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PURPOSE Panitumumab, a fully human antibody against the epidermal growth factor receptor (EGFR), has activity in a subset of patients with metastatic colorectal cancer (mCRC). Although activating mutations in KRAS, a small G-protein downstream of EGFR, correlate with poor response to anti-EGFR antibodies in mCRC, their role as a selection marker has not(More)
MOTIVATION Next generation sequencing technology generates high-throughput data, which allows us to detect fusion genes at both transcript and genomic levels. To detect fusion genes, the current bioinformatics tools heavily rely on paired-end approaches and overlook the importance of reads that span fusion junctions. Thus there is a need to develop an(More)
PURPOSE This phase II study investigated the efficacy and tolerability of motesanib, an investigational, highly selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit in advanced medullary thyroid cancer (MTC). PATIENTS AND METHODS Patients with locally advanced or metastatic,(More)
BACKGROUND The expression of vascular endothelial growth factor (VEGF) is characteristic of differentiated thyroid cancer and is associated with aggressive tumor behavior and a poor clinical outcome. Motesanib diphosphate (AMG 706) is a novel oral inhibitor of VEGF receptors, platelet-derived growth-factor receptor, and KIT. METHODS In an open-label,(More)
The vanilloid receptor TRPV1 (transient receptor potential vanilloid 1) is a cation channel that serves as a polymodal detector of pain-producing stimuli such as capsaicin, protons (pH <5.7), and heat. TRPV1 antagonists block pain behaviors in rodent models of inflammatory, neuropathic, and cancer pain, suggesting their utility as analgesics. Here, we(More)
Mammals mount a rapid inflammatory response to gram-negative bacteria by recognizing lipopolysaccharide (LPS, endotoxin). LPS binds to CD14, and the resulting LPS-CD14 complex induces synthesis of cytokines and up-regulation of adhesion molecules in a variety of cell types. Gram-positive bacteria provoke a very similar inflammatory response, but the(More)
PURPOSE Epratuzumab is a novel humanized antihuman CD22 IgG1 antibody that has recently shown promising clinical activity, both as a single agent and in combination with rituximab, in patients with non-Hodgkin's lymphomas (NHL). In an attempt to better understand the mode of action of epratuzumab, the antibody was tested in vitro in a variety of cell-based(More)
CD14 is a 55-kDa glycoprotein that binds lipopolysaccharide (LPS) and enables LPS-dependent responses in a variety of cells. Monoclonal antibodies of CD14 such as 3C10 and MEM-18 are known to neutralize biological activity of CD14. Recently, it has been demonstrated that MEM-18 recognizes the LPS-binding site of CD14, between amino acids 57 and 64. It has(More)
C3, the third component of complement, is critical in the host immune response in that it is involved in both the classical and alternative pathways of complement activation. We have previously shown that a region (bp -127 to -70) within the C3 promoter is indispensable for conferring interleukin 1 (IL-1) responsiveness to this gene. A sequence comparison(More)
Nicotinic acetylcholine receptors (nAChRs) are longstanding targets for a next generation of pain therapeutics, but the nAChR subtypes that govern analgesia remain unknown. We tested a series of nicotinic agonists, including many molecules used or tried clinically, on a panel of cloned neuronal nAChRs for potency and selectivity using patch-clamp(More)