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Lysophosphatidic acid (LPA) is a naturally occurring phospholipid that exhibits pleiotrophic biological activities, ranging from rapid morphological changes to long-term cellular effects such as induction of gene expression and stimulation of cell proliferation and survival on a wide spectrum of cell types. LPA binds and activates distinct members of the(More)
PURPOSE Vemurafenib, a selective inhibitor of BRAF(V600), has shown significant activity in BRAF(V600) melanoma but not in less than 10% of metastatic BRAF(V600) colorectal cancers (CRC), suggesting that studies of the unique hypermethylated phenotype and concurrent oncogenic activation of BRAF(mut) CRC may provide combinatorial strategies. EXPERIMENTAL(More)
Lysophosphatidic acid (LPA), the simplest of all phospholipids, exhibits pleiomorphic functions in multiple cell lineages. The effects of LPA appear to be mediated by binding of LPA to specific members of the endothelial differentiation gene (Edg) family of G protein-coupled receptors (GPCR). Edg 2, Edg4, and Edg7 are high affinity receptors for LPA, and(More)
3533 Background: Circulating angiogenic factors have been previously shown to be altered in patients (pts) with mCRC on bevacizumab (BV)-containing regimens. However, a systematic evaluation of alterations in levels of the VEGF family of ligands may provide insights into resistance mechanisms. METHODS 42 patients (pts) with mCRC were treated on a single(More)
Inactivation of the visual G-protein transducin by GTP hydrolysis is regulated by the GTPase-accelerating protein (GAP) RGS9-1. Regulation of RGS9-1 itself is poorly understood, but we found previously that it is subject to a light- and Ca(2+)-sensitive phosphorylation on Ser(475). Because there are much higher RGS9-1 levels in cones than in rods, we(More)
Light responses in photoreceptor cells are mediated by the action of the G protein transducin (G(t)) on the effector enzyme cGMP phosphodiesterase (PDE6) at the surface of disk membranes. The enzymatic components needed for phosphoinositide-based signaling are known to be present in rod cells, but it has remained uncertain what role phosphoinositides play(More)
Ascitic fluid and plasma from ovarian cancer patients, but not from patients with nongynecological tumors, contain elevated levels of the bioactive phospholipid lysophospha-tidic acid (LPA). We show that ovarian cancer cells consti-tutively produce increased amounts of LPA as compared with normal ovarian epithelium, the precursor of ovarian epithelial(More)
Purpose: Vemurafenib, a selective inhibitor of BRAF V600 , has shown significant activity in BRAF V600 melanoma but not in less than 10% of metastatic BRAF V600 colorectal cancers (CRC), suggesting that studies of the unique hypermethylated phenotype and concurrent oncogenic activation of BRAF mut CRC may provide combinatorial strategies. Experimental(More)
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