·AIM: To determine the effects of laser photocoagulation on serum levels of angiopoietin-1(Ang-1),angiopoietin-2(Ang-2), soluble angiopoietin receptor Tie-2(Tie-2), Ang-1/Ang-2 ratio and vascular endothelial grow...·AIM: To determine the effects of laser photocoagulation on serum levels of angiopoietin-1(Ang-1),angiopoietin-2(Ang-2), soluble angiopoietin receptor Tie-2(Tie-2), Ang-1/Ang-2 ratio and vascular endothelial growth factor(VEGF) in patients with type 2diabetes mellitus(T2DM) and proliferative diabetic retinopathy(PDR). We also explored the role of the Ang/Tie system in PDR.·METHODS:Totally 160patientswithT2 DM, including50 patients with non-diabetic retinopathy(NDR), 58 patients with non-proliferative diabetic retinopathy(NPDR), and52 patients with PDR were enrolled in this study. Serum Ang-1, Ang-2, Tie-2 receptor and VEGF levels were measured using enzyme-linked immunosorbent assays for all patients and were repeated in 26 patients who underwent laser photocoagulation two months after the procedure.·RESULTS:ThemedianlevelsofAng-2andVEGFinserum were significantly higher in the NPDR group(4.23 ng/mL and 303.2 pg/mL, respectively) compared to the NDR group(2.67 ng/mL and 159.8 pg/mL, respectively, P 【0.01), with the highest level in the PDR group(6.26 ng/mL and531.2 pg/mL, respectively, P 【0.01). The median level of Ang-1 was significantly higher in the NPDR group(10.77ng/mL) compared to the NDR group(9.31 ng/mL) and the PDR groups(9.54 ng/mL)(P 【0.05), while no difference was observed between the PDR and NDR groups. Ang-1/Ang-2 ratio of PDR group was lowest in three groups(1.49 vs 2.69 and 2.90, both P 【0.01). The median level of Tie-2was not significantly different among three groups(P 】0.05).Ang-2 was positively correlated with VEGF and Tie-2 in the PDR and NPDR groups(both P 【0.05). Among the 26 patients who underwent laser photocoagulation, serum Ang-2 and VEGF levels significantly decreased(both P 【0.05), whereas serum Ang-1 level and Ang-1/Ang-2ratio were weakly increased(P 】0.05). The median levels of Ang-2 and VEGF in serum were highest in PDR group,however, Ang-1/Ang-2 ratio of PDR group was lowest in three groups.·CONCLUSION: Laser photocoagulation can reduce serum Ang-2 and VEGF levels. The Ang/Tie system and VEGF play an important role in the development and progression of T2 DM patients with PDR.展开更多
AIM： To investigate the mechanism of pericyte migration through Angiopoietin-2 （Ang-2）/Tie-2 signaling pathway. METHODS： We divided the rats into 5 groups. Each diabetic rat model groups injected with Tie-2 inhibi...AIM： To investigate the mechanism of pericyte migration through Angiopoietin-2 （Ang-2）/Tie-2 signaling pathway. METHODS： We divided the rats into 5 groups. Each diabetic rat model groups injected with Tie-2 inhibitor, ERK1/2 inhibitor, Akt/PKB inhibitor, and DMSO intravitreal. Retinal digest preparation was done to examine the retinal vasculature including pericyte： endothelial ratio, and morphology of pericyte migration. Tie-2, ERKI/2 and Akt/PKB phosporylation were analyzed by confocal laser scanning microscopy. RESULTS： There was a correlation between pericyte migration with increasing Ang-2 （P〈0.05）. Pericyte number reduced by 40% （1：2.4） after 5wk diabetes on diabetic rats. The pericyte： endothelial ratio on group with Tie-2 inhibitor were 1：1.8. The same result shows on group with Akt/PKB inhibition. ERK1/2 inhibitor group shows the best results of pericyte： endothelial ratio （1：1,7）, Inhibition on Tie-2 receptor decreased the phosphorylation activity of Tie-2, ERK1/2 and Akt/PKB pathway. ERK1/2 inhibition also decreasing the phosphorylation of Tie-2 and Akt/PKB. But on Akt/PKB inhibition, the phosphorylation of Tie-2 and ERK1/2 were relative the same. CONCLUSION： Ang-2 has a role for pericyte migration on diabetic rats through Tie-2 receptor, ERKII2 and Akt/PKB pathways. ERK1/2 is a dominant pathway based on the ability to supress another pathway activity and decreasing pericyte migration on diabetic rats.展开更多
