Project description:We established 3 types of primary xenograft models (KURC;Kyoto University Renal Cancer-1,2,3) derived from human renal cell carcinoma tissues, and 40 mg/day of sunitinib was orally administered. We performed microarray analysis to compare the gene expression profile of sunitinib-treated primary xenograft tumors (sensitive or resistant status) with that of vehicle-treated.
Project description:We performed microarray analysis to compare the gene expression profile of sunitinib-treated primary xenograft tumors (sensitive or resistant status) with that of vehicle-treated.
Project description:We kept a primary xenograft models (KURC;Kyoto University Renal Cancer-3) derived from human renal cell carcinoma tissues, and 10 mg/kg of temsirolimus or vehicle was intraperitoneally administered.We performed DNA methylation analysis to compare the methylation profile of temsirolimus-treated primary xenograft tumors with that of vehicle-treated.
Project description:We kept 2 types of primary xenograft models (KURC;Kyoto University Renal Cancer-1,3) derived from human renal cell carcinoma tissues, and 10 mg/kg of temsirolimus or vehicle was intraperitoneally administered.We performed microarray analysis to compare the gene expression profile of temsirolimus-treated primary xenograft tumors with that of vehicle-treated.
Project description:In this project, we generated chronic sunitinib-treated 786-O cell, a renal cell carcinoma cell line. In order to investigate the possible effect of GPR30 agonist, G-1, on the growth-inhibtion related signaling pathways, we treated either parental both parental and chronic sunitinib-treated 786-O cells were treated either by vehicle-only (i.e. 0.1% DMSO) or 2 μM G-1 for 48 h. Therefore, there were three groups for comparison, including G-1 treatment (G-1 vs. parental), chronic sunitinib-treatment (SunR vs. parental), and G-1 treatment in SunR cells (SunR&G-1 vs. parental).
Project description:The aim of this study was to investigate the effect of VEGF targeted therapy (sunitinib) on intratumoral heterogeneity (ITH) in metastatic clear cell renal cancer (mRCC). To explore ITH in detail, multiple tumor samples were taken from the primary renal tumors of mRCC patients who were sunitinib treated (n=23) or untreated (n=23). ITH of pathological grade, DNA (using array-based comparative genomic hybridisation), RNA (Illumina Beadarray) and protein (reverse phase protein array) were evaluated. Tumor grade heterogeneity was greater in treated compared to untreated tumors (P=0.002). Unsupervised and supervised analysis, for renal cancer driver, hypoxia and stromal gene signatures, was then performed. In untreated patient tumor samples, significant ITH occurred in chromosomal aberrations, RNA and protein expression, with clustering of DNA and RNA correlating for individual patients. In unsupervised analysis sunitinib therapy was not associated with increased ITH in DNA or RNA. However there was an increase in ITH for the driver mutation and hypoxia gene signatures (DNA and RNA) as well as increasing variability of protein expression with treatment (p<0.05). Despite this variability, significant chromosomal and RNA changes to targets of sunitinib, such as VHL, PBRM1 and CAIX, occurred in the treated samples. Together these findings suggest that sunitinib treatment has significant effects on the expression and ITH of key tumor and treatment specific genes. The results do not support the hypothesis that resistant clones are selected and predominate after initiation of targeted therapy; instead it appears that an initial clonal diversification occurs, supporting the hypothesis of polyclonal drug resistance. 128 samples from patients with clear cell renal cell carcinoma, including biological replicates of nephrectomy samples. Source of samples includes both biopsy and nephrectomy. DNA extracted from FFPE and fresh frozen tissue samples.
Project description:Gene Evaluation of DNA expression from snap-frozen renal cell cancer tissue from 5 patients with locally advanced non-metastatic tumors, submitted to nephrectomy after being treated with 2 cycles of neoadjuvant Sunitinib were compared to match controls comprising of 6 patients with no neoadjuvant intervension using microarray platform Affymetrix Human Genome U133 Plus 2.0 containing 54675 probes. Validation followed using qRT-PCR Exploratory, prospective evaluation of gene expression in renal cell tumor snap frozen tissue after neoadjuvant Sunitinib compared to a control group with no neoadjuvant treatment
