AIM： To investigate the implication of the hypoxia inducible factor HIF-1α mRNA in gastric carcinoma and its relation to the expression of vascular endothelial growth factor （VEGF） protein, tumor angiogenesis inva...AIM： To investigate the implication of the hypoxia inducible factor HIF-1α mRNA in gastric carcinoma and its relation to the expression of vascular endothelial growth factor （VEGF） protein, tumor angiogenesis invasion/metastasis and the patient＇s survival. METHODS： In situ hybridization was used to examine expression of HIF-1α mRNA, and immunohistochemical staining was used to examine expression of VEGF protein and CD34 in 118 specimens from patients with gastric carcinoma. RESULTS： The positive rates of HIF-1α mRNA and VEGF protein were 49.15% and 55.92%, respectively. Positive expressions of HIF-1α and VEGF in stage T3-T4 tumors and those with vessel invasion, lymph node metastasis and distant metastasis were dramatically stronger than stage T1-T2 cases and those without vessel invasion, lymph node metastasis and distant metastasis. The mean microvascular density （MVD） in stage T3-T4 tumors and those with vessel invasion, lymph node metastasis and distant metastasis was significantly higher than stage T1-T2 tumors and those without vessel invasion, lymph node metastasis and distant metastasis. The mean MVD in tumors with positive HIF-1α and VEGF expression was significantly higher than that in tumors with negative HIF-1α and VEGF expression. The expression of HIF- 1α was positively correlated with VEGF protein. There were positive correlations between MVD and expression of HIF-1α and VEGF. The mean survival time and the S-year survival rate in cases with positive expression HIF-1α and VEGF and MVD value ≥ 41.5/0.72 mm^2 were significantly lower than those with negative expression of HIF-1α and VEGF and MVD value 〈 41.5/0.72 mm^2. CONCLUSION： Overexpression of HIF-1α is found in gastric carcinoma. HIF-1α may induce the angiogenesis in gastric carcinoma by upregulating the transcription of VEGF gene, and take part in tumor invasion and metastasis. They can be used as prognostic markers of gastric cancer in clinical practice.展开更多
AIM： To investigate integrin β3 mRNA and vascular endothelial growth factor （VEGF） protein expression in gastric carcinoma, and its correlation with microvascular density, growth-pattern, invasion, metastasis and ...AIM： To investigate integrin β3 mRNA and vascular endothelial growth factor （VEGF） protein expression in gastric carcinoma, and its correlation with microvascular density, growth-pattern, invasion, metastasis and prognosis. METHODS： In situ hybridization（ISH） of integrin β3 mRNA and immunohistochemistry of VEGF and CD34 protein were performed on samples from 118 patients with gastric cancer. RESULTS： The positive rate of integrin β3 mRNA in non-tumor gastric mucosa （20%） was significantly lower than that of the gastric cancer tissue （52.5%, X^2 = 10.20, P 〈 0.01）. In patients of infiltrating type, stage T3-T4, vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the positive expression rates of integrin β3 mRNA were significantly higher than those in patients of expanding type （P 〈 0.01）, stage T1-T2 （P 〈 0.01）, non-vessel invasion （P 〈 0.01）, without lymphatic metastasis （P 〈 0.01）, without hepatic and peritoneal metastasis （P 〈 0.01）, respectively. In patients of infiltrating type, stage T3-T4, vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the positive expression rates of VEGF protein were significantly higher than those in patients of expanding type （P 〈 0.01）, stage T1-T2 （P 〈 0.01）, non-vessel invasion （P 〈 0.01）, without lymphatic metastasis （P 〈 0.01）, without hepatic and peritoneal metastasis （P 〈 0.01）, respectively. In patients of infiltrating type, stage T3-T4, vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the mean MVD were significantly higher than those in patients of expanding type （P 〈 0.01）, stage T1-T2 （P 〈 0.01）, non-vessel invasion （P 〈 0.01）, without lymphatic metastasis （P 〈 0.01）, without hepatic and peritoneal metastasis （P 〈 0.01）, respectively. It was found that the