87 and DBTRG cells were transfected with 50 nM of miRNA-302a, miR-520b or

Article Snippet: Temozolomide and the multitargeted tyrosine kinase inhibitors sunitinib malate and axitinib were acquired from Selleckchem (Houston, USA) and stored at 20 C in DMSO.

Techniques: Expressing, Transfection

Journal: Human molecular genetics

Article Title: High-throughput screening uncovers miRNAs enhancing glioblastoma cell susceptibility to tyrosine kinase inhibitors.

doi: 10.1093/hmg/ddx323

Figure Lengend Snippet: Figure 5. Cellular DNA content increases upon miR-302a transfection and treatment with multitargeted tyrosine kinase inhibitors. Cells were incubated with miR-302a or control miRNA (cel-miR-239b) mimics for

Article Snippet: Temozolomide and the multitargeted tyrosine kinase inhibitors sunitinib malate and axitinib were acquired from Selleckchem (Houston, USA) and stored at 20 C in DMSO.

Techniques: Transfection, Incubation, Control

Journal: Nature Communications

Article Title: Simultaneously discovering the fate and biochemical effects of pharmaceuticals through untargeted metabolomics

doi: 10.1038/s41467-023-40333-7

Figure Lengend Snippet: a Pearson’s correlation-based network of putative sunitinib-related features ( n = 29 biologically independent samples). Edges present when Holm adjusted p value < 0.05 and R ≥ 0.75, node size is proportional to its degree of connectivity. Node colour highlights molecular ions ([M + H] + /[M − H] − ) of sunitinib (orange), molecular ions of biotransformation products of sunitinib (green), alternate ion forms (adducts and isotopes) of sunitinib or biotransformation products (pale blue), and unannotated features (dark blue). Node shape distinguishes between annotations based on MS 1 data only (circle) vs. more confident annotations also based on MS data ( triangle). The high density of this network is implicit of the expected strong correlations between features representing a single compound and chemically-related compounds. b The overlap of sunitinib biotransformation products reported in published literature , predicted by the ‘Generate Expected Compounds’ tool of Compound Discoverer (Thermo Scientific), and by SyGMa , and detected by untargeted metabolomics. c Number of molecular formulae-annotated (putative annotation) (purple) and structurally-annotated (MSI level 2) (green) biotransformation products of sunitinib detected by each UHPLC-MS metabolomics assay. The bars are annotated with the total number of biotransformation products detected by each UHPLC-MS metabolomics assay. d The proportion of Phase I (yellow) and Phase II (magenta) biotransformation products of sunitinib detected across all assays. e Representative comparison of measured MS fragmentation spectra for sunitinib in rat plasma (top) vs authentic chemical standard of sunitinib (bottom) and the corresponding MetFrag-annotated structures of major peaks. f A biotransformation map of sunitinib showing the biotransformation products discovered in the rat plasma UHPLC-MS untargeted metabolomics dataset (data from four assays – HILIC positive (*)/negative (†), RP C 18 positive (‡)/negative (§)) by the untargeted ADME/TK workflow. The colour of the arrow denotes type of transformation– Phase I (yellow) or Phase II (magenta). Extracted ion chromatograms and MS fragmentation spectra for these compounds are displayed in Supplementary Figs. and .

Article Snippet: Sunitinib malate was purchased from Carbosynth Ltd (UK).

Techniques: Comparison, Clinical Proteomics, Hydrophilic Interaction Liquid Chromatography, Transformation Assay

