The Experts below are selected from a list of 141 Experts worldwide ranked by ideXlab platform
Edmund J Miller - One of the best experts on this subject based on the ideXlab platform.
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a synthetic peptide inhibitor for Alpha Chemokines inhibits the tumour growth and pulmonary metastasis of human melanoma cells in nude mice
Melanoma Research, 1999Co-Authors: Nobumitsu Fujisawa, Shinichiro Hayashi, Edmund J MillerAbstract:: Growth-related oncogene-Alpha (GROAlpha) was first described as an autocrine mitogen and growth factor for melanoma cells. More recent studies show that GROAlpha, interleukin-8 (IL-8) and other members of the Alpha-chemokine superfamily are also angiogenic. Therefore, we sought to determine if inhibitors of the Alpha-chemokine receptor would be effective in inhibiting the tumour growth and pulmonary metastasis of human melanoma cells. We determined that melanocytes and 12 human melanoma cell lines produce both GROAlpha and IL-8. The proliferation of A375SM, a highly metastatic cell line, and C8161-C were significantly increased by human recombinant GROAlpha and inhibited by anti-human GROAlpha monoclonal antibody. Antileukinate, a potent inhibitor of Alpha-chemokine receptor binding, inhibited the binding of GROAlpha to its receptors in melanocytes and all 12 melanoma cell lines tested. Antileukinate also suppressed proliferation of A375SM and C8161-C cells in a dose-dependent manner, and the suppression was not due to cytotoxic effects. Furthermore, continuous administration of antileukinate inhibited the tumour growth and pulmonary metastasis of A375SM cells in athymic BALB/c nude mice. These findings suggest that antileukinate inhibits the growth of melanoma cells by preventing GROAlpha from binding to its receptors. This suggests a possible use of Alpha-chemokine receptor inhibitors such as antileukinate in the treatment of malignant melanoma.
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a synthetic peptide inhibitor for Alpha Chemokines inhibits the growth of melanoma cell lines
Journal of Clinical Investigation, 1997Co-Authors: Shinichiro Hayashi, Anna K Kurdowska, Allen B Cohen, Michael D Stevens, Nobumitsu Fujisawa, Edmund J MillerAbstract:Melanoma growth stimulatory activity (MGSA/GROAlpha) is a 73 amino acid peptide sharing sequence characteristics with the Alpha-chemokine superfamily. MGSA/GROAlpha is produced by diverse melanoma cell lines and reported to act as an autocrine growth factor for the cells. We tested the binding of MGSA/GROAlpha to melanoma cell lines, Hs 294T and RPMI7951, and found that these cells could bind to MGSA/GROAlpha but not to interleukin-8. Recently, we defined a novel hexapeptide, antileukinate, which is a potent inhibitor of binding of Alpha-Chemokines to their receptors on neutrophils. When antileukinate was added to melanoma cells, it inhibited the binding of MGSA/ GROAlpha. The growth of cells from both melanoma cell lines was suppressed completely in the presence of 100 microM peptide. The cell growth inhibition was reversed by the removal of the peptide from the culture media or by the addition of the excess amount of MGSA/GROAlpha. The viability of Hs 294T cells in the presence of 100 microM peptide was > 92%. These findings suggest that MGSA/GROAlpha is an essential autostimulatory growth factor for melanoma cells and antileukinate inhibits their growth by preventing MGSA/GROAlpha from binding to its receptors.
Ernst Brandt - One of the best experts on this subject based on the ideXlab platform.