positive expression rate of integrin β3 mRNA was positively related to that of VEGF protein （P 〈 0.01） and MVD （P 〈 0.05）, meanwhile the positive expression rate of VEGF protein was positively related to MVD （P 〈 0.05）. The mean survival period in patients with positive expression of integrin β3 mRNA and VEGF, and MVD ≥54.9/mm^2 was significantly shorter than that in patients with negative expression of integrin β3 mRNA （P 〈 0.05） and VEGF （P 〈 0.01）, and MVD 〈 54.9/mm^2 （P 〈 0.01）. Five-year survival rate in patients with positive expression of integrin β3 mRNA and VEGF, and MVD ≥54.9/mm^2 was significantly lower than those with negative expression of integrin β3 mRNA （P 〈 0.05）, VEGF （P 〈 0.05）, and MVD 〈 54.9/mm^2 （P 〈 0.01）. CONCLUSION： Integrin β3 and VEGF expression can synergistically enhance tumor angiogenesis, and may play a crucial role in invasion and metastasis of gastric carcinoma. Therefore, they may be prognostic biomarkers and novel molecular therapeutic targets.展开更多
AIM： To investigate the effects of high glucose levels and anti-vascular endothelial growth factor（VEGF） agents（bevacizumab,ranibizumab and aflibercept） on retinal pigment epithelium（RPE） cells.METHODS： ARPE-1...AIM： To investigate the effects of high glucose levels and anti-vascular endothelial growth factor（VEGF） agents（bevacizumab,ranibizumab and aflibercept） on retinal pigment epithelium（RPE） cells.METHODS： ARPE-19 cells were cultured at different glucose levels（5.5 mmol/L,25 mmol/L,and 75 mmol/L）.Cell viability was evaluated by MTT assay at 3d after treatment with D-glucose.Cell migration ability was measured by wound healing assay at 3d.A cell death detection kit was used to assess apoptosis at 3 and 14 d.Cell proliferation was assessed by EdU assay at 3d.The culture medium was treated with anti-VEGF agents at clinically relevant concentrations.The experiment was then repeated at a different glucose level.RESULTS： The viability and migration of ARPE-19 cells were significantly decreased in the presence of 75 mmol/L as compared to 5.5 mmol/L glucose.The percentage of TUNEL-positive cells was significantly increased and the proliferative potential was decreased with 75 mmol/L compared to 5.5 mmol/L glucose.There were no significant differences in the results between 25 mmol/L and 5.5 mmol/L glucose.In the presence of 75 mmol/L glucose,the groups treated with anti-VEGF showed decreased cell viability and proliferation and increased apoptosis.However,there were no significant differences between the anti-VEGF groups.CONCLUSION： High glucose level decreases the viability,wound healing ability,and proliferation of RPE cells,while increasing apoptosis.Furthermore,anti-VEGF agents interfered with the physiological functions of RPE cells under high-glucose conditions,accompanied by decreases in cell viability and proliferation.展开更多
Objective: To investigate the expression of vascular endothelial growth factor D (VEGF-D) in gastric cancer and its relationship with lymph node metastasis. Methods: 100 cases of gastric carcinoma tissues (50 cases wi...Objective: To investigate the expression of vascular endothelial growth factor D (VEGF-D) in gastric cancer and its relationship with lymph node metastasis. Methods: 100 cases of gastric carcinoma tissues (50 cases with lymph node metastasis, 50 cases negative) and 30 cases of normal gastric tissues were gathered to detect the expressions of VEGF-C and D proteins by immunohistochemistry. Results: VEGF-C and D were revealed in cytoplasm of gastric carcinoma tissues and normal gastric tissues. The positive rates of VEGF-C and D expressions were significantly higher in gastric cancer tissues than those in the normal ones (51%, 60% vs 10%, 20% respectively; both P < 0.05). There were significant correlations be- tween the positive expression of VEGF-D and lymph node metastasis, lymphatic invasion, positive expression of VEGF-C, but not with tumour size, tissue differentiation, and venous invasion. Conclusion: The expression of VEGF-D is closely related to lymph node metastasis in gastric carcinoma.展开更多
