AIM To evaluate the efficacy of peripheral blood concentrations of angiopoietins(Ang) as cirrhosis biomarkers of chronic hepatitis C(CHC).METHODS Ang1 and Ang2 serum levels were measured by enzyme-linked immunosorbent...AIM To evaluate the efficacy of peripheral blood concentrations of angiopoietins(Ang) as cirrhosis biomarkers of chronic hepatitis C(CHC).METHODS Ang1 and Ang2 serum levels were measured by enzyme-linked immunosorbent assays(ELISA) in samples from 179 cirrhotic and non-cirrhotic CHC patients, classified according to the METAVIR system.Groups were compared by non-parametric MannWhitney U test. Subsequently, the association of peripheral concentrations of angiopoietins with the stage of fibrosis was analyzed using Spearman correlation test. Finally, the accuracy, sensitivity and specificity of circulating angiopoietins for cirrhosis diagnosis were determined by the study of the respective area under the curve of receiver operator characteristics(AUC-ROC).RESULTS Peripheral blood concentrations of Ang1 and Ang2 in CHC patients were significantly related to fibrosis. While Ang1 was decreased in cirrhotic subjects compared to non-cirrhotic(P < 0.0001), Ang2 was significantly increased as CHC progressed to the end stage of liver disease(P < 0.0001). Consequently, Ang2/Ang1 ratio was notably amplified and significantly correlated with fibrosis(P < 0.0001). Interestingly, the individual performance of each angiopoietin for the diagnosis of cirrhosis reached notable AUC-ROC values(above 0.7, both), but the Ang2/Ang1 ratio was much better(AUC-ROC = 0.810) and displayed outstanding values of sensitivity(71%), specificity(84%) and accuracy(82.1%) at the optimal cut-off(10.33). Furthermore, Ang2/Ang1 ratio improved the performance of many other previously described biomarkers or scores of liver cirrhosis in CHC.CONCLUSION Ang2/Ang1 ratio might constitute a useful tool for monitoring the progression of chronic liver disease towards cirrhosis and play an important role as therapeutic target.展开更多
To explore the relationship of angiogenesis-related angiopoietin-2 gene and its receptor Tie2 with angiogenesis and the biology of hepatocellular carcinoma (HCC), angiopoietin-2 gene, Tie2 and CD34 protein expression ...To explore the relationship of angiogenesis-related angiopoietin-2 gene and its receptor Tie2 with angiogenesis and the biology of hepatocellular carcinoma (HCC), angiopoietin-2 gene, Tie2 and CD34 protein expression in 22 resected HCC, 8 cirrhotic and 8 control liver specimens were investigated by in situ hybridization and immunohistochemistry respectively, and the level of angiopoietin-2 and Tie2 expression in HCC were compared in terms of tumor biological parameters. It was found that CD34 was not expressed in control liver, expressed scarcely in cirrhotic liver (17 8±13 5/HP), but intensively expressed in HCC (86. 3±34. 8/HP, P<0. 01). Tie2 receptor was not expressed in controls, expressed at low level in cirrhotic liver (11. 3±8. 7/HP), while strongly positive in the microvascular endothelia of HCC (52. 4±16. 7/HP, P<0. 01). The level of Tie2 receptor expression in HCC was closely related with tumor diameter, angiogenesis and portal invasion. Angiopoietin-2 gene was not expressed in control liver, expressed mildly in cirrhotic liver (11. 2±9. 7/HP), but extensively in tumor zone (36. 4±17. 5/HP), the level of angiopoietin-2 expression was closely related with angiogenesis, portal invasion and histological grading of HCC. It is concluded that angiogenesis is increased in HCC; angiopoietin-2/Tie2 expression in human hepatic carcinoma is closely related with angiogenesis, which are probably involved in the HCC angiogenesis regulation, promoting the development and metastasis of human hepatic cancer.展开更多
To investigate the effect of meloxicam, a selected NSAIDs, on cell growth, expression of VEGF and angiopointin-2 （Ang-2） protein in HT-29 cell line, cultured HT-29 cells were treated with meloxicam of various concen...To investigate the effect of meloxicam, a selected NSAIDs, on cell growth, expression of VEGF and angiopointin-2 （Ang-2） protein in HT-29 cell line, cultured HT-29 cells were treated with meloxicam of various concentrations for various lengths of time. The proliferation of HT-29 was detected by cell counting kit-8 （CCK-8）, the cell cycle was determined by flow cytometer and the levels of VEGF and Ang-2 protein in supernatants were examined by enzyme linked immunosorbent assay （ELISA）. The mRNA expressions of VEGF and Ang-2 in cultured HT-29 were determined by real-time quantitative reverse-transcription polymerase chain reaction. Our results showed that treatment of meloxicam of different concentrations and for various lengths of time had a cytotoxicic effect on the cell proliferation of HT-29 cells in a concentration-dependant and time-dependant manner. Cell cycle analysis showed that the cells were mainly blocked in G0/G1 phase. The VEGF and Ang-2 protein levels in supernatants of the culture medium were decreased gradually in a concentration-dependent or time-dependent fashion. The mRNA expression of cox-2, VEGF and Ang-2 showed a gradual and concentration-dependent reduction. It is concluded that meloxicam can reduce the expression of VEGF and Ang-2 at the protein and mRNA level in colon carcinoma cell line.展开更多