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regulation of neutrophil activation by proteolytic processing of platelet derived Alpha Chemokines
Advances in Experimental Medicine and Biology, 1997Co-Authors: H D Flad, Luc Harter, Frank Petersen, Janerik Ehlert, Andreas Ludwig, Lothar Bock, Ernst BrandtAbstract:In recent years evidence has been accumulated that platelets besides their function in coagulation play an important role in inflammation and wound repair. Upon activation platelets release a variety of mediators, among which members of the α-chemokine subfamily of proinflammatory cytokines have been identified. These platelet-derived polypeptides do not only comprise members of the so-called s-thromboglobulin family, such as platelet basic protein (PBP), connective tissue-activating peptide III (CTAP-III), and neutrophil-activating peptide 2 (NAP-2)1, but also platelet factor 4 (PF4)2,3 and the s-chemokine RANTES (Regulated upon activation normal T cell expressed and probably secreted)4. While s-Chemokines have been shown to activate monocytes, T lymphocytes and eosinophils, α-Chemokines such as IL-8, NAP-2 and melanoma growth-stimulating activity (MGSA/gro-α) appear to represent rather selective activators of polymorphonuclear leukocytes (PMN)5. Importantly, their biological activity, such as chemotaxis and degranulation-inducing capacity, has been demonstrated to be closely connected with the presence of an N-terminal glutamic acid-leucine-arginine (ELR) motif. Only recently, attention has been paid to the regulatory properties of α-Chemokines. In the present article we will focus on two aspects of regulation of PMN functions, namely 1. the proteolytic processing of platelet-derived α-Chemokines as a regulatory event in the induction and modulation of PMN activation, and 2. the phenotypic and functional consequences for the PMN under the constraints of such regulatory events.
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tnf Alpha renders human neutrophils responsive to platelet factor 4 comparison of pf 4 and il 8 reveals different activity profiles of the two Chemokines
Journal of Immunology, 1996Co-Authors: Frank Petersen, H D Flad, Andreas Ludwig, Ernst BrandtAbstract:Platelet factor 4 (PF-4), like IL-8, is a member of the chemokine superfamily of proinflammatory cytokines. However, although the capacity of IL-8 to stimulate functions in neutrophils is well established, reports on PF-4 are still contradictory. In the present study, we have prepared highly purified PF-4 and examined its ability to induce chemotaxis, degranulation, adhesion to gelatin and plasma proteins, and changes in intracellular calcium levels. Even over a broad range of concentrations, PF-4 alone was unable to induce functional changes in PMN. However, neutrophils pre- or co-incubated with physiologically relevant concentrations of TNF-Alpha responded to PF-4 by the selective mobilization of the secondary granule marker lactoferrin but not of the primary granule marker elastase. Contrary to IL-8, PMN did not require pretreatment with cytochalasin B for PF-4-induced exocytosis of lactoferrin. The synergistic effect of PF-4 with TNF-Alpha was not a priming phenomenon because the cooperative response remained unchanged even when TNF-Alpha was added 5 min after the chemokine. In contrast, TNF-Alpha-treated PMN did not respond to PF-4 by chemotaxis or by an increase of intracellular calcium levels, and no competition of PF-4 for IL-8 receptors was observed. Our results suggest a mechanism as well as a biologic role of PF-4 in the regulation of neutrophil function, which is different from that of IL-8 and other Alpha-Chemokines.
Nobumitsu Fujisawa - One of the best experts on this subject based on the ideXlab platform.
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a synthetic peptide inhibitor for Alpha Chemokines inhibits the tumour growth and pulmonary metastasis of human melanoma cells in nude mice
Melanoma Research, 1999Co-Authors: Nobumitsu Fujisawa, Shinichiro Hayashi, Edmund J MillerAbstract:: Growth-related oncogene-Alpha (GROAlpha) was first described as an autocrine mitogen and growth factor for melanoma cells. More recent studies show that GROAlpha, interleukin-8 (IL-8) and other members of the Alpha-chemokine superfamily are also angiogenic. Therefore, we sought to determine if inhibitors of the Alpha-chemokine receptor would be effective in inhibiting the tumour growth and pulmonary metastasis of human melanoma cells. We determined that melanocytes and 12 human melanoma cell lines produce both GROAlpha and IL-8. The proliferation of A375SM, a highly metastatic cell line, and C8161-C were significantly increased by human recombinant GROAlpha and inhibited by anti-human GROAlpha monoclonal antibody. Antileukinate, a potent inhibitor of Alpha-chemokine receptor binding, inhibited the binding of GROAlpha to its receptors in melanocytes and all 12 melanoma cell lines tested. Antileukinate also suppressed proliferation of A375SM and C8161-C cells in a dose-dependent manner, and the suppression was not due to cytotoxic effects. Furthermore, continuous administration of antileukinate inhibited the tumour growth and pulmonary metastasis of A375SM cells in athymic BALB/c nude mice. These findings suggest that antileukinate inhibits the growth of melanoma cells by preventing GROAlpha from binding to its receptors. This suggests a possible use of Alpha-chemokine receptor inhibitors such as antileukinate in the treatment of malignant melanoma.
