scholarly journals Endostatin: A Promising Drug for Antiangiogenic Therapy

1999 ◽  
Vol 14 (4) ◽  
pp. 263-267 ◽  
Author(s):  
L. Cirri ◽  
S. Donnini ◽  
L. Morbidelli ◽  
P. Chiarugi ◽  
M. Ziche ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Antiangiogenic Therapy ◽  
Specific Inhibitor ◽  
Angiogenesis Inhibitors ◽  
Endothelial Cell Proliferation ◽  
Platelet Factor ◽  
Collagen Xviii ◽  
And Migration

Angiogenesis, the formation of new blood vessels from existing capillaries, is critical for tumors to grow beyond a few in size. Tumor cells produce one or more angiogenic factors including fibroblast growth factor and vascular endothelial growth factor. Surprisingly, antiangiogenic factors or angiogenesis inhibitors have been isolated from tumors. Some angiogenesis inhibitors, such as angiostatin, are associated with tumors while others, such as platelet-factor 4 and interferon-alpha are not. Endostatin, a C-terminal product of collagen XVIII, is a specific inhibitor of endothelial cell proliferation, migration and angiogenesis. The mechanism by which endostatin inhibits endothelial cell proliferation and migration is unknown. Endostatin was originally expressed in a prokaryotic system and, late, in a yeast system, thanks to which it is possible to obtain a sufficient quantity of the protein in a soluble and refolded form to be used in preclincial and clinical trials.

Oncostatin M induces basic fibroblast growth factor expression in endothelial cells and promotes endothelial cell proliferation, migration and spindle morphology

1997 ◽  
Vol 110 (7) ◽  
pp. 871-879 ◽  
Author(s):  
E.S. Wijelath ◽  
B. Carlsen ◽  
T. Cole ◽  
J. Chen ◽  
S. Kothari ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Oncostatin M ◽  
Endothelial Cell Proliferation ◽  
Fibroblast Growth ◽  
Cell Proliferation And Migration ◽  
Mrna Transcripts ◽  
And Migration ◽  
Proliferation And Migration

Oncostatin M (OSM), a pleiotropic cytokine originally isolated from supernatants of the U937 histiocytic lymphoma cell line, has been shown to have regulatory effects on a wide variety of cultured and tumor cells. We investigated the effects of OSM on basic fibroblast growth factor (bFGF) gene expression in bovine arterial endothelial (BAE) cells. Levels of bFGF mRNA transcripts were low in uninduced BAE cells, were maximal at 8 hours of exposure to OSM, and returned to control levels by 24 hours. Induction of bFGF mRNA transcripts by OSM was dose-dependent. Nuclear transcriptional run-on analysis demonstrated that exposure of BAE cells to OSM stimulated bFGF gene transcription. OSM treatment of BAE cells enhanced the synthesis of bFGF protein as determined by ELISA assays. Immunocytochemistry studies demonstrated the presence of low levels of bFGF protein within the cytoplasm in uninduced cells. After stimulation for 8 hours with OSM there was significant staining for bFGF in the cytoplasm. However, 24 hours after exposure to OSM, bFGF antigen was located only within the nuclei. Western blot analysis demonstrated that OSM stimulated predominantly the synthesis of a 22 kDa form of bFGF. In addition, OSM stimulated endothelial cell proliferation and migration as well as acquisition of a spindle shape. Phosphorothioate antisense oligonucleotide directed against bFGF inhibited OSM induced BAE cell proliferation and spindle shape formation but had only a minimal effect on migration. The levels of the 22 kDa form of bFGF were reduced by antisense treatment indicating that OSM induced proliferation and morphology change is likely to be regulated by intracellular bFGF. Our studies suggest that OSM released at sites of vascular injury could stimulate angiogenesis by inducing bFGF synthesis, endothelial cell proliferation and migration.

scholarly journals Identification of Kinases Activated by Multiple Pro-Angiogenic Growth Factors

