Objective: To explore the expression of vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(bFGF) in non-small cell lung cancer(NSCLC) and theIR clinical significance. Methods: The expression o...Objective: To explore the expression of vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(bFGF) in non-small cell lung cancer(NSCLC) and theIR clinical significance. Methods: The expression of VEGF and bFGF was examined at the protein levels by immunohistochemical staining in 96 NSCLC patients, and in 36 of which at the mRNA levels by reverse transcription-PCR analysis. Results: VEGF mRNAs were expressed predominately as its secretory forms (VEGF121 and VEGF165) in NSCLC tissues. The positive ratios of VEGF121 and VEGF165 were 69.5%(25 of 36) and 41.7%(15 of 36) respectively. The positive ratio of bFGF was 52.8(19 of 36) in the same tumor specimens. The positive ratios of VEGF and bFGF at protein levels were 55.55%(20 of 36) and 58.33%(21 of 36) respectively. A significant positive correlation was observed between VEGF and bFGF expression in NSCLC tissues(P=0.002). No significant interrelationship between VEGF, bFGF expression and clinical data(age, sex, histological subtype differentiation, P-stage, metastasis and survival) was found. Conclusions: VEGF and bFGF may play an important role in angiogenesis and act in a synergistic manner in NSCLC.展开更多
Summary: In order to investigate the expression of nerve growth factor (NGF) and hypoxia inducible factor-1α (HIF-1α) and its correlation with angiogenesis in non-small cell lung cancer (NSCLC), paraffin-embe...Summary: In order to investigate the expression of nerve growth factor (NGF) and hypoxia inducible factor-1α (HIF-1α) and its correlation with angiogenesis in non-small cell lung cancer (NSCLC), paraffin-embedded tissue blocks from 20 patients with NSCLC were examined. Twenty corresponding para-cancerous lung tissue specimens were obtained to serve as a control. The expression of NGF, HIF-1α, and vascular endothelial growth factor (VEGF) in the NSCLC tissues was detected by using immunohistochemistry. The microvascular density (MVD) was determined by CD31 staining. The resuits showed that the expression levels ofNGF, HIF-1α and VEGF in the NSCLC tissues were remarkably higher than those in the para-cancerous lung tissues (P〈0.05). There was significant difference in the MVD between the NSCLC tissues (9.19±1.43) and para-cancerous lung tissues (2.23±1.19) (P〈0.05). There were positive correlations between NGF and VEGF, between HIF-1α and VEGF, and between NGF and HIF-1α in NSCLC tissues, with the spearman correlation coefficient being 0.588, 0.519 and 0.588, respectively. In NSCLC tissues, the MVD had a positive correlation with the three factors (P〈0.05). Theses results suggest that NGF and HIF-1α are synergically involved in the angiogenesis of NSCLC.展开更多
The relationship between vascular endothelial growth factor-C (VEGF-C)/vascular endothelial growth factor receptor 3 (VEGFR-3) expression and clinicopathologic features of the patients with non-small cell lung can...The relationship between vascular endothelial growth factor-C (VEGF-C)/vascular endothelial growth factor receptor 3 (VEGFR-3) expression and clinicopathologic features of the patients with non-small cell lung cancer (NSCLC) was investigated. The expression of VEGF-C and VEGFR-3 was assessed in 65 patients with NSCLC by immunohistochemistry. The significance of VEGF-C and VEGFR-3 expression was analyzed statistically. The results showed that VEGF-C and VEGFR-3 were highly expressed in cytoplasm and membrane in lung cancer tissues with the positive rate being 55.4 % and 52.3 % respectively, while there was no expression in the normal lung tissues. The expression of VEGF-C was significantly increased in adenocacinoma as compared to other types of NSCLC (P〈0.05). The VEGFR-3 expression was closely related with lymph node metastasis (P〈0.01) and TNM stage (P〈0.05). There was a positive correlation between the VEGF-C and VEGFR-3 expression in NSCLC patients (r=-0.658, P〈0.01). It is suggested that VEGFR-3 plays an important role in the lymphatic metastasis of NSCLC. The interaction between VEGF-C and VEGFR-3 may be deeply involved in the mechanism of lung cancer metastasis.展开更多
