Edmond J Auzenne

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Numerous human tumor types, including ovarian cancer, display a significant expression of the CD44 family of cell surface proteoglycans. To develop tumor-targeted drugs, we have initially evaluated whether the CD44 ligand hyaluronic acid (HA) could serve as a backbone for paclitaxel (TXL) prodrugs. HA-TXL was prepared by modification of previous techniques.(More)
Previous preclinical studies with ectopic tumor models have demonstrated remarkable improvements in the therapeutic profile of paclitaxel, formulated as a copolymer with poly-L-glutamic acid, compared with paclitaxel in the clinical formulation, Taxol. In this study, we evaluated these formulations in two human ovarian carcinoma xenograft models, NMP-1 and(More)
PURPOSE Most primary human ovarian tumors and peritoneal implants, as well as tumor vascular endothelial cells, express the CD44 family of cell surface proteoglycans, the natural ligand for which is hyaluronic acid. Metronomic dosing, the frequent administration of chemotherapeutics at substantially lower than maximum tolerated doses (MTD), has been shown(More)
Signal transducer and activator of transcription 3 (Stat3) is constitutively activated in a number of human cancers and cancer cell lines. Via its Src homology 2 (SH2) domain, Stat3 is recruited to phosphotyrosine residues on intracellular domains of cytokine and growth factor receptors, whereupon it is phosphorylated on Tyr705, dimerizes, translocates to(More)
Poly-L-glutamic acid (PGA) has previously been demonstrated to be an effective backbone for creating a hydrophilic prodrug of the established anti-tumor agent, paclitaxel, the active agent in Taxol; this approach has obviated the need for the toxic Cremophor excipient, used to enhance the solubility of paclitaxel in the clinical formulation. In order to(More)
Macrophage-mediated inhibition of mitochondrial respiration in EMT-6 murine mammary adenocarcinoma cells can be mimicked in vitro by treatment of the cells with interferon-gamma (IFN-gamma) in combination with tumor necrosis factor, interleukin-1, or lipopolysaccharide. Conditioned supernatants obtained from activated macrophages appear to contain(More)
Coumarin derivatives of N,N-dimethylsphingosine (DMSP) were prepared and chemically characterized. They were apparently biologically equivalent to DMSP in terms of tumor cell cytotoxicity and were used to establish the rapid mitochondrial localization of this sphingolipid in tumor cells, followed closely by its marked reduction of mitochondrial membrane(More)
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