The Experts below are selected from a list of 261 Experts worldwide ranked by ideXlab platform
Manfred Westphal - One of the best experts on this subject based on the ideXlab platform.
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vascular endothelial Growth Factor hepatocyte Growth Factor scatter Factor basic fibroblast Growth Factor and placenta Growth Factor in human meningiomas and their relation to angiogenesis and malignancy
Neurosurgery, 2000Co-Authors: Katrin Lamszus, Ulrike Lengler, Suleyman Ergun, Dimitrios Stavrou, Nils-ole Schmidt, Manfred WestphalAbstract:OBJECTIVE: Angiogenesis is mediated by a number of different Growth Factors and appears vital for tumor Growth. The understanding of angiogenic mechanisms could offer new therapeutic perspectives; in this context, the role of four potentially angiogenic Growth Factors was analyzed in a large series of meningiomas of different grades. METHODS: Vascular endothelial Growth Factor (VEGF), placenta Growth Factor, hepatocyte Growth Factor/scatter Factor, and basic fibroblast Growth Factor were quantified in 69 tumors by enzyme-linked immunosorbent assay. Microvessel density and proliferative activity were determined on paraffin sections, and clinical tumor invasiveness was rated. Induction of endothelial chemotaxis and capillary-like tube formation were studied in vitro using modified Boyden chamber assays and three-dimensional collagen gel assays, respectively. RESULTS: Tumors included 40 benign (World Health Organization [WHO] Grade I), 21 atypical (WHO Grade II), and 8 anaplastic/malignant (WHO Grade III) meningiomas. We found a correlation between meningioma grade and VEGF content (r = 0.37, P = 0.002), which was 2-fold higher in atypical than in benign meningiomas (P = 0.022) and 10-fold higher in malignant than in benign meningiomas (P = 0.025). Among different subtypes of Grade I meningiomas, VEGF levels were 10-fold higher in meningothelial than in fibrous meningiomas (P = 0.015). None of the other three Factors investigated showed any association with tumor grade, microvessel density, or invasiveness, and VEGF also did not correlate with vascularity or invasiveness. Moreover, vascularity did not increase with malignancy grade. Endothelial chemotaxis and capillary-like tube formation in vitro were induced by meningioma extracts and were most effectively blocked by co-addition of antibodies against basic fibroblast Growth Factor, followed by anti-VEGF, whereas anti-hepatocyte Growth Factor/scatter Factor was not effective. The chemotactic activity of meningioma extracts on endothelial cells correlated with their VEGF content (r = 0.6, P = 0.003). CONCLUSION: Meningiomas do not show an angiogenic switch involving VEGF and/or hepatocyte Growth Factor/ scatter Factor, as has previously been found in gliomas. Nevertheless, the biological activity of VEGF and basic fibroblast Growth Factor in meningiomas suggests that both are potential targets for antiangiogenic therapy in meningiomas of all WHO grades.
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Vascular endothelial Growth Factor, hepatocyte Growth Factor/scatter Factor, basic fibroblast Growth Factor, and placenta Growth Factor in human meningiomas and their relation to angiogenesis and malignancy.
Neurosurgery, 2000Co-Authors: Katrin Lamszus, Ulrike Lengler, Suleyman Ergun, Dimitrios Stavrou, Nils-ole Schmidt, Manfred WestphalAbstract:OBJECTIVE: Angiogenesis is mediated by a number of different Growth Factors and appears vital for tumor Growth. The understanding of angiogenic mechanisms could offer new therapeutic perspectives; in this context, the role of four potentially angiogenic Growth Factors was analyzed in a large series of meningiomas of different grades. METHODS: Vascular endothelial Growth Factor (VEGF), placenta Growth Factor, hepatocyte Growth Factor/scatter Factor, and basic fibroblast Growth Factor were quantified in 69 tumors by enzyme-linked immunosorbent assay. Microvessel density and proliferative activity were determined on paraffin sections, and clinical tumor invasiveness was rated. Induction of endothelial chemotaxis and capillary-like tube formation were studied in vitro using modified Boyden chamber assays and three-dimensional collagen gel assays, respectively. RESULTS: Tumors included 40 benign (World Health Organization [WHO] Grade I), 21 atypical (WHO Grade II), and 8 anaplastic/malignant (WHO Grade III) meningiomas. We found a correlation between meningioma grade and VEGF content (r = 0.37, P = 0.002), which was 2-fold higher in atypical than in benign meningiomas (P = 0.022) and 10-fold higher in malignant than in benign meningiomas (P = 0.025). Among different subtypes of Grade I meningiomas, VEGF levels were 10-fold higher in meningothelial than in fibrous meningiomas (P = 0.015). None of the other three Factors investigated showed any association with tumor grade, microvessel density, or invasiveness, and VEGF also did not correlate with vascularity or invasiveness. Moreover, vascularity did not increase with malignancy grade. Endothelial chemotaxis and capillary-like tube formation in vitro were induced by meningioma extracts and were most effectively blocked by co-addition of antibodies against basic fibroblast Growth Factor, followed by anti-VEGF, whereas anti-hepatocyte Growth Factor/scatter Factor was not effective. The chemotactic activity of meningioma extracts on endothelial cells correlated with their VEGF content (r = 0.6, P = 0.003). CONCLUSION: Meningiomas do not show an angiogenic switch involving VEGF and/or hepatocyte Growth Factor/ scatter Factor, as has previously been found in gliomas. Nevertheless, the biological activity of VEGF and basic fibroblast Growth Factor in meningiomas suggests that both are potential targets for antiangiogenic therapy in meningiomas of all WHO grades.