Objective: Vascular-targeted therapy is gradually becoming more appealing for patients with lung cancer. It is unclear whether vascular endothelial growth factor receptor 2(VEGFR2) and neuropilin-1(NRP-1) can be ...Objective: Vascular-targeted therapy is gradually becoming more appealing for patients with lung cancer. It is unclear whether vascular endothelial growth factor receptor 2(VEGFR2) and neuropilin-1(NRP-1) can be biomarkers for clinical treatment. We aimed to investigate the expression levels of VEGFR2 and NRP-1 in human non-small cell lung cancer(NSCLC) and their clinical significance by observing patient prognosis. Methods: VEGFR2 and NRP-1 were assessed by immunohistochemistry(IHC) in 40 patients with NSCLC and in 10 patients with benign lesions of lung; kinase insert domain receptor(KDR) and NRP-1 copy number gain(CNG) was assessed by fluorescence in situ hybridization(FISH). The distributions of overall survival(OS) and progression-free survival(PFS) were estimated using the Kaplan-Meier method and compared between groups by log-rank test.Results: Rates of positive immunostaining for VEGFR2 and NRP-1 were 58% and 55%, respectively. KDR and NRP-1 CNG(+) were detected in 32.5% and 30% of tumors, respectively. Levels of both VEGFR2 and NRP-1 in lung tumors were significantly different than in the control tissue(χ2=11.22, P=0.001; χ2=9.82, P=0.001, respectively); similar results were obtained using CNGs(χ2=4.39, P=0.036; χ2=3.95, P=0.046, respectively). Statistically significant correlations were observed with histological grade, clinical TNM stage and the lymph node status(P〈0.05), but not age, gender or pathology type(P〉0.05). VEGFR2 showed a strong correlation with NRP-1(Rs=0.68, P=0.00); similar results were observed with KDR and NRP-1 CNG(Rs=0.32, P=0.04). Significant differences in OS and PFS were observed between the groups with higher VEGFR2 and NRP-1 and those with lower expression(P〈0.05). Conclusions: According to these data, VEGFR2 and NRP-1 are highly expressed in NSCLC. We can conclude that they play a key role in NSCLC occurrence, development and metastasis and are associated with patient prognosis(P〈0.05 for OS and PFS). This information will be beneficial for clinical antiangiogenic treatment in NSCLC.展开更多
Vascular endothelial growth factor (VEGF) is one of the most important and specific factors affecting angiogenesis in tumor development. VEGFR2 is a receptor encoded by the KDR gene. VEGF and VEGFR2 transmit a signal ...Vascular endothelial growth factor (VEGF) is one of the most important and specific factors affecting angiogenesis in tumor development. VEGFR2 is a receptor encoded by the KDR gene. VEGF and VEGFR2 transmit a signal to intracellular tyrosine kinase cascades. Polymorphic variants of the VEGF and KDR genes significantly influence the expression levels of the endothelial growth factor and its receptor, which leads to a change in the activation of angiogenesis in oncopathological processes. In this study, the relationship between the polymorphic variants rs2010963, rs699947 and rs3025039 of the VEGF gene and rs1870377 and rs2071559 of the KDR gene was analyzed with the development of a specific histological type of non-small cell lung cancer and its clinical and morphological characteristics. It was established that the development of squamous cell carcinoma is associated with -634CC genotype of the VEGF gene and the genotypes containing -2578A allele of the VEGF gene reduce the likelihood of this cancer type development. The development of adenocarcinoma is associated with +936CC VEGF/1719TT KDR and +936CT VEGF/1719TT KDR combinations. In women with non-small cell lung cancer, -634GC genotype of the VEGF gene is associated with a greater degree of the primary lesion spread. Genotype -2578СС of the VEGF gene is associated with a higher degree of the primary tumor spread in the general group of patients and with regional metastases in women. Haplotypes -634G/-2578C/+936C are risky for the occurrence of metastases in regional lymph nodes in women.展开更多
