4-Methylcyclophosphamide was synthesized and separated into cis and trans isomers by column chromatography. Isolation of these isomers permitted individual evaluation against murine leukemia L1210 in vivo and assessment of possible differences in antileukemic activity. Results indicate no appreciable difference in activity of the isomers, suggesting essentially equal facility for activation by ...

PURPOSE To determine the possibility of synergistic antileukemic activity and the underlying molecular mechanisms associated with cytarabine combined with valproic acid (VPA; a histone deacetylase inhibitor and a Food and Drug Administration-licensed drug for treating both children and adults with epilepsy) in pediatric acute myeloid leukemia (AML). EXPERIMENTAL DESIGN The type and extent of ...

Our previous study demonstrated that the 2-benzyloxybenzaldehyde analog CCY-1a-E2 is a potent compound against HL-60 human leukemia cell lines. To investigate the potential therapeutic application of CCY-1a-E2 for leukemia, we analyzed the antileukemic effects and safety of CCY-1a-E2 in the BALB/c mouse WEHI-3 allograft model. Our results showed that CCY-1a-E2 decreased the percentage of viable...

Tandutinib (MLN518/CT53518) is a novel quinazoline-based inhibitor of the type III receptor tyrosine kinases: FMS-like tyrosine kinase 3 (FLT3), platelet-derived growth factor receptor (PDGFR), and KIT. Because of the correlation between FLT3 internal tandem duplication (ITD) mutations and poor prognosis in acute myelogenous leukemia (AML), we conducted a phase 1 trial of tandutinib in 40 patie...

Chronic myelogenous leukemia (CML), a malignancy of a hematopoietic stem cell, is caused by the Bcr-Abl tyrosine kinase. STI571(formerly CGP 57148B), an Abl tyrosine kinase inhibitor, has specific in vitro antileukemic activity against Bcr-Abl-positive cells and is currently in Phase II clinical trials. As it is likely that resistance to a single agent would be observed, combinations of STI571 ...

PURPOSE The growth and survival of acute myeloid leukemia (AML) cells are enhanced by the deregulation of signaling pathways such as phosphoinositide 3-kinase (PI3K)/Akt and mammalian target of rapamycin (mTOR). Major efforts have thus been made to develop molecules targeting these activated pathways. The mTOR serine/threonine kinase belongs to two separate complexes: mTORC1 and mTORC2. The mTO...