Adrian L Harris - One of the best experts on this subject based on the ideXlab platform.
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expression of the angiogenic Factors vascular endothelial cell Growth Factor acidic and basic fibroblast Growth Factor tumor Growth Factor β 1 platelet derived endothelial cell Growth Factor placenta Growth Factor and pleiotrophin in human primary br
Cancer Research, 1997Co-Authors: Micheie Relf, Susan Lejeune, Prudence A E Scott, K C Smith, Russell Leek, Amir Moghaddam, R Whitehouse, Roy Bicknell, Adrian L HarrisAbstract:Abstract Angiogenesis is a significant prognostic Factor in breast cancer, but the Factors that control angiogenesis in vivo are not well defined. Multiple angiogenic polypeptides are known, and we have determined the expression of seven of these in primary human breast cancers; the relationship of expression to estrogen receptor and vascular density was also examined. Vascular endothelial Growth Factor (VEGF) and its four isoforms (121, 165, 189, and 206 amino acids), transforming Growth Factor (TGF)-β1, pleiotrophin, acidic and basic fibroblast Growth Factor (FGF), placental Growth Factor, and thymidine phosphorylase (platelet-derived endothelial cell Growth Factor) were quantitated by RNase protection analysis. β-FGF was also measured by ELISA. The estrogen receptor (ER), epidermal Growth Factor receptor, and vascular density were analyzed in 64 primary breast cancers. All tumors expressed at least six different vascular Growth Factors. VEGF was most abundant, and the transcript for the 121-amino acid form predominated. Other angiogenic Factors expressed at high levels were thymidine phosphorylase and TGF-β1. Expression of most of the angiogenic Factors did not correlate with that of ER or vascular density. However, thymidine phosphorylase did, with a correlation coefficient of 0.3 ( P = 0.03). There were significant associations of pleiotrophin with acidic FGF expression ( P = 0.001) and TGF-β with platelet-derived endothelial cell Growth Factor expression ( P = 0.001). Thus, angiogenesis may involve a coordinate regulation of some vascular Growth Factors. High VEGF expression correlated with poor prognosis in univariate analysis ( P = 0.03), as did ER and epidermal Growth Factor receptor expression. Basic FGF was also assessed by ELISA and was more highly expressed in tumors than normal breast tissues (median, 346 µg/ml cytosol; range, 54–1323 versus median, 149; range, 32–509; P = 0.01). Implications for therapy are that broad spectrum agents that block features common to these Factors may be useful ( e.g. , antagonism of heparin-binding activity agents), because so many angiogenic Factors are expressed. Inhibiting endothelial migration or agents directly toxic to endothelium would be of value in a combined approach to therapy.
