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Kiangteck J Yeo - One of the best experts on this subject based on the ideXlab platform.
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vascular Permeability Factor and vascular endothelial growth Factor in ovarian hyperstimulation syndrome a preliminary report
Fertility and Sterility, 1996Co-Authors: Kiangteck J Yeo, Joel S Krasnow, Sarah L Berga, David S Guzick, Anthony J ZeleznikAbstract:Objective To determine whether serum levels of vascular Permeability Factor (VPF) are elevated in patients with ovarian hyperstimulation syndrome (OHSS) and to determine if luteinizing granulosa cells may be a source of VPF. Design Prospective observational study. Setting University IVF and GIFT program. Patients Eight consecutive IVF and GIFT patients at high risk for OHSS. Main Outcome Measures Vascular Permeability Factor concentration in serum and follicular fluid. Results Serum VPF was significantly higher (15.2 ± 4.0 pM; mean ± SEM) on day +14 in the group who developed severe OHSS compared with those who did not. Follicular fluid VPF (171.5 ± 18.5 pM) was approximately 100-fold greater than serum (1.7 ± 1.3 pM) or peritoneal fluid (2.5 ± 1.3 pM) 36 hours after hCG administration. Conclusion Vascular Permeability Factor is elevated in patients with severe OHSS and the ovary may be a source of VPF secretion.
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Vascular Permeability Factor (vascular endothelial growth Factor) is strongly expressed in the normal male genital tract and is present in substantial quantities in semen.
The Journal of urology, 1995Co-Authors: Lawrence F. Brown, Brygida Berse, Harold F. Dvorak, Kiangteck J Yeo, Abraham Morgentaler, Seymour RosenAbstract:AbstractPurpose: Vascular Permeability Factor (VPF) is a potent inducer of microvascular hyperPermeability and stimulates endothelial cell growth and angiogenesis. This study examines expression of VPF in the male genital tract.Materials and Methods: Vascular Permeability Factor in seminal plasma was quantified by immunoassay. Vascular Permeability Factor mRNA and protein expression in tissue were studied by situ hybridization and immunohistochemistry.Results: All seminal plasmas studied contained high levels of VPF. Prostatic and seminal vesicle epithelium labeled strongly for VPF mRNA and protein.Conclusions: The strong expression of VPF in prostate and seminal vesicle and the high concentration of VPF in semen suggest an important role for this cytokine in male fertility.
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overexpression of vascular Permeability Factor vascular endothelial growth Factor and its receptors in psoriasis
Journal of Experimental Medicine, 1994Co-Authors: Michael Detmar, Lawrence F. Brown, Brygida Berse, Kiangteck J Yeo, Robert W Jackman, Kevin P. Claffey, Olivier Kocher, Harold F. DvorakAbstract:Psoriatic skin is characterized by microvascular hyperPermeability and angioproliferation, but the mechanisms responsible are unknown. We report here that the hyperplastic epidermis of psoriatic skin expresses strikingly increased amounts of vascular Permeability Factor (VPF; vascular endothelial growth Factor), a selective endothelial cell mitogen that enhances microvascular Permeability. Moreover, two VPF receptors, kdr and flt-1, are overexpressed by papillary dermal microvascular endothelial cells. Transforming growth Factor alpha (TGF-alpha), a cytokine that is also overexpressed in psoriatic epidermis, induced VPF gene expression by cultured epidermal keratinocytes. VPF secreted by TGF-alpha-stimulated keratinocytes was bioactive, as demonstrated by its mitogenic effect on dermal microvascular endothelial cells in vitro. Together, these findings suggest that TGF-alpha regulates VPF expression in psoriasis by an autocrine mechanism, leading to vascular hyperPermeability and angiogenesis. Similar mechanisms may operate in tumors and in healing skin wounds which also commonly express both VPF and TGF-alpha.
