The Experts below are selected from a list of 264 Experts worldwide ranked by ideXlab platform

K Man - One of the best experts on this subject based on the ideXlab platform.

  • Type III TGF-β Receptor Down-Regulation Promoted Tumor Progression via Complement Component C5a Induction in Hepatocellular Carcinoma.
    Cancers, 2021
    Co-Authors: Oscar Wai Ho Yeung, Li Pang, Hui Liu, Jiang Liu, K Man
    Abstract:

    Background and Aims-Transforming growth factor-beta (TGF-β) signaling orchestrates tumorigenesis and one of the family members, TGF-β receptor type III (TGFβR3), are distinctively under-expressed in numerous malignancies. Currently, the clinical impact of TGFβR3 down-regulation and the underlying mechanism remains unclear in hepatocellular carcinoma (HCC). Here, we aimed to identify the tumor-promoting roles of decreased TGFβR3 expression in HCC progression. Materials and Methods-For clinical analysis, plasma and liver specimens were collected from 100 HCC patients who underwent curative resection for the quantification of TGFβR3 by q-PCR and ELISA. To study the tumor-promoting mechanism of TGFβR3 downregulation, HCC mouse models and TGFβR3 knockout cell lines were applied. Results-Significant downregulation of TGFβR3 and its soluble form (sTGFβR3) were found in HCC tissues and plasma compared to healthy individuals (p < 0.01). Patients with

  • type iii tgf β receptor down regulation promoted tumor progression via Complement Component C5a induction in hepatocellular carcinoma
    Cancers, 2021
    Co-Authors: Oscar Wai Ho Yeung, Li Pang, Hui Liu, Jiang Liu, K Man
    Abstract:

    Background and Aims—Transforming growth factor-beta (TGF-β) signaling orchestrates tumorigenesis and one of the family members, TGF-β receptor type III (TGFβR3), are distinctively under-expressed in numerous malignancies. Currently, the clinical impact of TGFβR3 down-regulation and the underlying mechanism remains unclear in hepatocellular carcinoma (HCC). Here, we aimed to identify the tumor-promoting roles of decreased TGFβR3 expression in HCC progression. Materials and Methods—For clinical analysis, plasma and liver specimens were collected from 100 HCC patients who underwent curative resection for the quantification of TGFβR3 by q-PCR and ELISA. To study the tumor-promoting mechanism of TGFβR3 downregulation, HCC mouse models and TGFβR3 knockout cell lines were applied. Results—Significant downregulation of TGFβR3 and its soluble form (sTGFβR3) were found in HCC tissues and plasma compared to healthy individuals (p < 0.01). Patients with <9.4 ng/mL sTGFβR3 exhibited advanced tumor stage, higher recurrence rate and shorter disease-free survival (p < 0.05). The tumor-suppressive function of sTGFβR3 was further revealed in an orthotopic mouse HCC model, resulting in 2-fold tumor volume reduction. In TGFβR3 knockout hepatocyte and HCC cells, increased Complement Component C5a was observed and strongly correlated with shorter survival and advanced tumor stage (p < 0.01). Interestingly, C5a activated the tumor-promoting Th-17 response in tumor associated macrophages. Conclusion—TGFβR3 suppressed tumor progression, and decreased expression resulted in poor prognosis in HCC patients through upregulation of tumor-promoting Complement C5a.

Walter S. Speidl - One of the best experts on this subject based on the ideXlab platform.

  • the Complement Component C5a is present in human coronary lesions in vivo and induces the expression of mmp 1 and mmp 9 in human macrophages in vitro
    The FASEB Journal, 2011
    Co-Authors: Walter S. Speidl, Stefan P. Kastl, Gerald Maurer, Kurt Huber, Christoph Kaun, Katharina M. Katsaros, Randolph Hutter, Gerhard Bauriedel, Juan J. Badimon, Johann Wojta
    Abstract:

    The Complement Component C5a is formed during activation of the Complement cascade and exerts chemotactic and proinflammatory effects. Macrophages, which are localized in the rupture-prone shoulder regions of coronary plaques, are thought to play a major role in plaque destabilization and rupture through the production of matrix metalloproteinases (MMPs). When human monocyte-derived macrophages were stimulated in vitro with C5a, MMP-1 and MMP-9 mRNA levels were significantly increased. Furthermore, C5a up-regulated MMP-1 and MMP-9 antigens and activity, as determined by ELISA and specific activity assays. These effects were blocked by antibodies against the receptor C5aR/CD88. In addition, blocking experiments revealed that MMP-1 expression was mediated by activation of the transcription factor AP-1, and MMP-9 expression was induced by activation of NF-κB and AP-1. Immunohistochemical analysis of human coronary plaques demonstrated the colocalization of C5a, MMP-1, and MMP-9 in vivo. Together, these observations indicate that activation of the Complement cascade and formation of C5a may play a role in the onset of acute coronary events by induction of MMPs in atherosclerotic lesions.