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expression of the angiogenic Factors vascular endothelial cell Growth Factor acidic and basic fibroblast Growth Factor tumor Growth Factor beta 1 platelet derived endothelial cell Growth Factor placenta Growth Factor and pleiotrophin in human primary
Cancer Research, 1997Co-Authors: Micheie Relf, Susan Lejeune, Prudence A E Scott, Russell Leek, Amir Moghaddam, Roy Bicknell, Stephen B Fox, Ken R Smith, R M Whitehouse, Adrian L HarrisAbstract:Angiogenesis is a significant prognostic Factor in breast cancer, but the Factors that control angiogenesis in vivo are not well defined. Multiple angiogenic polypeptides are known, and we have determined the expression of seven of these in primary human breast cancers; the relationship of expression to estrogen receptor and vascular density was also examined. Vascular endothelial Growth Factor (VEGF) and its four isoforms (121, 165, 189, and 206 amino acids), transforming Growth Factor (TGF)-beta1, pleiotrophin, acidic and basic fibroblast Growth Factor (FGF), placental Growth Factor, and thymidine phosphorylase (platelet-derived endothelial cell Growth Factor) were quantitated by RNase protection analysis. beta-FGF was also measured by ELISA. The estrogen receptor (ER), epidermal Growth Factor receptor, and vascular density were analyzed in 64 primary breast cancers. All tumors expressed at least six different vascular Growth Factors. VEGF was most abundant, and the transcript for the 121-amino acid form predominated. Other angiogenic Factors expressed at high levels were thymidine phosphorylase and TGF-beta1. Expression of most of the angiogenic Factors did not correlate with that of ER or vascular density. However, thymidine phosphorylase did, with a correlation coefficient of 0.3 (P = 0.03). There were significant associations of pleiotrophin with acidic FGF expression (P = 0.001) and TGF-beta with platelet-derived endothelial cell Growth Factor expression (P = 0.001). Thus, angiogenesis may involve a coordinate regulation of some vascular Growth Factors. High VEGF expression correlated with poor prognosis in univariate analysis (P = 0.03), as did ER and epidermal Growth Factor receptor expression. Basic FGF was also assessed by ELISA and was more highly expressed in tumors than normal breast tissues (median, 346 microg/ml cytosol; range, 54-1323 versus median, 149; range, 32-509; P = 0.01). Implications for therapy are that broad spectrum agents that block features common to these Factors may be useful (e.g., antagonism of heparin-binding activity agents), because so many angiogenic Factors are expressed. Inhibiting endothelial migration or agents directly toxic to endothelium would be of value in a combined approach to therapy.
Jian Weng - One of the best experts on this subject based on the ideXlab platform.
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Hepatocyte Growth Factor, keratinocyte Growth Factor, and other Growth Factor-receptor systems in the lens.
Investigative Ophthalmology & Visual Science, 1997Co-Authors: Jian Weng, Qianwa Liang, Rajiv R Mohan, Qian Li, Steven E. WilsonAbstract:Purpose. To examine the expression and function of hepatocyte Growth Factor (HGF), keratinocyte Growth Factor (KGF), epidermal Growth Factor (EGF) and other Growth Factor-cytokine-receptor systems in lens epithelial cells. Methods. Reverse transcription - polymerase chain reaction (RT-PCR) and Northern blot analysis were used to examine the expression of messenger RNAs in primary cultured rabbit and human lens cells and in ex vivo rabbit lens tissue. Protein expression and the effect of HGF and KGF on crystallin expression in lens epithelial cells were evaluated by immunoprecipitation and Western blot analysis. The effect of exogenous HGF, KGF, and EGF and of the coculture of lens epithelial cells with corneal endothelial cells on the proliferation of rabbit lens cells in a Transwell system was determined by cell counting. Results. Messenger RNAs and proteins of HGF and KGF were expressed in primary rabbit lens epithelial cells and in ex vivo rabbit lens epithelial tissue. Human lens cells also expressed the mRNAs. Other Growth Factors and receptor messenger RNAs were also expressed. Hepatocyte and keratinocyte Growth Factors, and coculture with corneal endothelial cells stimulated proliferation of rabbit lens epithelial cells. In first-passage rabbit lens cells, HGF, KGF, and EGF increased the expression of alpha and beta crystallins. Conclusions. Hepatocyte and keratinocyte Growth Factor-receptor systems are expressed in lens cells. HGF and KGF are not expressed in epithelial cells in such tissues as skin, cornea, and lacrimal gland in which fibroblastic and epithelial cells interact in the formation of an organ. Expression of these Growth Factors in the lens may have evolved because the lens cells are relatively isolated within the anterior chamber of the eye. Our results suggest, however, that Growth Factors released by the corneal endothelium also could modulate lens functions (aquecrine interactions).
