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
Objective： To investigate the expressions of vascular endothelial growth factor （VEGF） and proliferating cell nuclear antigen （Ki-67） in patients with rectal adenocarcinoma and their associations with neoadjuvant...Objective： To investigate the expressions of vascular endothelial growth factor （VEGF） and proliferating cell nuclear antigen （Ki-67） in patients with rectal adenocarcinoma and their associations with neoadjuvant therapy. Methods： The expressions of Ki-67 and VEGF in 32 cases of rectal adenocarcinoma, including both pretreatment tumor biopsies and postoperative specimen, were detected by immunohistochemistry using specific antibodies, and were correlated with clinicopathological factors. Results： The intensity of VEGF staining was significantly correlated with lymph nodal metastasis （P =0.033）, depth of tumor invasion （P =0.007） and tumor stage （P= 0.016）, but not with histological types, tumor sizes, patients＇ ages and genders （P 〉 0.05）. Low level of VEGF expression had significant correlation with the high sensitivity of response to neoadjuvant therapy （P = 0.016）. The transient increase of VEGF expression could be seen after neoadjuvant therapy （P = 0.035）. Ki-67 labeling index （Ki-67-LI） was significantly correlated with lymph node metastasis （P = 0.028）, but not correlated to tumor sizes, patients＇ ages and genders （P 〉 0.05）. Tumors with lower Ki-67-LI were more sensitive to neoadjuvant therapy （P = 0.032）. The Ki-67 level decreased after neoadjuvant therapy, but no statistical significance was found （P 〉 0.05）. Conclusion： Our results demonstrate that the expression of VEGF and Ki-67 in pretreatment rectal adenocarcinoma biopsies may be predictive of tumor response to neoadjuvant therapy.展开更多
AIM： To determine whether insulin could promote sinusoidal endothelial cell （SEC） proliferation mediated by upregulation of vascular endothelial growth factor （VEGF） in regenerating rat liver after partial hepate...AIM： To determine whether insulin could promote sinusoidal endothelial cell （SEC） proliferation mediated by upregulation of vascular endothelial growth factor （VEGF） in regenerating rat liver after partial hepatectomy （PHx）. METHODS： Adult male Sprague-Dawley rats undergoing 70% PHx were injected with insulin （300 MU/kg） or saline via the tail veins every 8 h after surgery for 7 d and killed at 0, 24, 48, 72, 96, 120, 144, and 168 h after surgery. Proliferation of both hepatocytes and SECs was monitored by evaluating the proliferating cell nuclear antigen （PCNA） labeling index （LI）. The expression of VEGF protein was evaluated by immunohistochemistJv. The mRNA expressions of VEGF and its receptors FIt-1 and FIk-1 were evaluated by semi-quantitative reverse transcription-PCR. RESULTS： Insulin markedly increased the expression of VEGF mRNA between 24 and 120 h after hepatectomy compared to controls. Similarly, insulin significantly increased the expression of Fit-1 between 24 and 96 h. However, insulin had no significant effect on FIk-1. Furthermore, the immunohistochemical staining revealed that expression of VEGF protein increased in the insulin groups. Insulin significantly increased the PCNA LI of hepatocytes and SECs compared to controls. CONCLUSION： Exogenous insulin may promote SEC proliferation with an enhanced expression of VEGF and its receptor Fit-1 in regenerating rat liver after PHx.展开更多
Objective： The aim of our study was to investigate whether Jinshuixian has the abilities of inhibiting tumor growth and radio-sensitivity effect. Methods： Cultured lung A549 ceils were randomly divided into 6 groups...Objective： The aim of our study was to investigate whether Jinshuixian has the abilities of inhibiting tumor growth and radio-sensitivity effect. Methods： Cultured lung A549 ceils were randomly divided into 6 groups： normal control group （NC）, the Jinshuixian group （JSX）, radiotherapy （RT）, JSX for the first day and the next day followed by RT group （JSX~ RT）, RT for the first day and the next day followed by JSX group （RT→JSX） and RT ＋ JSX concomitantly group （JSX ＋ RT）. MTT was applied to measure the cell viability, RT-PCR and ELISA were used to test the expression of mRNA and