AIM: There is strong evidence that tyrosine kinases are involved in the regulation of tumor progression, cellular growth and differentiation. Recently, many kinds of tyrosine kinase receptors have been reported, among...AIM: There is strong evidence that tyrosine kinases are involved in the regulation of tumor progression, cellular growth and differentiation. Recently, many kinds of tyrosine kinase receptors have been reported, among them Tie-1 and Tie-2 receptors constitute a major class.Angiopoietin (Ang)-1 is known as a ligand ofTie-2 tyrosine kinase receptor. The objective of this study was to establish a comprehensive Tie-1 and Tie-2 and Ang-1, 2 and 4expression profile in human colorectal adenocarcinomas.METHODS: We examined 96 cases of surgically resected human colorectal adenocarcinoma by immunohistochemistry and investigated the statistical correlation between the expressions of Ties and Angs and clinicopathological factors.RESULTS: Among the 96 cases of adenocarcinoma, 87(90.6%), 92 (95.8%), 83 (86.5%), 89 (92.7%), and 76cases (79.2%) showed positive staining in the cytoplasm of carcinoma cells for the Tie-1 and Tie-2 and Ang-1, 2and 4 proteins, respectively. Histologically, the expressions of Ties and Angs were variable. The expressions of Ties and Angs were correlated with several clinicopathological factors, but did not correlate with the presence of lymph node metastasis. Ties and Angs were highly expressed in human colorectal adenocarcinoma cells.CONCLUSION: These findings suggest that the Tie-Ang receptor-ligand complex is one of the factors involved in the cellular differentiation and progression of human colorectal adenocarcinoma.展开更多
AIM: To study the regulatory mechanisms of sinusoidal regeneration after partial hepatectomy.METHODS: We investigated the expression of angiopoietin (Ang)-1, Ang-2, Tie-2, and vascular endothelial growth factor (VEGF)...AIM: To study the regulatory mechanisms of sinusoidal regeneration after partial hepatectomy.METHODS: We investigated the expression of angiopoietin (Ang)-1, Ang-2, Tie-2, and vascular endothelial growth factor (VEGF) in regenerating liver tissue by quantitative reverse-transcription polymerase chain reaction (RT-PCR) using a LightCycler (Roche Diagnostics) and also immunohistochemical staining after 70% hepatectomy in rats. In the next step, we isolated liver cells (hepatocytes,sinusoidal endothelial cell (SEC), Kupffer cell, and hepatic stellate cells (HSC)) from regenerating liver tissue by in situ collagenase perfusion and counterflow elutriation,to determine potential cellular sources of these angiogenic factors after hepatectomy. Proliferation and apoptosis of SECs were also evaluated by proliferating cell nuclear antigen (PCNA) staining and the terminal deoxynucleotidyl transferase d-uridine triphosphate nick end labeling (TUNEL) assay, respectively.RESULTS: VEGF mRNA expression increased with a peak at 72 h after hepatectomy, decreasing thereafter.The expression of Ang-1 mRNA was present at detectable levels before hepatectomy and increased slowly with a peak at 96 h. Meanwhile, Ang-2 mRNA was hardly detected before hepatectomy, but was remarkably induced at 120 and 144 h. In isolated cells, VEGF mRNA expression was found mainly in the hepatocyte fraction.Meanwhile, mRNA for Ang-1 and Ang-2 was foundin the SEC and HSC fractions, but was more prominent in the latter. The PCNA labeling index of SECs increased slowly,reaching a peak at 72 h, whereas apoptotic SECs were detected between 120 h and 144 h.CONCLUSION: Ang-Tie system, together with VEGF,plays a critical role in regulating balance between SEC proliferation and apoptosis during sinusoidal regeneration after hepatectomy. However, the VEGF system plays a more important role in the early phase of sinusoidal regeneration than angiopoietin/Tie system.展开更多
