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Masahiko Shimura - One of the best experts on this subject based on the ideXlab platform.
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role of soluble vascular endothelial growth factor receptors 1 and 2 their ligands and other factors in branch retinal vein occlusion with macular edema
Investigative Ophthalmology & Visual Science, 2014Co-Authors: Hidetaka Noma, Tatsuya Mimura, Kanako Yasuda, Masahiko ShimuraAbstract:Purpose To evaluate the association between multiple factors in aqueous humor and the severity of macular edema in patients with branch retinal vein occlusion (BRVO). Methods We measured the aqueous humor levels of 11 factors (including vascular endothelial growth factor receptors, growth factors, and inflammatory factors) in BRVO patients with macular edema and in cataract patients as controls. Aqueous humor samples were obtained from 40 patients (31 patients with BRVO and 9 with cataract). Then the levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor (sVEGFR)-1, sVEGFR-2, placental growth factor (PlGF), soluble intercellular adhesion molecule (sICAM)-1, monocyte chemotactic protein (MCP)-1, platelet-derived growth factor (PDGF)-AA, interleukin (IL)-6, IL-8, IL-12(p70), and IL-13 were measured by the suspension array method. Macular edema was examined by optical coherence tomography, and its severity was determined from the central macular thickness (CMT), neurosensory retinal thickness (TNeuro), and subfoveal serous retinal thickness (SRT). Results Aqueous humor levels of growth factors, sVEGFR-1, sVEGFR-2, and inflammatory factors were significantly higher in eyes with BRVO than in control eyes. Aqueous levels of sVEGFR-1 and -2 were significantly correlated with the SRT, as well as with the levels of growth factors (PIGF and PDGF-AA) and various inflammatory factors (sICAM-1, MCP-1, IL-6, and IL-8). Levels of the growth factors (VEGF, PlGF, and PDGF-AA) were also significantly correlated with each other. Conclusions These findings suggest the importance of the cytokine network in BRVO patients, and may contribute to understanding the mechanism of macular edema associated with BRVO and to development of new treatments.
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role of soluble vascular endothelial growth factor receptors 1 and 2 their ligands and other factors in branch retinal vein occlusion with macular edema
Investigative Ophthalmology & Visual Science, 2014Co-Authors: Hidetaka Noma, Tatsuya Mimura, Kanako Yasuda, Masahiko ShimuraAbstract:METHODS. We measured the aqueous humor levels of 11 factors (including vascular endothelial growth factor receptors, growth factors, and inflammatory factors) in BRVO patients with macular edema and in cataract patients as controls. Aqueous humor samples were obtained from 40 patients (31 patients with BRVO and 9 with cataract). Then the levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor (sVEGFR)-1, sVEGFR-2, placental growth factor (PlGF), soluble intercellular adhesion molecule (sICAM)1, monocyte chemotactic protein (MCP)-1, platelet-derived growth factor (PDGF)-AA, interleukin (IL)-6, IL-8, IL-12(p70), and IL-13 were measured by the suspension array method. Macular edema was examined by optical coherence tomography, and its severity was determined from the central macular thickness (CMT), neurosensory retinal thickness (TNeuro), and subfoveal serous retinal thickness (SRT). RESULTS. Aqueous humor levels of growth factors, sVEGFR-1, sVEGFR-2, and inflammatory factors were significantly higher in eyes with BRVO than in control eyes. Aqueous levels of sVEGFR-1 and -2 were significantly correlated with the SRT, as well as with the levels of growth factors (PIGF and PDGF-AA) and various inflammatory factors (sICAM-1, MCP-1, IL-6, and IL-8). Levels of the growth factors (VEGF, PlGF, and PDGF-AA) were also significantly correlated with each other. CONCLUSIONS. These findings suggest the importance of the cytokine network in BRVO patients, and may contribute to understanding the mechanism of macular edema associated with BRVO and to development of new treatments.
Hidetaka Noma - One of the best experts on this subject based on the ideXlab platform.
