BACKGROUND: Angiogenesis is known to be essential to the survival, growth, invasion, and metastasis of tumor cells. Vascular endothelial growth factor (VEGF) are an important angiogenic factor regulating tumor angioge...BACKGROUND: Angiogenesis is known to be essential to the survival, growth, invasion, and metastasis of tumor cells. Vascular endothelial growth factor (VEGF) are an important angiogenic factor regulating tumor angiogenesis, but its significance and tumor pathologic features are un- clear in hepatocellular carcinoma (HCC). In the present study, we analyzed expression of tissue VEGF, alteration of microvascular density (MVD) in microvessel angiogenesis, development and metastasis of HCC, and level of serum VEGF in differential diagnosis of benign and malignant liv- er diseases. METHODS: Tumor specimens were prospectively collected from HCC patients undergoing resection. Total RNAs were extracted and the expression levels were detected from different parts of HCC tissues. The cellular distributions of VEGF and MVD of liver tumors and their paracancerous and distal cancerous tissues were investigated by streptavi- din peroxidase (S-P) immunohistochemistry, respectively. The VEGF levels of circulating blood and hepatoma tissues were measured by enzyme-linked immunosorbent assay. RESULTS: The incidence of VEGF expression was 63.9% in HCCs (23/36 cases), 78.3% in non-encapsulated HCCs (18/23), and 90.9% in HCCs with extrahepatic metastasis (10/11), respectively. The VEGF expression was tightly correlated with MVD (P <0.01). The MVD in HCC with metastasis, low differentiation or non-encapsulation was significantly higher than that in HCC with intact capsule, high differentiation, or no metastasis. No significant diffe- rence was found between VEGF, MVD, tumor size, and hepatitis virus infection. The level of total RNA in HCC tis- sues was significantly lower but the VEGF level significantly higher than those in paracancerous or distal cancerous ones (P<0.01). The abnormal expression levels of VEGF in sera of HCC patients were directly correlated with the me- tastasis and recurrence of tumors. CONCLUSION: The high expression of VEGF and abnor- mality of tissue MVD are useful predictors for vascular inva- sion and metastasis of liver tumors.展开更多
AIM: To investigate the mRNA expressions of bFGF and MMP-9 in gastric carcinomas so as to reveal their correlations with tumor microvascular density (MVD), invasion, metastasis, and prognosis.METHODS: In situ hybridiz...AIM: To investigate the mRNA expressions of bFGF and MMP-9 in gastric carcinomas so as to reveal their correlations with tumor microvascular density (MVD), invasion, metastasis, and prognosis.METHODS: In situ hybridization and immunohistochemical techniques were used to detect the expressions of bFGFmRNA and MMP-9mRNA and the proteins of CD34 in 105 specimens of gastric carcinomas.RESULTS: In situ hybridization study showed that positive rates of bFGF mRNA and MMP-9mRNA expressions were 60.95% and 59.19%; the mean MVD was 46.09±11.52 and 43.75±13.41, respectively in piece/0.72 mm2 in tumors with bFGFmRNA and MMP-9mRNA positive expressions,which were significantly higher than those with negative expression (29.41±12.47; 33.45±13.92 piece/0.72 mm2,respectively). The positive expression rates of bFGFmRNA and MMP-9mRNA were correlated to the tumor invasion depth (rs = 0.211, P= 0.031; rs = 0.335, P= 0.001), growing pattern (rs= 0.324, P= 0.001; rs= 0.267, P= 0.006), vessel invasion (rs = 0.579, P = 0.001; rs = 0.209, P = 0.032),lymph node metastasis (rs = 0.405, P = 0.001; rs= 0.343,P = 0.001) and distant metastasis (rs= 0.474, P = 0.001;rs = 0.468, P = 0.001), but not correlated to tumortype (rs= 0.134, P= 0.173; rs= 0.103, P= 0.145) anddifferentiations (rs = 0.096, P= 0.332; rs = 0.102, P= 0.298).The