2021 ◽  
Author(s):  
Jonathan Scott Gruver ◽  
Scott Rata ◽  
Leonid Peshkin ◽  
Marc W Kirschner
Keyword(s):  
Cell Proliferation ◽  
Growth Factors ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Antiangiogenic Therapy ◽  
Growth Factor Receptors ◽  
Endothelial Cell Proliferation ◽  
Angiogenic Growth Factors

Antiangiogenic therapy began as an effort to inhibit VEGF signaling, which was thought to be the sole factor driving tumor angiogenesis. It has become clear that there are more pro-angiogenic growth factors that can substitute for VEGF during tumor vascularization. This has led to the development of multi-kinase inhibitors which simultaneously target multiple growth factor receptors. These inhibitors perform better than monotherapies yet to date no multi-kinase inhibitor targets all receptors known to be involved in pro-angiogenic signaling and resistance inevitably occurs. Given the large number of pro-angiogenic growth factors identified, it may be impossible to simultaneously target all pro-angiogenic growth factor receptors. Here we search for kinase targets, some which may be intracellularly localized, that are critical in endothelial cell proliferation irrespective of the growth factor used. We develop a quantitative endothelial cell proliferation assay and combine it with "kinome regression" or KIR, a recently developed method capable of identifying kinases that influence a quantitative phenotype. We report the kinases implicated by KIR and provide orthogonal evidence of their importance in endothelial cell proliferation. Our approach points to a new strategy to develop a more complete anti-angiogenic blockade.

scholarly journals Comparative Effects of Basic Fibroblast Growth Factor Delivery or Voluntary Exercise on Muscle Regeneration after Volumetric Muscle Loss

2022 ◽  
Vol 9 (1) ◽  
pp. 37
Author(s):  
Caroline Hu ◽  
Bugra Ayan ◽  
Gladys Chiang ◽  
Alex H. P. Chan ◽  
Thomas A. Rando ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Muscle Regeneration ◽  
Collagen Scaffold ◽  
Voluntary Exercise ◽  
Endothelial Cell Proliferation ◽  
Fibroblast Growth ◽  
Muscle Loss ◽  
Volumetric Muscle Loss

Volumetric muscle loss (VML) is associated with irreversibly impaired muscle function due to traumatic injury. Experimental approaches to treat VML include the delivery of basic fibroblast growth factor (bFGF) or rehabilitative exercise. The objective of this study was to compare the effects of spatially nanopatterned collagen scaffold implants with either bFGF delivery or in conjunction with voluntary exercise. Aligned nanofibrillar collagen scaffold bundles were adsorbed with bFGF, and the bioactivity of bFGF-laden scaffolds was examined by skeletal myoblast or endothelial cell proliferation. The therapeutic efficacy of scaffold implants with either bFGF release or exercise was examined in a murine VML model. Our results show an initial burst release of bFGF from the scaffolds, followed by a slower release over 21 days. The released bFGF induced myoblast and endothelial cell proliferation in vitro. After 3 weeks of implantation in a mouse VML model, twitch force generation was significantly higher in mice treated with bFGF-laden scaffolds compared to bFGF-laden scaffolds with exercise. However, myofiber density was not significantly improved with bFGF scaffolds or voluntary exercise. In contrast, the scaffold implant with exercise induced more re-innervation than all other groups. These results highlight the differential effects of bFGF and exercise on muscle regeneration.

scholarly journals Des-γ-carboxyl Prothrombin-promoted Vascular Endothelial Cell Proliferation and Migration

2007 ◽  
Vol 282 (12) ◽  
pp. 8741-8748 ◽  
Author(s):  
Tatsuya Fujikawa ◽  
Hidenori Shiraha ◽  
Naoki Ueda ◽  
Nobuyuki Takaoka ◽  
Yutaka Nakanishi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cell ◽  
Vascular Endothelial Cell ◽  
Endothelial Cell Proliferation ◽  
Vascular Endothelial ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration
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