Objective： To explore angiopoietins （Ang-1, Ang-2）/Tie-2 expression and angiogenesis in stomach carcinomas. Methods： RT-PCR and immunohistochemistry were used to detect angiopoietins/Tie- 2 mRNA and protein expres...Objective： To explore angiopoietins （Ang-1, Ang-2）/Tie-2 expression and angiogenesis in stomach carcinomas. Methods： RT-PCR and immunohistochemistry were used to detect angiopoietins/Tie- 2 mRNA and protein expression in stomach carcinomas and their adjacent normal mucosa. Microvessel density （MVD） was counted according to CD34 immunohistochemical staining. Results： There was positive expression of Angiopoietins/Tie-2 mRNA and protein in stomach carcinomas and their paired adjacent normal mucosa. It was found that correlation between Ang-1 protein, Tie-2 mRNA expression and MVD was negative （F=-0.440, F=-0.267; P〈0.05）, while the correlation between Ang-2 mRNA and its protein, Ang-2/Ang-1 protein ratio and MVD was positive （F=0.319, F=-729, F=739; P〈0.05）. Moreover, MVD in groups with Ang-2 mRNAT/N ratio over 1.2 （the ratio of Ang-2 mRNA in stomach carcinoma to its adjacent normal mucosa） was higher than those with the ratio under 1.2. Conclusion： It was suggested that Ang-1 and Ang-2 antagonizes in the angiogenesis and the anglogenesis in tumor ultimately depended on Ang-2/Ang-1 ratio, once the expression of Ang-2 is higher than Ang-1 in some degree, the angiogenesis in tumors was promoted, otherwise oppositely. In other words, Ang-2 plays dominant role in the action of angiogenesis in tumors.展开更多
Ephrin-B2 has been shown to participate in angiogenesis, but the underlying mechanisms involved remain unclear. In this study, a rat model of local cerebral ischemia was prepared by focal middle cerebral artery occlus...Ephrin-B2 has been shown to participate in angiogenesis, but the underlying mechanisms involved remain unclear. In this study, a rat model of local cerebral ischemia was prepared by focal middle cerebral artery occlusion, followed by 24-hour reperfusion. Then, ephrin-B2 protein was administered intracerebroventricularly for 3 consecutive days via a micro-osmotic pump. Western blot assay and quantitative real-time reverse transcription PCR demonstrated the expression levels of angiopoietin-1 （Ang-1） mRNA and protein in the penumbra cortex of the ephrin-B2 treated group were decreased at day 4 after reperfusion, and increased at day 28, while the expression levels of angiopoietin-2 （Ang-2） were highly up-regulated at all time points tested. Double immunofluorescent staining indicated that Ang-1 and Ang-2 were both expressed in vascular endothelial cells positive for CD31. These findings indicate that ephrin-B2 influences the expressions of Ang-1 and Ang-2 during angiogenesis following transient focal cerebral ischemia.展开更多
AIM： TO investigate the significance of angiopoietins, Tie2 and vascular endothelial growth factor （VEGF） expression in the angiogenesis and progress of hepatocellular carcinoma （HCC）. METHODS： Fresh surgically ...AIM： TO investigate the significance of angiopoietins, Tie2 and vascular endothelial growth factor （VEGF） expression in the angiogenesis and progress of hepatocellular carcinoma （HCC）. METHODS： Fresh surgically resected specimens of HCC and noncancerous liver （NCL） tissue from 38 patients with HCC were obtained, and expression of angiopoietin-1 （Ang-1）, angiopoietin-2 （Ang-2）, Tie2, and VEGF messenger RNA （mRNA） was examined by real-time quantitative reverse transcription-polymerase chain reaction （RT-PCR）. Expression pattern of each gene in HCC and NCL tissue specimens was compared and the potential role and interaction in angiogenesis of HCC were analyzed. Genes＇ expression level