Introduction: Endometriosis affects up to 1 every 5 women at their reproductive age, with variable and complex symptomatology. Patients may be asymptomatic but may have pain episodes or subfertility. Its negative impa...Introduction: Endometriosis affects up to 1 every 5 women at their reproductive age, with variable and complex symptomatology. Patients may be asymptomatic but may have pain episodes or subfertility. Its negative impact is on patients’ health and quality of life. Objective: it was to investigate the serum and peritoneal fluid (PF) concentrations of Angiopoietin- 2, Interleukin-1β, and Vascular Endothelial Growth Factor, aiming to evaluate their diagnostic performance in endometriosis. Methods: Serum and peritoneal fluid samples were taken from 112 women undergoing laparoscopy for infertility, pelvic pain or adnexal masses. 61 diagnosed with endometriosis and 51 controlled. Primary outcome was to estimate serum and PF concentrations of Angio-2, IL-1β and VEGF and secondarily correlate these concentrations to disease stages thus assuming their diagnostic potential. Results: Significant differences were found between patients and control as regards serum and PF concentration of all studied markers except serum IL-1β. Serum Angio-2 and PF VEGF showed a significantly higher level in more advanced stages of endometriosis. PF VEGF showed a positively significant correlation with the stage of the disease, spearman coefficient t = 0.442 p = 0.014. PF concentrations of Angio-2 and Serum VEGF did not show significant pattern changes with stage-related levels. Diagnostic potential of serum and PF concentrations of the 3 markers were assessed by the ROC curve. Angio-2 proved an excellent diagnostic ability for endometriosis. PF and serum VEGF proved an equal diagnostic performance, whereas, PF IL-1β was the least efficient. Based on the results, we suggested preliminary serum threshold values for these markers to be used as diagnostic or follow-up landmarks with relatively acceptable sensitivity, specificity, positive and negative predictive values. Conclusion: Non-invasive predictive biomarkers for endometriosis were Serum Angio-2, IL-1β, and VEGF independently or in combination with the estimated threshold values. Serum Angio-2 merit is considered as a novel marker for endometriosis due to its diagnostic power.展开更多
AIM： To investigate angiopoietin-2 （Ang-2）/Tie2 signaling pathway involving in inflammatory angiogenesis. METHODS： Three interrupted 11-0 nylon sutures were placed into the corneal stroma of BALB/c mice （6wk old...AIM： To investigate angiopoietin-2 （Ang-2）/Tie2 signaling pathway involving in inflammatory angiogenesis. METHODS： Three interrupted 11-0 nylon sutures were placed into the corneal stroma of BALB/c mice （6wk old） to induce inflammatory neovascularization. Expression of Ang-2 and Tie2 protein on neovascularization were examined by immunofluorescence. The dynamic expression of Ang-2 mRNA on neovascularization was examined by quantitative real-time reverse transcriptase-polymerase chain reaction （RT-PCR）. Finally, the mouse model of suture- induced corneal neovascularization was used to assess the role of Ang-2/Tie2 signaling pathway in inflammatory angiogenesis by systemic application of L1-10, an Ang-2 specific inhibitor. Mouse corneal hemangiogenesis were evaluated by whole mount immunofluorescence. RESULTS： Both Ang-2 and Tie2 were expressed on newly generated blood vessels in inflammatory cornea. Ang-2 expression was gradually upregulated around 2wk following injury, which was concurrent with an increased number of blood vessels. Blockade of Ang-2/Tie2 signaling pathway obviously promoted angiogenesis in inflammatory cornea. CONCLUSION： Ang-2/Tie2 signaling pathway seems to play an important role during angiogenesis in inflammatory cornea. This may open new therapeutic applications in pathological processes such as corneal graft survival, wound healing and carcinogenesis.展开更多