Non-small-cell lung cancer(NSCLC)remains the leading cause of cancer-related death in both men and women in the United States.Platinum-based doublet chemotherapy has been a standard for patients with advanced stage di...Non-small-cell lung cancer(NSCLC)remains the leading cause of cancer-related death in both men and women in the United States.Platinum-based doublet chemotherapy has been a standard for patients with advanced stage disease.Improvements in overall survival and quality of life have been modest.Improved knowledge of the aberrant molecular signaling pathways found in NSCLC has led to the development of biomarkers with associated targeted therapeutics,thus changing the treatment paradigm for many NSCLC patients.In this review,we present a summary of many of the currently investigated biologic targets in NSCLC,discuss their current clinical trial status,and also discuss the potential for development of other targeted agents.展开更多
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
Objective: To explore the effect and mechanism of ginsenoside Rg3 (Shenyi Capsule, 参一胶囊) on the postoperative life span of patients with non-small cell lung cancer (NSCLC). Methods: The prospective, randomiz...Objective: To explore the effect and mechanism of ginsenoside Rg3 (Shenyi Capsule, 参一胶囊) on the postoperative life span of patients with non-small cell lung cancer (NSCLC). Methods: The prospective, randomized, controlled method was adopted. One hundred and thirty- three patients with NSCLC were randomly assigned to 3 groups: Shenyi Capsule group (43 cases), combined therapy group (Shenyi Capsule plus chemotherapy, 46 cases), and chemotherapy group (44 cases). The survival rates, immune function and the correlation between vascular endothelial growth factor (VEGF) expression and clinical effect were analyzed in the three groups. Results: (1) The 1-year survival rate in the Shenyi group, the combined group and the chemotherapy group was 76.7% (33/43), 82.6% (38/46), and 79.5% (35/44), respectively; the 2-year survival rate was 67.4% (29/43), 71.7% (33/46), and 70.5% (31/44), respectively; and the 3-year survival rate was 46.5% (20/43), 54.3% (25/46), and 47.7% (21/44), respectively. There was no significant difference among the 3 groups (P〉0.05). (2) NK cells were increased to different degrees and the ratio of CD4/CD8 was normal in the Shenyi Capsule group and the combined group, while the ratio of CD4/CD8 was disproportional in the chemotherapy group. (3) In the chemotherapy group, the 3-year survival rate was lower in patients with positive expression of VEGF than in patients with negative expression (37.0% vs 64.7%, χ^2=17.9, P〈0.01), but no significant statistical difference was shown in the other two groups (53.6% vs 55.6%, P〉0.05; 44.4% vs 50.0%, P〉0.05). Conclusion: Shenyi Capsule, especially in combination with chemotherapy, can improve the life span of patients with NSCLC after operation. The mechanism might be correlated with improving the immune function and anti-tumor angiogenesis.展开更多
基金This work was supported by a grant from the Beijing Natural Science Foundation (No.7992005) and from plan of new star of science and technology of Beijing(No. 99-148).
文摘Objective: To explore the expression of vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(bFGF) in non-small cell lung cancer(NSCLC) and theIR clinical significance. Methods: The expression of VEGF and bFGF was examined at the protein levels by immunohistochemical staining in 96 NSCLC patients, and in 36 of which at the mRNA levels by reverse transcription-PCR analysis. Results: VEGF mRNAs were expressed predominately as its secretory forms (VEGF121 and VEGF165) in NSCLC tissues. The positive ratios of VEGF121 and VEGF165 were 69.5%(25 of 36) and 41.7%(15 of 36) respectively. The positive ratio of bFGF was 52.8(19 of 36) in the same tumor specimens. The positive ratios of VEGF and bFGF at protein levels were 55.55%(20 of 36) and 58.33%(21 of 36) respectively. A significant positive correlation was observed between VEGF and bFGF expression in NSCLC tissues(P=0.002). No significant interrelationship between VEGF, bFGF expression and clinical data(age, sex, histological subtype differentiation, P-stage, metastasis and survival) was found. Conclusions: VEGF and bFGF may play an important role in angiogenesis and act in a synergistic manner in NSCLC.
