Ralph J. Abi-Habib

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Native proaerolysin is a channel-forming bacterial protoxin that binds to cell-surface receptors and then is activated by furin or furin-like proteases. We genetically engineered proaerolysin by replacing the furin-cleavage sequence with a prostate-specific antigen-selective sequence. The recombinant modified proaerolysin was expressed and purified from(More)
PURPOSE Status epilepticus (SE) can result in acute neuronal injury with subsequent long-term age-dependent behavioral and histologic sequelae. To investigate potential mechanisms that may underlie SE-related neuronal injury, we studied the occurrence of programmed cell death (PCD) in the hippocampus in the kainic acid (KA) model. METHODS In adult rats,(More)
Urokinase plasminogen activator (uPA) is a tumor-specific protease highly expressed in several types of solid tumors and rarely present on normal cells under physiologic conditions. Due to its high expression on metastatic tumors, several different strategies have been used to target the urokinase system. These have mostly led to tumor growth inhibition(More)
Anthrax lethal toxin, composed of protective antigen and lethal factor, was tested for cytotoxicity to human melanoma cell lines and normal human cells. Eleven of 18 melanoma cell lines were sensitive to anthrax lethal toxin (IC(50) < 400 pmol/L) and 10 of these 11 sensitive cell lines carried the V599E BRAF mutation. Most normal cell types (10 of 15) were(More)
In this study, we attempt to target Arginine auxotrophy in glioblastoma multiforme (GBM) cells using a pegylated recombinant human Arginase I cobalt [HuArgI (Co)-PEG5000]. We tested and characterized the activity of HuArgI (Co)-PEG5000 on a panel of 9 GBM cell lines and on human fetal glial cells (SVG-p12). HuArgI (Co)-PEG5000 was cytotoxic to all GBM cells(More)
PURPOSE Anthrax Lethal Toxin (LeTx), composed of protective antigen and lethal factor, catalytically cleaves mitogen-activated protein kinase (MAPK) kinases and inhibits the MAPK signaling pathways. The majority of metastatic melanomas possess the V599E BRAF mutation, which constitutively activates MAPK1/2 signaling. LeTx is cytotoxic to BRAF mutant(More)
Novel agents to treat acute myeloid leukemia (AML) are needed with increased efficacy and specificity. We have synthesized a dual-specificity fusion toxin DTU2GMCSF composed of the catalytic and translocation domains of diphtheria toxin (DT) fused to the granulocyte-macrophage colony-stimulating factor (GM-CSF) in which the DT furin cleavage site(More)
DT388GMCSF, a fusion toxin composed of the NH2-terminal region of diphtheria toxin (DT) fused to human granulocyte-macrophage colony-stimulating factor (GMCSF) has shown efficacy in the treatment of acute myeloid leukemia. However, the primary dose-limiting side effect is liver toxicity. We have reproduced liver toxicity in rats using the rodent cell-tropic(More)
In this study, we attempt to target the mitogen-activated protein kinase (MAPK) pathway in acute myeloid leukemia (AML) cells using a recombinant anthrax lethal toxin (LeTx). LeTx consists of protective antigen (PrAg) and lethal factor (LF). PrAg binds cells, is cleaved by furin, oligomerizes, binds three to four molecules of LF, and undergoes endocytosis,(More)
In this study, we target arginine auxotrophy of AML cell lines using human arginase I cobalt-PEG5000. HuArgI(Co)-PEG5000 was cytotoxic to all AML cell lines tested. Mononuclear cells and CD34(+) blasts were not sensitive demonstrating the selectivity of HuArgI(Co)-PEG5000-induced arginine deprivation. Addition of L-citrulline led to the rescue of five cell(More)