Hypoxia-inducible factor-1 (HIF-1) has been recognized as an important cancer drug target. Many recent studies have provided convincing evidences of strong correlation between elevated levels of HIF-1 and tumor metast...Hypoxia-inducible factor-1 (HIF-1) has been recognized as an important cancer drug target. Many recent studies have provided convincing evidences of strong correlation between elevated levels of HIF-1 and tumor metastasis, angiogenesis, poor patient prognosis as well as tumor resistance therapy. It was found that hypoxia (low O<sub>2</sub> levels) is a common character in many types of solid tumors. As an adaptive response to hypoxic stress, hypoxic tumor cells activate several survival pathways to carry out their essential biological processes in different ways compared with normal cells. Recent advances in cancer biology at the cellular and molecular levels highlighted the HIF-1α pathway as a crucial survival pathway for which novel strategies of cancer therapy could be developed. However, targeting the HIF-1α pathway has been a challenging but promising progresses have been made in the past twenty years. This review summarizes the role and regulation of the HIF-1α in cancer, and recent therapeutic approaches targeting this important pathway.展开更多
AIM: To study the expression of hypoxia-inducible factor 1α(HIF-1α) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) and the impact on neovascularization and survival. METHODS: Express...AIM: To study the expression of hypoxia-inducible factor 1α(HIF-1α) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) and the impact on neovascularization and survival. METHODS: Expressions of HIF-1α, VEGF and microvessel density (MVD) are studied through immunohistochemistry in 36 cases of HCC and the corresponding paraneoplastic tissue and 6 cases of normal liver tissue. The relationship of the expressions of HIF-1α and VEGF with the clinicopathological data and survival are analyzed. RESULTS: The positive rate of VEGF in HCC was 32/36, which is significantly higher than that in paraneoplastic tissue and normal liver tissue (P<0.05). The expression of HIF-1aaaaaa in HCC tissue is 24/36, also higher than that in paraneoplastic tissue and normal liver tissue (P<0.05). The expression of VEGF and HIF-1α in HCC with microscopic venous invasion is significantly higher than that in HCC without microscopic venous invasion (P<0.05). Spearman correlation analysis does not only show the expression of HIF-1α as correlated with the expression of VEGF (rs = 0.459, P<0.01), but it also shows the expression of HIF-1α and VEGF as correlated with MVD (rs=0.412 and 0.336, respectively, P<0.05). The differences of the survival rates among VEGF positive group and VEGF negative group are significant (P<0.05), whereas the differences of the survival rates among the HIF-1α negative group and positive group are not significant (P>0.05). CONCLUSION: HIF-1α plays important roles in neovascularization in HCC possibly through regulation of VEGF transcription.展开更多
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
基金partially supported by the NIH grant 1R01CA148706funds from the University of Tennessee Health Science Center, College of Pharmacy
文摘Hypoxia-inducible factor-1 (HIF-1) has been recognized as an important cancer drug target. Many recent studies have provided convincing evidences of strong correlation between elevated levels of HIF-1 and tumor metastasis, angiogenesis, poor patient prognosis as well as tumor resistance therapy. It was found that hypoxia (low O<sub>2</sub> levels) is a common character in many types of solid tumors. As an adaptive response to hypoxic stress, hypoxic tumor cells activate several survival pathways to carry out their essential biological processes in different ways compared with normal cells. Recent advances in cancer biology at the cellular and molecular levels highlighted the HIF-1α pathway as a crucial survival pathway for which novel strategies of cancer therapy could be developed. However, targeting the HIF-1α pathway has been a challenging but promising progresses have been made in the past twenty years. This review summarizes the role and regulation of the HIF-1α in cancer, and recent therapeutic approaches targeting this important pathway.
文摘AIM: To study the expression of hypoxia-inducible factor 1α(HIF-1α) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) and the impact on neovascularization and survival. METHODS: Expressions of HIF-1α, VEGF and microvessel density (MVD) are studied through immunohistochemistry in 36 cases of HCC and the corresponding paraneoplastic tissue and 6 cases of normal liver tissue. The relationship of the expressions of HIF-1α and VEGF with the clinicopathological data and survival are analyzed. RESULTS: The positive rate of VEGF in HCC was 32/36, which is significantly higher than that in paraneoplastic tissue and normal liver tissue (P<0.05). The expression of HIF-1aaaaaa in HCC tissue is 24/36, also higher than that in paraneoplastic tissue and normal liver tissue (P<0.05). The expression of VEGF and HIF-1α in HCC with microscopic venous invasion is significantly higher than that in HCC without microscopic venous invasion (P<0.05). Spearman correlation analysis does not only show the expression of HIF-1α as correlated with the expression of VEGF (rs = 0.459, P<0.01), but it also shows the expression of HIF-1α and VEGF as correlated with MVD (rs=0.412 and 0.336, respectively, P<0.05). The differences of the survival rates among VEGF positive group and VEGF negative group are significant (P<0.05), whereas the differences of the survival rates among the HIF-1α negative group and positive group are not significant (P>0.05). CONCLUSION: HIF-1α plays important roles in neovascularization in HCC possibly through regulation of VEGF transcription.
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.