  • The Complement Component C5a is present in human coronary lesions in vivo and induces the expression of MMP-1 and MMP-9 in human macrophages in vitro
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2010
    Co-Authors: Walter S. Speidl, Stefan P. Kastl, Gerald Maurer, Kurt Huber, Christoph Kaun, Katharina M. Katsaros, Randolph Hutter, Gerhard Bauriedel, Juan J. Badimon, Johann Wojta
    Abstract:

    The Complement Component C5a is formed during activation of the Complement cascade and exerts chemotactic and proinflammatory effects. Macrophages, which are localized in the rupture-prone shoulder regions of coronary plaques, are thought to play a major role in plaque destabilization and rupture through the production of matrix metalloproteinases (MMPs). When human monocyte-derived macrophages were stimulated in vitro with C5a, MMP-1 and MMP-9 mRNA levels were significantly increased. Furthermore, C5a up-regulated MMP-1 and MMP-9 antigens and activity, as determined by ELISA and specific activity assays. These effects were blocked by antibodies against the receptor C5aR/CD88. In addition, blocking experiments revealed that MMP-1 expression was mediated by activation of the transcription factor AP-1, and MMP-9 expression was induced by activation of NF-κB and AP-1. Immunohistochemical analysis of human coronary plaques demonstrated the colocalization of C5a, MMP-1, and MMP-9 in vivo. Together, these obser...

  • In Human Macrophages the Complement Component C5a Induces the Expression of Oncostatin M via AP-1 Activation
    Arteriosclerosis thrombosis and vascular biology, 2008
    Co-Authors: Stefan P. Kastl, Walter S. Speidl, Christoph Kaun, Katharina M. Katsaros, Gersina Rega, Taras Afonyushkin, Valery N. Bochkov, Peter Valent, Afshin Assadian, Georg W. Hagmueller
    Abstract:

    Objective— Macrophages produce the cytokine oncostatin M (OSM), which beside other functions is also involved in inflammation. The Complement Component C5a mobilizes and activates these cells at inflammatory sites. We examined the effect of C5a on OSM production in human monocytes and in human monocyte-derived macrophages. Methods and Results— For macrophage transformation peripheral blood monocytes were cultivated for 8 to 10 days in the presence of human serum. C5a significantly increased in these cells OSM antigen as determined by specific ELISA and mRNA as quantitated by real-time polymerase chain reaction in these cells as well as in plaque macrophages. This effect was blocked by antibodies against the receptor C5aR/CD88 and by pertussis toxin. The C5a-induced phosphorylation of p38 and JNK and the C5a-induced increase in OSM production in macrophages was abolished by 2 p38 inhibitors and by a JNK inhibitor. Furthermore C5a increased the nuclear translocation of c-fos and c-jun. Using different OSM promoter deletion mutant constructs we show that the putative AP-1 element is responsible for activation of OSM promoter activity by C5a. Conclusion— Our data establish a link between the Complement system and the gp130 receptor cytokine family with possible implications for the pathology of inflammatory diseases.

  • Complement Component C5a predicts restenosis after superficial femoral artery balloon angioplasty
    Journal of Endovascular Therapy, 2007
    Co-Authors: Walter S. Speidl, Markus Exner, Jasmin Amighi, Stefan P. Kastl, Gerlinde Zorn, Gerald Maurer, Oswald Wagner, Wolfgang Mlekusch, Schila Sabeti, Kurt Huber
    Abstract:

