Acute Myeloid Leukemia (AML) has grave prognosis due to aggressive nature of the disease, the toxicity of standard treatment, and overall low cure rates. We recently showed that AML cells in established culture treated with Cytarabine (AraC) and a differentiation agent combination show enhancement of AraC cytotoxicity. Here we elucidate molecular changes which underlie this observation with foc...

We recently found that CD82 inhibits matrix metalloproteinase 9 and augments adhesion of CD34(+) /CD38(-) acute myelogenous leukemia (AML) cells to the bone marrow (BM) microenvironment. The present study found that the use of an anti-CD82 monoclonal antibody (CD82 mAb) mobilized CD34(+) leukemia cells from BM into the peripheral blood in a humanized AML murine model. The use of CD82 mAb in com...

The role of nuclear lamins in DNA replication is unclear. To address this, nuclei were assembled in Xenopus extracts containing AraC, a reversible inhibitor that blocks near the onset of the elongation phase of replication. Dominant-negative lamin mutants lacking their NH(2)-terminal domains were added to assembled nuclei to disrupt lamin organization. This prevented the resumption of DNA repli...

In a clinical phase-II study 11 patients with refractory ALL were treated with high-dose AraC and mitoxantrone in combination (HAM). Refractoriness was defined as: 1. primary resistance against the BMFT induction protocol; 2. first relapse with non-response to the B-ALL/NHL regimen as salvage treatment; 3. second and subsequent relapses. Therapy consisted of HD-AraC 3 g/m2 every 12 h by a 3-h i...

To understand the mechanism of cellular resistance to the nucleoside analogue cytarabine (1-beta-D-arabinofuranosylcytosine, AraC), two resistant derivatives of the human leukemic line CCRF-CEM were obtained by stepwise selection in different concentrations of AraC. CEM/4xAraC cells showed low AraC resistance, whereas CEM/20xAraC cells showed high resistance. Both cell lines showed similar patt...

The E-arabinose operon is under both positive and negative control by the product of its regulatory gene, UrQc. We have measured transcription of the arabinose genes by hybridization of 3H-labeled messenger RNA to single-stranded DNA from an arabinose transducing phage in order to study the effect of the regulatory gene on transcription. In strains in which the arabinose regulatory gene is comp...

The E-arabinose operon is under both positive and negative control by the product of its regulatory gene, UrQc. We have measured transcription of the arabinose genes by hybridization of 3H-labeled messenger RNA to single-stranded DNA from an arabinose transducing phage in order to study the effect of the regulatory gene on transcription. In strains in which the arabinose regulatory gene is comp...

The crystal structure of the sugar-binding and dimerization domain of the Escherichia coli gene regulatory protein, AraC, has been determined in complex with the competitive inhibitor D-fucose at pH 5.5 to a resolution of 1.6 A. An in-depth analysis shows that the structural basis for AraC carbohydrate specificity arises from the precise arrangement of hydrogen bond-forming protein side-chains ...

BACKGROUND Sensorineural deafness is mainly caused by damage to hair cells and degeneration of the spiral ganglion neurons (SGN). Cochlear implants can functionally replace lost hair cells and stimulate the SGN electrically. The benefit from cochlear implantation depends on the number and excitability of these neurons. To identify potential therapies for SGN protection, in vitro tests are carri...

Previous reports suggest that the resistance of neuronal cytoskeleton to drug toxicity may vary with age and gender. The aim of the present study was to assess the impact of cytosine arabinoside (AraC) treatment on neurofilament (NF) levels and phosphorylation status in the developing cerebellum of male, female and testosterone propionate (1.25 mg/rat)-androgenized female rats. AraC (200 mg/kg ...