mean MVD was much higher in the tumors withinfiltrating growth at stage T3-T4, with vessel invasion, lymph node metastasis and distant metastasis than those with expanding growth type (t = 10.105, P= 0.001) at stage T1-T2 (t = 5.961, P = 0.001), with non-vessel invasion (t= 7.394, P= 0.001), non-lymph node metastasis (t= 3.819, P= 0.01) and non-distant metastasis (t= 10.578, P = 0.001). Positive correlation was observed between MVD and the expressions of bFGFmRNA and MMP-9mRNA(t= 3.207, P= 0.002; t= 7.035, P= 0.001, respectively). The mean survival time and 5-year survival rate werelower in cases with MVD over 39.5 and the positive expressions of bFGFmRNA and MMP-9mRNA than those with MVD less than 39.5 and the negative expressions of bFGFmRNA and MMP-9mRNA.CONCLUSION: bFGF and MMP-9 promote the angiogenesis of the gastric cancers. Detection of the expressions of bF-GF and MMP-9 can serve as a useful index to determine the angiogenesis, invasion, metastasis, and prognosis of gastric cancers.展开更多
The relationship between the expression of vascular endothelial growth factor（VEGF） and microvascular density（MVD） marked by CD105（CD105-MVD）,and that between CD105-MVD and the clinicopathological characteristic...The relationship between the expression of vascular endothelial growth factor（VEGF） and microvascular density（MVD） marked by CD105（CD105-MVD）,and that between CD105-MVD and the clinicopathological characteristics of primary pterygium were investigated.The streptavidin-biotin complex（SABC） immunohistochemical staining in paraffin-embedded tissues was used to detect the expression of VEGF in 23 cases of primary pterygia and 7 normal conjunctival specimens.The antibody against CD105 was used to display vascular endothelial cells,and MVD was examined by counting the CD105-positive vascular endothelial cells.The correlations of VEGF and CD105-MVD,and those of CD105-MVD and clinicopathological data were analyzed by using SPSS 12.0.The expression of VEGF was significantly increased in epithelia（P=0.000）,endothelia and stroma cells（P=0.005） in primary pterygia as compared with normal conjunctivae.The CD105-MVD in pterygia（mean 19.22±6.68） was higher than that in normal conjunctivae（mean 4.00±2.15,P=0.000）.MVD in pterygia was significantly associated with the Tan classification（P=0.000） and the VEGF expression level in the stroma（P=0.020）,but not with sex（P=0.61）,age（P=0.150） or the VEGF expression level in the epithelia（P=0.518）.Our results suggest that over-expression of VEGF and high CD105-MVD in primary pterygium may contribute to the progression by increasing angiogenesis and growth of primary pterygium.展开更多
The effects of transforming growth factor-β1 （TGF-β1） are currently controversial. Whether TGF-β1 promotes or inhibits revascularization under different conditions remains poorly understood. Based on previous stu...The effects of transforming growth factor-β1 （TGF-β1） are currently controversial. Whether TGF-β1 promotes or inhibits revascularization under different conditions remains poorly understood. Based on previous studies, the current experiment established rat models of cerebral ischemia and reperfusion injury （IRI）, and demonstrated that pathological and functional damage was also increased after IRI. The most serious damage was observed at 3 days after reperfusion, at which time microvascular density fell to its lowest level. Soon afterwards, microvascular density increased, new collateral circulation was gradually established at 4 to 7 days after reperfusion, and pathological damage and neurological deficits were improved. TGF-β1, activin receptor-like kinase 5 （ALK5） mRNA and protein expression levels increased gradually over time. In contrast, ALK1 mRNA and protein expression decreased over the same period. A significant negative correlation was detected between microvascular density and expression of the ALK5 gene transcript. There was no correlation between microvascular density and ALK1 gene transcriptional expression following cerebral IRI in a rat model. These findings suggest that ALK5, rather than ALK1, is the critical receptor in the TGF-β1 signal pathways after cerebral IRI.展开更多