基金supported by the Scientific Research Program of Health Department of Hubei Province,China(No.JX6B04)
文摘Summary: In order to investigate the expression of nerve growth factor (NGF) and hypoxia inducible factor-1α (HIF-1α) and its correlation with angiogenesis in non-small cell lung cancer (NSCLC), paraffin-embedded tissue blocks from 20 patients with NSCLC were examined. Twenty corresponding para-cancerous lung tissue specimens were obtained to serve as a control. The expression of NGF, HIF-1α, and vascular endothelial growth factor (VEGF) in the NSCLC tissues was detected by using immunohistochemistry. The microvascular density (MVD) was determined by CD31 staining. The resuits showed that the expression levels ofNGF, HIF-1α and VEGF in the NSCLC tissues were remarkably higher than those in the para-cancerous lung tissues (P〈0.05). There was significant difference in the MVD between the NSCLC tissues (9.19±1.43) and para-cancerous lung tissues (2.23±1.19) (P〈0.05). There were positive correlations between NGF and VEGF, between HIF-1α and VEGF, and between NGF and HIF-1α in NSCLC tissues, with the spearman correlation coefficient being 0.588, 0.519 and 0.588, respectively. In NSCLC tissues, the MVD had a positive correlation with the three factors (P〈0.05). Theses results suggest that NGF and HIF-1α are synergically involved in the angiogenesis of NSCLC.
文摘The relationship between vascular endothelial growth factor-C (VEGF-C)/vascular endothelial growth factor receptor 3 (VEGFR-3) expression and clinicopathologic features of the patients with non-small cell lung cancer (NSCLC) was investigated. The expression of VEGF-C and VEGFR-3 was assessed in 65 patients with NSCLC by immunohistochemistry. The significance of VEGF-C and VEGFR-3 expression was analyzed statistically. The results showed that VEGF-C and VEGFR-3 were highly expressed in cytoplasm and membrane in lung cancer tissues with the positive rate being 55.4 % and 52.3 % respectively, while there was no expression in the normal lung tissues. The expression of VEGF-C was significantly increased in adenocacinoma as compared to other types of NSCLC (P〈0.05). The VEGFR-3 expression was closely related with lymph node metastasis (P〈0.01) and TNM stage (P〈0.05). There was a positive correlation between the VEGF-C and VEGFR-3 expression in NSCLC patients (r=-0.658, P〈0.01). It is suggested that VEGFR-3 plays an important role in the lymphatic metastasis of NSCLC. The interaction between VEGF-C and VEGFR-3 may be deeply involved in the mechanism of lung cancer metastasis.
基金supported by National Natural Science Foundation of China [81472792]Ministry of Health of China (W201210)Jiangsu Natural Science Foundation of China (BK2012661)
文摘Objective: Vascular-targeted therapy is gradually becoming more appealing for patients with lung cancer. It is unclear whether vascular endothelial growth factor receptor 2(VEGFR2) and neuropilin-1(NRP-1) can be biomarkers for clinical treatment. We aimed to investigate the expression levels of VEGFR2 and NRP-1 in human non-small cell lung cancer(NSCLC) and their clinical significance by observing patient prognosis. Methods: VEGFR2 and NRP-1 were assessed by immunohistochemistry(IHC) in 40 patients with NSCLC and in 10 patients with benign lesions of lung; kinase insert domain receptor(KDR) and NRP-1 copy number gain(CNG) was assessed by fluorescence in situ hybridization(FISH). The distributions of overall survival(OS) and progression-free survival(PFS) were estimated using the Kaplan-Meier method and compared between groups by log-rank test.Results: Rates of positive immunostaining for VEGFR2 and NRP-1 were 58% and 55%, respectively. KDR and NRP-1 CNG(+) were detected in 32.5% and 30% of tumors, respectively. Levels of both VEGFR2 and NRP-1 in lung tumors were significantly different than in the control tissue(χ2=11.22, P=0.001; χ2=9.82, P=0.001, respectively); similar results were obtained using CNGs(χ2=4.39, P=0.036; χ2=3.95, P=0.046, respectively). Statistically significant correlations were observed with histological grade, clinical TNM stage and the lymph node status(P〈0.05), but not age, gender or pathology type(P〉0.05). VEGFR2 showed a strong correlation with NRP-1(Rs=0.68, P=0.00); similar results were observed with KDR and NRP-1 CNG(Rs=0.32, P=0.04). Significant differences in OS and PFS were observed between the groups with higher VEGFR2 and NRP-1 and those with lower expression(P〈0.05). Conclusions: According to these data, VEGFR2 and NRP-1 are highly expressed in NSCLC. We can conclude that they play a key role in NSCLC occurrence, development and metastasis and are associated with patient prognosis(P〈0.05 for OS and PFS). This information will be beneficial for clinical antiangiogenic treatment in NSCLC.
