Imatinib mesylate induces quiescence in gastrointestinal stromal tumor cells through the CDH1-SKP2-p27Kip1 signaling axis.

Gastrointestinal stromal tumors (GIST) are caused by activating mutations in the KIT or platelet-derived growth factor receptor alpha receptor tyrosine kinase genes. Approximately 85% of GIST patients treated with imatinib mesylate achieve disease stabilization, however, often in the presence of residual tumor masses. Complete remissions are rare and a substantial proportion of patients develop resistance to imatinib.

Histone H2AX is a mediator of gastrointestinal stromal tumor cell apoptosis following treatment with imatinib mesylate.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and are caused by activating mutations of the KIT or platelet-derived growth factor receptor alpha (PDGFRA) tyrosine kinases. GISTs can be successfully treated with imatinib mesylate, a selective small-molecule protein kinase inhibitor that was first clinically approved to target the oncogenic BCR-ABL fusion protein kinase in chronic myelogenous leukemia, but which also potently inhibits KIT and PDGFR family members. The mechanistic events by which KIT/PDGFRA kinase inhibition leads to clinical responses in GIST patients are not known in detail.

Glycemic and insulinemic meal responses modulate postprandial hepatic and intestinal lipoprotein accumulation in obese, insulin-resistant subjects.

Background: Exacerbated postprandial lipemia is a risk factor for cardiovascular disease and is linked to insulin status. Limited data on the effect of dietary carbohydrate on postprandial lipoprotein accumulation are available.

Objective: We tested the hypothesis that dietary carbohydrates with different glucose availability alter postprandial lipoprotein metabolism differently in obese, insulin-resistant subjects.