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vascular Permeability Factor vpf vegf in tumor biology
Cancer and Metastasis Reviews, 1993Co-Authors: Donald R. Senger, Lawrence F. Brown, Brygida Berse, Kiangteck J Yeo, Tetkin Yeo, L Van De Water, Janice A Nagy, Robert W Jackman, Ann M Dvorak, Harold F. DvorakAbstract:Vascular Permeability Factor (VPF), also known as vascular endothelial growth Factor (VEGF), is a multifunctional cytokine expressed and secreted at high levels by many tumor cells of animal and human origin. As secreted by tumor cells, VPF/VEGF is a 34–42 kDa heparin-binding, dimeric, disulfide-bonded glycoprotein that acts directly on endothelial cells (EC) by way of specific receptors to activate phospholipase C and induce [Ca2+]i transients. Two high affinity VPF/VEGF receptors, both tyrosine kinases, have thus far been described. VPF/VEGF is likely to have a number of important roles in tumor biology related, but not limited to, the process of tumor angiogenesis. As a potent Permeability Factor, VPF/VEGF promotes extravasation of plasma fibrinogen, leading to fibrin deposition which alters the tumor extracellular matrix. This matrix promotes the ingrowth of macrophages, fibroblasts, and endothelial cells. Moreover, VPF/VEGF is a selective endothelial cell (EC) growth Factorin vitro, and it presumably stimulates EC proliferationin vivo. Furthermore, VPF/VEGF has been found in animal and human tumor effusions by immunoassay and by functional assays and very likely accounts for the induction of malignant ascites. In addition to its role in tumors, VPF/VEGF has recently been found to have a role in wound healing and its expression by activated macrophages suggests that it probably also participates in certain types of chronic inflammation. VPF/VEGF is expressed in normal development and in certain normal adult organs, notably kidney, heart, adrenal gland and lung. Its functions in normal adult tissues are under investigation.
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synthesis and secretion of vascular Permeability Factor vascular endothelial growth Factor by human retinal pigment epithelial cells
Biochemical and Biophysical Research Communications, 1993Co-Authors: Anthony P Adamis, Lawrence F. Brown, Brygida Berse, David T Shima, Kiangteck J Yeo, Tetkin Yeo, Patricia A Damore, Judah FolkmanAbstract:The presence of the secreted angiogenic molecule, vascular Permeability Factor/vascular endothelial growth Factor, was investigated in human retinal pigment epithelial cells. Northern and in situ hybridization analysis of cultured cells identified vascular Permeability Factor/vascular endothelial growth Factor mRNA. Western analysis of cell lysates identified a 42 kD protein that comigrated with human recombinant vascular Permeability Factor/vascular endothelial growth Factor. Immunoassay measurements detected vascular Permeability Factor/vascular endothelial growth Factor protein in cell lysates and conditioned media in vitro and in cell lysates isolated directly from post-mortem eyes. These data demonstrate that human retinal pigment epithelial cells can synthesize the secreted angiogenic peptide vascular Permeability Factor/vascular endothelial growth Factor in vitro and in situ. The production and secretion of this Factor by human retinal pigment epithelial cells may be important in the pathogenesis of ocular neovascularization.
Lawrence F. Brown - One of the best experts on this subject based on the ideXlab platform.
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Heterogeneity of the angiogenic response induced in different normal adult tissues by vascular Permeability Factor/vascular endothelial growth Factor.
Laboratory investigation; a journal of technical methods and pathology, 2000Co-Authors: Anna Pettersson, Lawrence F. Brown, Janice A Nagy, Christian Sundberg, Ellen S Morgan, Jose Eduardo Krieger, Jungles S, Carter R, Eleanor J. ManseauAbstract:Heterogeneity of the Angiogenic Response Induced in Different Normal Adult Tissues by Vascular Permeability Factor/Vascular Endothelial Growth Factor
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heterogeneity of the angiogenic response induced in different normal adult tissues by vascular Permeability Factor vascular endothelial growth Factor
Laboratory Investigation, 2000Co-Authors: Anna Pettersson, Lawrence F. Brown, Janice A Nagy, Christian Sundberg, Ellen S Morgan, S Jungles, R Carter, Jose Eduardo Krieger, Eleanor J. ManseauAbstract:Heterogeneity of the Angiogenic Response Induced in Different Normal Adult Tissues by Vascular Permeability Factor/Vascular Endothelial Growth Factor