Journal: Nature Communications

Article Title: Simultaneously discovering the fate and biochemical effects of pharmaceuticals through untargeted metabolomics

doi: 10.1038/s41467-023-40333-7

Figure Lengend Snippet: a Relationship between UHPLC-MS untargeted metabolomics peak intensity measurements of sunitinib (HILIC positive assay) and the absolute quantification of sunitinib using conventional targeted LC-MS/MS. b Mean peak intensity (cross) of sunitinib over the duration of the 15-day study, as measured by UHPLC-MS untargeted metabolomics. Individual data points are also displayed (open circle). Error bars show standard error. Arrows indicate time of dosing. c Median peak intensities, measured by UHPLC-MS untargeted metabolomics and scaled by unit variance, of sunitinib and its biotransformation products over the duration of the 15-day exposure study, clustered by an unsupervised k-means approach ( k = 6, optimal value determined by the Elbow Method). Cluster 1: M11, M15, M17, and M19. Cluster 2: sunitinib, M1, M2 and M9. Cluster 3: M16. Cluster 4: M7. Cluster 5: M5, M8, M13 and M20. Cluster 6: M3, M4, M6, M12, M14, and M18. Statistical analysis ( b , c ) was conducted by one-way ANOVA followed by Tukey’s post-hoc test. Significance is displayed as follows: * p < 0.05 vs. day 1, † p < 0.05 vs. day 2, ‡ p < 0.05 vs. day 4, ¥ p < 0.05 vs. day 8). Specifically, b p = 0.019 (day 15 vs. day 4) and p = 0.0435 (day 15 vs. day 8); c , cluster 1: p = 0.0001 (day 4 vs day 1), p = 0.0010 (day 8 vs. day 1), p = 0.0046 (day 15 vs. day 4) and p = 0.0382 (day 15 vs. day 8); cluster 2: p = 0.0491 (day 2 vs. day 1), p = 0.0001 (day 4 vs. day 1), p ≤ 0.0001 (day 8 vs. day 1), p = 0.0015 (day 15 vs. day 2), p ≤ 0.0001 (day 15 vs. day 4 and day 15 vs. day 8); cluster 6: p = 0.0001 (day 8 vs. day 1), p = 0.0001 (day 15 vs. day 2), p = 0.0001 (day 15 vs. day 4), p < 0.0001 (day 15 vs. day 8). N = 5 individual animals on days 1, 2, 4, and 8; n = 9 individual animals on day 15. Source data for this figure are provided in the file.

Article Snippet: Sunitinib malate was purchased from Carbosynth Ltd (UK).

Techniques: Hydrophilic Interaction Liquid Chromatography, Quantitative Proteomics, Liquid Chromatography with Mass Spectroscopy

Journal: Nature Communications

Article Title: Simultaneously discovering the fate and biochemical effects of pharmaceuticals through untargeted metabolomics

doi: 10.1038/s41467-023-40333-7

Figure Lengend Snippet: PCA scores and loadings plots of plasma samples from rats exposed to sunitinib (red) for ( a ) 1 and ( b ) 15 days and time-matched biological control rats (blue) measured by HILIC UHPLC-MS in positive ion mode before and after removal of putative sunitinib-related features (green in loadings plots). c Correlation network of sunitinib and MSI level 2 annotated lipids: ceramides (cer), lysophosphatidylethanolamines (LPE), methyl phosphatidylcholine (MePC), phosphatidylcholines (PC), phosphatidylethanolamines (PE), phosphatidylserines (PS), sphingomyelins (SM/SPH) and triacylglycerols (TG), in cardiac tissue of rats exposed to sunitinib ( N = 5). Node size is proportional to its degree of connectivity. Edges represent significant Spearman’s correlation ( p < 0.05 and, | ρ | ≥ 0.9) between compounds. All nodes displayed are significantly correlated to sunitinib. d Box plots showing significantly increased plasma levels of four sphingomyelins found to be associated with sunitinib levels at the site of toxicity, in rats exposed to sunitinib (red) for 15 days, compared to time-matched biological controls (blue). Boxes show the interquartile range (IQR), with the line representing the median, and the whiskers showing 1.5× IQR. Data is from n = 9 individual animals. Fold change and q values (FDR-corrected p values calculated by Student’s two-tailed t -test) are displayed. Source data for ( d ) are provided in the file.

Article Snippet: Sunitinib malate was purchased from Carbosynth Ltd (UK).