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Epidermal Growth Factor, transforming Growth Factor alpha, transforming Growth Factor beta, acidic fibroblast Growth Factor, basic fibroblast Growth Factor, and interleukin-1 proteins in the cornea
Experimental eye research, 1994Co-Authors: Steven E. Wilson, Gregory S. Schultz, Nasser Chegini, Jian WengAbstract:Abstract The purpose of this study was to determine whether epidermal Growth Factor (EGF), EGF receptor, transforming Growth Factor alpha (TGF-alpha), transforming Growth Factor beta (TGF-beta), acidic fibroblast Growth Factor (acidic-FGF), basic fibroblast Growth Factor (basic-FCF), and interleukin-1-alpha (IL-1-alpha) proteins were present in cultures of human corneal cells and/or in sections of human corneal tissue. Immunohistochemistry was performed on human corneal sections. Immunofluorescent cell staining was used to evaluate corneal epithelial, stromal fibroblast, and endothelial cells in primary culture. Basic-FGF production was evaluated in culture cells using immunoprecipitation. EGF, TCF-alpha, TGF-beta-1, and IL-1-alpha were detected by immunohistochemistry in cells in all three layers of the cornea. EGF receptor and acidic FCF were detected by immunohistochemistry in epithelial and endothelial cells, but not in stromal fibroblast cells. Differences in distribution of the Growth Factors were noted within individual layers of the cornea. EGF and basic-FGF proteins were detected in all three predominant cell types of the cornea using immunocytology. IL-1-alpha protein was detected by immunocytology in corneal epithelial and endothelial cells, but not stromal fibroblasts. Immunoprecipitation confirmed the production of basic-FGF in all three cell types. IL-1-alpha protein detection in the corneal stroma by immunohistology, but not by immunocytology in first passage stromal fibroblasts, suggests that IL-1-alpha may localize to the corneal stroma after production by corneal epithelial and/or endothelial cells.
Nelson Fausto - One of the best experts on this subject based on the ideXlab platform.
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Transforming Growth Factor‐α expression during liver regeneration after partial hepatectomy and toxic injury, and potential interactions between transforming Growth Factor‐α and hepatocyte Growth Factor
Hepatology, 1993Co-Authors: Eric M. Webber, Pamela I. Brown, Molly H. Bartlett, Mark J Fitzgerald, Nelson FaustoAbstract:Transforming Growth Factor-α and hepatocyte Growth Factor are important stimulators of hepatocyte proliferation. In this series of experiments we sought to measure the expression of transforming Growth Factor-α mRNA by hepatocytes in response to toxic liver injury produced by carbon tetrachloride or galactosamine and to perform a more detailed analysis of transforming Growth Factor-α expression after partial hepatectomy. We also explored the interactions of transforming Growth Factor-α and hepatocyte Growth Factor in their effects on hepatocytes in vitro and tested the ability of these Factors to stimulate endogenous transforming Growth Factor-α production by hepatocytes. In previous work we have used oligonucleotide probes to measure transforming Growth Factor-α mRNA expression after partial hepatectomy. In this study we used a rat transforming Growth Factor-α cDNA probe and found that the level of liver transforming Growth Factor-α mRNA increases 4 hr after partial hepatectomy, shows peak expression at 18 hr and returns to the normal level by 36 to 48 hr. Measurement of the corresponding peptide in the liver by means of radioimmunoassay shows that the level of transforming Growth Factor-α rises by 12 hr, peaks at 24 hr and remains significantly increased at 48 hr compared with the levels in sham-operated rats. Carbon tetrachloride and galactosamine are known to produce different patterns of acute liver injury, with maximal hepatocyte DNA synthesis at 48 hr and 5 days, respectively. After carbon tetrachloride administration the profiles of the transforming Growth Factor-α and hepatocyte Growth Factor mRNA expression are similar, each showing two peaks: the first at 12 hr and the second at 48 hr. In contrast, after galactosamineinduced liver injury the expression patterns of transforming Growth Factor-α and hepatocyte Growth Factor mRNAs differ: hepatocyte Growth Factor shows a major peak at 24 hr, with a smaller increase at 5 days, whereas transforming Growth Factor-α begins to increase after 2 days, with a single peak occurring at 5 days. In primary hepatocyte cultures, transforming Growth Factor-α and hepatocyte Growth Factor appear to have complementary effects. The maximal hepatocyte nuclear labeling index induced by hepatocyte Growth Factor was 42%; the addition of transforming Growth Factor-α increased this to 74%. Exogenous transforming Growth Factor-α, but not hepatocyte Growth Factor, stimulates the production of the transforming Growth Factor-α peptide by hepatocytes. However, when hepatocyte Growth Factor is added to cultures already containing transforming Growth Factor-α it further increases the amount of transforming Growth Factor-α-stimulated transforming Growth Factor-α synthesis by approximately 40%. These results strengthen the view that transforming Growth Factor-α is an important physiological stimulator of hepatocyte replication in liver Growth induced by partial hepatectomy and toxic injury and that hepatocyte Growth Factor may modulate hepatocyte transforming Growth Factor-α secretion. (HEPATOLOGY 1993;18:1422–1431.)