    PURPOSE To investigate whether balloon angioplasty of the superficial femoral artery (SFA) increases serum levels of C5a and whether C5a predicts risk of restenosis. METHODS C5a antigen was measured at baseline and 8 hours after intervention in 131 consecutive patients (76 women; median age 72 years) with intermittent claudication who underwent successful primary SFA balloon angioplasty. Patients were followed for a median 10 months [interquartile range (IQR) 6 to 14] for the occurrence of >50% restenosis by duplex ultrasound. RESULTS Median C5a levels increased significantly from 39.7 ng/mL (IQR 27.8 to 55.0) at baseline to 53.8 ng/mL (IQR 35.6 to 85.1, p<0.001) 8 hours post intervention. During the follow-up period, 70 (53%) patients developed restenosis. Increasing levels of C5a (quartiles) at baseline were significantly associated with an increased risk for restenosis (p=0.0092). Adjusted hazard ratios (95% confidence intervals) for restenosis with increasing quartiles of baseline serum C5a levels were 1.24 (0.60 to 2.58), 1.93 (0.95 to 3.93), and 2.08 (1.02 to 4.21), respectively, compared to the lowest quartile. This effect was independent of nonspecific inflammation as reflected by plasma levels of C-reactive protein. CONCLUSION Inflammatory mechanisms play a major role in the development of restenosis after angioplasty. The Complement Component C5a exerts strong chemotactic and proinflammatory effects. Enhanced Complement activation prior to PTA, as measured by higher levels of C5a, was significantly associated with restenosis after SFA balloon angioplasty. Pathways of Complement inhibition thus may be worth investigating with respect to improving patency rates.

  • Complement Component C5a predicts restenosis after superficial femoral artery balloon angioplasty.
    Journal of endovascular therapy : an official journal of the International Society of Endovascular Specialists, 2007
    Co-Authors: Walter S. Speidl, Markus Exner, Jasmin Amighi, Stefan P. Kastl, Gerlinde Zorn, Gerald Maurer, Oswald Wagner, Wolfgang Mlekusch, Schila Sabeti, Kurt Huber
    Abstract:

    PURPOSE To investigate whether balloon angioplasty of the superficial femoral artery (SFA) increases serum levels of C5a and whether C5a predicts risk of restenosis. METHODS C5a antigen was measured at baseline and 8 hours after intervention in 131 consecutive patients (76 women; median age 72 years) with intermittent claudication who underwent successful primary SFA balloon angioplasty. Patients were followed for a median 10 months [interquartile range (IQR) 6 to 14] for the occurrence of >50% restenosis by duplex ultrasound. RESULTS Median C5a levels increased significantly from 39.7 ng/mL (IQR 27.8 to 55.0) at baseline to 53.8 ng/mL (IQR 35.6 to 85.1, p

Kurt Huber - One of the best experts on this subject based on the ideXlab platform.

  • the Complement Component C5a is present in human coronary lesions in vivo and induces the expression of mmp 1 and mmp 9 in human macrophages in vitro
    The FASEB Journal, 2011
    Co-Authors: Walter S. Speidl, Stefan P. Kastl, Gerald Maurer, Kurt Huber, Christoph Kaun, Katharina M. Katsaros, Randolph Hutter, Gerhard Bauriedel, Juan J. Badimon, Johann Wojta
    Abstract:

    The Complement Component C5a is formed during activation of the Complement cascade and exerts chemotactic and proinflammatory effects. Macrophages, which are localized in the rupture-prone shoulder regions of coronary plaques, are thought to play a major role in plaque destabilization and rupture through the production of matrix metalloproteinases (MMPs). When human monocyte-derived macrophages were stimulated in vitro with C5a, MMP-1 and MMP-9 mRNA levels were significantly increased. Furthermore, C5a up-regulated MMP-1 and MMP-9 antigens and activity, as determined by ELISA and specific activity assays. These effects were blocked by antibodies against the receptor C5aR/CD88. In addition, blocking experiments revealed that MMP-1 expression was mediated by activation of the transcription factor AP-1, and MMP-9 expression was induced by activation of NF-κB and AP-1. Immunohistochemical analysis of human coronary plaques demonstrated the colocalization of C5a, MMP-1, and MMP-9 in vivo. Together, these observations indicate that activation of the Complement cascade and formation of C5a may play a role in the onset of acute coronary events by induction of MMPs in atherosclerotic lesions.