Background: Cardiovascular complications are a major clinical problem in uremic patients accounting for 44% of all deaths in this population. Angiopoietin cytokines are involved with controlling micro vascular permeab...Background: Cardiovascular complications are a major clinical problem in uremic patients accounting for 44% of all deaths in this population. Angiopoietin cytokines are involved with controlling micro vascular permeability, vasodilatation and vasoconstriction by signaling smooth muscle cells surrounding vessels. Aim: To assess Angiopoietin-2 serum level as an early marker of cardiovascular risks in children with chronic kidney disease on regular hemodialysis and correlate with intimal medial thickness and echo data in those children. Patients and methods: The study included 40 children with CKD on regular hemodialysis (HD), and they were selected from the hemodialysis unit of Al-Zahraa Hospital, Al-Azhar University, during the period from December 2014 to April 2015. Another group of 40 apparently healthy children, matches age and sex with patients group as a controls. Angiopoietin-2 serum level, Doppler ultrasound (U/S) to assess: intima-media thickness (IMT) and the peak systolic velocity (PSV) of the main arteries including the (aorta, carotid and femoral) arteries, conventional echo and tissue Doppler imaging (TDI) of mitral and tricuspid annular velocities are obtained for both groups. Results: Children on regular HD have significantly higher (Angiopoietin-2) serum level compared to their controls, and it is (161.35 ± 38.30 ng/ml) and (9.25 ± 12.64 ng/ml) respectively (p, 0.000) and increases in the aorta, carotid and femoral (IMT) with significant increase in their mean systolic velocities in patients group compared to the controls. Significant increase in tricuspid valve late diastolic velocity (TVA vel m/s) and (E/e’ ratio) obtained by (TDI), its abnormalities threshold is detected in patients group than controls, with significant increase right ventricular systolic pulmonary pressure in patients compared to the controls. Conclusions: Higher prevalence of right ventricular dysfunction is detected by conventional and TDI echo in children on hemodialysis. Angiopoietin-2 can be used as an ideal biomarker which may progress to play an adjunctive role with echocardiography in assessing cardiovascular risk of children with CKD on regular hemodialysis.展开更多
文摘目的:探讨检测血管内皮生长因子(vascular endothelial growth factor,VEGF)及血管生成素-2(An-giopoietin-2,Ang-2)对恶性胸腔积液的诊断价值。方法:选择恶性胸腔积液患者31例,良性胸腔积液3例,(ROC)曲线计算上述指标的诊断敏感度、特异度及ROC曲线下面积。并对VEGF及Ang-2之间的相关性进行分析。结果:恶性胸腔积液中的VEGF及Ang-2含量(1106±555 vs 527±229,19.26±6.39 vs 12.25±7.1)明显高于良性胸腔积液(P<0.05);VEGF诊断恶性胸腔积液的敏感度及特异度分别是:82%和90%,Ang-2诊断的敏感度及特异度分别是:65%和71%;恶性胸腔积液中Ang-2的含量与VEGF的含量呈正相关。结论:VEGF及Ang-2可作为恶性胸腔积液诊断的良好指标,可指导选择对患者进行进一步的侵入性检查。
基金Supported by the Ministerio de Ciencia e Innovación(SAF:2010/21805,partially)CIBERehd(Instituto de Salud CarlosⅢ,Madrid)+1 种基金Fundación Mutua Madrile■a(to Moreno-Otero R)a grant from Asociación Espa■ola Contra el Cáncer(AIO 2010,AECC,to Sanz-Cameno P)
文摘AIM To evaluate the efficacy of peripheral blood concentrations of angiopoietins(Ang) as cirrhosis biomarkers of chronic hepatitis C(CHC).METHODS Ang1 and Ang2 serum levels were measured by enzyme-linked immunosorbent assays(ELISA) in samples from 179 cirrhotic and non-cirrhotic CHC patients, classified according to the METAVIR system.Groups were compared by non-parametric MannWhitney U test. Subsequently, the association of peripheral concentrations of angiopoietins with the stage of fibrosis was analyzed using Spearman correlation test. Finally, the accuracy, sensitivity and specificity of circulating angiopoietins for cirrhosis diagnosis were determined by the study of the respective area under the curve of receiver operator characteristics(AUC-ROC).RESULTS Peripheral blood concentrations of Ang1 and Ang2 in CHC patients were significantly related to fibrosis. While Ang1 was decreased in cirrhotic subjects compared to non-cirrhotic(P < 0.0001), Ang2 was significantly increased as CHC progressed to the end stage of liver disease(P < 0.0001). Consequently, Ang2/Ang1 ratio was notably amplified and significantly correlated with fibrosis(P < 0.0001). Interestingly, the individual performance of each angiopoietin for the diagnosis of cirrhosis reached notable AUC-ROC values(above 0.7, both), but the Ang2/Ang1 ratio was much better(AUC-ROC = 0.810) and displayed outstanding values of sensitivity(71%), specificity(84%) and accuracy(82.1%) at the optimal cut-off(10.33). Furthermore, Ang2/Ang1 ratio improved the performance of many other previously described biomarkers or scores of liver cirrhosis in CHC.CONCLUSION Ang2/Ang1 ratio might constitute a useful tool for monitoring the progression of chronic liver disease towards cirrhosis and play an important role as therapeutic target.
