The Drosophila sugarless and sulfateless genes encode enzymes required for the biosynthesis of heparan sulfate glycosaminoglycans. Biochemical studies have shown that heparan sulfate glycosaminoglycans are involved in signaling by fibroblast growth factor receptors, but evidence for such a requirement in an intact organism has not been available. We now demonstrate that sugarless and sulfateles...

The treatment of metastatic urothelial cancer (mUC) has been transformed by recent progress in clinical trials and drug development. There are now three therapeutic classes with proven benefits mUC: chemotherapy, immunotherapy, targeted therapy. optimal sequence combination these remain to be defined. Biomarker development is essential guide selection at each juncture. Two biomarkers, programme...

BACKGROUND/AIMS Fibroblast growth factor signaling is involved in hepatocarcinogenesis. The aim of this study was to determine the fibroblast growth factor receptor (FGFR) isotype expression in hepatocellular carcinoma (HCC) and neighboring nonneoplastic liver tissue, and elucidate its prognostic implications. METHODS Immunohistochemical staining of FGFR1, -2, -3, and -4 was performed in the ...

FGF1 is a signal peptide-less nonclassically released growth factor that is involved in angiogenesis, tissue repair, inflammation, and carcinogenesis. The effects of nonclassical FGF export in vivo are not sufficiently studied. We produced transgenic mice expressing FGF1 in endothelial cells (EC), which allowed the detection of FGF1 export to the vasculature, and studied the efficiency of posti...

Understanding growth factor function during wound repair is necessary for the development of therapeutic interventions to improve healing outcomes. In the current study, we compare the effects of serum and purified growth factors on human fibroblast function in three different collagen matrix models: cell migration in nested matrices, floating matrix contraction, and stressed-released matrix co...

Thrombin and factor Xa (FXa) are agonists for G protein-coupled receptors (GPRCs) and may contribute to vascular lesion formation by stimulating proliferation of vascular smooth muscle cells (SMCs). Mitogenic signaling of GPCRs requires transactivation of receptor tyrosine kinases (RTKs). In rat SMCs, thrombin transactivates the epidermal growth factor receptor (EGFR) via a pathway that involve...

The coagulation cascade protease thrombin is a fibroblast mitogen, but the proliferative potential of other coagulation proteases is not known. In this study we show that factor Xa stimulated human fetal lung fibroblast DNA synthesis in a concentration-dependent manner from 1 nM onward with a fourfold increase at 200 nM. The mitogenic effect of factor Xa was confirmed using a colorimetric proli...

The initiation and morphogenesis of cutaneous appendages depend on a series of reciprocal signaling events between the epithelium and mesenchyme of the embryonic skin. In the development of feather germs, early dermal signals induce the formation of epidermal placodes that in turn signal the mesoderm to form dermal condensations immediately beneath them. We find a spatially and temporally restr...