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vascular Permeability Factor vascular endothelial growth Factor and the significance of microvascular hyperPermeability in angiogenesis
Current Topics in Microbiology and Immunology, 1999Co-Authors: Lawrence F. Brown, Harold F. Dvorak, Janice A Nagy, Ann M Dvorak, Dian FengAbstract:Vascular Permeability Factor/vascular endothelial growth Factor (VPF/VEGF) was originally discovered in the late 1970s because of its capacity to increase the Permeability of microvessels to plasma and plasma proteins (Dvorak et al. 1979a,b). Using plastic-embedded, light microscopic section and, subsequent, immunohistochemistry, we noted that transplantable tumors growing in guinea pigs and rodents exhibit substantial deposits of fibrin in their stroma. Fibrin results from the clotting of fibrinogen, a 340kDa plasma protein which, under normal circumstances, is retained almost quantitatively within the blood vasculature. For fibrin to be deposited outside of blood vessels in tumor stroma, it was necessary that two requirements be met; namely, (1) that microvessels be abnormally hyperpermeable to permit the escape of fibrinogen and other plasma proteins necessary for blood clotting and (2) that there be a mechanism in place for activating the clotting system. In fact, both requirements were found to be met in tumors. The microvessels supplying tumors were hyperpermeable to fibrinogen and other plasma proteins, and both tumor cells and host stromal cells were capable of initiating extravascular coagulation via the tissue-Factor pathway. Encouraged by these findings, we initiated a search for a tumor product that could account for tumor-vessels hyperPermeability. A potent vascular permeabilizing protein was soon found in serum-free tumor culture supernatants (Dvorak et al. 1979a,b) and was subsequently purified to homogeneity and given the name vascular Permeability Factor (VPF) (Senger et al. 1983, 1986, 1987, 1990).
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Vascular Permeability Factor/vascular endothelial growth Factor and the significance of microvascular hyperPermeability in angiogenesis.
Current topics in microbiology and immunology, 1999Co-Authors: Harold F. Dvorak, Lawrence F. Brown, Janice A Nagy, Dian Feng, Ann M DvorakAbstract:Vascular Permeability Factor/vascular endothelial growth Factor (VPF/VEGF) was originally discovered in the late 1970s because of its capacity to increase the Permeability of microvessels to plasma and plasma proteins (Dvorak et al. 1979a,b). Using plastic-embedded, light microscopic section and, subsequent, immunohistochemistry, we noted that transplantable tumors growing in guinea pigs and rodents exhibit substantial deposits of fibrin in their stroma. Fibrin results from the clotting of fibrinogen, a 340kDa plasma protein which, under normal circumstances, is retained almost quantitatively within the blood vasculature. For fibrin to be deposited outside of blood vessels in tumor stroma, it was necessary that two requirements be met; namely, (1) that microvessels be abnormally hyperpermeable to permit the escape of fibrinogen and other plasma proteins necessary for blood clotting and (2) that there be a mechanism in place for activating the clotting system. In fact, both requirements were found to be met in tumors. The microvessels supplying tumors were hyperpermeable to fibrinogen and other plasma proteins, and both tumor cells and host stromal cells were capable of initiating extravascular coagulation via the tissue-Factor pathway. Encouraged by these findings, we initiated a search for a tumor product that could account for tumor-vessels hyperPermeability. A potent vascular permeabilizing protein was soon found in serum-free tumor culture supernatants (Dvorak et al. 1979a,b) and was subsequently purified to homogeneity and given the name vascular Permeability Factor (VPF) (Senger et al. 1983, 1986, 1987, 1990).
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Vascular Permeability Factor/Vascular Endothelial Growth Factor and Vascular Stroma Formation in Neoplasia: Insights from In Situ Hybridization Studies
The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society, 1998Co-Authors: Lawrence F. Brown, Kathi Tognazzi, Anthony J Guidi, Harold F. DvorakAbstract:The formation of vascular stroma plays an important role in the pathophysiology of malignancy. We describe the use of in situ hybridization in our laboratory as a tool to study the role of vascular Permeability Factor/vascular endothelial growth Factor in the angiogenesis associated with malignancy.
Harold F. Dvorak - One of the best experts on this subject based on the ideXlab platform.
