Hypoxia-inducible factor-1 alpha（HIF-1α） plays a vital role in the initiation, evaluation and prognosis in lung cancer. The prognostic value of HIF-1α reported in diverse study remains disputable. Accordingly, a m...Hypoxia-inducible factor-1 alpha（HIF-1α） plays a vital role in the initiation, evaluation and prognosis in lung cancer. The prognostic value of HIF-1α reported in diverse study remains disputable. Accordingly, a meta-analysis was implemented to further understand the prognostic role of HIF-1α in lung cancer. The relationship between HIF-1α and the clinicopathological characteristics and prognosis of lung cancer were investigated by a meta-analysis. Pub Med and Embase were searched from their inception to January 2015 for observational studies. Fixed-effects or random-effects meta-analyses were used to calculate odds ratios and 95% confidence intervals of different comparisons. A total of 20 studies met the criteria. The results showed that HIF-1α expression in lung cancer tissues was significantly higher than that in normal lung tissues. Expression of HIF-1α in patients with squamous cell carcinoma was significantly higher than that of patients with adenocarcinomas. Similarly, non-small cell lung cancer（NSCLC） patients had higher HIF-1α expression than small cell lung cancer（SCLC） patients. Moreover, lymph node metastasized tissues had higher HIF-1α expression than non-lymph node metastasized tissues. A high level HIF-1α expression was well correlated with the expression of vascular endothelial growth factor and epidermal growth factor receptor in the NSCLC. Notably, NSCLC or SCLC patients with positive HIF-1α expression in tumor tissues had lower overall survival rate than patients with negative HIF-1α expression. It was suggested that HIF-1α expression may be a prognostic biomarker and a potential therapeutic target for lung cancer.展开更多
To investigate the expression of hypoxia inducible factor 1-alpha (HIF-1α) and its correlation with P53 and vascular endothelial growth factor (VEGF), immunohistochemical technique was employed to detect the protein ...To investigate the expression of hypoxia inducible factor 1-alpha (HIF-1α) and its correlation with P53 and vascular endothelial growth factor (VEGF), immunohistochemical technique was employed to detect the protein expressions of HIF-1α, P53 and VEGF in specimens from 57 patients with lung cancer. The results indicated that the total positive proportion of HIF-1α expression was 63 % and the HIF-1α expression was more frequent in bronchiole-alveolar carcinoma (86 %) than in other lung cancer. There was a strong association of HIF-1α with VEGF and P53 protein expressions. It is concluded that HIF-1α overexpression is a common event in lung cancer, which may be related to the up-regulation of the angiogenic factor VEGF and oncogene mutant P53 protein.展开更多
Background Hypoxia promotes tumor angiogenesis and hypoxia-inducible factor-1 alpha （HIF-lg） plays a pivotal role in this process. Recently identified pro-angiogenic factor, semaphorin4D （Sema4D） also promotes ang...Background Hypoxia promotes tumor angiogenesis and hypoxia-inducible factor-1 alpha （HIF-lg） plays a pivotal role in this process. Recently identified pro-angiogenic factor, semaphorin4D （Sema4D） also promotes angiogenesis and enhances invasive proliferation in some tumors. Furthermore, tumor-associated macrophages （TAMs） can increase the expression of HIF-la and Sema4D in cancer cells and thus influence tumor growth and progression. The purpose of this study was to evaluate the effect of TAMs on the expression of Sema4D and HIF-la and the impact of biologic behavior in colon cancer cells. Methods Immunohistochemistry was used to analyze HIF-la and Sema4D expression in 86 curatively resected colon cancer samples and 52 normal colon tissues samples. The relationship between their expression and clinicopathological factors was analyzed. Furthermore, macrophage-tumor cell interactions, such as metastasis, angiogenesis, were also studied using in vitro co-culture systems. Statistical analysis was performed using SPSS 17.0 software （SPSS Inc., USA）. Differences between two groups were analyzed with Student＇s t test. Results HIF-la （58%） and Sema4D （60%） were expressed at a significantly higher level in tumors than in normal tissues （P 〈0.01, for both）. Furthermore, HIF-la and Sema4D expression was significantly correlated with lymphatic metastasis, specific histological types and TNM stages （P 〈0.05）, but not with age and tumor size （P 〉0.05）. Sema4D expression was correlated with that of HIF-la （r=0.567, P 〈0.01）. TAMs markedly induced HIF-la and Sema4D expression in colon cancer calls and subsequently increased their migration and invasion. Conclusions HIF-la and Sema4D expression are closely related to lymphatic metastasis, specific histological types and TNM stages in colon cancer. Furthermore, TAMs promote migration and invasion of colon cancer cells and endothelial tube formation, possibly through up-regulation of HIF-la and Sema4D.展开更多