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role of soluble vascular endothelial growth factor receptors 1 and 2 their ligands and other factors in branch retinal vein occlusion with macular edema
Investigative Ophthalmology & Visual Science, 2014Co-Authors: Hidetaka Noma, Tatsuya Mimura, Kanako Yasuda, Masahiko ShimuraAbstract:Purpose To evaluate the association between multiple factors in aqueous humor and the severity of macular edema in patients with branch retinal vein occlusion (BRVO). Methods We measured the aqueous humor levels of 11 factors (including vascular endothelial growth factor receptors, growth factors, and inflammatory factors) in BRVO patients with macular edema and in cataract patients as controls. Aqueous humor samples were obtained from 40 patients (31 patients with BRVO and 9 with cataract). Then the levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor (sVEGFR)-1, sVEGFR-2, placental growth factor (PlGF), soluble intercellular adhesion molecule (sICAM)-1, monocyte chemotactic protein (MCP)-1, platelet-derived growth factor (PDGF)-AA, interleukin (IL)-6, IL-8, IL-12(p70), and IL-13 were measured by the suspension array method. Macular edema was examined by optical coherence tomography, and its severity was determined from the central macular thickness (CMT), neurosensory retinal thickness (TNeuro), and subfoveal serous retinal thickness (SRT). Results Aqueous humor levels of growth factors, sVEGFR-1, sVEGFR-2, and inflammatory factors were significantly higher in eyes with BRVO than in control eyes. Aqueous levels of sVEGFR-1 and -2 were significantly correlated with the SRT, as well as with the levels of growth factors (PIGF and PDGF-AA) and various inflammatory factors (sICAM-1, MCP-1, IL-6, and IL-8). Levels of the growth factors (VEGF, PlGF, and PDGF-AA) were also significantly correlated with each other. Conclusions These findings suggest the importance of the cytokine network in BRVO patients, and may contribute to understanding the mechanism of macular edema associated with BRVO and to development of new treatments.
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role of soluble vascular endothelial growth factor receptors 1 and 2 their ligands and other factors in branch retinal vein occlusion with macular edema
Investigative Ophthalmology & Visual Science, 2014Co-Authors: Hidetaka Noma, Tatsuya Mimura, Kanako Yasuda, Masahiko ShimuraAbstract:METHODS. We measured the aqueous humor levels of 11 factors (including vascular endothelial growth factor receptors, growth factors, and inflammatory factors) in BRVO patients with macular edema and in cataract patients as controls. Aqueous humor samples were obtained from 40 patients (31 patients with BRVO and 9 with cataract). Then the levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor (sVEGFR)-1, sVEGFR-2, placental growth factor (PlGF), soluble intercellular adhesion molecule (sICAM)1, monocyte chemotactic protein (MCP)-1, platelet-derived growth factor (PDGF)-AA, interleukin (IL)-6, IL-8, IL-12(p70), and IL-13 were measured by the suspension array method. Macular edema was examined by optical coherence tomography, and its severity was determined from the central macular thickness (CMT), neurosensory retinal thickness (TNeuro), and subfoveal serous retinal thickness (SRT). RESULTS. Aqueous humor levels of growth factors, sVEGFR-1, sVEGFR-2, and inflammatory factors were significantly higher in eyes with BRVO than in control eyes. Aqueous levels of sVEGFR-1 and -2 were significantly correlated with the SRT, as well as with the levels of growth factors (PIGF and PDGF-AA) and various inflammatory factors (sICAM-1, MCP-1, IL-6, and IL-8). Levels of the growth factors (VEGF, PlGF, and PDGF-AA) were also significantly correlated with each other. CONCLUSIONS. These findings suggest the importance of the cytokine network in BRVO patients, and may contribute to understanding the mechanism of macular edema associated with BRVO and to development of new treatments.
Carlhenrik Heldin - One of the best experts on this subject based on the ideXlab platform.