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the neurotransmitter dopamine inhibits angiogenesis induced by vascular Permeability Factor vascular endothelial growth Factor
Nature Medicine, 2001Co-Authors: Sujit Basu, Eleanor J. Manseau, Harold F. Dvorak, Janice A Nagy, Eliza Vasile, Isabelle A Eckelhoefer, Susan V Bliss, Partha S Dasgupta, Debabrata MukhopadhyayAbstract:Angiogenesis has an essential role in many important pathological and physiological settings. It has been shown that vascular Permeability Factor/vascular endothelial growth Factor (VPF/VEGF), a potent cytokine expressed by most malignant tumors, has critical roles in vasculogenesis and both physiological and pathological angiogenesis. We report here that at non-toxic levels, the neurotransmitter dopamine strongly and selectively inhibited the vascular permeabilizing and angiogenic activities of VPF/VEGF. Dopamine acted through D2 dopamine receptors to induce endocytosis of VEGF receptor 2, which is critical for promoting angiogenesis, thereby preventing VPF/VEGF binding, receptor phosphorylation and subsequent signaling steps. The action of dopamine was specific for VPF/VEGF and did not affect other mediators of microvascular Permeability or endothelial-cell proliferation or migration. These results reveal a new link between the nervous system and angiogenesis and indicate that dopamine and other D2 receptors, already in clinical use for other purposes, might have value in anti-angiogenesis therapy.
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Vascular Permeability Factor/vascular endothelial growth Factor and the significance of microvascular hyperPermeability in angiogenesis.
Current topics in microbiology and immunology, 1999Co-Authors: Harold F. Dvorak, Lawrence F. Brown, Janice A Nagy, Dian Feng, Ann M DvorakAbstract:Vascular Permeability Factor/vascular endothelial growth Factor (VPF/VEGF) was originally discovered in the late 1970s because of its capacity to increase the Permeability of microvessels to plasma and plasma proteins (Dvorak et al. 1979a,b). Using plastic-embedded, light microscopic section and, subsequent, immunohistochemistry, we noted that transplantable tumors growing in guinea pigs and rodents exhibit substantial deposits of fibrin in their stroma. Fibrin results from the clotting of fibrinogen, a 340kDa plasma protein which, under normal circumstances, is retained almost quantitatively within the blood vasculature. For fibrin to be deposited outside of blood vessels in tumor stroma, it was necessary that two requirements be met; namely, (1) that microvessels be abnormally hyperpermeable to permit the escape of fibrinogen and other plasma proteins necessary for blood clotting and (2) that there be a mechanism in place for activating the clotting system. In fact, both requirements were found to be met in tumors. The microvessels supplying tumors were hyperpermeable to fibrinogen and other plasma proteins, and both tumor cells and host stromal cells were capable of initiating extravascular coagulation via the tissue-Factor pathway. Encouraged by these findings, we initiated a search for a tumor product that could account for tumor-vessels hyperPermeability. A potent vascular permeabilizing protein was soon found in serum-free tumor culture supernatants (Dvorak et al. 1979a,b) and was subsequently purified to homogeneity and given the name vascular Permeability Factor (VPF) (Senger et al. 1983, 1986, 1987, 1990).
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vascular Permeability Factor vascular endothelial growth Factor and the significance of microvascular hyperPermeability in angiogenesis
Current Topics in Microbiology and Immunology, 1999Co-Authors: Lawrence F. Brown, Harold F. Dvorak, Janice A Nagy, Ann M Dvorak, Dian FengAbstract:Vascular Permeability Factor/vascular endothelial growth Factor (VPF/VEGF) was originally discovered in the late 1970s because of its capacity to increase the Permeability of microvessels to plasma and plasma proteins (Dvorak et al. 1979a,b). Using plastic-embedded, light microscopic section and, subsequent, immunohistochemistry, we noted that transplantable tumors growing in guinea pigs and rodents exhibit substantial deposits of fibrin in their stroma. Fibrin results from the clotting of fibrinogen, a 340kDa plasma protein which, under normal circumstances, is retained almost quantitatively within the blood vasculature. For fibrin to be deposited outside of blood vessels in tumor stroma, it was necessary that two requirements be met; namely, (1) that microvessels be abnormally hyperpermeable to permit the escape of fibrinogen and other plasma proteins necessary for blood clotting and (2) that there be a mechanism in place for activating the clotting system. In fact, both requirements were found to be met in tumors. The microvessels supplying tumors were hyperpermeable to fibrinogen and other plasma proteins, and both tumor cells and host stromal cells were capable of initiating extravascular coagulation via the tissue-Factor pathway. Encouraged by these findings, we initiated a search for a tumor product that could account for tumor-vessels hyperPermeability. A potent vascular permeabilizing protein was soon found in serum-free tumor culture supernatants (Dvorak et al. 1979a,b) and was subsequently purified to homogeneity and given the name vascular Permeability Factor (VPF) (Senger et al. 1983, 1986, 1987, 1990).