and its relationship with tumor＇s clinicopathological parameters were also investigated. Immunohistochemical staining of CD34 was performed to determine the microvessel density （MVD） and Ang-2/Ang-1 ratio was calculated. Relationships between Ang-2/Ang-1 ratio, VEGF and MVD and clinicopathological features were also tested so as to evaluate their significance in the progression of HCC. RESULTS： Ang-2 and VEGF mRNAs in HCC were significantly higher than those in NCL tissue （P 〈 0.05）, whereas the Ang-1 and Tie2 mRNAs showed no statistical significance （P 〉 0.05）, though slightly lower level of Ang-1 mRNA in HCC was observed. Ang-2/ Ang-1 ratio and VEGF were both positively correlated to MVD. The Ang-2/Ang-1 ratio, Ang-2 and VEGF were all associated with tumor＇s clinicopathological parameters （P 〈 0.05） except for histological grades （P 〉 0.05）. Ang-1 and Tie2 levels in different clinicopathological groups were not significantly different （P 〉 0.05）. CONCLUSION： Dominant Ang-2 expression against Ang-1 through Tie2 receptor in the presence of VEGF plays a critical role in initiating early neovascularization and transformation of noncancerous liver to hepatocellular carcinoma. Its consequently constant operation in formed HCC induces further angiogenesis and progression of HCC.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
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
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
BACKGROUND： Estrogen has been clinically demonstrated to attenuate ischemic brain injury. However, the precise mechanisms remain controversial. OBJECTIVE： To investigate the effects of estradiol on angiopoietin-1 mR...BACKGROUND： Estrogen has been clinically demonstrated to attenuate ischemic brain injury. However, the precise mechanisms remain controversial. OBJECTIVE： To investigate the effects of estradiol on angiopoietin-1 mRNA and Bcl-2 expression, as well as apoptosis and cerebral blood flow, in ovadectomized rats with focal cerebral ischemia following reperfusion. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiment. The study was performed at the Central Laboratory, Chongqing Medical University from September to December 2005. MATERIALS： Estradiol benzoate was purchased from Shanghai Ninth Pharmaceutical Factory; corn oil was purchased from Walmart Supercenter; TUNEL kit, rabbit anti-rat Bcl-2 polyclonal antibody, and biotin-labeled goat anti-rabbit antibody were purchased from Wuhan Boster, China. METHODS： Healthy, female, 6-month-old Wistar rats-wild-type and estrogen alpha receptor gene knockout （ERKO）-were randomly divided into estradiol and control groups with 25 animals in each group. The rats were intramuscularly injected with estradiol benzoate （100 μg/kg per day） at 30 days following bilateral ovariectomy or corn oil （1 mL/kg per day） for seven consecutive days. Following administration, cerebral ischemia/reperfusion models were established using the right middle cerebral artery occlusion （MCAO） method. After 30 minutes of MCAO, estradiol and control groups were separately injected with estradiol benzoate and corn oil with the above-mentioned doses. MAIN OUTCOME MEASURES： Cell apoptosis was determined by TUNEL; angiopoietin-1 mRNA and Bcl-2 gene expression was determined, respectively, by immunohistochemical staining and RT-PCR. In addition, changes in cerebral blood flow were measured by laser Doppler flowmetry. RESULTS： Changes in angiopoietin-1 mRNA and cerebral blood flow in estradiol-treated, wild-type, MCAO rats following ischemia/reperfusion were greater than in control rats （P 〈 0.01 or 0.05）. However, no significant difference was observed between estradiol-treated ERKO MCAO rats and control rats. In addition, estradiol-treated wild-type and ERKO MCAO rats exhibited significantly increased Bcl-2 expression （P 〈 0.05） and decreased number of apoptotic cells in brain tissues compared with control groups （P 〈 0.05）. CONCLUSION： Estradiol upregulated angiopoietin-1 mRNA and Bcl-2 expression, suggesting that estradiol might be involved in protective mechanisms of cerebral ischemia/reperfusion injury.展开更多