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transforming Growth Factor α expression during liver regeneration after partial hepatectomy and toxic injury and potential interactions between transforming Growth Factor α and hepatocyte Growth Factor
Hepatology, 1993Co-Authors: Eric M. Webber, Pamela I. Brown, Molly H. Bartlett, Mark J Fitzgerald, Nelson FaustoAbstract:Transforming Growth Factor-α and hepatocyte Growth Factor are important stimulators of hepatocyte proliferation. In this series of experiments we sought to measure the expression of transforming Growth Factor-α mRNA by hepatocytes in response to toxic liver injury produced by carbon tetrachloride or galactosamine and to perform a more detailed analysis of transforming Growth Factor-α expression after partial hepatectomy. We also explored the interactions of transforming Growth Factor-α and hepatocyte Growth Factor in their effects on hepatocytes in vitro and tested the ability of these Factors to stimulate endogenous transforming Growth Factor-α production by hepatocytes. In previous work we have used oligonucleotide probes to measure transforming Growth Factor-α mRNA expression after partial hepatectomy. In this study we used a rat transforming Growth Factor-α cDNA probe and found that the level of liver transforming Growth Factor-α mRNA increases 4 hr after partial hepatectomy, shows peak expression at 18 hr and returns to the normal level by 36 to 48 hr. Measurement of the corresponding peptide in the liver by means of radioimmunoassay shows that the level of transforming Growth Factor-α rises by 12 hr, peaks at 24 hr and remains significantly increased at 48 hr compared with the levels in sham-operated rats. Carbon tetrachloride and galactosamine are known to produce different patterns of acute liver injury, with maximal hepatocyte DNA synthesis at 48 hr and 5 days, respectively. After carbon tetrachloride administration the profiles of the transforming Growth Factor-α and hepatocyte Growth Factor mRNA expression are similar, each showing two peaks: the first at 12 hr and the second at 48 hr. In contrast, after galactosamineinduced liver injury the expression patterns of transforming Growth Factor-α and hepatocyte Growth Factor mRNAs differ: hepatocyte Growth Factor shows a major peak at 24 hr, with a smaller increase at 5 days, whereas transforming Growth Factor-α begins to increase after 2 days, with a single peak occurring at 5 days. In primary hepatocyte cultures, transforming Growth Factor-α and hepatocyte Growth Factor appear to have complementary effects. The maximal hepatocyte nuclear labeling index induced by hepatocyte Growth Factor was 42%; the addition of transforming Growth Factor-α increased this to 74%. Exogenous transforming Growth Factor-α, but not hepatocyte Growth Factor, stimulates the production of the transforming Growth Factor-α peptide by hepatocytes. However, when hepatocyte Growth Factor is added to cultures already containing transforming Growth Factor-α it further increases the amount of transforming Growth Factor-α-stimulated transforming Growth Factor-α synthesis by approximately 40%. These results strengthen the view that transforming Growth Factor-α is an important physiological stimulator of hepatocyte replication in liver Growth induced by partial hepatectomy and toxic injury and that hepatocyte Growth Factor may modulate hepatocyte transforming Growth Factor-α secretion. (HEPATOLOGY 1993;18:1422–1431.)
J B Tuttle - One of the best experts on this subject based on the ideXlab platform.
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Nerve Growth Factor synthesis in vascular smooth muscle.
Hypertension, 1991Co-Authors: D Creedon, J B TuttleAbstract:Details of the interdependent, trophic relation between smooth muscle and its neural innervation are not well known despite suggestions that neural influences may contribute significantly to hypertensive and other cardiovascular disease. Vascular smooth muscle is a major target of innervation by neurons of the sympathetic nervous system. Sympathetic neurons depend on a constant supply of the potent neurotrophic peptide nerve Growth Factor. Nerve Growth Factor regulates an impressive list of neuronal and perhaps muscle properties, yet its source in vessels and the determinants of its synthesis are not known. We have taken advantage of the cytoarchitecture of the aorta to demonstrate that vascular smooth muscle cells synthesize nerve Growth Factor. The survival of cultured sympathetic neurons is supported in a nerve Growth Factor-dependent manner by co-culture with pure rat aortic vascular smooth muscle cells. Furthermore, pure smooth muscle cell cultures contain nerve Growth Factor-specific messenger RNA. Levels of messenger nucleic acid coding for nerve Growth Factor in smooth muscle are regulated by contractile agonists (angiotensin II, arginine vasopressin) and the adrenergic agonist phenylephrine. This suggests a link between muscle activity and Growth Factor production. Secretion of nerve Growth Factor protein by vascular smooth muscle was measured using a sensitive two-site immunoassay. Secretion is highest during muscle Growth. Secretion is elevated by angiotensin II and arginine vasopressin but slightly inhibited by phenylephrine. These results suggest that cultured vascular smooth muscle can serve as a useful model in which to study the cellular regulation of trophic Factor synthesis in health and disease.