文摘To explore the relationship of angiogenesis-related angiopoietin-2 gene and its receptor Tie2 with angiogenesis and the biology of hepatocellular carcinoma (HCC), angiopoietin-2 gene, Tie2 and CD34 protein expression in 22 resected HCC, 8 cirrhotic and 8 control liver specimens were investigated by in situ hybridization and immunohistochemistry respectively, and the level of angiopoietin-2 and Tie2 expression in HCC were compared in terms of tumor biological parameters. It was found that CD34 was not expressed in control liver, expressed scarcely in cirrhotic liver (17 8±13 5/HP), but intensively expressed in HCC (86. 3±34. 8/HP, P<0. 01). Tie2 receptor was not expressed in controls, expressed at low level in cirrhotic liver (11. 3±8. 7/HP), while strongly positive in the microvascular endothelia of HCC (52. 4±16. 7/HP, P<0. 01). The level of Tie2 receptor expression in HCC was closely related with tumor diameter, angiogenesis and portal invasion. Angiopoietin-2 gene was not expressed in control liver, expressed mildly in cirrhotic liver (11. 2±9. 7/HP), but extensively in tumor zone (36. 4±17. 5/HP), the level of angiopoietin-2 expression was closely related with angiogenesis, portal invasion and histological grading of HCC. It is concluded that angiogenesis is increased in HCC; angiopoietin-2/Tie2 expression in human hepatic carcinoma is closely related with angiogenesis, which are probably involved in the HCC angiogenesis regulation, promoting the development and metastasis of human hepatic cancer.
基金This project was supported by a grant from R&D program of Hubei Provincial government (No 2005AA304B09)
文摘To investigate the effect of meloxicam, a selected NSAIDs, on cell growth, expression of VEGF and angiopointin-2 （Ang-2） protein in HT-29 cell line, cultured HT-29 cells were treated with meloxicam of various concentrations for various lengths of time. The proliferation of HT-29 was detected by cell counting kit-8 （CCK-8）, the cell cycle was determined by flow cytometer and the levels of VEGF and Ang-2 protein in supernatants were examined by enzyme linked immunosorbent assay （ELISA）. The mRNA expressions of VEGF and Ang-2 in cultured HT-29 were determined by real-time quantitative reverse-transcription polymerase chain reaction. Our results showed that treatment of meloxicam of different concentrations and for various lengths of time had a cytotoxicic effect on the cell proliferation of HT-29 cells in a concentration-dependant and time-dependant manner. Cell cycle analysis showed that the cells were mainly blocked in G0/G1 phase. The VEGF and Ang-2 protein levels in supernatants of the culture medium were decreased gradually in a concentration-dependent or time-dependent fashion. The mRNA expression of cox-2, VEGF and Ang-2 showed a gradual and concentration-dependent reduction. It is concluded that meloxicam can reduce the expression of VEGF and Ang-2 at the protein and mRNA level in colon carcinoma cell line.