Techniques: Clinical Proteomics, Control, Hydrophilic Interaction Liquid Chromatography, Two Tailed Test

Journal: Nature Communications

Article Title: Simultaneously discovering the fate and biochemical effects of pharmaceuticals through untargeted metabolomics

doi: 10.1038/s41467-023-40333-7

Figure Lengend Snippet: Euler diagram depicting in which biological samples (rat plasma, rat cardiac tissue, the intracellular extracts and culture medium of hiPSC-CM cultures) sunitinib and its biotransformation products were detected.

Article Snippet: Sunitinib malate was purchased from Carbosynth Ltd (UK).

Techniques: Clinical Proteomics

Journal: Journal of Experimental & Clinical Cancer Research : CR

Article Title: Y-box binding protein-1 is crucial in acquired drug resistance development in metastatic clear-cell renal cell carcinoma

doi: 10.1186/s13046-020-1527-y

Figure Lengend Snippet: Phenotypic difference between sunitinib-resistant and sensitive mccRCC. a Endothelial cells (HUVEC), sunitinib-sensitive Caki-1WT and sunitinib-conditioned Caki-1 DC were exposed to different concentrations of sunitinib (SUT), and cell viability was measured by MTS assay (IC 50 of HUVEC = 3.322 ± 0.558, Caki-1WT = 6.699 ± 0.781 and Caki-1 DC = 16.899 ± 1.383). b Phase contrast microscopy showing changes in cell morphology between Caki-1WT and Caki-1 DC. c Western blot showing increased protein levels of β-Catenin, SOX2 and GSK-3β that suggests cancer stem-cell like properties and epithelial-to-mesenchymal characteristics of Caki-1 DC vs. Caki-1WT. d Scratch assay showing increased migration of Caki-1 DC compared to Caki-1WT. e A schematic diagram showing the indirect and direct effects of sunitinib on cancer cells. Microscopic images were taken at 5X magnification. Data are mean ± SEM and normalised to matched controls. Results are representative of three independent experiments. * p < 0.05, ** p < 0.01

Article Snippet: The following reagents were purchased for this study: Sunitinib malate (Sutent, LC Laboratories, MA, USA); Elacridar (Toronto Research Chemicals, ON, CA); Mitomycin C and LY294002 (Sigma-Aldrich, MO, USA); AZD5363 and AZD8186 (Selleckchem, TX, USA); SL0101 (Calbiochem, CA, USA) and INK128 (Cayman Chemicals, MI, USA).

Techniques: MTS Assay, Microscopy, Western Blot, Wound Healing Assay, Migration

Journal: Journal of Experimental & Clinical Cancer Research : CR

Article Title: Y-box binding protein-1 is crucial in acquired drug resistance development in metastatic clear-cell renal cell carcinoma

doi: 10.1186/s13046-020-1527-y

Figure Lengend Snippet: Direct effect of sunitinib on mccRCC cells. The parental mccRCC cell-line, Caki-1WT, was exposed to different concentrations of sunitinib (SUT) for 24 h. a Significant increase in apoptosis of the cells was observed with increasing concentration of the drug, but the population of non-apoptotic dead cells among different treatment groups were not significant. b With increasing concentrations of SUT, decrease in proliferation was observed with G2M phase using DAPI staining. Data are average of three independent experiments, mean ± SEM and normalised to matched controls. * p < 0.05, ** p < 0.01, *** p < 0.001

Article Snippet: The following reagents were purchased for this study: Sunitinib malate (Sutent, LC Laboratories, MA, USA); Elacridar (Toronto Research Chemicals, ON, CA); Mitomycin C and LY294002 (Sigma-Aldrich, MO, USA); AZD5363 and AZD8186 (Selleckchem, TX, USA); SL0101 (Calbiochem, CA, USA) and INK128 (Cayman Chemicals, MI, USA).