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Vascular Permeability Factor/Vascular Endothelial Growth Factor and Vascular Stroma Formation in Neoplasia: Insights from In Situ Hybridization Studies
The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society, 1998Co-Authors: Lawrence F. Brown, Kathi Tognazzi, Anthony J Guidi, Harold F. DvorakAbstract:The formation of vascular stroma plays an important role in the pathophysiology of malignancy. We describe the use of in situ hybridization in our laboratory as a tool to study the role of vascular Permeability Factor/vascular endothelial growth Factor in the angiogenesis associated with malignancy.
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vascular Permeability Factor vascular endothelial growth Factor an important mediator of angiogenesis in malignancy and inflammation
International Archives of Allergy and Immunology, 1995Co-Authors: Harold F. Dvorak, Livingston Van De Water, Janice A Nagy, Kevin P. Claffey, Michael Detmar, Donald R. SengerAbstract:Vascular Permeability Factor (VPF), also known as vascular endothelial growth Factor (VEGF), is a multifunctional cytokine that is overexpressed in many transplantable animal and autochtonous human cancers, in healing wounds, and in chronic inflammatory disorders such as psoriasis and rheumatoid arthritis. All of these entities are characterized by angiogenesis, altered extracellular matrix, and variable degrees of hypoxia. In addition, two VPF/VEGF receptors, flt-1 and kdr, are overexpressed by endothelial cells that line the microvessels that supply these tumors/inflammatory reactions. On the basis of these and other data, we have proposed a model of angiogenesis in which VPF/VEGF plays a central role; this model is applicable to tumors and also to the angiogenesis that occurs in non-neoplastic processes.
Brygida Berse - One of the best experts on this subject based on the ideXlab platform.
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expression of vascular Permeability Factor vascular endothelial growth Factor and its receptors in breast cancer
Human Pathology, 1995Co-Authors: Lawrence F. Brown, Brygida Berse, Donald R. Senger, Harold F. Dvorak, Robert W Jackman, K Tognazzi, Anthony J Guidi, James L Connolly, Stuart J SchnittAbstract:Abstract Solid tumors must induce a vascular stroma to grow beyond a minimal size, and the intensity of the angiogenic response has been correlated with prognosis in breast cancer patients. Vascular Permeability Factor (VPF), also known as vascular endothelial growth Factor (VEGF), is a secreted protein that has been implicated in tumor-associated angiogenesis. Vascular Permeability Factor directly stimulates endothelial cell growth and also increases microvascular Permeability, leading to the extravasation of plasma proteins, which alter the extracellular matrix in a manner that promotes angiogenesis. To determine whether VPF has a role in breast cancer, we used in situ hybridization to study VPF mRNA expression in normal breast tissue (13 specimens), comedo-type ductal carcinoma in situ (DCIS) (four specimens), infiltrating ductal carcinoma (12 specimens), infiltrating lobular carcinoma (two specimens), metastatic ductal carcinoma (three specimens) and metastatic lobular carcinoma (one specimen). Vascular Permeability Factor mRNA was expressed at a low level by normal duct epithelium but was expressed at high levels in tumor cells in all cases of comedo-type DCIS, infiltrating ductal carcinoma, and metastatic ductal carcinoma. In contrast, VPF mRNA was not expressed at high levels in infiltrating lobular carcinoma. We also used in situ hybridization to study the expression of two recently described endothelial cell surface VPF receptors, flt-1 and kdr. Vascular Permeability Factor receptor mRNA was strongly expressed in endothelial cells of small vessels adjacent to malignant tumor cells in DCIS, infiltrating ductal carcinoma, and metastatic ductal carcinoma. In contrast, no definite labeling for receptor mRNA was detected in infiltrating lobular carcinoma or nonmalignant breast tissue. The intense expression of VPF mRNA by breast carcinoma cells and of VPF receptor mRNA by endothelial cells of adjacent small blood vessels provides strong evidence linking VPF expression to the angiogenesis associated with comedo-type DCIS, infiltrating ductal, and metastatic ductal breast carcinoma.