Objective: The aim of this study was to investigate the effect of grape proanthocyanidins(GPC) on the growth and angiogenesis of hepatocellular carcinoma H22 cells xenograft in mice. Methods: The xenograft model was e...Objective: The aim of this study was to investigate the effect of grape proanthocyanidins(GPC) on the growth and angiogenesis of hepatocellular carcinoma H22 cells xenograft in mice. Methods: The xenograft model was established using injected subcutaneously H22 cells into the right axilla of the mice. Each group was treated with different doses of GPC and Endostar. All these treatments were maintained for 10 days, and mice were sacrificed. The xenograft tumors in mice were measured. The proliferation activity level of H22 cells was determined by MTT assay, and the levels of vascular endothelial growth factor(VEGF) protein were examined by immunohistochemistry. Results: When treated with 50, 100 and 200 mg/kg of GPC and Endostar, the tumor inhibition rates were 13.17%, 23.37%, 36.15% and 14.71%, respectively. The tumor weight of xenograft was significantly lighter in high GPC group than the control group(P < 0.05). The ODs in GPC groups were 0.835, 0.666 and 0.519, respectively. The absorbances in middle and high GPC groups were statistically significant, compared with control group(P < 0.01). Immunohistochemical technique showed the expression of VEGF of the GPC groups was downregulated significantly compared with the control group(P < 0.01). Conclusion: GPC can inhibit the growth of hepatocellular carcinoma H22 cell xenograft in mice. The inhibition of angiogenesis by the down-regulation of VEGF expression may play a key role in the anti-neoplastic effect of GPC.展开更多
早产儿视网膜病变(retinopathy of prematurity,ROP)是目前全世界儿童致盲的主要原因之一[1]。以往对于阈值期和高危阈值前期的ROP采用激光或冷凝治疗,因激光和冷凝术均是破坏性的,不可避免地导致周边视野永久丧失,且并发症较多,术后仍...早产儿视网膜病变(retinopathy of prematurity,ROP)是目前全世界儿童致盲的主要原因之一[1]。以往对于阈值期和高危阈值前期的ROP采用激光或冷凝治疗,因激光和冷凝术均是破坏性的,不可避免地导致周边视野永久丧失,且并发症较多,术后仍有部分患儿病情无法控制,最终视力完全丧失。因此需要寻找新的治疗方法,近年来有较多的临床数据表明,玻璃体内注射抗血管内皮生长因子(anti-vascular endothelial growth factor,anti-VEGF)治疗ROP是一种有效的治疗方法。我们将对抗VEGF药物在ROP治疗的研究进展进行近期的文献综述。展开更多
基金grant from Zhejiang Province Natural Science Foundation, No. M303843
文摘AIM： To investigate the implication of the hypoxia inducible factor HIF-1α mRNA in gastric carcinoma and its relation to the expression of vascular endothelial growth factor （VEGF） protein, tumor angiogenesis invasion/metastasis and the patient＇s survival. METHODS： In situ hybridization was used to examine expression of HIF-1α mRNA, and immunohistochemical staining was used to examine expression of VEGF protein and CD34 in 118 specimens from patients with gastric carcinoma. RESULTS： The positive rates of HIF-1α mRNA and VEGF protein were 49.15% and 55.92%, respectively. Positive expressions of HIF-1α and VEGF in stage T3-T4 tumors and those with vessel invasion, lymph node metastasis and distant metastasis were dramatically stronger than stage T1-T2 cases and those without vessel invasion, lymph node metastasis and distant metastasis. The mean microvascular density （MVD） in stage T3-T4 tumors and those with vessel invasion, lymph node metastasis and distant metastasis was significantly higher than stage T1-T2 tumors and those without vessel invasion, lymph node metastasis and distant metastasis. The mean MVD in tumors with positive HIF-1α and VEGF expression was significantly higher than that in tumors with negative HIF-1α and VEGF expression. The expression of HIF- 1α was positively correlated with VEGF protein. There were positive correlations between MVD and expression of HIF-1α and VEGF. The mean survival time and the S-year survival rate in cases with positive expression HIF-1α and VEGF and MVD value ≥ 41.5/0.72 mm^2 were significantly lower than those with negative expression of HIF-1α and VEGF and MVD value 〈 41.5/0.72 mm^2. CONCLUSION： Overexpression of HIF-1α is found in gastric carcinoma. HIF-1α may induce the angiogenesis in gastric carcinoma by upregulating the transcription of VEGF gene, and take part in tumor invasion and metastasis. They can be used as prognostic markers of gastric cancer in clinical practice.