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platelet derived growth factor production by b16 melanoma cells leads to increased pericyte abundance in tumors and an associated increase in tumor growth rate
Cancer Research, 2004Co-Authors: Masao Furuhashi, Ulf Eriksson, Christer Betsholtz, Tobias Sjoblom, Alexandra Abramsson, Jens Ellingsen, Patrick Micke, Erika Bergstenfolestad, Rainer Heuchel, Carlhenrik HeldinAbstract:Platelet-derived growth factor (PDGF) receptor signaling participates in different processes in solid tumors, including autocrine stimulation of tumor cell growth, recruitment of tumor stroma fibroblasts, and stimulation of tumor angiogenesis. In the present study, the B16 mouse melanoma tumor model was used to investigate the functional consequences of paracrine PDGF stimulation of host-derived cells. Production of PDGF-BB or PDGF-DD by tumor cells was associated with an increased tumor growth rate. Characterization of tumors revealed an increase in pericyte abundance in tumors derived from B16 cells producing PDGF-BB or PDGF-DD. The increased tumor growth rate associated with PDGF-DD production was not seen in mice expressing an attenuated PDGF β-receptor and was thus dependent on host PDGF β-receptor signaling. The increased pericyte abundance was not associated with an increased tumor vessel density. However, tumor cell apoptosis, but not proliferation, was reduced in tumors displaying PDGF-induced increased pericyte coverage. Our findings thus demonstrate that paracrine PDGF production stimulates pericyte recruitment to tumor vessels and suggest that pericyte abundance influences tumor cell apoptosis and tumor growth.
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mechanism of action and in vivo role of platelet derived growth factor
Physiological Reviews, 1999Co-Authors: Carlhenrik Heldin, Bengt WestermarkAbstract:Platelet-derived growth factor (PDGF) is a major mitogen for connective tissue cells and certain other cell types. It is a dimeric molecule consisting of disulfide-bonded, structurally similar A- and B-polypeptide chains, which combine to homo- and heterodimers. The PDGF isoforms exert their cellular effects by binding to and activating two structurally related protein tyrosine kinase receptors, denoted the alpha-receptor and the beta-receptor. Activation of PDGF receptors leads to stimulation of cell growth, but also to changes in cell shape and motility; PDGF induces reorganization of the actin filament system and stimulates chemotaxis, i.e., a directed cell movement toward a gradient of PDGF. In vivo, PDGF has important roles during the embryonic development as well as during wound healing. Moreover, overactivity of PDGF has been implicated in several pathological conditions. The sis oncogene of simian sarcoma virus (SSV) is related to the B-chain of PDGF, and SSV transformation involves autocrine stimulation by a PDGF-like molecule. Similarly, overproduction of PDGF may be involved in autocrine and paracrine growth stimulation of human tumors. Overactivity of PDGF has, in addition, been implicated in nonmalignant conditions characterized by an increased cell proliferation, such as atherosclerosis and fibrotic conditions. This review discusses structural and functional properties of PDGF and PDGF receptors, the mechanism whereby PDGF exerts its cellular effects, and the role of PDGF in normal and diseased tissues.
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expression of platelet derived growth factor and its receptors in neuroendocrine tumors of the digestive system
Cancer Research, 1992Co-Authors: Arvind Chaudhry, Carlhenrik Heldin, Vasilis Papanicolaou, Kjell Oberg, Keiko FunaAbstract:Abstract Carcinoid tumors are slowly growing neuroendocrine neoplasms which often present pronounced fibrosis around the tumor cells. We have previously shown by immunohistochemistry that carcinoid tumors express platelet-derived growth factor (PDGF) β-receptors on surrounding stromal cells. In this report, 22 midgut carcinoids and 5 endocrine pancreatic tumors were examined for the presence of PDGF with a monoclonal antibody raised against a peptide corresponding to a part of the B-chain of PDGF which reacts strongly with the B-chain and weakly with the A-chain. They were also examined for PDGF α-receptors with an affinity-purified polyclonal peptide antibody and for PDGF β-receptor with the monoclonal antibody PDGFR-B2. PDGF was expressed on tumor cells and on adjacent stroma. PDGF α-receptor was seen on clusters of tumor cells and occasionally on adjacent stroma, whereas β-receptors were seen only in the stroma. Tissue sections from some of these midgut carcinoids were also investigated by in situ hybridization for mRNA of PDGF A- and B-chains as well as α- and β-receptors. By in situ hybridization, abundant expression of mRNA for PDGF β-receptor and PDGF A-chain was observed in stromal cells adjacent to carcinoid tumor cell clusters, but the mRNA expression in the tumor cells themselves was at a low level. A few clustered tumor cells and stromal cells expressed mRNA for the PDGF α-receptor, thus consolidating the immunohistochemical findings. mRNA for the PDGF B-chain was detected in both tumor cells and stroma, but only at low levels. Our data suggest that PDGF is involved in the growth stimulation of the carcinoid tumor cells in an autocrine fashion and in the stimulation of stromal cell growth through paracrine and possibly autocrine mechanisms. Moreover, remarkably strong immunostaining of PDGF and the PDGF α-receptor was seen on peripheral nerve fibers.