文摘·AIM: To determine the effects of laser photocoagulation on serum levels of angiopoietin-1(Ang-1),angiopoietin-2(Ang-2), soluble angiopoietin receptor Tie-2(Tie-2), Ang-1/Ang-2 ratio and vascular endothelial growth factor(VEGF) in patients with type 2diabetes mellitus(T2DM) and proliferative diabetic retinopathy(PDR). We also explored the role of the Ang/Tie system in PDR.·METHODS:Totally 160patientswithT2 DM, including50 patients with non-diabetic retinopathy(NDR), 58 patients with non-proliferative diabetic retinopathy(NPDR), and52 patients with PDR were enrolled in this study. Serum Ang-1, Ang-2, Tie-2 receptor and VEGF levels were measured using enzyme-linked immunosorbent assays for all patients and were repeated in 26 patients who underwent laser photocoagulation two months after the procedure.·RESULTS:ThemedianlevelsofAng-2andVEGFinserum were significantly higher in the NPDR group(4.23 ng/mL and 303.2 pg/mL, respectively) compared to the NDR group(2.67 ng/mL and 159.8 pg/mL, respectively, P 【0.01), with the highest level in the PDR group(6.26 ng/mL and531.2 pg/mL, respectively, P 【0.01). The median level of Ang-1 was significantly higher in the NPDR group(10.77ng/mL) compared to the NDR group(9.31 ng/mL) and the PDR groups(9.54 ng/mL)(P 【0.05), while no difference was observed between the PDR and NDR groups. Ang-1/Ang-2 ratio of PDR group was lowest in three groups(1.49 vs 2.69 and 2.90, both P 【0.01). The median level of Tie-2was not significantly different among three groups(P 】0.05).Ang-2 was positively correlated with VEGF and Tie-2 in the PDR and NPDR groups(both P 【0.05). Among the 26 patients who underwent laser photocoagulation, serum Ang-2 and VEGF levels significantly decreased(both P 【0.05), whereas serum Ang-1 level and Ang-1/Ang-2ratio were weakly increased(P 】0.05). The median levels of Ang-2 and VEGF in serum were highest in PDR group,however, Ang-1/Ang-2 ratio of PDR group was lowest in three groups.·CONCLUSION: Laser photocoagulation can reduce serum Ang-2 and VEGF levels. The Ang/Tie system and VEGF play an important role in the development and progression of T2 DM patients with PDR.
文摘AIM： To investigate the mechanism of pericyte migration through Angiopoietin-2 （Ang-2）/Tie-2 signaling pathway. METHODS： We divided the rats into 5 groups. Each diabetic rat model groups injected with Tie-2 inhibitor, ERK1/2 inhibitor, Akt/PKB inhibitor, and DMSO intravitreal. Retinal digest preparation was done to examine the retinal vasculature including pericyte： endothelial ratio, and morphology of pericyte migration. Tie-2, ERKI/2 and Akt/PKB phosporylation were analyzed by confocal laser scanning microscopy. RESULTS： There was a correlation between pericyte migration with increasing Ang-2 （P〈0.05）. Pericyte number reduced by 40% （1：2.4） after 5wk diabetes on diabetic rats. The pericyte： endothelial ratio on group with Tie-2 inhibitor were 1：1.8. The same result shows on group with Akt/PKB inhibition. ERK1/2 inhibitor group shows the best results of pericyte： endothelial ratio （1：1,7）, Inhibition on Tie-2 receptor decreased the phosphorylation activity of Tie-2, ERK1/2 and Akt/PKB pathway. ERK1/2 inhibition also decreasing the phosphorylation of Tie-2 and Akt/PKB. But on Akt/PKB inhibition, the phosphorylation of Tie-2 and ERK1/2 were relative the same. CONCLUSION： Ang-2 has a role for pericyte migration on diabetic rats through Tie-2 receptor, ERKII2 and Akt/PKB pathways. ERK1/2 is a dominant pathway based on the ability to supress another pathway activity and decreasing pericyte migration on diabetic rats.