目的:探讨miR-455在宫颈癌中的表达及其与微血管密度(MVD)及血管内皮生长因子(VEGF)表达的关系。方法:采用实时荧光定量PCR技术检测68例宫颈癌患者和49例慢性宫颈炎(对照组)组织中miR-455的表达。免疫组化方法检测组织内MVD及VEGF蛋白...目的:探讨miR-455在宫颈癌中的表达及其与微血管密度(MVD)及血管内皮生长因子(VEGF)表达的关系。方法:采用实时荧光定量PCR技术检测68例宫颈癌患者和49例慢性宫颈炎(对照组)组织中miR-455的表达。免疫组化方法检测组织内MVD及VEGF蛋白表达水平。结果:宫颈癌组织内miR-455的相对表达量显著低于慢性宫颈炎(1.17±0.59 vs 2.58±0.83,P<0.01)。68例宫颈癌标本MVD表达的计数结果为30.45±7.9。Pearson相关分析结果显示,宫颈癌组织内miR-455表达水平与MVD呈负相关(r=-0.835,P<0.01。宫颈癌VEGF表达为阴性、弱阳性、中度阳性和强阳性组中,miR-455相对表达定量(RQ)分别为1.77±0.58、1.59±0.50、1.34±0.35和0.68±0.26,Spearman等级相关分析结果显示,miR-455表达水平与VEGF的表达呈负等级相关(r s=-0.857,P<0.01)。结论:miR-455低表达可能通过VEGF信号通路促进宫颈癌内微血管形成,是一个潜在的抑癌miRNA。展开更多
目的:探讨高迁移率族蛋白1(High mobility group protein box-1,HMGB1)在肝细胞癌组织中的表达及其与血管内皮生长因子(Vascular endothelial growth factor,VEGF)表达、肿瘤微血管密度(Microvascular density,MVD)的关系和临床意义。方...目的:探讨高迁移率族蛋白1(High mobility group protein box-1,HMGB1)在肝细胞癌组织中的表达及其与血管内皮生长因子(Vascular endothelial growth factor,VEGF)表达、肿瘤微血管密度(Microvascular density,MVD)的关系和临床意义。方法:免疫组织化学SP法检测HMGB1、VEGF和CD34在37例人肝癌组织及相应癌旁肝组织和10例人正常肝组织中的表达;并用抗CD34抗体标记微血管,计数微血管密度;应用Western blot技术定量检测HMGB1在10例肝癌及相应癌旁和5例正常肝组织的表达情况。结果:HMGB1蛋白在肝癌组织中的表达明显高于癌旁组织及正常肝组织。HMGB1的表达与肿瘤大小、门静脉侵犯相关(P=0.018;P=0.036)。肝癌组织中HMGB1表达与VEGF表达及MVD间均呈正相关(r=0.544,P=0.001;r=0.672,P<0.05)。结论:肝癌组织中异常表达增高的HMGB1、VEGF与肝癌微血管生成过程相关,HMGB1可能成为阻断肝癌血管生成的有效靶点。展开更多
基金This study was supported in part by grant from the KeyProject Foundation of Medical Sciences of Jiangsu province(RC2003100)
文摘BACKGROUND: Angiogenesis is known to be essential to the survival, growth, invasion, and metastasis of tumor cells. Vascular endothelial growth factor (VEGF) are an important angiogenic factor regulating tumor angiogenesis, but its significance and tumor pathologic features are un- clear in hepatocellular carcinoma (HCC). In the present study, we analyzed expression of tissue VEGF, alteration of microvascular density (MVD) in microvessel angiogenesis, development and metastasis of HCC, and level of serum VEGF in differential diagnosis of benign and malignant liv- er diseases. METHODS: Tumor specimens were prospectively collected from HCC patients undergoing resection. Total RNAs were extracted and the expression levels were detected from different parts of HCC tissues. The cellular distributions of VEGF and MVD of liver tumors and their paracancerous and distal cancerous tissues were investigated by streptavi- din peroxidase (S-P) immunohistochemistry, respectively. The VEGF levels of circulating blood and hepatoma tissues were measured by enzyme-linked immunosorbent assay. RESULTS: The incidence of VEGF expression was 63.9% in HCCs (23/36 cases), 78.3% in non-encapsulated HCCs (18/23), and 90.9% in HCCs with extrahepatic metastasis (10/11), respectively. The VEGF expression was tightly correlated with MVD (P <0.01). The MVD in HCC with metastasis, low differentiation or non-encapsulation was significantly higher than that in HCC with intact capsule, high differentiation, or no metastasis. No significant diffe- rence was found between VEGF, MVD, tumor size, and hepatitis virus infection. The level of total RNA in HCC tis- sues was significantly lower but the VEGF level significantly higher than those in paracancerous or distal cancerous ones (P<0.01). The abnormal expression levels of VEGF in sera of HCC patients were directly correlated with the me- tastasis and recurrence of tumors. CONCLUSION: The high expression of VEGF and abnor- mality of tissue MVD are useful predictors for vascular inva- sion and metastasis of liver tumors.