文摘Introduction: Endometriosis affects up to 1 every 5 women at their reproductive age, with variable and complex symptomatology. Patients may be asymptomatic but may have pain episodes or subfertility. Its negative impact is on patients’ health and quality of life. Objective: it was to investigate the serum and peritoneal fluid (PF) concentrations of Angiopoietin- 2, Interleukin-1β, and Vascular Endothelial Growth Factor, aiming to evaluate their diagnostic performance in endometriosis. Methods: Serum and peritoneal fluid samples were taken from 112 women undergoing laparoscopy for infertility, pelvic pain or adnexal masses. 61 diagnosed with endometriosis and 51 controlled. Primary outcome was to estimate serum and PF concentrations of Angio-2, IL-1β and VEGF and secondarily correlate these concentrations to disease stages thus assuming their diagnostic potential. Results: Significant differences were found between patients and control as regards serum and PF concentration of all studied markers except serum IL-1β. Serum Angio-2 and PF VEGF showed a significantly higher level in more advanced stages of endometriosis. PF VEGF showed a positively significant correlation with the stage of the disease, spearman coefficient t = 0.442 p = 0.014. PF concentrations of Angio-2 and Serum VEGF did not show significant pattern changes with stage-related levels. Diagnostic potential of serum and PF concentrations of the 3 markers were assessed by the ROC curve. Angio-2 proved an excellent diagnostic ability for endometriosis. PF and serum VEGF proved an equal diagnostic performance, whereas, PF IL-1β was the least efficient. Based on the results, we suggested preliminary serum threshold values for these markers to be used as diagnostic or follow-up landmarks with relatively acceptable sensitivity, specificity, positive and negative predictive values. Conclusion: Non-invasive predictive biomarkers for endometriosis were Serum Angio-2, IL-1β, and VEGF independently or in combination with the estimated threshold values. Serum Angio-2 merit is considered as a novel marker for endometriosis due to its diagnostic power.
基金Supported by National Natural Science Foundation of China(No.81641174No.30772262)
文摘AIM： To investigate angiopoietin-2 （Ang-2）/Tie2 signaling pathway involving in inflammatory angiogenesis. METHODS： Three interrupted 11-0 nylon sutures were placed into the corneal stroma of BALB/c mice （6wk old） to induce inflammatory neovascularization. Expression of Ang-2 and Tie2 protein on neovascularization were examined by immunofluorescence. The dynamic expression of Ang-2 mRNA on neovascularization was examined by quantitative real-time reverse transcriptase-polymerase chain reaction （RT-PCR）. Finally, the mouse model of suture- induced corneal neovascularization was used to assess the role of Ang-2/Tie2 signaling pathway in inflammatory angiogenesis by systemic application of L1-10, an Ang-2 specific inhibitor. Mouse corneal hemangiogenesis were evaluated by whole mount immunofluorescence. RESULTS： Both Ang-2 and Tie2 were expressed on newly generated blood vessels in inflammatory cornea. Ang-2 expression was gradually upregulated around 2wk following injury, which was concurrent with an increased number of blood vessels. Blockade of Ang-2/Tie2 signaling pathway obviously promoted angiogenesis in inflammatory cornea. CONCLUSION： Ang-2/Tie2 signaling pathway seems to play an important role during angiogenesis in inflammatory cornea. This may open new therapeutic applications in pathological processes such as corneal graft survival, wound healing and carcinogenesis.
文摘Background: Cardiovascular complications are a major clinical problem in uremic patients accounting for 44% of all deaths in this population. Angiopoietin cytokines are involved with controlling micro vascular permeability, vasodilatation and vasoconstriction by signaling smooth muscle cells surrounding vessels. Aim: To assess Angiopoietin-2 serum level as an early marker of cardiovascular risks in children with chronic kidney disease on regular hemodialysis and correlate with intimal medial thickness and echo data in those children. Patients and methods: The study included 40 children with CKD on regular hemodialysis (HD), and they were selected from the hemodialysis unit of Al-Zahraa Hospital, Al-Azhar University, during the period from December 2014 to April 2015. Another group of 40 apparently healthy children, matches age and sex with patients group as a controls. Angiopoietin-2 serum level, Doppler ultrasound (U/S) to assess: intima-media thickness (IMT) and the peak systolic velocity (PSV) of the main arteries including the (aorta, carotid and femoral) arteries, conventional echo and tissue Doppler imaging (TDI) of mitral and tricuspid annular velocities are obtained for both groups. Results: Children on regular HD have significantly higher (Angiopoietin-2) serum level compared to their controls, and it is (161.35 ± 38.30 ng/ml) and (9.25 ± 12.64 ng/ml) respectively (p, 0.000) and increases in the aorta, carotid and femoral (IMT) with significant increase in their mean systolic velocities in patients group compared to the controls. Significant increase in tricuspid valve late diastolic velocity (TVA vel m/s) and (E/e’ ratio) obtained by (TDI), its abnormalities threshold is detected in patients group than controls, with significant increase right ventricular systolic pulmonary pressure in patients compared to the controls. Conclusions: Higher prevalence of right ventricular dysfunction is detected by conventional and TDI echo in children on hemodialysis. Angiopoietin-2 can be used as an ideal biomarker which may progress to play an adjunctive role with echocardiography in assessing cardiovascular risk of children with CKD on regular hemodialysis.
