Journal: PLoS ONE

Article Title: Evaluation of Tyrosine Kinase Inhibitor Combinations for Glioblastoma Therapy

doi: 10.1371/journal.pone.0044372

Figure Lengend Snippet: Fold change in proliferation is shown for 020913 (A) and 060919 (B) cells when treated with FDA-approved RTK inhibitors at 25% of their IC 50 concentration. Combination of gefitinib (5 µM) and sunitinib (10 µM) demonstrate synergism in inhibiting cell growth. Other combinations of gefitinib and imatinib (15 µM), sunitinib and sorafenib (1 µM), and imatinib and sunitinib also showed increased growth inhibition of GBM cells. C and D: Caspase 3/7 assay demonstrating that sunitinib alone induces caspase 3/7 expression in 020913 cells (C) and 060919 cells (D), whereas treatment with Gefitinib, Imatinib and Sorafenib did not show caspase 3/7 release. Also, combinations containing sunitinib did not demonstrate an increased caspase release.

Article Snippet: Sunitinib malate (SutentTM) and sorafenib p -toluenesulfonate (NexavarTM) were purchased from LC laboratories (Woburn, MA).

Techniques: Concentration Assay, Inhibition, Expressing

Journal: PLoS ONE

Article Title: Evaluation of Tyrosine Kinase Inhibitor Combinations for Glioblastoma Therapy

doi: 10.1371/journal.pone.0044372

Figure Lengend Snippet: The drug was withdrawn after 24 hours and the cells were allowed to grow for 2 weeks. Treated cells were analyzed for their growth kinetics using alamar blue assay. GBM cells treated with the RTK combination consisting of gefitinib and sunitinib were unable to re-grow, whereas GBM cells treated with other drugs or combinations survived and re-grew. Analysis of neurosphere formation ability demonstrated that 020913 cells treated with gefitinib (C) or sunitinib (D) or other combinations like sunitinib and sorafenib (F) could form neurospheres after withdrawal of the drug, whereas cells treated with gefitinib and sunitinib (E) could not form any neurospheres.

Article Snippet: Sunitinib malate (SutentTM) and sorafenib p -toluenesulfonate (NexavarTM) were purchased from LC laboratories (Woburn, MA).

Techniques: Alamar Blue Assay

Journal: PLoS ONE

Article Title: Evaluation of Tyrosine Kinase Inhibitor Combinations for Glioblastoma Therapy

doi: 10.1371/journal.pone.0044372

Figure Lengend Snippet: A. Combining receptor tyrosine kinase inhibitors suppress downstream effectors of growth factor signaling. p-STAT3 was blocked only by the combination treatment, whereas p-AKT was blocked by all the drugs either as single agents or in combinations. The combinations of gefitinib and sunitinib as well as sunitinib and sorafenib were able to inhibit p-AKT, p-MAPK and p-STAT3 in both the GBM oncosphere lines.

Article Snippet: Sunitinib malate (SutentTM) and sorafenib p -toluenesulfonate (NexavarTM) were purchased from LC laboratories (Woburn, MA).

Techniques:

Journal: PLoS ONE

Article Title: Evaluation of Tyrosine Kinase Inhibitor Combinations for Glioblastoma Therapy

doi: 10.1371/journal.pone.0044372

Figure Lengend Snippet: ). Gefitinib alone could significantly (p = 0.0001) improve survival in the animals compared to control animals. Sunitinib did not show any efficacy either when used alone (p = 0.13, compared to control) or when combined with gefitinib (p = 0.18, compared to gefitinib alone). Rats were implanted intracranially with 9L tumor 1 mm 3 tumor pieces. Rats were then treated with gefitinib (50 mg/kg), sunitinib (8 mg/kg) and a combination of gefitinib (50 mg/kg) and sunitinib (8 mg/kg). None of the drugs including the combination of gefitinib and sunitinib showed any efficacy (p = 0.9).

Article Snippet: Sunitinib malate (SutentTM) and sorafenib p -toluenesulfonate (NexavarTM) were purchased from LC laboratories (Woburn, MA).

Techniques: Control

Journal: Oncotarget

Article Title: Dynamic epigenetic changes to VHL occur with sunitinib in metastatic clear cell renal cancer

doi: 10.18632/oncotarget.8308

Figure Lengend Snippet: a. Comparison of biopsy and nephrectomy for all patients. Target label displayed in each subplot. False discovery rate (FDR) is provided in parenthesis. NA = no methylation core was present, either because the target's regions were filtered due to low average counts, or because no methylation cores were present for the target in the methylome map. If there was more than one region for a certain target, the Figure only shows the most significantly differential region according to P -value. VHL is the only target that has FDR under the 0.1 significance level ( i.e. 0.077). The P -value is 0.00086 and the logFC -0.8734. The latter implies that the post-treatment samples are more methylated in average than the pre-treatment ones. This is only the case for the methylation core in the VHL promoter region 7896829 located from nt 10183068 to nt 10183220 on chromosome 3; other VHL regions are not found to be differentially methylated under this significance level. b. Per patient methylation of VHL at region 7896829. For all samples methylation was greater in the post-treatment nephrectomy samples than the pre-treatment biopsy. Results divided into patients who had a good or poor response to treatment, there was no significant difference in the VHL hypermethylation seen in patients with a good vs poor response to sunitinib ( P = 0.896, Student's t -test).

Article Snippet: Primary tumor tissue (the “sunitinib set”) was collected and snap frozen from mccRCC patients treated with three cycles of pre-surgical sunitinib (SutentTM, Pfizer, Sandwich, UK), for 18 weeks, as a translational endpoint of a previously reported prospective clinical trial (SuMR; NCT01024205) [ ].

Techniques: Comparison, Methylation