Ulf Eriksson - One of the best experts on this subject based on the ideXlab platform.
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platelet derived growth factor production by b16 melanoma cells leads to increased pericyte abundance in tumors and an associated increase in tumor growth rate
Cancer Research, 2004Co-Authors: Masao Furuhashi, Ulf Eriksson, Christer Betsholtz, Tobias Sjoblom, Alexandra Abramsson, Jens Ellingsen, Patrick Micke, Erika Bergstenfolestad, Rainer Heuchel, Carlhenrik HeldinAbstract:Platelet-derived growth factor (PDGF) receptor signaling participates in different processes in solid tumors, including autocrine stimulation of tumor cell growth, recruitment of tumor stroma fibroblasts, and stimulation of tumor angiogenesis. In the present study, the B16 mouse melanoma tumor model was used to investigate the functional consequences of paracrine PDGF stimulation of host-derived cells. Production of PDGF-BB or PDGF-DD by tumor cells was associated with an increased tumor growth rate. Characterization of tumors revealed an increase in pericyte abundance in tumors derived from B16 cells producing PDGF-BB or PDGF-DD. The increased tumor growth rate associated with PDGF-DD production was not seen in mice expressing an attenuated PDGF β-receptor and was thus dependent on host PDGF β-receptor signaling. The increased pericyte abundance was not associated with an increased tumor vessel density. However, tumor cell apoptosis, but not proliferation, was reduced in tumors displaying PDGF-induced increased pericyte coverage. Our findings thus demonstrate that paracrine PDGF production stimulates pericyte recruitment to tumor vessels and suggest that pericyte abundance influences tumor cell apoptosis and tumor growth.
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structure expression and receptor binding properties of novel vascular endothelial growth factors
Current Topics in Microbiology and Immunology, 1999Co-Authors: Ulf ErikssonAbstract:Vascular endothelial growth factor (VEGF), an important regulator of endothelial cell physiology, was identified some 10 years ago and has, since then, been recognised as the major growth factor relatively specific for endothelial cells (reviewed in Ferrara and Davis-Smyth 1997). VEGF is a dimeric glycoprotein, closely related to placenta growth factor (PIGF). Both VEGF and PIGF are distantly related in structure to the platelet-derived growth factors A and B (PDGF A and PDGF B) (Heldin et al. 1993). Three novel growth factors belonging to the family of VEGF, PIGF and the two PDGFs were recently discovered. These growth factors, termed vascular endothelial growth factor B/VEGF-related factor (VEGF-B/VRF) (Grimmond et al. 1996; Olofsson et al. 1996a), vascular endothelial growth factor C/VEGF-related protein (VEGF-C/VRP) (Joukov et al. 1996; Lee et al. 1996)] and c-fos-induced growth factor (F1GF) (Orlandini et al. 1996) share structural features typical of the VEGF/PDGF growth factor family. The prominent structural similarities between VEGF-related growth factors, several of which target endothelial cells, and FIGF suggest the possibility that F1GF also targets endothelial cells, despite its identification as a fibroblast growth factor. Based on these criteria, we propose that the name FIGF should be changed to VEGF-D to indicate its structural and functional relatedness to other VEGFs.
