Project description:To reveal mechanisms for acquired imatinib resistance in gastrointestinal stromal tumor (GIST), we have analyzed several cell lines with resistance to imatinib.
Project description:The heterogeneous nature of tumors presents a considerable obstacle in addressing imatinib resistance in advanced cases of gastrointestinal stromal tumors (GIST). To address this issue, we conducted single-cell RNA-sequencing in primary tumors as well as peritoneal and liver metastases from patients diagnosed with locally advanced or advanced GIST. Single-cell transcriptomic signatures of tumor microenvironment (TME) were analyzed. This analysis revealed unique tumor evolutionary patterns, transcriptome features, dynamic cell-state changes, and different metabolic reprogramming.
Project description:siRNA knock-down of ZNF genes determined to impact gastrointestinal stromal tumor response to imatinib were used to determine functional significance of ZNFs and identify key targets related to imatinib resistance.
Project description:We performed miRNA expression profiling in a series of fresh-frozen neoadjuvantly imatinib treated gastrointestinal stromal tumors (GIST), using a microarray approach. Significant differentially expressed miRNAs among imatinib-resistant and imatinib-sensitive groups were identified using SAM analysis.
Project description:siRNA knock-down of ZNF genes determined to impact gastrointestinal stromal tumor response to imatinib were used to determine functional significance of ZNFs and identify key targets related to imatinib resistance. exploratory array design to identify candidate effector genes for targeted study
Project description:We performed microRNA expression profiling in a series of fresh-frozen neoadjuvantly imatinib-treated and non-treated gastrointestinal stromal tumors (GIST), using a microarray approach. Significant differentially expressed microRNAs among imatinib-treated and non-treated groups were identified using SAM analysis.
Project description:We performed miRNA expression profiling in a series of fresh-frozen neoadjuvantly imatinib treated gastrointestinal stromal tumors (GIST), using a microarray approach. Significant differentially expressed miRNAs among imatinib-resistant and imatinib-sensitive groups were identified using SAM analysis. Agilent microarray platform with probes matching 903 human miRNAs was used to determine miRNA expression profiles in 17 GISTs (imatinib-sensitive and 7 imatinib-resistant). To validate the microarray platform, the expression levels of selected miRNAs were evaluated using qRT-PCR.
Project description:Gastrointestinal Stromal Tumor frequently harbor mutations in the KIT receptor tyrosine kinase and depend on its activity for growth. This underlies the efficacy of imatinib, a inhibitor of KIT activity, in GIST management. GIST882 is a patient derived GIST cell line that harbor a K640E exon 13 KIT mutation and is sensitive to imatinib treatment. To analyze the downstream effect of KIT inhibition, GIST882 cells were treated for 8 hours with 1μM Imatinib.
Project description:Gastrointestinal Stromal Tumor frequently harbor mutations in the KIT receptor tyrosine kinase and depend on its activity for growth. This underlies the efficacy of imatinib, a inhibitor of KIT activity, in GIST management. GIST882 is a patient derived GIST cell line that harbor a K640E exon 13 KIT mutation and is sensitive to imatinib treatment. To analyze the downstream effect of KIT inhibition, GIST882 cells were treated for 8 hours with 1μM Imatinib. GIST882 cells were treated in triplicate with 0.1% DMSO or 1μM Imatinib for 8 hours. RNA was isolated and analyzed by Illumina Human HT-12 beadarray.