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Vascular Permeability Factor (vascular endothelial growth Factor) is strongly expressed in the normal male genital tract and is present in substantial quantities in semen.
The Journal of urology, 1995Co-Authors: Lawrence F. Brown, Brygida Berse, Harold F. Dvorak, Kiangteck J Yeo, Abraham Morgentaler, Seymour RosenAbstract:AbstractPurpose: Vascular Permeability Factor (VPF) is a potent inducer of microvascular hyperPermeability and stimulates endothelial cell growth and angiogenesis. This study examines expression of VPF in the male genital tract.Materials and Methods: Vascular Permeability Factor in seminal plasma was quantified by immunoassay. Vascular Permeability Factor mRNA and protein expression in tissue were studied by situ hybridization and immunohistochemistry.Results: All seminal plasmas studied contained high levels of VPF. Prostatic and seminal vesicle epithelium labeled strongly for VPF mRNA and protein.Conclusions: The strong expression of VPF in prostate and seminal vesicle and the high concentration of VPF in semen suggest an important role for this cytokine in male fertility.
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overexpression of vascular Permeability Factor vascular endothelial growth Factor and its receptors in psoriasis
Journal of Experimental Medicine, 1994Co-Authors: Michael Detmar, Lawrence F. Brown, Brygida Berse, Kiangteck J Yeo, Robert W Jackman, Kevin P. Claffey, Olivier Kocher, Harold F. DvorakAbstract:Psoriatic skin is characterized by microvascular hyperPermeability and angioproliferation, but the mechanisms responsible are unknown. We report here that the hyperplastic epidermis of psoriatic skin expresses strikingly increased amounts of vascular Permeability Factor (VPF; vascular endothelial growth Factor), a selective endothelial cell mitogen that enhances microvascular Permeability. Moreover, two VPF receptors, kdr and flt-1, are overexpressed by papillary dermal microvascular endothelial cells. Transforming growth Factor alpha (TGF-alpha), a cytokine that is also overexpressed in psoriatic epidermis, induced VPF gene expression by cultured epidermal keratinocytes. VPF secreted by TGF-alpha-stimulated keratinocytes was bioactive, as demonstrated by its mitogenic effect on dermal microvascular endothelial cells in vitro. Together, these findings suggest that TGF-alpha regulates VPF expression in psoriasis by an autocrine mechanism, leading to vascular hyperPermeability and angiogenesis. Similar mechanisms may operate in tumors and in healing skin wounds which also commonly express both VPF and TGF-alpha.
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vascular Permeability Factor vpf vegf in tumor biology
Cancer and Metastasis Reviews, 1993Co-Authors: Donald R. Senger, Lawrence F. Brown, Brygida Berse, Kiangteck J Yeo, Tetkin Yeo, L Van De Water, Janice A Nagy, Robert W Jackman, Ann M Dvorak, Harold F. DvorakAbstract:Vascular Permeability Factor (VPF), also known as vascular endothelial growth Factor (VEGF), is a multifunctional cytokine expressed and secreted at high levels by many tumor cells of animal and human origin. As secreted by tumor cells, VPF/VEGF is a 34–42 kDa heparin-binding, dimeric, disulfide-bonded glycoprotein that acts directly on endothelial cells (EC) by way of specific receptors to activate phospholipase C and induce [Ca2+]i transients. Two high affinity VPF/VEGF receptors, both tyrosine kinases, have thus far been described. VPF/VEGF is likely to have a number of important roles in tumor biology related, but not limited to, the process of tumor angiogenesis. As a potent Permeability Factor, VPF/VEGF promotes extravasation of plasma fibrinogen, leading to fibrin deposition which alters the tumor extracellular matrix. This matrix promotes the ingrowth of macrophages, fibroblasts, and endothelial cells. Moreover, VPF/VEGF is a selective endothelial cell (EC) growth Factorin vitro, and it presumably stimulates EC proliferationin vivo. Furthermore, VPF/VEGF has been found in animal and human tumor effusions by immunoassay and by functional assays and very likely accounts for the induction of malignant ascites. In addition to its role in tumors, VPF/VEGF has recently been found to have a role in wound healing and its expression by activated macrophages suggests that it probably also participates in certain types of chronic inflammation. VPF/VEGF is expressed in normal development and in certain normal adult organs, notably kidney, heart, adrenal gland and lung. Its functions in normal adult tissues are under investigation.