Techniques: Concentration Assay, Staining

Journal: Journal of Experimental & Clinical Cancer Research : CR

Article Title: Y-box binding protein-1 is crucial in acquired drug resistance development in metastatic clear-cell renal cell carcinoma

doi: 10.1186/s13046-020-1527-y

Figure Lengend Snippet: Increased expression of YB-1 and ABCB-1 in sunitinib-resistant compared to sunitinib-sensitive phenotypes. a Western blot and RT-PCR results show significant increase in YB-1 and ABCB-1 protein and mRNA levels in Caki-1 DC compared to Caki-1WT. b Increased YB-1 and ABCB-1 was also observed by immunofluorescence staining evaluation. c Immunohistochemical staining of YB-1 and ABCB-1 in our acquired sunitinib-resistant mouse model ( n = 3–4) and patient samples ( n = 5–7). d Western blot and RT-PCR results of YB-1 knockdown in Caki-1WT and Caki-1 DC showing significant downregulation of YB-1 protein and mRNA levels. The protein expression of its downstream target, ABCB-1, also decreased but the mRNA level remained unchanged. Data are mean ± SEM. Immunohistochemical images at scale bar 100 μm. Results are representative of three independent experiments. * p < 0.05, ** p < 0.01, *** p < 0.0005, **** p < 0.0001

Article Snippet: The following reagents were purchased for this study: Sunitinib malate (Sutent, LC Laboratories, MA, USA); Elacridar (Toronto Research Chemicals, ON, CA); Mitomycin C and LY294002 (Sigma-Aldrich, MO, USA); AZD5363 and AZD8186 (Selleckchem, TX, USA); SL0101 (Calbiochem, CA, USA) and INK128 (Cayman Chemicals, MI, USA).

Techniques: Expressing, Western Blot, Reverse Transcription Polymerase Chain Reaction, Immunofluorescence, Staining, Immunohistochemical staining, Knockdown

Journal: Journal of Experimental & Clinical Cancer Research : CR

Article Title: Y-box binding protein-1 is crucial in acquired drug resistance development in metastatic clear-cell renal cell carcinoma

doi: 10.1186/s13046-020-1527-y

Figure Lengend Snippet: Inhibition of oncogenic pathways regulated aberrant expression of YB-1 and ABCB-1. a Different small-molecule inhibitors for Akt/PI3K, RSK and mTOR pathways show differential activation of Akt (phosphorylation at serine-473) and ABCB1 expression levels in Caki-1WT and Caki-1 DC. b Western blot results showing significant downregulation of YB-1 and ABCB-1 protein expression when treated with 0.5 μM INK128. c RT-PCR data shows a marked change in YB-1 mRNA level with 0.5 μM INK128 in Caki-1 DC compared to Caki-1WT, but no significant difference in ABCB-1 mRNA levels. d Cell viability assay demonstrating sensitization of Caki-1 DC cells to sunitinib. The response of Caki-1WT and Caki-1 DC are comparable, and a pronounced increase in cell death is observed with the combination therapy. e To simulate sequential treatment as applied in the clinic, Caki-1WT and Caki-1 DC were treated with different doses (0.25 μM, 0.5 μM and 1 μM) of INK128 for 48 h, washed off the drug with 1X PBS and then re-challenged with 5 μM SUT for 24 h to observe re-sensitization of Caki-1 DC to sunitinib. Our data shows significant cell death with sequential treatment and the drug-resistant phenotype Caki-1 DC had substantial effect, which is comparable to the parental Caki-1WT. SUT: sunitinib, AZD5363: Akt inhibitor, AZD8186: PI3K inhibitor, LY294002: Akt/PI3K pan inhibitor, SL0101: RSK inhibitor and INK128: mTOR inhibitor. Data are mean ± SEM and normalised to matched controls, n = 3–4 independent experiments. * p < 0.05, ** p < 0.01, *** p < 0.0005, **** p < 0.0001

Article Snippet: The following reagents were purchased for this study: Sunitinib malate (Sutent, LC Laboratories, MA, USA); Elacridar (Toronto Research Chemicals, ON, CA); Mitomycin C and LY294002 (Sigma-Aldrich, MO, USA); AZD5363 and AZD8186 (Selleckchem, TX, USA); SL0101 (Calbiochem, CA, USA) and INK128 (Cayman Chemicals, MI, USA).