文摘AIM: To investigate the mRNA expressions of bFGF and MMP-9 in gastric carcinomas so as to reveal their correlations with tumor microvascular density (MVD), invasion, metastasis, and prognosis.METHODS: In situ hybridization and immunohistochemical techniques were used to detect the expressions of bFGFmRNA and MMP-9mRNA and the proteins of CD34 in 105 specimens of gastric carcinomas.RESULTS: In situ hybridization study showed that positive rates of bFGF mRNA and MMP-9mRNA expressions were 60.95% and 59.19%; the mean MVD was 46.09±11.52 and 43.75±13.41, respectively in piece/0.72 mm2 in tumors with bFGFmRNA and MMP-9mRNA positive expressions,which were significantly higher than those with negative expression (29.41±12.47; 33.45±13.92 piece/0.72 mm2,respectively). The positive expression rates of bFGFmRNA and MMP-9mRNA were correlated to the tumor invasion depth (rs = 0.211, P= 0.031; rs = 0.335, P= 0.001), growing pattern (rs= 0.324, P= 0.001; rs= 0.267, P= 0.006), vessel invasion (rs = 0.579, P = 0.001; rs = 0.209, P = 0.032),lymph node metastasis (rs = 0.405, P = 0.001; rs= 0.343,P = 0.001) and distant metastasis (rs= 0.474, P = 0.001;rs = 0.468, P = 0.001), but not correlated to tumortype (rs= 0.134, P= 0.173; rs= 0.103, P= 0.145) anddifferentiations (rs = 0.096, P= 0.332; rs = 0.102, P= 0.298).The mean MVD was much higher in the tumors withinfiltrating growth at stage T3-T4, with vessel invasion, lymph node metastasis and distant metastasis than those with expanding growth type (t = 10.105, P= 0.001) at stage T1-T2 (t = 5.961, P = 0.001), with non-vessel invasion (t= 7.394, P= 0.001), non-lymph node metastasis (t= 3.819, P= 0.01) and non-distant metastasis (t= 10.578, P = 0.001). Positive correlation was observed between MVD and the expressions of bFGFmRNA and MMP-9mRNA(t= 3.207, P= 0.002; t= 7.035, P= 0.001, respectively). The mean survival time and 5-year survival rate werelower in cases with MVD over 39.5 and the positive expressions of bFGFmRNA and MMP-9mRNA than those with MVD less than 39.5 and the negative expressions of bFGFmRNA and MMP-9mRNA.CONCLUSION: bFGF and MMP-9 promote the angiogenesis of the gastric cancers. Detection of the expressions of bF-GF and MMP-9 can serve as a useful index to determine the angiogenesis, invasion, metastasis, and prognosis of gastric cancers.
文摘The relationship between the expression of vascular endothelial growth factor（VEGF） and microvascular density（MVD） marked by CD105（CD105-MVD）,and that between CD105-MVD and the clinicopathological characteristics of primary pterygium were investigated.The streptavidin-biotin complex（SABC） immunohistochemical staining in paraffin-embedded tissues was used to detect the expression of VEGF in 23 cases of primary pterygia and 7 normal conjunctival specimens.The antibody against CD105 was used to display vascular endothelial cells,and MVD was examined by counting the CD105-positive vascular endothelial cells.The correlations of VEGF and CD105-MVD,and those of CD105-MVD and clinicopathological data were analyzed by using SPSS 12.0.The expression of VEGF was significantly increased in epithelia（P=0.000）,endothelia and stroma cells（P=0.005） in primary pterygia as compared with normal conjunctivae.The CD105-MVD in pterygia（mean 19.22±6.68） was higher than that in normal conjunctivae（mean 4.00±2.15,P=0.000）.MVD in pterygia was significantly associated with the Tan classification（P=0.000） and the VEGF expression level in the stroma（P=0.020）,but not with sex（P=0.61）,age（P=0.150） or the VEGF expression level in the epithelia（P=0.518）.Our results suggest that over-expression of VEGF and high CD105-MVD in primary pterygium may contribute to the progression by increasing angiogenesis and growth of primary pterygium.
