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Full-Text Articles in Medicine and Health Sciences
Bim Mediates Imatinib-Induced Apoptosis Of Gastrointestinal Stromal Tumors: Translational Implications, David Reynoso
Bim Mediates Imatinib-Induced Apoptosis Of Gastrointestinal Stromal Tumors: Translational Implications, David Reynoso
Dissertations & Theses (Open Access)
Gastrointestinal stromal tumors (GISTs) are oncogene-addicted cancers driven by activating mutations in the genes encoding receptor tyrosine kinases KIT and PDGFR-α. Imatinib mesylate, a specific inhibitor of KIT and PDGFR-α signaling, delays progression of GIST, but is incapable of achieving cure. Thus, most patients who initially respond to imatinib therapy eventually experience tumor progression, and have limited therapeutic options thereafter. To address imatinib-resistance and tumor progression, these studies sought to understand the molecular mechanisms that regulate apoptosis in GIST, and evaluate combination therapies that kill GISTs cells via complementary, but independent, mechanisms. BIM (Bcl-2 interacting mediator …
Biological Mechanisms And Clinical Implications Of Bcr-Abl-Induced Mitochondrial Oxidative Stress And Cell Survival In Chronic Myeloid Leukemia, Hui Zhang
Dissertations & Theses (Open Access)
Chronic myeloid leukemia (CML), a myeloproliferative disorder, represents approximately 15-20% of all adult leukemia. The development of CML is clearly linked to the constitutively active protein-tyrosine kinase BCR-ABL, which is encoded by BCR-ABL fusion gene as the result of chromosome 9/22 translocation (Philadelphia chromosome). Previous studies have demonstrated that oxidative stress-associated genetic, metabolic and biological alterations contribute to CML cell survival and drug refractory. Mitochondria and NAD(P)H oxidase (NOX) are the major sources of BCR-ABL-induced cellular reactive oxygen species (ROS) production. However, it is still unknown how CML cells maintain the altered redox status, while escaping from the persistent oxidative …