Immediate action of imatinib mesylate on calcium signaling in gastrointestinal stromal tumors (GIST).
2011
e20503 Background: In the majority of gastrointestinal stromal tumors (GISTs) mutation in tyrosine kinase receptors, c-KIT or PDGFRA, is thought to be the primary event. Both of these receptors are targets of tyrosine kinase inhibitors (TKIs) like imatinib mesylate. Downstream of the receptors the cellular signaling machinery is still obscure. In many cell types, including interstitial cells of Cajal, intracellular calcium (Cai) is accepted as an essential part of cell signaling and cellular function, including apoptosis. In this study we have evaluated Cai handling using electrophysiology and cell imaging in primary gastric GISTs. Methods: GIST cell cultures were prepared from primary untreated GISTs taken directly from surgery. Samples were also taken for pathology examination, verifying GIST diagnosis, and analyzed for mutations, showing a c-KIT exon 11 mutation in all included material. Measurements of Cai by Fura-2/AM fluorescence, patch-clamp techniques and molecular biology techniques were used in ...
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