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Adaphostin is a dihydroquinone derivative that is undergoing extensive preclinical testing as a potential anticancer drug. Previous studies have suggested that the generation of reactive oxygen species (ROS) plays a critical role in the cytotoxicity of this agent. In this study, we investigated the source of these ROS. Consistent with the known chemical(More)
Adaphostin (NSC 680410), an analog of the tyrphostin AG957, was previously shown to induce Bcr/abl down-regulation followed by loss of clonogenic survival in chronic myelogenous leukemia (CML) cell lines and clinical samples. Adaphostin demonstrated selectivity for CML myeloid progenitors in vitro and remained active in K562 cells selected for imatinib(More)
The farnesyltransferase inhibitor tipifarnib exhibits modest activity against acute myelogenous leukemia. To build on these results, we examined the effect of combining tipifarnib with other agents. Tipifarnib inhibited signaling downstream of the farnesylated small G protein Rheb and synergistically enhanced etoposide-induced antiproliferative effects in(More)
1Division of Hematologic Malignancies, Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, MD; 2Department of Oncology, Mayo Clinic College of Medicine, Rochester, MN; 3Department of Hematology/Oncology, New York Presbyterian Hospital, Cornell Medical Center, New York; 4Bone Marrow Transplant Group of Georgia, Atlanta; 5Investigational Drug Branch, Cancer(More)
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