Marrow specimens obtained from 23 patients with acute myelocytic leukemia were exposed to cytosine arabinoside and/or daunorubicin in vitro, and the effects of these agents on colony formation in vitro was determined. Thymidine suicide indices were determined as well, which permitted a distinction to be made between kinetic and metabolic resistance to cytosine arabinoside. The sensitivity of th...

Microorganisms reduced the side-chain carbonyl of daunorubicin to yield 13-dihydrodaunorubicin (daunorubicinol; daunomycinol). This microbial transformation occurred under aerobic conditions in agitated baffled shake flasks incubated at 37 degrees C. The microorganisms were first grown in a medium which supported dense growth. Daunorubicin-HCl was then added. Following a period of incubation, b...

Cytosolic proliferating cell nuclear antigen (PCNA), a scaffolding protein involved in DNA replication, has been described as a key element in survival of mature neutrophil granulocytes, which are non-proliferating cells. Herein, we demonstrated an active export of PCNA involved in cell survival and chemotherapy resistance. Notably, daunorubicin-resistant HL-60 cells (HL-60R) have a prominent c...

N-acetyl-dinaline (CI-994) is an investigational anti-cancer drug which inhibits histone deacetylases. We evaluated the interaction between CI-994 and conventional chemotherapeutics used in acute myeloid leukemia (AML) in a rat model for AML and Brown Norway rat acute myelocytic leukemia (BNML). In vitro, CI-994 in combination with cytarabine (ara-C), daunorubicin and mitoxantrone, resulted in ...

In this study we report that the multidrug resistance protein (MRP) transports calcein from the cytoplasmic compartment of tumor cells, in contrast to P-glycoprotein which transports calcein acetoxymethyl ester from the plasmamembrane. The transport of calcein by MRP is ATP-dependent and is inhibited by probenecid and vincristine. Intracellular glutathione (GSH) depletion which occurred when ce...

Nuclei isolated from rat liver, heart, and kidney catalyze oxygen consumption in the presence of reduced pyridine nucleotide (NADPH) and quinone or quinone-imine antibiotics such as Adriamycin, daunorubicin, actinomycin D, mitomycin C, and streptonigrin. The Km and Vmax values for NADPH were 2.4 x 10(-3) M and 3 x 10(-8) mol O2 per min per mg protein and Km values for the antibiotics ranged fro...

Several studies have suggested that diacylglycerol can affect the induction of apoptosis induced by toxicants and ceramide. The present study demonstrates that clinically relevant concentrations of the chemotherapeutic drugs daunorubicin and mitoxantrone (0.2-1 microM) transiently stimulated concurrently with sphingomyelin-derived ceramide generation and diacylglycerol and phosphorylcholine pro...

N-Tnifluoroacetyladniamycin-1 4-valemate(A032) and N-tn fluonoacetyladniamycmn (AD41) have been compared with Adniamycin and daunorubicin in CCRF-CEM human lyrn phoblastic cells. All four agents produce DNA damage, as measured by alkaline. unwinding methods. Thymidine incor poration, a measure of DNA synthesis, is inhibited by AO32 and AO41 and completely blocked by the other drugs. AO32 and AO...

Two girls, each less than 2 yr of age, developed acute megakaryoblastic leukemia (malignant myelosclerosis). Both presented with anemia, severe thrombocytopenia, and a low percentage of blasts in their peripheral blood. Their marrow showed marked reticulin fibrosis with an increase in blasts and immature megakaryocytes. The blasts stained negatively for myeloperoxidase and Sudan Black B, but sh...

Daunorubicin is biotransformed anaerobically by rat liver microsomes with a reduced nicotinamide adenine dinucleotide phosphate-generating system to form a series of aglycones. The first reaction, reductive cleavage of daunosamine (at C-7 in ring A) to form the 7- deoxyaglycone , is followed by reduction of the C-13 keto group. The 7- hydroxyaglycone may also form by hydrolytic cleavage of the ...