A potential pathological role of angiopoietins (Ang) in glomeruli following podocyte injury-induced progressive glomerulosclerosis was explored. Eighty male Wistar rats were randomly allocated into sham operation grou...A potential pathological role of angiopoietins (Ang) in glomeruli following podocyte injury-induced progressive glomerulosclerosis was explored. Eighty male Wistar rats were randomly allocated into sham operation group (Sham, n=25), Uninephrectomy group (UPHT, n=25) and Uninephrectomy+Daunorubicin group (DRB, n=30). In DRB group, daunorubicin (5 mg/kg) was injected via tail vein on the 7th and 14th day after uninephrectomy. At week 1, 2, 4, 6 and 8 respectively following establishment of the animal model, 5 rats in Sham group and UPHT group, and 6 in DRB group were taken respectively for determining 24-h urinary protein excretion rate (24hUPER), blood urea nitrogen (BUN) and serum creatinine (Scr). The sections of kidneys were examined by an electric microscope, PAS staining, immunohistochemical staining and in situ hybridization histochemistry. The results showed that 24hUPER, BUN and Scr in DRB group were more than those in Sham group and UPHT group at the same time points, and there was a trend towards an increase on level of GSI in DRB group from week 2 to week 8. Electric microscopy revealed that podocyte injury presented in DRB group. The expression of Ang1 mRNA and protein in glomeruli of DRB group was decreased, while the expression of Ang2 protein in glomeruli of DRB group increased. Meanwhile, the expression of Ang1 mRNA had a negative correlation with the expression of Ang2 mRNA, and the expression of Ang1 protein had a positive correlation with the expression of Ang1 mRNA, and had a negative correlation with 24hUPER, BUN, Scr, glomerular sclerotic index (GSI), the expression of Ang2 protein and CoIV protein. The expression of Ang2 protein had a positive correlation with the expression of Ang2 mRNA, and had a positive correlation with 24hUPER, BUN, Scr, GSI, the expression of CoIV protein. It was concluded that podocyte injury might lead to an alteration in the expression of Ang1 and Ang2 within glomeruli. Ang2 may get rid of inhibition from Ang1 for downregulation of the Ang1 expression, which facilitate upregulation of the Ang2 expression in glomeruli to promote progressive glomerulosclerosis in the 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 expression...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 stom- ach carcinomas and their adjacent normal mucosa. Microvessel density (MVD) was counted according to CD34 immunohisto- chemical 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 (r=–0.440, r=–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 (r=0.319, r=729, r=739; P<0.05). Moreover, MVD in groups with Ang-2 mRNA T/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 angiogenesis 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
文摘AIM: There is strong evidence that tyrosine kinases are involved in the regulation of tumor progression, cellular growth and differentiation. Recently, many kinds of tyrosine kinase receptors have been reported, among them Tie-1 and Tie-2 receptors constitute a major class.Angiopoietin (Ang)-1 is known as a ligand ofTie-2 tyrosine kinase receptor. The objective of this study was to establish a comprehensive Tie-1 and Tie-2 and Ang-1, 2 and 4expression profile in human colorectal adenocarcinomas.METHODS: We examined 96 cases of surgically resected human colorectal adenocarcinoma by immunohistochemistry and investigated the statistical correlation between the expressions of Ties and Angs and clinicopathological factors.RESULTS: Among the 96 cases of adenocarcinoma, 87(90.6%), 92 (95.8%), 83 (86.5%), 89 (92.7%), and 76cases (79.2%) showed positive staining in the cytoplasm of carcinoma cells for the Tie-1 and Tie-2 and Ang-1, 2and 4 proteins, respectively. Histologically, the expressions of Ties and Angs were variable. The expressions of Ties and Angs were correlated with several clinicopathological factors, but did not correlate with the presence of lymph node metastasis. Ties and Angs were highly expressed in human colorectal adenocarcinoma cells.CONCLUSION: These findings suggest that the Tie-Ang receptor-ligand complex is one of the factors involved in the cellular differentiation and progression of human colorectal adenocarcinoma.