protein of VEGF. Results： The proliferation of A549 cells were inhibited in JSX and combined groups and the inhibiting effects were time dependent. The expression of VEGF in RT group was increased, however, VEGF in JSX and combination groups were largely decreased over time when compared to NC group. Results in JSX→RT, RT→JSX and JSX ＋ RT groups did not achieve significantly differences. Conclusion： JSX has the ability of anti-tumor growth in vitro accompanied down-regulating of VEGF, especially when combined with radiotherapy, and its effect is time-dependent. However, more studies in vivo and in vitro are needed to further supporting these effects.展开更多
Objective： To explore the application of MR perfusion-weighted imaging （PWI） in the benign and malignant prostate diseases, and evaluate the correlations of PWl features with vascular endothelial growth factor （V...Objective： To explore the application of MR perfusion-weighted imaging （PWI） in the benign and malignant prostate diseases, and evaluate the correlations of PWl features with vascular endothelial growth factor （VEGF） and microvessel density （MVD）. Methods： Seventy-four consecutive patients who were diagnosed clinically for the prostate diseases, including forty-four cases with benign prostate hyperplasia and thirty cases with prostatic cancer proved pathologically, were examined by PWI. MVD and VEGF were stained with immunohistochemical methods. Some parameters of PWl, including the steepest slope of signal intensity-time curve （SSmax） and the change in relaxation rate （ΔR2^＊ peak） at lesions, were analyzed. Correlation analysis was used to determine the relationship between the results of PWl and immunohistochemistry. Results： （1） In the benign prostate hyperplasia （BPH）, SSmax and ΔR2^＊ peak of perfusion curve were 34.2 ± 2.9 and 1.49 ± 0.11, respectively; however, in the prostatic cancer （Pca）, they were 58.6± 4.8 and 3.18 ±0.49 respectively; there were statistical differences （t = 2.16 and 2.31, P 〈 0.05）. （2） The VEGF and MVD expressions of thirty Pca patients were significantly higher than those of forty-four BPH patients （x2 = 28.64, P 〈 0.01; t = 21.2, P 〈 0.01）. MVD expressions of Pca and BPH groups showed positive associations with VEGF expressions （P 〈 0.01）. On MR perfusion-weighted imaging, SSmax and ΔR2^＊ peak showed associations with MVD and VEGF expressions （P 〈 0.01）. Conclusion： On MR perfusion-weighted imaging, SSmax and ΔR2^＊ peak can reflect MVD and VEGF expression levels in the benign and malignant prostate diseases and might be implied the tumor angiogenesis so as to distinguish benign from malignant and provide the important information for the surgeon to diagnose and treat the prostatic diseases.展开更多
1,2,5,6-Dianhydro-3,4-diacetyl-galactitol （DADAG）, an alkylating sugar alcohol derivative, has been shown effective against tumor growth. In this research, we explored the effect of DADAG on angiogenesis in chick ch...1,2,5,6-Dianhydro-3,4-diacetyl-galactitol （DADAG）, an alkylating sugar alcohol derivative, has been shown effective against tumor growth. In this research, we explored the effect of DADAG on angiogenesis in chick chorioallantoic membrane （CAM） model and on the proliferation and migration of human umbilical vein endothelial cells （HUVECs）. We also studied the possible mechanism of the anti-angiogenesis effect of DADAG. The results showed that DADAG （100, 500 and 1000μnol/L） inhibited angiogenesis in CAM model dose-dependently. Sulforhodamine B （SRB） assay indicated that DADAG （45, 90, 135, 180 and 225 μmol/L） suppressed HUVECs proliferation in a dose-dependent and time-dependent manner. High Content Screening （HCS, Cellomics） assay, in which the influence of cell proliferation on migration could be excluded, indicated that DADAG （45, 135 and 225 ~xmol/L） directly inhibited the motility ofHUVECs. Immunofiuorescence assay suggested that DADAG inhibited angiogenesis possibly by decreasing vascular endothelial growth factor （VEGF） expression in HUVECs. Our findings reveal that DADAG show anti-angiogenic activity in vivo and in vitro, which is related to the downregulation of VEGF expression in endothelial cells.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.