  • The Complement Component C5a is present in human coronary lesions in vivo and induces the expression of MMP-1 and MMP-9 in human macrophages in vitro
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2010
    Co-Authors: Walter S. Speidl, Stefan P. Kastl, Gerald Maurer, Kurt Huber, Christoph Kaun, Katharina M. Katsaros, Randolph Hutter, Gerhard Bauriedel, Juan J. Badimon, Johann Wojta
    Abstract:

    The Complement Component C5a is formed during activation of the Complement cascade and exerts chemotactic and proinflammatory effects. Macrophages, which are localized in the rupture-prone shoulder regions of coronary plaques, are thought to play a major role in plaque destabilization and rupture through the production of matrix metalloproteinases (MMPs). When human monocyte-derived macrophages were stimulated in vitro with C5a, MMP-1 and MMP-9 mRNA levels were significantly increased. Furthermore, C5a up-regulated MMP-1 and MMP-9 antigens and activity, as determined by ELISA and specific activity assays. These effects were blocked by antibodies against the receptor C5aR/CD88. In addition, blocking experiments revealed that MMP-1 expression was mediated by activation of the transcription factor AP-1, and MMP-9 expression was induced by activation of NF-κB and AP-1. Immunohistochemical analysis of human coronary plaques demonstrated the colocalization of C5a, MMP-1, and MMP-9 in vivo. Together, these obser...

  • Complement Component C5a predicts restenosis after superficial femoral artery balloon angioplasty
    Journal of Endovascular Therapy, 2007
    Co-Authors: Walter S. Speidl, Markus Exner, Jasmin Amighi, Stefan P. Kastl, Gerlinde Zorn, Gerald Maurer, Oswald Wagner, Wolfgang Mlekusch, Schila Sabeti, Kurt Huber
    Abstract:

    PURPOSE To investigate whether balloon angioplasty of the superficial femoral artery (SFA) increases serum levels of C5a and whether C5a predicts risk of restenosis. METHODS C5a antigen was measured at baseline and 8 hours after intervention in 131 consecutive patients (76 women; median age 72 years) with intermittent claudication who underwent successful primary SFA balloon angioplasty. Patients were followed for a median 10 months [interquartile range (IQR) 6 to 14] for the occurrence of >50% restenosis by duplex ultrasound. RESULTS Median C5a levels increased significantly from 39.7 ng/mL (IQR 27.8 to 55.0) at baseline to 53.8 ng/mL (IQR 35.6 to 85.1, p<0.001) 8 hours post intervention. During the follow-up period, 70 (53%) patients developed restenosis. Increasing levels of C5a (quartiles) at baseline were significantly associated with an increased risk for restenosis (p=0.0092). Adjusted hazard ratios (95% confidence intervals) for restenosis with increasing quartiles of baseline serum C5a levels were 1.24 (0.60 to 2.58), 1.93 (0.95 to 3.93), and 2.08 (1.02 to 4.21), respectively, compared to the lowest quartile. This effect was independent of nonspecific inflammation as reflected by plasma levels of C-reactive protein. CONCLUSION Inflammatory mechanisms play a major role in the development of restenosis after angioplasty. The Complement Component C5a exerts strong chemotactic and proinflammatory effects. Enhanced Complement activation prior to PTA, as measured by higher levels of C5a, was significantly associated with restenosis after SFA balloon angioplasty. Pathways of Complement inhibition thus may be worth investigating with respect to improving patency rates.

  • Complement Component C5a predicts restenosis after superficial femoral artery balloon angioplasty.
    Journal of endovascular therapy : an official journal of the International Society of Endovascular Specialists, 2007
    Co-Authors: Walter S. Speidl, Markus Exner, Jasmin Amighi, Stefan P. Kastl, Gerlinde Zorn, Gerald Maurer, Oswald Wagner, Wolfgang Mlekusch, Schila Sabeti, Kurt Huber
    Abstract:

    PURPOSE To investigate whether balloon angioplasty of the superficial femoral artery (SFA) increases serum levels of C5a and whether C5a predicts risk of restenosis. METHODS C5a antigen was measured at baseline and 8 hours after intervention in 131 consecutive patients (76 women; median age 72 years) with intermittent claudication who underwent successful primary SFA balloon angioplasty. Patients were followed for a median 10 months [interquartile range (IQR) 6 to 14] for the occurrence of >50% restenosis by duplex ultrasound. RESULTS Median C5a levels increased significantly from 39.7 ng/mL (IQR 27.8 to 55.0) at baseline to 53.8 ng/mL (IQR 35.6 to 85.1, p