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synthesis and secretion of vascular Permeability Factor vascular endothelial growth Factor by human retinal pigment epithelial cells
Biochemical and Biophysical Research Communications, 1993Co-Authors: Anthony P Adamis, Lawrence F. Brown, Brygida Berse, David T Shima, Kiangteck J Yeo, Tetkin Yeo, Patricia A Damore, Judah FolkmanAbstract:The presence of the secreted angiogenic molecule, vascular Permeability Factor/vascular endothelial growth Factor, was investigated in human retinal pigment epithelial cells. Northern and in situ hybridization analysis of cultured cells identified vascular Permeability Factor/vascular endothelial growth Factor mRNA. Western analysis of cell lysates identified a 42 kD protein that comigrated with human recombinant vascular Permeability Factor/vascular endothelial growth Factor. Immunoassay measurements detected vascular Permeability Factor/vascular endothelial growth Factor protein in cell lysates and conditioned media in vitro and in cell lysates isolated directly from post-mortem eyes. These data demonstrate that human retinal pigment epithelial cells can synthesize the secreted angiogenic peptide vascular Permeability Factor/vascular endothelial growth Factor in vitro and in situ. The production and secretion of this Factor by human retinal pigment epithelial cells may be important in the pathogenesis of ocular neovascularization.
Tetkin Yeo - One of the best experts on this subject based on the ideXlab platform.
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vascular Permeability Factor vpf vegf in tumor biology
Cancer and Metastasis Reviews, 1993Co-Authors: Donald R. Senger, Lawrence F. Brown, Brygida Berse, Kiangteck J Yeo, Tetkin Yeo, L Van De Water, Janice A Nagy, Robert W Jackman, Ann M Dvorak, Harold F. DvorakAbstract:Vascular Permeability Factor (VPF), also known as vascular endothelial growth Factor (VEGF), is a multifunctional cytokine expressed and secreted at high levels by many tumor cells of animal and human origin. As secreted by tumor cells, VPF/VEGF is a 34–42 kDa heparin-binding, dimeric, disulfide-bonded glycoprotein that acts directly on endothelial cells (EC) by way of specific receptors to activate phospholipase C and induce [Ca2+]i transients. Two high affinity VPF/VEGF receptors, both tyrosine kinases, have thus far been described. VPF/VEGF is likely to have a number of important roles in tumor biology related, but not limited to, the process of tumor angiogenesis. As a potent Permeability Factor, VPF/VEGF promotes extravasation of plasma fibrinogen, leading to fibrin deposition which alters the tumor extracellular matrix. This matrix promotes the ingrowth of macrophages, fibroblasts, and endothelial cells. Moreover, VPF/VEGF is a selective endothelial cell (EC) growth Factorin vitro, and it presumably stimulates EC proliferationin vivo. Furthermore, VPF/VEGF has been found in animal and human tumor effusions by immunoassay and by functional assays and very likely accounts for the induction of malignant ascites. In addition to its role in tumors, VPF/VEGF has recently been found to have a role in wound healing and its expression by activated macrophages suggests that it probably also participates in certain types of chronic inflammation. VPF/VEGF is expressed in normal development and in certain normal adult organs, notably kidney, heart, adrenal gland and lung. Its functions in normal adult tissues are under investigation.
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synthesis and secretion of vascular Permeability Factor vascular endothelial growth Factor by human retinal pigment epithelial cells
Biochemical and Biophysical Research Communications, 1993Co-Authors: Anthony P Adamis, Lawrence F. Brown, Brygida Berse, David T Shima, Kiangteck J Yeo, Tetkin Yeo, Patricia A Damore, Judah FolkmanAbstract:The presence of the secreted angiogenic molecule, vascular Permeability Factor/vascular endothelial growth Factor, was investigated in human retinal pigment epithelial cells. Northern and in situ hybridization analysis of cultured cells identified vascular Permeability Factor/vascular endothelial growth Factor mRNA. Western analysis of cell lysates identified a 42 kD protein that comigrated with human recombinant vascular Permeability Factor/vascular endothelial growth Factor. Immunoassay measurements detected vascular Permeability Factor/vascular endothelial growth Factor protein in cell lysates and conditioned media in vitro and in cell lysates isolated directly from post-mortem eyes. These data demonstrate that human retinal pigment epithelial cells can synthesize the secreted angiogenic peptide vascular Permeability Factor/vascular endothelial growth Factor in vitro and in situ. The production and secretion of this Factor by human retinal pigment epithelial cells may be important in the pathogenesis of ocular neovascularization.