基金a grant of Supportive Fund for Young Scientists from the Department of Science & Technology of Shandong Province, China, No. 2004BS03013
文摘The effects of transforming growth factor-β1 （TGF-β1） are currently controversial. Whether TGF-β1 promotes or inhibits revascularization under different conditions remains poorly understood. Based on previous studies, the current experiment established rat models of cerebral ischemia and reperfusion injury （IRI）, and demonstrated that pathological and functional damage was also increased after IRI. The most serious damage was observed at 3 days after reperfusion, at which time microvascular density fell to its lowest level. Soon afterwards, microvascular density increased, new collateral circulation was gradually established at 4 to 7 days after reperfusion, and pathological damage and neurological deficits were improved. TGF-β1, activin receptor-like kinase 5 （ALK5） mRNA and protein expression levels increased gradually over time. In contrast, ALK1 mRNA and protein expression decreased over the same period. A significant negative correlation was detected between microvascular density and expression of the ALK5 gene transcript. There was no correlation between microvascular density and ALK1 gene transcriptional expression following cerebral IRI in a rat model. These findings suggest that ALK5, rather than ALK1, is the critical receptor in the TGF-β1 signal pathways after cerebral IRI.
文摘目的:探讨miR-455在宫颈癌中的表达及其与微血管密度(MVD)及血管内皮生长因子(VEGF)表达的关系。方法:采用实时荧光定量PCR技术检测68例宫颈癌患者和49例慢性宫颈炎(对照组)组织中miR-455的表达。免疫组化方法检测组织内MVD及VEGF蛋白表达水平。结果:宫颈癌组织内miR-455的相对表达量显著低于慢性宫颈炎(1.17±0.59 vs 2.58±0.83,P<0.01)。68例宫颈癌标本MVD表达的计数结果为30.45±7.9。Pearson相关分析结果显示,宫颈癌组织内miR-455表达水平与MVD呈负相关(r=-0.835,P<0.01。宫颈癌VEGF表达为阴性、弱阳性、中度阳性和强阳性组中,miR-455相对表达定量(RQ)分别为1.77±0.58、1.59±0.50、1.34±0.35和0.68±0.26,Spearman等级相关分析结果显示,miR-455表达水平与VEGF的表达呈负等级相关(r s=-0.857,P<0.01)。结论:miR-455低表达可能通过VEGF信号通路促进宫颈癌内微血管形成,是一个潜在的抑癌miRNA。
文摘目的:探讨高迁移率族蛋白1(High mobility group protein box-1,HMGB1)在肝细胞癌组织中的表达及其与血管内皮生长因子(Vascular endothelial growth factor,VEGF)表达、肿瘤微血管密度(Microvascular density,MVD)的关系和临床意义。方法:免疫组织化学SP法检测HMGB1、VEGF和CD34在37例人肝癌组织及相应癌旁肝组织和10例人正常肝组织中的表达;并用抗CD34抗体标记微血管,计数微血管密度;应用Western blot技术定量检测HMGB1在10例肝癌及相应癌旁和5例正常肝组织的表达情况。结果:HMGB1蛋白在肝癌组织中的表达明显高于癌旁组织及正常肝组织。HMGB1的表达与肿瘤大小、门静脉侵犯相关(P=0.018;P=0.036)。肝癌组织中HMGB1表达与VEGF表达及MVD间均呈正相关(r=0.544,P=0.001;r=0.672,P<0.05)。结论:肝癌组织中异常表达增高的HMGB1、VEGF与肝癌微血管生成过程相关,HMGB1可能成为阻断肝癌血管生成的有效靶点。