基金Supported by a grant from the Natural Sciences Foundation of Fujian (No. C0110013).
文摘Objective： To explore angiopoietins （Ang-1, Ang-2）/Tie-2 expression and angiogenesis in stomach carcinomas. Methods： RT-PCR and immunohistochemistry were used to detect angiopoietins/Tie- 2 mRNA and protein expression in stomach carcinomas and their adjacent normal mucosa. Microvessel density （MVD） was counted according to CD34 immunohistochemical staining. Results： There was positive expression of Angiopoietins/Tie-2 mRNA and protein in stomach carcinomas and their paired adjacent normal mucosa. It was found that correlation between Ang-1 protein, Tie-2 mRNA expression and MVD was negative （F=-0.440, F=-0.267; P〈0.05）, while the correlation between Ang-2 mRNA and its protein, Ang-2/Ang-1 protein ratio and MVD was positive （F=0.319, F=-729, F=739; P〈0.05）. Moreover, MVD in groups with Ang-2 mRNAT/N ratio over 1.2 （the ratio of Ang-2 mRNA in stomach carcinoma to its adjacent normal mucosa） was higher than those with the ratio under 1.2. Conclusion： It was suggested that Ang-1 and Ang-2 antagonizes in the angiogenesis and the anglogenesis in tumor ultimately depended on Ang-2/Ang-1 ratio, once the expression of Ang-2 is higher than Ang-1 in some degree, the angiogenesis in tumors was promoted, otherwise oppositely. In other words, Ang-2 plays dominant role in the action of angiogenesis in tumors.
文摘Ephrin-B2 has been shown to participate in angiogenesis, but the underlying mechanisms involved remain unclear. In this study, a rat model of local cerebral ischemia was prepared by focal middle cerebral artery occlusion, followed by 24-hour reperfusion. Then, ephrin-B2 protein was administered intracerebroventricularly for 3 consecutive days via a micro-osmotic pump. Western blot assay and quantitative real-time reverse transcription PCR demonstrated the expression levels of angiopoietin-1 （Ang-1） mRNA and protein in the penumbra cortex of the ephrin-B2 treated group were decreased at day 4 after reperfusion, and increased at day 28, while the expression levels of angiopoietin-2 （Ang-2） were highly up-regulated at all time points tested. Double immunofluorescent staining indicated that Ang-1 and Ang-2 were both expressed in vascular endothelial cells positive for CD31. These findings indicate that ephrin-B2 influences the expressions of Ang-1 and Ang-2 during angiogenesis following transient focal cerebral ischemia.