文摘Hypoxia-inducible factor-1 alpha（HIF-1α） plays a vital role in the initiation, evaluation and prognosis in lung cancer. The prognostic value of HIF-1α reported in diverse study remains disputable. Accordingly, a meta-analysis was implemented to further understand the prognostic role of HIF-1α in lung cancer. The relationship between HIF-1α and the clinicopathological characteristics and prognosis of lung cancer were investigated by a meta-analysis. Pub Med and Embase were searched from their inception to January 2015 for observational studies. Fixed-effects or random-effects meta-analyses were used to calculate odds ratios and 95% confidence intervals of different comparisons. A total of 20 studies met the criteria. The results showed that HIF-1α expression in lung cancer tissues was significantly higher than that in normal lung tissues. Expression of HIF-1α in patients with squamous cell carcinoma was significantly higher than that of patients with adenocarcinomas. Similarly, non-small cell lung cancer（NSCLC） patients had higher HIF-1α expression than small cell lung cancer（SCLC） patients. Moreover, lymph node metastasized tissues had higher HIF-1α expression than non-lymph node metastasized tissues. A high level HIF-1α expression was well correlated with the expression of vascular endothelial growth factor and epidermal growth factor receptor in the NSCLC. Notably, NSCLC or SCLC patients with positive HIF-1α expression in tumor tissues had lower overall survival rate than patients with negative HIF-1α expression. It was suggested that HIF-1α expression may be a prognostic biomarker and a potential therapeutic target for lung cancer.
文摘To investigate the expression of hypoxia inducible factor 1-alpha (HIF-1α) and its correlation with P53 and vascular endothelial growth factor (VEGF), immunohistochemical technique was employed to detect the protein expressions of HIF-1α, P53 and VEGF in specimens from 57 patients with lung cancer. The results indicated that the total positive proportion of HIF-1α expression was 63 % and the HIF-1α expression was more frequent in bronchiole-alveolar carcinoma (86 %) than in other lung cancer. There was a strong association of HIF-1α with VEGF and P53 protein expressions. It is concluded that HIF-1α overexpression is a common event in lung cancer, which may be related to the up-regulation of the angiogenic factor VEGF and oncogene mutant P53 protein.
基金This study was supported in part by grants from the National Youthful Science Foundation of China （No. 81101858） and the Natural Science Foundation of Shandong Province of China （No. BS2011 SW046）. Conflict of interest： none.
文摘Background Hypoxia promotes tumor angiogenesis and hypoxia-inducible factor-1 alpha （HIF-lg） plays a pivotal role in this process. Recently identified pro-angiogenic factor, semaphorin4D （Sema4D） also promotes angiogenesis and enhances invasive proliferation in some tumors. Furthermore, tumor-associated macrophages （TAMs） can increase the expression of HIF-la and Sema4D in cancer cells and thus influence tumor growth and progression. The purpose of this study was to evaluate the effect of TAMs on the expression of Sema4D and HIF-la and the impact of biologic behavior in colon cancer cells. Methods Immunohistochemistry was used to analyze HIF-la and Sema4D expression in 86 curatively resected colon cancer samples and 52 normal colon tissues samples. The relationship between their expression and clinicopathological factors was analyzed. Furthermore, macrophage-tumor cell interactions, such as metastasis, angiogenesis, were also studied using in vitro co-culture systems. Statistical analysis was performed using SPSS 17.0 software （SPSS Inc., USA）. Differences between two groups were analyzed with Student＇s t test. Results HIF-la （58%） and Sema4D （60%） were expressed at a significantly higher level in tumors than in normal tissues （P 〈0.01, for both）. Furthermore, HIF-la and Sema4D expression was significantly correlated with lymphatic metastasis, specific histological types and TNM stages （P 〈0.05）, but not with age and tumor size （P 〉0.05）. Sema4D expression was correlated with that of HIF-la （r=0.567, P 〈0.01）. TAMs markedly induced HIF-la and Sema4D expression in colon cancer calls and subsequently increased their migration and invasion. Conclusions HIF-la and Sema4D expression are closely related to lymphatic metastasis, specific histological types and TNM stages in colon cancer. Furthermore, TAMs promote migration and invasion of colon cancer cells and endothelial tube formation, possibly through up-regulation of HIF-la and Sema4D.