  • The Complement Component C5a induces the expression of plasminogen activator inhibitor‐1 in human macrophages via NF‐κB activation
    Journal of thrombosis and haemostasis : JTH, 2006
    Co-Authors: Stefan P. Kastl, Walter S. Speidl, Gerald Maurer, Christoph Kaun, Gersina Rega, Peter Valent, Afshin Assadian, Georg W. Hagmueller, Thomas W. Weiss, Kurt Huber
    Abstract:

    Summary. Background: Atherosclerosis is considered to be a chronic inflammatory disorder. Activation of the Complement cascade is a major aspect of chronic inflammatory diseases. Complement Components were identified in atherosclerotic plaques, and a correlation between adverse events and C5a plasma levels was found. These findings support the notion that Complement activation contributes to development and progression of atherosclerotic lesions. Objectives: We investigated whether Complement Components C3a and C5a regulate plasminogen activator inhibitor (PAI-1) in human macrophages. Methods: Human monocyte-derived macrophages (MDM) and human plaque macrophages were cultured and incubated with the Complement Component C5a. Results: C5a increased PAI-1 up to 11-fold in human MDM and up to 2.7-fold in human plaque macrophages. These results were confirmed at the mRNA level using real time-polymerase chain reaction. Pertussis toxin or anti-C5aR/CD88 antibody completely abolished the effect of recombinant human C5a on PAI-1 production, suggesting a role of the C5a receptor. Experiments with antitumor necrosis factor (TNF)-α antibodies and tiron showed that the effect of C5a was not mediated by TNF-α or oxidative burst. Furthermore C5a induced NF-κB binding to the cis element in human macrophages and the C5a-induced increase in PAI-1 was completely abolished by an NF-κB inhibitor. Conclusions: We conclude that C5a upregulates PAI-1 in macrophages via NF-κB activation. We hypothesize that – if operative in vivo– this effect could favor thrombus development and thrombus stabilization in the lesion area. On the other hand one could speculate that C5a-induced upregulation of PAI-1 in plaque macrophages could act as a defense mechanism against plaque destabilization and rupture.

Stefan P. Kastl - One of the best experts on this subject based on the ideXlab platform.

  • the Complement Component C5a is present in human coronary lesions in vivo and induces the expression of mmp 1 and mmp 9 in human macrophages in vitro
    The FASEB Journal, 2011
    Co-Authors: Walter S. Speidl, Stefan P. Kastl, Gerald Maurer, Kurt Huber, Christoph Kaun, Katharina M. Katsaros, Randolph Hutter, Gerhard Bauriedel, Juan J. Badimon, Johann Wojta
    Abstract:

    The Complement Component C5a is formed during activation of the Complement cascade and exerts chemotactic and proinflammatory effects. Macrophages, which are localized in the rupture-prone shoulder regions of coronary plaques, are thought to play a major role in plaque destabilization and rupture through the production of matrix metalloproteinases (MMPs). When human monocyte-derived macrophages were stimulated in vitro with C5a, MMP-1 and MMP-9 mRNA levels were significantly increased. Furthermore, C5a up-regulated MMP-1 and MMP-9 antigens and activity, as determined by ELISA and specific activity assays. These effects were blocked by antibodies against the receptor C5aR/CD88. In addition, blocking experiments revealed that MMP-1 expression was mediated by activation of the transcription factor AP-1, and MMP-9 expression was induced by activation of NF-κB and AP-1. Immunohistochemical analysis of human coronary plaques demonstrated the colocalization of C5a, MMP-1, and MMP-9 in vivo. Together, these observations indicate that activation of the Complement cascade and formation of C5a may play a role in the onset of acute coronary events by induction of MMPs in atherosclerotic lesions.

  • The Complement Component C5a is present in human coronary lesions in vivo and induces the expression of MMP-1 and MMP-9 in human macrophages in vitro
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2010
    Co-Authors: Walter S. Speidl, Stefan P. Kastl, Gerald Maurer, Kurt Huber, Christoph Kaun, Katharina M. Katsaros, Randolph Hutter, Gerhard Bauriedel, Juan J. Badimon, Johann Wojta
    Abstract:

    The Complement Component C5a is formed during activation of the Complement cascade and exerts chemotactic and proinflammatory effects. Macrophages, which are localized in the rupture-prone shoulder regions of coronary plaques, are thought to play a major role in plaque destabilization and rupture through the production of matrix metalloproteinases (MMPs). When human monocyte-derived macrophages were stimulated in vitro with C5a, MMP-1 and MMP-9 mRNA levels were significantly increased. Furthermore, C5a up-regulated MMP-1 and MMP-9 antigens and activity, as determined by ELISA and specific activity assays. These effects were blocked by antibodies against the receptor C5aR/CD88. In addition, blocking experiments revealed that MMP-1 expression was mediated by activation of the transcription factor AP-1, and MMP-9 expression was induced by activation of NF-κB and AP-1. Immunohistochemical analysis of human coronary plaques demonstrated the colocalization of C5a, MMP-1, and MMP-9 in vivo. Together, these obser...