基金a grant from Zhejiang Province Natural Science Foundation, No. M303843
文摘AIM： To investigate integrin β3 mRNA and vascular endothelial growth factor （VEGF） protein expression in gastric carcinoma, and its correlation with microvascular density, growth-pattern, invasion, metastasis and prognosis. METHODS： In situ hybridization（ISH） of integrin β3 mRNA and immunohistochemistry of VEGF and CD34 protein were performed on samples from 118 patients with gastric cancer. RESULTS： The positive rate of integrin β3 mRNA in non-tumor gastric mucosa （20%） was significantly lower than that of the gastric cancer tissue （52.5%, X^2 = 10.20, P 〈 0.01）. In patients of infiltrating type, stage T3-T4, vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the positive expression rates of integrin β3 mRNA were significantly higher than those in patients of expanding type （P 〈 0.01）, stage T1-T2 （P 〈 0.01）, non-vessel invasion （P 〈 0.01）, without lymphatic metastasis （P 〈 0.01）, without hepatic and peritoneal metastasis （P 〈 0.01）, respectively. In patients of infiltrating type, stage T3-T4, vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the positive expression rates of VEGF protein were significantly higher than those in patients of expanding type （P 〈 0.01）, stage T1-T2 （P 〈 0.01）, non-vessel invasion （P 〈 0.01）, without lymphatic metastasis （P 〈 0.01）, without hepatic and peritoneal metastasis （P 〈 0.01）, respectively. In patients of infiltrating type, stage T3-T4, vessel invasion, lymphatic metastasis, hepatic or peritoneal metastasis, the mean MVD were significantly higher than those in patients of expanding type （P 〈 0.01）, stage T1-T2 （P 〈 0.01）, non-vessel invasion （P 〈 0.01）, without lymphatic metastasis （P 〈 0.01）, without hepatic and peritoneal metastasis （P 〈 0.01）, respectively. It was found that the positive expression rate of integrin β3 mRNA was positively related to that of VEGF protein （P 〈 0.01） and MVD （P 〈 0.05）, meanwhile the positive expression rate of VEGF protein was positively related to MVD （P 〈 0.05）. The mean survival period in patients with positive expression of integrin β3 mRNA and VEGF, and MVD ≥54.9/mm^2 was significantly shorter than that in patients with negative expression of integrin β3 mRNA （P 〈 0.05） and VEGF （P 〈 0.01）, and MVD 〈 54.9/mm^2 （P 〈 0.01）. Five-year survival rate in patients with positive expression of integrin β3 mRNA and VEGF, and MVD ≥54.9/mm^2 was significantly lower than those with negative expression of integrin β3 mRNA （P 〈 0.05）, VEGF （P 〈 0.05）, and MVD 〈 54.9/mm^2 （P 〈 0.01）. CONCLUSION： Integrin β3 and VEGF expression can synergistically enhance tumor angiogenesis, and may play a crucial role in invasion and metastasis of gastric carcinoma. Therefore, they may be prognostic biomarkers and novel molecular therapeutic targets.
