Platelet factor 4 (PF-4) inhibits angiogenesis in vitro and in vivo. The mechanism of inhibition is poorly understood. We have investigated the mechanism of inhibition by examining the interaction of PF-4 and the fibroblast growth factor-2 (FGF-2)/fibroblast growth factor receptor (FGFR) system. PF-4 inhibited the binding of FGF-2 to high-affinity and low-affinity binding sites in murine microv...

Fibroblast growth factor receptor 3 (FGFR-3) is expressed in the lower crypt epithelium, where stem cells of the intestine reside. The role of FGFR-3 signaling in regulating features of intestinal morphogenesis was examined in FGFR-3-null (FGFR-3(-/-)) mice. FGFR-3(-/-) mice had only about half the number of intestinal crypts and a marked decrease in the number of functional clonogenic stem cel...

Epithelial growth factor (EGF) and basic fibroblast growth factor (bFGF), and their receptors, epithelial growth factor receptor (EGFR) and bFGF receptor (bFGFR), are frequently overexpressed in high-grade gliomas. In the present study, the EGF and bFGF levels in U251 glioblastoma cell culture supernatants were determined by ELISA, and enhanced green fluorescent protein (EGFP)-labeled recombina...

PURPOSE Hepatocellular carcinoma (HCC) is the fifth most common primary neoplasm; surgery is the only curative option but 5-year survival rates are only 25% to 50%. Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) are known to be involved in growth and neovascularization of HCC. Therefore, agents that target these pathways may be effective in the treatment of HCC. Th...

Cholangiocarcinomas (CCAs) are rare but aggressive tumours of the bile ducts, which often diagnosed at an advanced stage and have poor outcomes on systemic therapy. Somatic alterations with therapeutic implications been identified in almost half CCAs, particular intrahepatic CCA (iCCA), subtype arising from ducts within liver. Among patients CCA, fibroblast growth factor receptor 2 (FGFR2) fusi...

AIMS Ginsenoside-Rg1, the most prevalent active constituent of Panax ginseng, has been shown to possess potent pro-angiogenic properties and therefore poses special interest for the development as a novel modality for angiotherapy. Rg1 can activate the glucocorticoid receptor (GR). However, the mechanism that transmits these pro-angiogenic effects is still unclear. METHODS AND RESULTS By usin...

How is information communicated both within and between cells of living systems with high signal to noise? We discuss transmembrane signaling models involving two receptor tyrosine kinases: the fibroblast growth factor receptor (FGFR) and the MET receptor. We suggest that simple dimerization models might occur opportunistically giving rise to noise but cooperative clustering of the receptor tyr...

Host arginase 1 (arg1) expression is a significant contributor to the pathogenesis of progressive visceral leishmaniasis (VL), a neglected tropical disease caused by the intracellular protozoan Leishmania donovani. Previously we found that parasite-induced arg1 expression in macrophages was dependent on STAT6 activation. Arg1 expression was amplified by, but did not require, IL-4, and required ...

We have cloned a new member of the fibroblast growth factor receptor family from avian embryonic RNA. The FREK (for fibroblast growth factor receptor-like embryonic kinase) primary transcript can be alternatively spliced in a tissue- and stage-specific manner to give rise to molecules containing either two or three Ig-like domains. During elongating primitive streak stages, FREK is expressed in...