  • In Human Macrophages the Complement Component C5a Induces the Expression of Oncostatin M via AP-1 Activation
    Arteriosclerosis thrombosis and vascular biology, 2008
    Co-Authors: Stefan P. Kastl, Walter S. Speidl, Christoph Kaun, Katharina M. Katsaros, Gersina Rega, Taras Afonyushkin, Valery N. Bochkov, Peter Valent, Afshin Assadian, Georg W. Hagmueller
    Abstract:

    Objective— Macrophages produce the cytokine oncostatin M (OSM), which beside other functions is also involved in inflammation. The Complement Component C5a mobilizes and activates these cells at inflammatory sites. We examined the effect of C5a on OSM production in human monocytes and in human monocyte-derived macrophages. Methods and Results— For macrophage transformation peripheral blood monocytes were cultivated for 8 to 10 days in the presence of human serum. C5a significantly increased in these cells OSM antigen as determined by specific ELISA and mRNA as quantitated by real-time polymerase chain reaction in these cells as well as in plaque macrophages. This effect was blocked by antibodies against the receptor C5aR/CD88 and by pertussis toxin. The C5a-induced phosphorylation of p38 and JNK and the C5a-induced increase in OSM production in macrophages was abolished by 2 p38 inhibitors and by a JNK inhibitor. Furthermore C5a increased the nuclear translocation of c-fos and c-jun. Using different OSM promoter deletion mutant constructs we show that the putative AP-1 element is responsible for activation of OSM promoter activity by C5a. Conclusion— Our data establish a link between the Complement system and the gp130 receptor cytokine family with possible implications for the pathology of inflammatory diseases.

  • Complement Component C5a predicts restenosis after superficial femoral artery balloon angioplasty
    Journal of Endovascular Therapy, 2007
    Co-Authors: Walter S. Speidl, Markus Exner, Jasmin Amighi, Stefan P. Kastl, Gerlinde Zorn, Gerald Maurer, Oswald Wagner, Wolfgang Mlekusch, Schila Sabeti, Kurt Huber
    Abstract:

    PURPOSE To investigate whether balloon angioplasty of the superficial femoral artery (SFA) increases serum levels of C5a and whether C5a predicts risk of restenosis. METHODS C5a antigen was measured at baseline and 8 hours after intervention in 131 consecutive patients (76 women; median age 72 years) with intermittent claudication who underwent successful primary SFA balloon angioplasty. Patients were followed for a median 10 months [interquartile range (IQR) 6 to 14] for the occurrence of >50% restenosis by duplex ultrasound. RESULTS Median C5a levels increased significantly from 39.7 ng/mL (IQR 27.8 to 55.0) at baseline to 53.8 ng/mL (IQR 35.6 to 85.1, p<0.001) 8 hours post intervention. During the follow-up period, 70 (53%) patients developed restenosis. Increasing levels of C5a (quartiles) at baseline were significantly associated with an increased risk for restenosis (p=0.0092). Adjusted hazard ratios (95% confidence intervals) for restenosis with increasing quartiles of baseline serum C5a levels were 1.24 (0.60 to 2.58), 1.93 (0.95 to 3.93), and 2.08 (1.02 to 4.21), respectively, compared to the lowest quartile. This effect was independent of nonspecific inflammation as reflected by plasma levels of C-reactive protein. CONCLUSION Inflammatory mechanisms play a major role in the development of restenosis after angioplasty. The Complement Component C5a exerts strong chemotactic and proinflammatory effects. Enhanced Complement activation prior to PTA, as measured by higher levels of C5a, was significantly associated with restenosis after SFA balloon angioplasty. Pathways of Complement inhibition thus may be worth investigating with respect to improving patency rates.