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a synthetic peptide inhibitor for Alpha Chemokines inhibits the growth of melanoma cell lines
Journal of Clinical Investigation, 1997Co-Authors: Shinichiro Hayashi, Anna K Kurdowska, Allen B Cohen, Michael D Stevens, Nobumitsu Fujisawa, Edmund J MillerAbstract:Melanoma growth stimulatory activity (MGSA/GROAlpha) is a 73 amino acid peptide sharing sequence characteristics with the Alpha-chemokine superfamily. MGSA/GROAlpha is produced by diverse melanoma cell lines and reported to act as an autocrine growth factor for the cells. We tested the binding of MGSA/GROAlpha to melanoma cell lines, Hs 294T and RPMI7951, and found that these cells could bind to MGSA/GROAlpha but not to interleukin-8. Recently, we defined a novel hexapeptide, antileukinate, which is a potent inhibitor of binding of Alpha-Chemokines to their receptors on neutrophils. When antileukinate was added to melanoma cells, it inhibited the binding of MGSA/ GROAlpha. The growth of cells from both melanoma cell lines was suppressed completely in the presence of 100 microM peptide. The cell growth inhibition was reversed by the removal of the peptide from the culture media or by the addition of the excess amount of MGSA/GROAlpha. The viability of Hs 294T cells in the presence of 100 microM peptide was > 92%. These findings suggest that MGSA/GROAlpha is an essential autostimulatory growth factor for melanoma cells and antileukinate inhibits their growth by preventing MGSA/GROAlpha from binding to its receptors.
Shinichiro Hayashi - One of the best experts on this subject based on the ideXlab platform.
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a synthetic peptide inhibitor for Alpha Chemokines inhibits the tumour growth and pulmonary metastasis of human melanoma cells in nude mice
Melanoma Research, 1999Co-Authors: Nobumitsu Fujisawa, Shinichiro Hayashi, Edmund J MillerAbstract:: Growth-related oncogene-Alpha (GROAlpha) was first described as an autocrine mitogen and growth factor for melanoma cells. More recent studies show that GROAlpha, interleukin-8 (IL-8) and other members of the Alpha-chemokine superfamily are also angiogenic. Therefore, we sought to determine if inhibitors of the Alpha-chemokine receptor would be effective in inhibiting the tumour growth and pulmonary metastasis of human melanoma cells. We determined that melanocytes and 12 human melanoma cell lines produce both GROAlpha and IL-8. The proliferation of A375SM, a highly metastatic cell line, and C8161-C were significantly increased by human recombinant GROAlpha and inhibited by anti-human GROAlpha monoclonal antibody. Antileukinate, a potent inhibitor of Alpha-chemokine receptor binding, inhibited the binding of GROAlpha to its receptors in melanocytes and all 12 melanoma cell lines tested. Antileukinate also suppressed proliferation of A375SM and C8161-C cells in a dose-dependent manner, and the suppression was not due to cytotoxic effects. Furthermore, continuous administration of antileukinate inhibited the tumour growth and pulmonary metastasis of A375SM cells in athymic BALB/c nude mice. These findings suggest that antileukinate inhibits the growth of melanoma cells by preventing GROAlpha from binding to its receptors. This suggests a possible use of Alpha-chemokine receptor inhibitors such as antileukinate in the treatment of malignant melanoma.