基金Supported by grants from Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the ministry of Education,Science,and Technology(No.2016R1A2B4008376Seoul,Republic of Korea)partially supported by the Soonchunhyang University Research Fund
文摘AIM： To investigate the effects of high glucose levels and anti-vascular endothelial growth factor（VEGF） agents（bevacizumab,ranibizumab and aflibercept） on retinal pigment epithelium（RPE） cells.METHODS： ARPE-19 cells were cultured at different glucose levels（5.5 mmol/L,25 mmol/L,and 75 mmol/L）.Cell viability was evaluated by MTT assay at 3d after treatment with D-glucose.Cell migration ability was measured by wound healing assay at 3d.A cell death detection kit was used to assess apoptosis at 3 and 14 d.Cell proliferation was assessed by EdU assay at 3d.The culture medium was treated with anti-VEGF agents at clinically relevant concentrations.The experiment was then repeated at a different glucose level.RESULTS： The viability and migration of ARPE-19 cells were significantly decreased in the presence of 75 mmol/L as compared to 5.5 mmol/L glucose.The percentage of TUNEL-positive cells was significantly increased and the proliferative potential was decreased with 75 mmol/L compared to 5.5 mmol/L glucose.There were no significant differences in the results between 25 mmol/L and 5.5 mmol/L glucose.In the presence of 75 mmol/L glucose,the groups treated with anti-VEGF showed decreased cell viability and proliferation and increased apoptosis.However,there were no significant differences between the anti-VEGF groups.CONCLUSION： High glucose level decreases the viability,wound healing ability,and proliferation of RPE cells,while increasing apoptosis.Furthermore,anti-VEGF agents interfered with the physiological functions of RPE cells under high-glucose conditions,accompanied by decreases in cell viability and proliferation.
基金Supported by a grant from Importance Introduction Person with Ability Startup Fund of Jiangsu University Affiliated Hospital (Number: p-67).
文摘Objective: To investigate the expression of vascular endothelial growth factor D (VEGF-D) in gastric cancer and its relationship with lymph node metastasis. Methods: 100 cases of gastric carcinoma tissues (50 cases with lymph node metastasis, 50 cases negative) and 30 cases of normal gastric tissues were gathered to detect the expressions of VEGF-C and D proteins by immunohistochemistry. Results: VEGF-C and D were revealed in cytoplasm of gastric carcinoma tissues and normal gastric tissues. The positive rates of VEGF-C and D expressions were significantly higher in gastric cancer tissues than those in the normal ones (51%, 60% vs 10%, 20% respectively; both P < 0.05). There were significant correlations be- tween the positive expression of VEGF-D and lymph node metastasis, lymphatic invasion, positive expression of VEGF-C, but not with tumour size, tissue differentiation, and venous invasion. Conclusion: The expression of VEGF-D is closely related to lymph node metastasis in gastric carcinoma.
基金supported by Department of Oncology, the Affiliated Hospital of Qingdao University, China
文摘Objective: The aim of this study was to investigate the effect of grape proanthocyanidins(GPC) on the growth and angiogenesis of hepatocellular carcinoma H22 cells xenograft in mice. Methods: The xenograft model was established using injected subcutaneously H22 cells into the right axilla of the mice. Each group was treated with different doses of GPC and Endostar. All these treatments were maintained for 10 days, and mice were sacrificed. The xenograft tumors in mice were measured. The proliferation activity level of H22 cells was determined by MTT assay, and the levels of vascular endothelial growth factor(VEGF) protein were examined by immunohistochemistry. Results: When treated with 50, 100 and 200 mg/kg of GPC and Endostar, the tumor inhibition rates were 13.17%, 23.37%, 36.15% and 14.71%, respectively. The tumor weight of xenograft was significantly lighter in high GPC group than the control group(P < 0.05). The ODs in GPC groups were 0.835, 0.666 and 0.519, respectively. The absorbances in middle and high GPC groups were statistically significant, compared with control group(P < 0.01). Immunohistochemical technique showed the expression of VEGF of the GPC groups was downregulated significantly compared with the control group(P < 0.01). Conclusion: GPC can inhibit the growth of hepatocellular carcinoma H22 cell xenograft in mice. The inhibition of angiogenesis by the down-regulation of VEGF expression may play a key role in the anti-neoplastic effect of GPC.