文摘Objective： To investigate the expressions of vascular endothelial growth factor （VEGF） and proliferating cell nuclear antigen （Ki-67） in patients with rectal adenocarcinoma and their associations with neoadjuvant therapy. Methods： The expressions of Ki-67 and VEGF in 32 cases of rectal adenocarcinoma, including both pretreatment tumor biopsies and postoperative specimen, were detected by immunohistochemistry using specific antibodies, and were correlated with clinicopathological factors. Results： The intensity of VEGF staining was significantly correlated with lymph nodal metastasis （P =0.033）, depth of tumor invasion （P =0.007） and tumor stage （P= 0.016）, but not with histological types, tumor sizes, patients＇ ages and genders （P 〉 0.05）. Low level of VEGF expression had significant correlation with the high sensitivity of response to neoadjuvant therapy （P = 0.016）. The transient increase of VEGF expression could be seen after neoadjuvant therapy （P = 0.035）. Ki-67 labeling index （Ki-67-LI） was significantly correlated with lymph node metastasis （P = 0.028）, but not correlated to tumor sizes, patients＇ ages and genders （P 〉 0.05）. Tumors with lower Ki-67-LI were more sensitive to neoadjuvant therapy （P = 0.032）. The Ki-67 level decreased after neoadjuvant therapy, but no statistical significance was found （P 〉 0.05）. Conclusion： Our results demonstrate that the expression of VEGF and Ki-67 in pretreatment rectal adenocarcinoma biopsies may be predictive of tumor response to neoadjuvant therapy.
文摘AIM： To determine whether insulin could promote sinusoidal endothelial cell （SEC） proliferation mediated by upregulation of vascular endothelial growth factor （VEGF） in regenerating rat liver after partial hepatectomy （PHx）. METHODS： Adult male Sprague-Dawley rats undergoing 70% PHx were injected with insulin （300 MU/kg） or saline via the tail veins every 8 h after surgery for 7 d and killed at 0, 24, 48, 72, 96, 120, 144, and 168 h after surgery. Proliferation of both hepatocytes and SECs was monitored by evaluating the proliferating cell nuclear antigen （PCNA） labeling index （LI）. The expression of VEGF protein was evaluated by immunohistochemistJv. The mRNA expressions of VEGF and its receptors FIt-1 and FIk-1 were evaluated by semi-quantitative reverse transcription-PCR. RESULTS： Insulin markedly increased the expression of VEGF mRNA between 24 and 120 h after hepatectomy compared to controls. Similarly, insulin significantly increased the expression of Fit-1 between 24 and 96 h. However, insulin had no significant effect on FIk-1. Furthermore, the immunohistochemical staining revealed that expression of VEGF protein increased in the insulin groups. Insulin significantly increased the PCNA LI of hepatocytes and SECs compared to controls. CONCLUSION： Exogenous insulin may promote SEC proliferation with an enhanced expression of VEGF and its receptor Fit-1 in regenerating rat liver after PHx.
