Joseph A. Fuselier

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Tumor necrosis factor-a (TNF-a) has been shown to induce insulin resistance in cultured cells as well as in animal models. The aim of this study was to map the in vivo mechanism whereby TNF-a contributes to the pathogenesis of impaired insulin signaling, using obese and lean Zucker rats in which TNF-a activity was inhibited through adenovirus-mediated gene(More)
The effects of camptothecin-somatostatin (CPT-SS) conjugates were investigated on small cell lung cancer (SCLC) cells. CPT was coupled to a SS agonist (SSA), c(Cys-Phe-DTrp-Lys-Thr-Cys)Thr-NH2 using the built in nucleophile assisted-releasing group (L1) N-methyl-aminoethyl-Gly-Dser-Nle-Dtyr-Dser or (L2) aminoethyl-Gly-Dser-Nle-Dtyr-Dser. The resulting(More)
Peptide hormones are often rapidly internalized after binding to and activation of their receptors which are sometimes over-expressed on tumor cells. Thus, peptide ligands are increasingly being utilized for specific tumor cell targeting and internalization of radioactive isotopes for tumor imaging and for specifically delivering and internalizing cytotoxic(More)
Camptothecin (CPT) was conjugated to the N-terminal of a somatostatin analog (SSA) directly via a carbamate group and a basic N-terminal linking motif, D-Lys-D-Tyr-Lys-D-Tyr-D-Lys. This new CPT-SSA conjugate termed JF-10-81 was evaluated as a receptor-specific delivery system for its anti-invasive and anti-angiogenic activities. It was found that, in(More)
Two CPT-SSA conjugates, JF-10-71 and JF-10-81, containing a chemically adjustable release-rate carbamate linker, have been reported previously by us to potently inhibit growth of human neuroblastoma IMR32 cells overexpressing somatostatin receptor type II (SSTR2) but are stable under buffer incubation conditions or in rat plasma. Further experiments now(More)
Most human tumors overexpress or ectopically express peptide hormone/neurotransmitter receptors, which are being increasingly studied as a means to selectively deliver cytotoxic agents. Although a number of peptide ligand-constructs demonstrate tumor cytotoxicity, the role of specific tumoral receptor interaction in its mediation is unclear. To address this(More)
A series of novel 1,4-diaryl-2-azetidinones was prepared by stereospecific Staudinger reaction as conformationally restricted analogues of combretastatin A-4 because molecular modeling studies suggested close geometric similarities. They were evaluated for cytotoxicity against a number of human tumor and normal cell lines. Strong potencies were observed,(More)
The role of Notch signaling in cervical cancer is seemingly controversial. To confirm the function of Notch signaling in this type of cancer, we established a stable Notch1-activated cervical cancer HeLa cell line. We found that Notch1 activation resulted in apoptosis, cell cycle arrest, and tumor suppression. At the molecular level, we found that a variety(More)
Tumor necrosis factor-alpha (TNF-alpha) has been shown to induce insulin resistance in cultured cells as well as in animal models. The aim of this study was to map the in vivo mechanism whereby TNF-alpha contributes to the pathogenesis of impaired insulin signaling, using obese and lean Zucker rats in which TNF-alpha activity was inhibited through(More)