Browsing by Author "Tseng, Feng-Jen"

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A fusion protein composed of receptor binding domain of vascular endothelial growth factor-A and constant region fragment of antibody: angiogenesis antagonistic activity
(2011-05-01)
Tseng, Feng-Jen
;
Liu, Yen-Ku
;
Chung, Yo-Shong
;
Lin, Yu-Ling
;
Chen, Chia-Hung
Vascular endothelial growth factor (VEGF) promotes the growth of solid tumor mainly via VEGF receptor-1 and receptor-2, which are expressed preferentially in proliferating endothelial cells. Therefore, a strategy for simultaneous blockage of both VEGF receptors may have a useful therapeutic effect in tumor growth. In this study, we utilized a fusion protein which is composed of receptor binding domain of VEGF-A (RBDV) and the constant region fragment (Fc) of a human immunoglobulin G1 (IgG1), to interfere with the growth of human umbilical vein endothelial cells (HUVECs) via VEGF receptors. The results showed that RBDV-IgG1 Fc was able to bind with both VEGF receptor-1 and receptor-2. In addition, RBDV-IgG1 Fc could decrease VEGF-induced proliferation and tube formation among HUVECs. Moreover, the cytotoxic test showed RBDV-IgG1 Fc could also enhance the cytotoxic activity of human natural killing cells. The data are suggesting that the fusion protein, RBDV-IgG1 Fc, may have potential as an angiogenesis antagonist for future tumor therapy.
A fusion protein with the receptor binding domain of vascular endothelial growth factor-A (VEGF-A) is an antagonist of angiogenesis in cancer treatment
(2010-11-01)
Tseng, Feng-Jen
;
Chen, Yu-Cheng
;
Lin, Yu-Ling
;
Tsai, Nu-Man
;
Lee, Ru-Ping
Vascular endothelial growth factor (VEGF) is an angiogenic factor that signals through VEGFR-1 and VEGFR-2, which are expressed preferentially in proliferating endothelial cells. Thus, simultaneous blockage of both VEGF receptors may provide a more efficient therapeutic response in cancer treatment. We created a recombinant fusion protein (RBDV-IgG1 Fc), which is composed of the receptor binding domain of human VEGF-A (residues 8-109) and the Fc region of human IgG1 immunoglobulin. The recombinant protein can bind to both mouse VEGFR-1 and VEGFR-2 to decrease VEGF-induced proliferation and tube formation of endothelial cells in vitro. In this study, the RBDV-IgG1 Fc fusion protein reduced the effects of proliferation, migration and tube formation induced by VEGF in murine endothelial cells in vitro. In vivo tumor therapy with RBDV-IgG1 Fc resulted in tumor inhibition by reducing angiogenesis. Pathological evidence also shows that RBDV-IgG1 Fc can seriously damage vessels, causing the death of tumor cells. These findings suggest that this chimeric protein has potential as an angiogenesis antagonist in tumor therapy.
The treatment of propofol induced the TGF-beta 1 expression in human endothelial cells to suppress endocytosis activities of monocytes
(2010-12-01)
Li, Chi-Han
;
Lee, Ru-Ping
;
Lin, Yu-Ling
;
Lin, Chen-Si
;
Hsu, Bang-Gee
Propofol anesthesia and sedation are known to downregulate the functions of many hematopoietic cells, such as macrophages and neutrophils, in vivo. However, the effects of propofol on secretion of the regulatory cytokine transforming growth factor beta 1 (TGF-beta 1) in vivo are unknown. In this study, the effects of propofol on TGF-beta 1 expression in human peripheral blood mononuclear cells, umbilical vein endothelial cells (HUVECs), lymphocytes (Jurkat) and monocytes (THP-1) were tested. Moreover, these sera were also tested for regulatory activity on monocyte endocytosis with or without treatment with the TGF-beta 1 pathway inhibitor SB431542. Propofol raised levels of both total and activated TGF-beta 1 in propofol-treated patient sera after surgical operations. Furthermore, propofol induced secretion of latent TGF-beta 1 in HUVEC cells and enhanced TGF-beta 1 activation in THP-1 and Jurkat cells in vitro. Additionally, sera from propofol-treated patients suppressed monocyte endocytosis ex vivo, an effect that was abrogated by the TGF-beta 1 pathway inhibitor SB431542. (C) 2010 Elsevier Ltd. All rights reserved.