We report for the first time the use of a selective small-molecule inhibitor of DNA repair to potentiate topoisomerase II (topo II) poisons, identifying DNA-dependent protein kinase (DNA-PK) as a potential target for leukemia therapy. Topo II poisons form cleavable complexes that are processed to DNA double-strand breaks (DSBs). DNA-PK mediates nonhomologous end joining (NHEJ). Inhibition of th...

To study the mechanisms by which monocytes/macrophages and smooth muscle cells contribute to atherosclerotic lesions, we studied atherosclerotic plaque formation in cholesterol-fed rabbits treated with etoposide, a drug that has been shown to have several effects that could interfere with the proposed interactions between these two cell types (M.W. Aarnoudes et al, Virchows Arch B 1984;47:211-2...

BACKGROUND Histone deacetylase inhibitors (HDACi) have been extensively studied as potential candidates for treatment of various malignancies, including leukemia, since they not only induce growth inhibition, cell cycle arrest and apoptosis of cancer cells, but can also increase the sensitivity of cancer cells to chemotherapeutic drugs. The aim of this study was to investigate the effect of two...

OBJECTIVE This dose escalation was conducted to evaluate the applicability of Chatelut's dosing, and to determine the efficacy and toxicity of carboplatin with etoposide in previously untreated elderly patients (>70 years) with small cell lung cancer. PATIENTS AND METHODS Seventeen patients were treated with etoposide for 3 days and carboplatin calculated dose using Chatelut's formula on day ...

Overexpression of ecotropic viral integration site 1 (EVI1) is associated with aggressive disease in acute myeloid leukemia (AML). Despite of its clinical importance, little is known about the mechanism through which EVI1 confers resistance to antileukemic drugs. Here, we show that a human myeloid cell line constitutively overexpressing EVI1 after infection with a retroviral vector (U937_EVI1) ...

Solid lipid nanoparticles (SLNs) comprising complex internal lipids were conjugated with melanotransferrin antibody (MA) to carry anticancer etoposide across the blood–brain barrier (BBB) for managing glioblastoma multiforme (GBM). MA was crosslinked on the surface of etoposide-loaded SLNs (ETP-SLNs) to target human brain-microvascular endothelial cells (HBMECs) and U87MG cells. The experimenta...

In mammalian cells, the H2AX histone is rapidly phosphorylated upon the induction of DNA double strand breaks and promotes their repair, which is required for preserving genomic integrity. Etoposide is an inhibitor of DNA topoisomerase II, which causes DNA breaks and induces H2AX phosphorylation. To elucidate whether H2AX may affect cellular sensitivity to etoposide, we studied the response to ...

We studied the pharmacokinetics of etoposide in 45 children treated for newly diagnosed acute myeloid leukemia. Etoposide, 100 mg/m body surface area/24 h, was administered by 96-h continuous intravenous infusion. Concomitantly, the children received cytarabine 200 mg/m/24 h by intravenous infusion and 6-thioguanine 100 mg/m twice daily orally. Median total body clearance in children 0.5-1.8 (n...

Abstract Local intracranial drug delivery for high-grade glioma has been developed over the last two decades with chemotherapeutic agents administered immediately adjuvant to neurosurgery overcome poor blood brain barrier permeability. In addition this, incorporation of nanoparticles (NPs) into local systems (DDS) can result in increased penetration chemotherapeutics through parenchyma, transpo...

THE REGULATION OF RNA POLYMERASE I-MEDIATED TRANSCRIPTION IN FOREBRAIN NEURONS Scott Carl Smith November 29,2011 Ribosomal biogenesis failure may contribute to neurodegenerative diseases, while its excessive activation has been shown to drive tumor growth. As ribosomal production is initiated and regulated by the Poll-mediated transcription of rRNA genes in the nucleolus, the latter process had...