文摘Objective： The aim of our study was to investigate whether Jinshuixian has the abilities of inhibiting tumor growth and radio-sensitivity effect. Methods： Cultured lung A549 ceils were randomly divided into 6 groups： normal control group （NC）, the Jinshuixian group （JSX）, radiotherapy （RT）, JSX for the first day and the next day followed by RT group （JSX~ RT）, RT for the first day and the next day followed by JSX group （RT→JSX） and RT ＋ JSX concomitantly group （JSX ＋ RT）. MTT was applied to measure the cell viability, RT-PCR and ELISA were used to test the expression of mRNA and protein of VEGF. Results： The proliferation of A549 cells were inhibited in JSX and combined groups and the inhibiting effects were time dependent. The expression of VEGF in RT group was increased, however, VEGF in JSX and combination groups were largely decreased over time when compared to NC group. Results in JSX→RT, RT→JSX and JSX ＋ RT groups did not achieve significantly differences. Conclusion： JSX has the ability of anti-tumor growth in vitro accompanied down-regulating of VEGF, especially when combined with radiotherapy, and its effect is time-dependent. However, more studies in vivo and in vitro are needed to further supporting these effects.
文摘Objective： To explore the application of MR perfusion-weighted imaging （PWI） in the benign and malignant prostate diseases, and evaluate the correlations of PWl features with vascular endothelial growth factor （VEGF） and microvessel density （MVD）. Methods： Seventy-four consecutive patients who were diagnosed clinically for the prostate diseases, including forty-four cases with benign prostate hyperplasia and thirty cases with prostatic cancer proved pathologically, were examined by PWI. MVD and VEGF were stained with immunohistochemical methods. Some parameters of PWl, including the steepest slope of signal intensity-time curve （SSmax） and the change in relaxation rate （ΔR2^＊ peak） at lesions, were analyzed. Correlation analysis was used to determine the relationship between the results of PWl and immunohistochemistry. Results： （1） In the benign prostate hyperplasia （BPH）, SSmax and ΔR2^＊ peak of perfusion curve were 34.2 ± 2.9 and 1.49 ± 0.11, respectively; however, in the prostatic cancer （Pca）, they were 58.6± 4.8 and 3.18 ±0.49 respectively; there were statistical differences （t = 2.16 and 2.31, P 〈 0.05）. （2） The VEGF and MVD expressions of thirty Pca patients were significantly higher than those of forty-four BPH patients （x2 = 28.64, P 〈 0.01; t = 21.2, P 〈 0.01）. MVD expressions of Pca and BPH groups showed positive associations with VEGF expressions （P 〈 0.01）. On MR perfusion-weighted imaging, SSmax and ΔR2^＊ peak showed associations with MVD and VEGF expressions （P 〈 0.01）. Conclusion： On MR perfusion-weighted imaging, SSmax and ΔR2^＊ peak can reflect MVD and VEGF expression levels in the benign and malignant prostate diseases and might be implied the tumor angiogenesis so as to distinguish benign from malignant and provide the important information for the surgeon to diagnose and treat the prostatic diseases.
文摘1,2,5,6-Dianhydro-3,4-diacetyl-galactitol （DADAG）, an alkylating sugar alcohol derivative, has been shown effective against tumor growth. In this research, we explored the effect of DADAG on angiogenesis in chick chorioallantoic membrane （CAM） model and on the proliferation and migration of human umbilical vein endothelial cells （HUVECs）. We also studied the possible mechanism of the anti-angiogenesis effect of DADAG. The results showed that DADAG （100, 500 and 1000μnol/L） inhibited angiogenesis in CAM model dose-dependently. Sulforhodamine B （SRB） assay indicated that DADAG （45, 90, 135, 180 and 225 μmol/L） suppressed HUVECs proliferation in a dose-dependent and time-dependent manner. High Content Screening （HCS, Cellomics） assay, in which the influence of cell proliferation on migration could be excluded, indicated that DADAG （45, 135 and 225 ~xmol/L） directly inhibited the motility ofHUVECs. Immunofiuorescence assay suggested that DADAG inhibited angiogenesis possibly by decreasing vascular endothelial growth factor （VEGF） expression in HUVECs. Our findings reveal that DADAG show anti-angiogenic activity in vivo and in vitro, which is related to the downregulation of VEGF expression in endothelial cells.