文摘Vascular endothelial growth factor (VEGF) is one of the most important and specific factors affecting angiogenesis in tumor development. VEGFR2 is a receptor encoded by the KDR gene. VEGF and VEGFR2 transmit a signal to intracellular tyrosine kinase cascades. Polymorphic variants of the VEGF and KDR genes significantly influence the expression levels of the endothelial growth factor and its receptor, which leads to a change in the activation of angiogenesis in oncopathological processes. In this study, the relationship between the polymorphic variants rs2010963, rs699947 and rs3025039 of the VEGF gene and rs1870377 and rs2071559 of the KDR gene was analyzed with the development of a specific histological type of non-small cell lung cancer and its clinical and morphological characteristics. It was established that the development of squamous cell carcinoma is associated with -634CC genotype of the VEGF gene and the genotypes containing -2578A allele of the VEGF gene reduce the likelihood of this cancer type development. The development of adenocarcinoma is associated with +936CC VEGF/1719TT KDR and +936CT VEGF/1719TT KDR combinations. In women with non-small cell lung cancer, -634GC genotype of the VEGF gene is associated with a greater degree of the primary lesion spread. Genotype -2578СС of the VEGF gene is associated with a higher degree of the primary tumor spread in the general group of patients and with regional metastases in women. Haplotypes -634G/-2578C/+936C are risky for the occurrence of metastases in regional lymph nodes in women.
文摘Non-small-cell lung cancer(NSCLC)remains the leading cause of cancer-related death in both men and women in the United States.Platinum-based doublet chemotherapy has been a standard for patients with advanced stage disease.Improvements in overall survival and quality of life have been modest.Improved knowledge of the aberrant molecular signaling pathways found in NSCLC has led to the development of biomarkers with associated targeted therapeutics,thus changing the treatment paradigm for many NSCLC patients.In this review,we present a summary of many of the currently investigated biologic targets in NSCLC,discuss their current clinical trial status,and also discuss the potential for development of other targeted agents.
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Objective: To explore the effect and mechanism of ginsenoside Rg3 (Shenyi Capsule, 参一胶囊) on the postoperative life span of patients with non-small cell lung cancer (NSCLC). Methods: The prospective, randomized, controlled method was adopted. One hundred and thirty- three patients with NSCLC were randomly assigned to 3 groups: Shenyi Capsule group (43 cases), combined therapy group (Shenyi Capsule plus chemotherapy, 46 cases), and chemotherapy group (44 cases). The survival rates, immune function and the correlation between vascular endothelial growth factor (VEGF) expression and clinical effect were analyzed in the three groups. Results: (1) The 1-year survival rate in the Shenyi group, the combined group and the chemotherapy group was 76.7% (33/43), 82.6% (38/46), and 79.5% (35/44), respectively; the 2-year survival rate was 67.4% (29/43), 71.7% (33/46), and 70.5% (31/44), respectively; and the 3-year survival rate was 46.5% (20/43), 54.3% (25/46), and 47.7% (21/44), respectively. There was no significant difference among the 3 groups (P〉0.05). (2) NK cells were increased to different degrees and the ratio of CD4/CD8 was normal in the Shenyi Capsule group and the combined group, while the ratio of CD4/CD8 was disproportional in the chemotherapy group. (3) In the chemotherapy group, the 3-year survival rate was lower in patients with positive expression of VEGF than in patients with negative expression (37.0% vs 64.7%, χ^2=17.9, P〈0.01), but no significant statistical difference was shown in the other two groups (53.6% vs 55.6%, P〉0.05; 44.4% vs 50.0%, P〉0.05). Conclusion: Shenyi Capsule, especially in combination with chemotherapy, can improve the life span of patients with NSCLC after operation. The mechanism might be correlated with improving the immune function and anti-tumor angiogenesis.