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Synthesis and secretion of vascular Permeability Factor/vascular endothelial growth Factor by human retinal pigment epithelial cells
Biochemical and biophysical research communications, 1993Co-Authors: Anthony P Adamis, Lawrence F. Brown, Brygida Berse, David T Shima, Kiangteck J Yeo, Tetkin Yeo, Patricia A. D'amore, Judah FolkmanAbstract:The presence of the secreted angiogenic molecule, vascular Permeability Factor/vascular endothelial growth Factor, was investigated in human retinal pigment epithelial cells. Northern and in situ hybridization analysis of cultured cells identified vascular Permeability Factor/vascular endothelial growth Factor mRNA. Western analysis of cell lysates identified a 42 kD protein that comigrated with human recombinant vascular Permeability Factor/vascular endothelial growth Factor. Immunoassay measurements detected vascular Permeability Factor/vascular endothelial growth Factor protein in cell lysates and conditioned media in vitro and in cell lysates isolated directly from post-mortem eyes. These data demonstrate that human retinal pigment epithelial cells can synthesize the secreted angiogenic peptide vascular Permeability Factor/vascular endothelial growth Factor in vitro and in situ. The production and secretion of this Factor by human retinal pigment epithelial cells may be important in the pathogenesis of ocular neovascularization.
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Development of time-resolved immunofluorometric assay of vascular Permeability Factor.
Clinical chemistry, 1992Co-Authors: Kiangteck J Yeo, Donald R. Senger, Tracy M. Sioussat, James D. Faix, Tetkin YeoAbstract:We describe a two-site time-resolved immunofluorometric assay for guinea pig vascular Permeability Factor (VPF) for quantifying VPF in different biological fluids. Antibody against the carboxy terminus (C-IgG) is immobilized on microtiter wells, and antibody against the amino terminus (N-IgG) is labeled with Eu(3+)-chelate. Line 10 tumor culture medium, known to be rich in VPF, is assayed in a two-step incubation. Bound Eu3+ is then quantified by dissociation into a fluorescent enhancement solution, with measurement of the time-resolved fluorescence. The analytical sensitivity is 0.35 VPF unit, and the intra-assay CV is about 20%. The assay is specific for VPF, because pre-treatment with the appropriate C- or N-peptide, or pre-extraction of VPF, greatly decreases fluorescence. The VPF immunoassay is highly correlated (r2 = 0.94) with the Miles Permeability assay, the classical bioassay of VPF. In addition, the immunofluorometric assay is about 30-fold more sensitive than the Miles assay.
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Glycosylation is essential for efficient secretion but not for Permeability-enhancing activity of vascular Permeability Factor (vascular endothelial growth Factor).
Biochemical and biophysical research communications, 1991Co-Authors: Tetkin Yeo, Donald R. Senger, Harold F. Dvorak, Lisa Freter, Kiangteck J YeoAbstract:Summary The hyperPermeability of the microvasculature supplying solid tumors is largely attributable to a heterodimeric M r 34,000–43,000 tumor-secreted protein, vascular Permeability Factor. Upon reduction, the vascular Permeability Factor secreted by line 10 tumor cells is resolved by SDS-PAGE into 3 discrete bands of M r 24,000, 19,500, and 15,000. We demonstrate here that line 10 vascular Permeability Factor is an N-linked glycoprotein. Nonglycosylated vascular Permeability Factor migrates on reduced SDS-PAGE as two bands of M r 20,000 and 15,000. Pulse-chase studies demonstrated that all three chains of native vascular Permeability Factor were secreted rapidly following synthesis and at equal rates, with a cellular half-retention time of ∼37 min. When glycosylation was prevented by tunicamycin, individual bands of nonglycosylated vascular Permeability Factor were also secreted at equivalent rates, but much more slowly (∼60 min) than native glycoprotein. Both glycosylated and nonglycosylated forms of vascular Permeability Factor were equally potent at increasing dermal vessel Permeability.