文摘AIM: To study the regulatory mechanisms of sinusoidal regeneration after partial hepatectomy.METHODS: We investigated the expression of angiopoietin (Ang)-1, Ang-2, Tie-2, and vascular endothelial growth factor (VEGF) in regenerating liver tissue by quantitative reverse-transcription polymerase chain reaction (RT-PCR) using a LightCycler (Roche Diagnostics) and also immunohistochemical staining after 70% hepatectomy in rats. In the next step, we isolated liver cells (hepatocytes,sinusoidal endothelial cell (SEC), Kupffer cell, and hepatic stellate cells (HSC)) from regenerating liver tissue by in situ collagenase perfusion and counterflow elutriation,to determine potential cellular sources of these angiogenic factors after hepatectomy. Proliferation and apoptosis of SECs were also evaluated by proliferating cell nuclear antigen (PCNA) staining and the terminal deoxynucleotidyl transferase d-uridine triphosphate nick end labeling (TUNEL) assay, respectively.RESULTS: VEGF mRNA expression increased with a peak at 72 h after hepatectomy, decreasing thereafter.The expression of Ang-1 mRNA was present at detectable levels before hepatectomy and increased slowly with a peak at 96 h. Meanwhile, Ang-2 mRNA was hardly detected before hepatectomy, but was remarkably induced at 120 and 144 h. In isolated cells, VEGF mRNA expression was found mainly in the hepatocyte fraction.Meanwhile, mRNA for Ang-1 and Ang-2 was foundin the SEC and HSC fractions, but was more prominent in the latter. The PCNA labeling index of SECs increased slowly,reaching a peak at 72 h, whereas apoptotic SECs were detected between 120 h and 144 h.CONCLUSION: Ang-Tie system, together with VEGF,plays a critical role in regulating balance between SEC proliferation and apoptosis during sinusoidal regeneration after hepatectomy. However, the VEGF system plays a more important role in the early phase of sinusoidal regeneration than angiopoietin/Tie system.
文摘A potential pathological role of angiopoietins (Ang) in glomeruli following podocyte injury-induced progressive glomerulosclerosis was explored. Eighty male Wistar rats were randomly allocated into sham operation group (Sham, n=25), Uninephrectomy group (UPHT, n=25) and Uninephrectomy+Daunorubicin group (DRB, n=30). In DRB group, daunorubicin (5 mg/kg) was injected via tail vein on the 7th and 14th day after uninephrectomy. At week 1, 2, 4, 6 and 8 respectively following establishment of the animal model, 5 rats in Sham group and UPHT group, and 6 in DRB group were taken respectively for determining 24-h urinary protein excretion rate (24hUPER), blood urea nitrogen (BUN) and serum creatinine (Scr). The sections of kidneys were examined by an electric microscope, PAS staining, immunohistochemical staining and in situ hybridization histochemistry. The results showed that 24hUPER, BUN and Scr in DRB group were more than those in Sham group and UPHT group at the same time points, and there was a trend towards an increase on level of GSI in DRB group from week 2 to week 8. Electric microscopy revealed that podocyte injury presented in DRB group. The expression of Ang1 mRNA and protein in glomeruli of DRB group was decreased, while the expression of Ang2 protein in glomeruli of DRB group increased. Meanwhile, the expression of Ang1 mRNA had a negative correlation with the expression of Ang2 mRNA, and the expression of Ang1 protein had a positive correlation with the expression of Ang1 mRNA, and had a negative correlation with 24hUPER, BUN, Scr, glomerular sclerotic index (GSI), the expression of Ang2 protein and CoIV protein. The expression of Ang2 protein had a positive correlation with the expression of Ang2 mRNA, and had a positive correlation with 24hUPER, BUN, Scr, GSI, the expression of CoIV protein. It was concluded that podocyte injury might lead to an alteration in the expression of Ang1 and Ang2 within glomeruli. Ang2 may get rid of inhibition from Ang1 for downregulation of the Ang1 expression, which facilitate upregulation of the Ang2 expression in glomeruli to promote progressive glomerulosclerosis in the 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 stom- ach carcinomas and their adjacent normal mucosa. Microvessel density (MVD) was counted according to CD34 immunohisto- chemical 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 (r=–0.440, r=–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 (r=0.319, r=729, r=739; P<0.05). Moreover, MVD in groups with Ang-2 mRNA T/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 angiogenesis 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.