Tatsuya Mimura - One of the best experts on this subject based on the ideXlab platform.
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role of soluble vascular endothelial growth factor receptors 1 and 2 their ligands and other factors in branch retinal vein occlusion with macular edema
Investigative Ophthalmology & Visual Science, 2014Co-Authors: Hidetaka Noma, Tatsuya Mimura, Kanako Yasuda, Masahiko ShimuraAbstract:Purpose To evaluate the association between multiple factors in aqueous humor and the severity of macular edema in patients with branch retinal vein occlusion (BRVO). Methods We measured the aqueous humor levels of 11 factors (including vascular endothelial growth factor receptors, growth factors, and inflammatory factors) in BRVO patients with macular edema and in cataract patients as controls. Aqueous humor samples were obtained from 40 patients (31 patients with BRVO and 9 with cataract). Then the levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor (sVEGFR)-1, sVEGFR-2, placental growth factor (PlGF), soluble intercellular adhesion molecule (sICAM)-1, monocyte chemotactic protein (MCP)-1, platelet-derived growth factor (PDGF)-AA, interleukin (IL)-6, IL-8, IL-12(p70), and IL-13 were measured by the suspension array method. Macular edema was examined by optical coherence tomography, and its severity was determined from the central macular thickness (CMT), neurosensory retinal thickness (TNeuro), and subfoveal serous retinal thickness (SRT). Results Aqueous humor levels of growth factors, sVEGFR-1, sVEGFR-2, and inflammatory factors were significantly higher in eyes with BRVO than in control eyes. Aqueous levels of sVEGFR-1 and -2 were significantly correlated with the SRT, as well as with the levels of growth factors (PIGF and PDGF-AA) and various inflammatory factors (sICAM-1, MCP-1, IL-6, and IL-8). Levels of the growth factors (VEGF, PlGF, and PDGF-AA) were also significantly correlated with each other. Conclusions These findings suggest the importance of the cytokine network in BRVO patients, and may contribute to understanding the mechanism of macular edema associated with BRVO and to development of new treatments.
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role of soluble vascular endothelial growth factor receptors 1 and 2 their ligands and other factors in branch retinal vein occlusion with macular edema
Investigative Ophthalmology & Visual Science, 2014Co-Authors: Hidetaka Noma, Tatsuya Mimura, Kanako Yasuda, Masahiko ShimuraAbstract:METHODS. We measured the aqueous humor levels of 11 factors (including vascular endothelial growth factor receptors, growth factors, and inflammatory factors) in BRVO patients with macular edema and in cataract patients as controls. Aqueous humor samples were obtained from 40 patients (31 patients with BRVO and 9 with cataract). Then the levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor (sVEGFR)-1, sVEGFR-2, placental growth factor (PlGF), soluble intercellular adhesion molecule (sICAM)1, monocyte chemotactic protein (MCP)-1, platelet-derived growth factor (PDGF)-AA, interleukin (IL)-6, IL-8, IL-12(p70), and IL-13 were measured by the suspension array method. Macular edema was examined by optical coherence tomography, and its severity was determined from the central macular thickness (CMT), neurosensory retinal thickness (TNeuro), and subfoveal serous retinal thickness (SRT). RESULTS. Aqueous humor levels of growth factors, sVEGFR-1, sVEGFR-2, and inflammatory factors were significantly higher in eyes with BRVO than in control eyes. Aqueous levels of sVEGFR-1 and -2 were significantly correlated with the SRT, as well as with the levels of growth factors (PIGF and PDGF-AA) and various inflammatory factors (sICAM-1, MCP-1, IL-6, and IL-8). Levels of the growth factors (VEGF, PlGF, and PDGF-AA) were also significantly correlated with each other. CONCLUSIONS. These findings suggest the importance of the cytokine network in BRVO patients, and may contribute to understanding the mechanism of macular edema associated with BRVO and to development of new treatments.