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a synthetic peptide inhibitor for Alpha Chemokines inhibits the growth of melanoma cell lines
Journal of Clinical Investigation, 1997Co-Authors: Shinichiro Hayashi, Anna K Kurdowska, Allen B Cohen, Michael D Stevens, Nobumitsu Fujisawa, Edmund J MillerAbstract:Melanoma growth stimulatory activity (MGSA/GROAlpha) is a 73 amino acid peptide sharing sequence characteristics with the Alpha-chemokine superfamily. MGSA/GROAlpha is produced by diverse melanoma cell lines and reported to act as an autocrine growth factor for the cells. We tested the binding of MGSA/GROAlpha to melanoma cell lines, Hs 294T and RPMI7951, and found that these cells could bind to MGSA/GROAlpha but not to interleukin-8. Recently, we defined a novel hexapeptide, antileukinate, which is a potent inhibitor of binding of Alpha-Chemokines to their receptors on neutrophils. When antileukinate was added to melanoma cells, it inhibited the binding of MGSA/ GROAlpha. The growth of cells from both melanoma cell lines was suppressed completely in the presence of 100 microM peptide. The cell growth inhibition was reversed by the removal of the peptide from the culture media or by the addition of the excess amount of MGSA/GROAlpha. The viability of Hs 294T cells in the presence of 100 microM peptide was > 92%. These findings suggest that MGSA/GROAlpha is an essential autostimulatory growth factor for melanoma cells and antileukinate inhibits their growth by preventing MGSA/GROAlpha from binding to its receptors.
Frank Petersen - One of the best experts on this subject based on the ideXlab platform.
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regulation of neutrophil activation by proteolytic processing of platelet derived Alpha Chemokines
Advances in Experimental Medicine and Biology, 1997Co-Authors: H D Flad, Luc Harter, Frank Petersen, Janerik Ehlert, Andreas Ludwig, Lothar Bock, Ernst BrandtAbstract:In recent years evidence has been accumulated that platelets besides their function in coagulation play an important role in inflammation and wound repair. Upon activation platelets release a variety of mediators, among which members of the α-chemokine subfamily of proinflammatory cytokines have been identified. These platelet-derived polypeptides do not only comprise members of the so-called s-thromboglobulin family, such as platelet basic protein (PBP), connective tissue-activating peptide III (CTAP-III), and neutrophil-activating peptide 2 (NAP-2)1, but also platelet factor 4 (PF4)2,3 and the s-chemokine RANTES (Regulated upon activation normal T cell expressed and probably secreted)4. While s-Chemokines have been shown to activate monocytes, T lymphocytes and eosinophils, α-Chemokines such as IL-8, NAP-2 and melanoma growth-stimulating activity (MGSA/gro-α) appear to represent rather selective activators of polymorphonuclear leukocytes (PMN)5. Importantly, their biological activity, such as chemotaxis and degranulation-inducing capacity, has been demonstrated to be closely connected with the presence of an N-terminal glutamic acid-leucine-arginine (ELR) motif. Only recently, attention has been paid to the regulatory properties of α-Chemokines. In the present article we will focus on two aspects of regulation of PMN functions, namely 1. the proteolytic processing of platelet-derived α-Chemokines as a regulatory event in the induction and modulation of PMN activation, and 2. the phenotypic and functional consequences for the PMN under the constraints of such regulatory events.
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tnf Alpha renders human neutrophils responsive to platelet factor 4 comparison of pf 4 and il 8 reveals different activity profiles of the two Chemokines
Journal of Immunology, 1996Co-Authors: Frank Petersen, H D Flad, Andreas Ludwig, Ernst BrandtAbstract:Platelet factor 4 (PF-4), like IL-8, is a member of the chemokine superfamily of proinflammatory cytokines. However, although the capacity of IL-8 to stimulate functions in neutrophils is well established, reports on PF-4 are still contradictory. In the present study, we have prepared highly purified PF-4 and examined its ability to induce chemotaxis, degranulation, adhesion to gelatin and plasma proteins, and changes in intracellular calcium levels. Even over a broad range of concentrations, PF-4 alone was unable to induce functional changes in PMN. However, neutrophils pre- or co-incubated with physiologically relevant concentrations of TNF-Alpha responded to PF-4 by the selective mobilization of the secondary granule marker lactoferrin but not of the primary granule marker elastase. Contrary to IL-8, PMN did not require pretreatment with cytochalasin B for PF-4-induced exocytosis of lactoferrin. The synergistic effect of PF-4 with TNF-Alpha was not a priming phenomenon because the cooperative response remained unchanged even when TNF-Alpha was added 5 min after the chemokine. In contrast, TNF-Alpha-treated PMN did not respond to PF-4 by chemotaxis or by an increase of intracellular calcium levels, and no competition of PF-4 for IL-8 receptors was observed. Our results suggest a mechanism as well as a biologic role of PF-4 in the regulation of neutrophil function, which is different from that of IL-8 and other Alpha-Chemokines.