Techniques: Inhibition, Expressing, Activation Assay, Phospho-proteomics, Western Blot, Reverse Transcription Polymerase Chain Reaction, Viability Assay

Journal: Journal of Experimental & Clinical Cancer Research : CR

Article Title: Y-box binding protein-1 is crucial in acquired drug resistance development in metastatic clear-cell renal cell carcinoma

doi: 10.1186/s13046-020-1527-y

Figure Lengend Snippet: ABCB-1 inhibitor, elacridar, increases the efficacy of sunitinib. a Cell viability assay of sunitinib-sensitive Caki-1WT and the conditioned cell-line Caki-1 DC showing that ABCB-1 inhibition with elacridar significantly decreased cell viability of Caki-1 DC, which is comparable to Caki-1WT and b ) Western blot showing slight increase of ABCB-1 protein level with sunitinib treatment in both Caki-1WT and Caki-1 DC, which did not change with elacridar. c Caki-1WT bearing embryos were treated with either vehicle, 10 μM SUT, 5 μM ELA or 10 μM SUT with 5 μM ELA combination treatment (left). The tumor size significantly decreased with SUT monotherapy and SUT with ELA combination treatment evaluated by optical image and optical coherence tomography (OCT) (bar-graph, right). d However, Caki-1 DC inoculated embryos responded only to 10 μM SUT and 5 μM ELA combination treatment and not to vehicle or monotherapies (bar-graph, right). SUT: sunitinib. ELA: elacridar. Data are mean ± SEM and normalised to matched controls, n = 3–5 independent experiments. Average of 3 to 5 CAM tumor bearing embryos. * p < 0.05, ** p < 0.005, *** p < 0.0005, **** p < 0.0001

Article Snippet: The following reagents were purchased for this study: Sunitinib malate (Sutent, LC Laboratories, MA, USA); Elacridar (Toronto Research Chemicals, ON, CA); Mitomycin C and LY294002 (Sigma-Aldrich, MO, USA); AZD5363 and AZD8186 (Selleckchem, TX, USA); SL0101 (Calbiochem, CA, USA) and INK128 (Cayman Chemicals, MI, USA).

Techniques: Viability Assay, Inhibition, Western Blot, Tomography

Journal: Journal of Experimental & Clinical Cancer Research : CR

Article Title: Y-box binding protein-1 is crucial in acquired drug resistance development in metastatic clear-cell renal cell carcinoma

doi: 10.1186/s13046-020-1527-y

Figure Lengend Snippet: In vivo study using out sunitinib-resistant mccRCC mouse model. a Mice with Caki-1WT tumor responded to low dose of SUT (40 mg/kg, dark blue line) compared to vehicle treated mice (light blue line). b Caki-1 DC tumors kept growing while on SUT treatment and the dose escalated (40 mg/kg to 80 mg/kg, orange line). The tumor continued to grow in high dose of SUT therapy but the size decreased with the 80 mg/kg SUT with 40 mg/kg ELA combination therapy (red line). c Immunohistochemical staining of Caki-1WT and DC tumors for YB-1 and ABCB-1. d A graph comparing the rate of tumor growth (slope) within the same group of mice injected with Caki-1 DC that received combination therapy. The rate of tumor growth substantially decreased with the initiation of combination therapy compared to monotherapy in the same animals. e Schematic diagram of our proposed mechanism of sunitinib-resistance development and a, potential, therapy option to overcome sunitinib-resistance. SUT: sunitinib. ELA: elacridar. Data as mean ± SEM, n = 5–6 animals/group.* p < 0.05, ** p < 0.005, *** p < 0.0005, **** p < 0.0001

Article Snippet: The following reagents were purchased for this study: Sunitinib malate (Sutent, LC Laboratories, MA, USA); Elacridar (Toronto Research Chemicals, ON, CA); Mitomycin C and LY294002 (Sigma-Aldrich, MO, USA); AZD5363 and AZD8186 (Selleckchem, TX, USA); SL0101 (Calbiochem, CA, USA) and INK128 (Cayman Chemicals, MI, USA).

Techniques: In Vivo, Immunohistochemical staining, Staining, Injection