文摘AIM： TO investigate the significance of angiopoietins, Tie2 and vascular endothelial growth factor （VEGF） expression in the angiogenesis and progress of hepatocellular carcinoma （HCC）. METHODS： Fresh surgically resected specimens of HCC and noncancerous liver （NCL） tissue from 38 patients with HCC were obtained, and expression of angiopoietin-1 （Ang-1）, angiopoietin-2 （Ang-2）, Tie2, and VEGF messenger RNA （mRNA） was examined by real-time quantitative reverse transcription-polymerase chain reaction （RT-PCR）. Expression pattern of each gene in HCC and NCL tissue specimens was compared and the potential role and interaction in angiogenesis of HCC were analyzed. Genes＇ expression level and its relationship with tumor＇s clinicopathological parameters were also investigated. Immunohistochemical staining of CD34 was performed to determine the microvessel density （MVD） and Ang-2/Ang-1 ratio was calculated. Relationships between Ang-2/Ang-1 ratio, VEGF and MVD and clinicopathological features were also tested so as to evaluate their significance in the progression of HCC. RESULTS： Ang-2 and VEGF mRNAs in HCC were significantly higher than those in NCL tissue （P 〈 0.05）, whereas the Ang-1 and Tie2 mRNAs showed no statistical significance （P 〉 0.05）, though slightly lower level of Ang-1 mRNA in HCC was observed. Ang-2/ Ang-1 ratio and VEGF were both positively correlated to MVD. The Ang-2/Ang-1 ratio, Ang-2 and VEGF were all associated with tumor＇s clinicopathological parameters （P 〈 0.05） except for histological grades （P 〉 0.05）. Ang-1 and Tie2 levels in different clinicopathological groups were not significantly different （P 〉 0.05）. CONCLUSION： Dominant Ang-2 expression against Ang-1 through Tie2 receptor in the presence of VEGF plays a critical role in initiating early neovascularization and transformation of noncancerous liver to hepatocellular carcinoma. Its consequently constant operation in formed HCC induces further angiogenesis and progression of HCC.
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。
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.
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.
基金Supported by:the Natural Science Foundation of Chongqing,No. CSTC2006EB5030
文摘BACKGROUND： Estrogen has been clinically demonstrated to attenuate ischemic brain injury. However, the precise mechanisms remain controversial. OBJECTIVE： To investigate the effects of estradiol on angiopoietin-1 mRNA and Bcl-2 expression, as well as apoptosis and cerebral blood flow, in ovadectomized rats with focal cerebral ischemia following reperfusion. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiment. The study was performed at the Central Laboratory, Chongqing Medical University from September to December 2005. MATERIALS： Estradiol benzoate was purchased from Shanghai Ninth Pharmaceutical Factory; corn oil was purchased from Walmart Supercenter; TUNEL kit, rabbit anti-rat Bcl-2 polyclonal antibody, and biotin-labeled goat anti-rabbit antibody were purchased from Wuhan Boster, China. METHODS： Healthy, female, 6-month-old Wistar rats-wild-type and estrogen alpha receptor gene knockout （ERKO）-were randomly divided into estradiol and control groups with 25 animals in each group. The rats were intramuscularly injected with estradiol benzoate （100 μg/kg per day） at 30 days following bilateral ovariectomy or corn oil （1 mL/kg per day） for seven consecutive days. Following administration, cerebral ischemia/reperfusion models were established using the right middle cerebral artery occlusion （MCAO） method. After 30 minutes of MCAO, estradiol and control groups were separately injected with estradiol benzoate and corn oil with the above-mentioned doses. MAIN OUTCOME MEASURES： Cell apoptosis was determined by TUNEL; angiopoietin-1 mRNA and Bcl-2 gene expression was determined, respectively, by immunohistochemical staining and RT-PCR. In addition, changes in cerebral blood flow were measured by laser Doppler flowmetry. RESULTS： Changes in angiopoietin-1 mRNA and cerebral blood flow in estradiol-treated, wild-type, MCAO rats following ischemia/reperfusion were greater than in control rats （P 〈 0.01 or 0.05）. However, no significant difference was observed between estradiol-treated ERKO MCAO rats and control rats. In addition, estradiol-treated wild-type and ERKO MCAO rats exhibited significantly increased Bcl-2 expression （P 〈 0.05） and decreased number of apoptotic cells in brain tissues compared with control groups （P 〈 0.05）. CONCLUSION： Estradiol upregulated angiopoietin-1 mRNA and Bcl-2 expression, suggesting that estradiol might be involved in protective mechanisms of cerebral ischemia/reperfusion injury.
