Objective: Angiogenesis is a crucial step for tumor growth and progression. Changes of liver angiogenesis (without metastatic invasion) in response to primary tumors are not known. The aim of the study was to investig...Objective: Angiogenesis is a crucial step for tumor growth and progression. Changes of liver angiogenesis (without metastatic invasion) in response to primary tumors are not known. The aim of the study was to investigate the liver angiogenesis in non-metastatic colorectal cancer (CRC). Methods: Human colorectal adenocarcinoma tumors were grown subcutaneously in nude mice. All animals showed tumor growth locally without macroscopic or microscopic evidence of liver metastases. Livers were investigated for their microvessel density (MVD) at different stages of tumor growth (as small, medium, and large-sized tumors). Normal non-tumor-bearing mice served as controls. To assess MVD, two endothelial cell markers (anti-CD34 and -CD31 antibodies), image analysis, and immunofluorescent technique were utilized. Enumeration of positive stained endothelial cells revealed the MVD. Results: Non-metastatic livers showed increased levels of MVD vs. control. Moreover, levels of MVD were higher in small and medium-sized tumor groups versus large sized tumor groups. Conclusion: The present data indicate that angiogenesis in the liver is induced in early-stages of CRC. However, this effect is suppressed with advanced tumor growth. These results provide an additional rationale for including antiangiogenic therapy in the treatment of early stages of CRC.展开更多
Hypoxia is a hallmark of solid tumors.Hypoxia increases the progression of malignancy and metastasis by promoting angiogenesis and triggering the over-expression of various protein products critical for tumor growth.T...Hypoxia is a hallmark of solid tumors.Hypoxia increases the progression of malignancy and metastasis by promoting angiogenesis and triggering the over-expression of various protein products critical for tumor growth.The transcription factor HIF-1 mediates cellular response to hypoxia by promoting processes,such as glycolysis and angiogenesis.Clinical evidence has demonstrated that expression of HIF-1 is strongly associated with poor patient prognosis and activation of HIF-1 contributes to malignant behavior and therapeutic resistance.Therefore,HIF-1 is a viable target for cancer therapy.This review summarizes agents that have been described in the literature as HIF-1 inhibitors.The majority of these compounds are indirect inhibitors of HIF-1.展开更多
文摘Objective: Angiogenesis is a crucial step for tumor growth and progression. Changes of liver angiogenesis (without metastatic invasion) in response to primary tumors are not known. The aim of the study was to investigate the liver angiogenesis in non-metastatic colorectal cancer (CRC). Methods: Human colorectal adenocarcinoma tumors were grown subcutaneously in nude mice. All animals showed tumor growth locally without macroscopic or microscopic evidence of liver metastases. Livers were investigated for their microvessel density (MVD) at different stages of tumor growth (as small, medium, and large-sized tumors). Normal non-tumor-bearing mice served as controls. To assess MVD, two endothelial cell markers (anti-CD34 and -CD31 antibodies), image analysis, and immunofluorescent technique were utilized. Enumeration of positive stained endothelial cells revealed the MVD. Results: Non-metastatic livers showed increased levels of MVD vs. control. Moreover, levels of MVD were higher in small and medium-sized tumor groups versus large sized tumor groups. Conclusion: The present data indicate that angiogenesis in the liver is induced in early-stages of CRC. However, this effect is suppressed with advanced tumor growth. These results provide an additional rationale for including antiangiogenic therapy in the treatment of early stages of CRC.
基金supported by the National Institutes of Health(CA122536 and a minority supplement)the GSU MBD program through a fellowship to SRM
文摘Hypoxia is a hallmark of solid tumors.Hypoxia increases the progression of malignancy and metastasis by promoting angiogenesis and triggering the over-expression of various protein products critical for tumor growth.The transcription factor HIF-1 mediates cellular response to hypoxia by promoting processes,such as glycolysis and angiogenesis.Clinical evidence has demonstrated that expression of HIF-1 is strongly associated with poor patient prognosis and activation of HIF-1 contributes to malignant behavior and therapeutic resistance.Therefore,HIF-1 is a viable target for cancer therapy.This review summarizes agents that have been described in the literature as HIF-1 inhibitors.The majority of these compounds are indirect inhibitors of HIF-1.