  • Complement Component C5a predicts restenosis after superficial femoral artery balloon angioplasty.
    Journal of endovascular therapy : an official journal of the International Society of Endovascular Specialists, 2007
    Co-Authors: Walter S. Speidl, Markus Exner, Jasmin Amighi, Stefan P. Kastl, Gerlinde Zorn, Gerald Maurer, Oswald Wagner, Wolfgang Mlekusch, Schila Sabeti, Kurt Huber
    Abstract:

    PURPOSE To investigate whether balloon angioplasty of the superficial femoral artery (SFA) increases serum levels of C5a and whether C5a predicts risk of restenosis. METHODS C5a antigen was measured at baseline and 8 hours after intervention in 131 consecutive patients (76 women; median age 72 years) with intermittent claudication who underwent successful primary SFA balloon angioplasty. Patients were followed for a median 10 months [interquartile range (IQR) 6 to 14] for the occurrence of >50% restenosis by duplex ultrasound. RESULTS Median C5a levels increased significantly from 39.7 ng/mL (IQR 27.8 to 55.0) at baseline to 53.8 ng/mL (IQR 35.6 to 85.1, p

Oscar Wai Ho Yeung - One of the best experts on this subject based on the ideXlab platform.

  • Type III TGF-β Receptor Down-Regulation Promoted Tumor Progression via Complement Component C5a Induction in Hepatocellular Carcinoma.
    Cancers, 2021
    Co-Authors: Oscar Wai Ho Yeung, Li Pang, Hui Liu, Jiang Liu, K Man
    Abstract:

    Background and Aims-Transforming growth factor-beta (TGF-β) signaling orchestrates tumorigenesis and one of the family members, TGF-β receptor type III (TGFβR3), are distinctively under-expressed in numerous malignancies. Currently, the clinical impact of TGFβR3 down-regulation and the underlying mechanism remains unclear in hepatocellular carcinoma (HCC). Here, we aimed to identify the tumor-promoting roles of decreased TGFβR3 expression in HCC progression. Materials and Methods-For clinical analysis, plasma and liver specimens were collected from 100 HCC patients who underwent curative resection for the quantification of TGFβR3 by q-PCR and ELISA. To study the tumor-promoting mechanism of TGFβR3 downregulation, HCC mouse models and TGFβR3 knockout cell lines were applied. Results-Significant downregulation of TGFβR3 and its soluble form (sTGFβR3) were found in HCC tissues and plasma compared to healthy individuals (p < 0.01). Patients with

  • type iii tgf β receptor down regulation promoted tumor progression via Complement Component C5a induction in hepatocellular carcinoma
    Cancers, 2021
    Co-Authors: Oscar Wai Ho Yeung, Li Pang, Hui Liu, Jiang Liu, K Man
    Abstract:

    Background and Aims—Transforming growth factor-beta (TGF-β) signaling orchestrates tumorigenesis and one of the family members, TGF-β receptor type III (TGFβR3), are distinctively under-expressed in numerous malignancies. Currently, the clinical impact of TGFβR3 down-regulation and the underlying mechanism remains unclear in hepatocellular carcinoma (HCC). Here, we aimed to identify the tumor-promoting roles of decreased TGFβR3 expression in HCC progression. Materials and Methods—For clinical analysis, plasma and liver specimens were collected from 100 HCC patients who underwent curative resection for the quantification of TGFβR3 by q-PCR and ELISA. To study the tumor-promoting mechanism of TGFβR3 downregulation, HCC mouse models and TGFβR3 knockout cell lines were applied. Results—Significant downregulation of TGFβR3 and its soluble form (sTGFβR3) were found in HCC tissues and plasma compared to healthy individuals (p < 0.01). Patients with <9.4 ng/mL sTGFβR3 exhibited advanced tumor stage, higher recurrence rate and shorter disease-free survival (p < 0.05). The tumor-suppressive function of sTGFβR3 was further revealed in an orthotopic mouse HCC model, resulting in 2-fold tumor volume reduction. In TGFβR3 knockout hepatocyte and HCC cells, increased Complement Component C5a was observed and strongly correlated with shorter survival and advanced tumor stage (p < 0.01). Interestingly, C5a activated the tumor-promoting Th-17 response in tumor associated macrophages. Conclusion—TGFβR3 suppressed tumor progression, and decreased expression resulted in poor prognosis in HCC patients through upregulation of tumor-promoting Complement C5a.