Vascular endothelial growth factor gene-460 C/T polymorphism is a biomarker for oral cancer

Oral cancer is one of the most common malignant diseases in Taiwan. The incidence of male oral cancer is 9.01 times than that of female. The formation or progression of oral cancer may be associated with a polymorphism of the vascular endothelial growth factor (VEGF) gene. The most frequently seen polymorphism is BstUI (C to T) located at the -460th nucleotide upstream of the VEGF gene. We investigated whether this polymorphism could be a genetic marker of oral cancer. A normal control group of 230 healthy people and 137 patients with oral cancer were examined. The polymorphism was detected by polymerase chain reaction-based restriction analysis. The analysis revealed significant differences between normal individuals and patients with cancer (P<0.001). The distribution of the "TT" homozygote in the patient group was greater than that in the control group. The odds ratio per copy of the "T/C" ratio was 9.62 (95% confidence interval 5.81-15.87), which means that for a group of people with a higher T/C ratio have higher risk in getting oral cancer. There is no gender difference in this VEGF gene polymorphism. Therefore, the BstUI polymorphism of the VEGF gene is a suitable genetic marker of oral cancer.     

A common 936 C/T gene polymorphism of vascular endothelial growth factor is associated with decreased breast cancer risk

A common 936 C/T polymorphism in the gene for the vascular endothelial growth factor (VEGF) has been associated with VEGF plasma levels. In our case-control study, we investigated the role of this polymorphism for breast cancer risk. VEGF genotype was determined in 500 women with breast cancer and 500 sex- and age-matched healthy control subjects. Carriers of a 936T-allele were more frequent among controls (29.4%) than among patients (17.6%; p = 0.000014). The odds ratio for carriers of a 936T-allele for breast cancer was 0.51 (95% confidence interval 0.38-0.70). Additionally, VEGF plasma levels were determined in 21 nonsmoking post-menopausal controls; carriers of a 936T allele had significantly lower levels (median 23 pg/ml; range 6-50 pg/ml) than noncarriers (37; 21-387; p = 0.034). We conclude that carriers of a VEGF 936T-allele are at decreased risk for breast cancer, this, however, requiring further confirmation in a larger study.     

Association of a vascular endothelial growth factor gene 936 C/T polymorphism with breast cancer risk: a meta-analysis

Published studies on the association between the vascular endothelial growth factor (VEGF) gene 936 C/T polymorphism and breast cancer risk are inconclusive, and a meta-analysis is required to verify the association. Nine studies, including a total of 4,973 cases and 5,035 controls, were subjected to meta-analysis. When all eligible subjects were pooled for meta-analysis, the CT + TT genotypes were not associated with a significant decrease in breast cancer risk (odds ratio = 0.87; 95% confidence interval 0.75–1.02; P = 0.087). We also categorized by ethnicity (Caucasian, Asian, or mixed) for subgroup analysis, however, according to this subgroup analysis, we found no significant association between the CT and TT versus CC genotype with breast cancer risk reduction in any of the subgroups. We conclude that the VEGF gene 936 C/T polymorphism does not affect breast cancer risk.     

Vascular endothelial growth factor gene polymorphism (-634G/C) and breast cancer risk

The aim of this meta-analysis was to assess if the -634G/C polymorphism represents a predisposition factor for the risk of breast cancer. We included eight published case-control studies, in which a total of 6,175 cancer cases and 6,421 cancer-free controls were included. Pooled ORs and 95 % CIs were calculated by the fixed effects model to evaluate the association of the -634G/C polymorphism and breast cancer risk. When all studies were pooled, we did not find statistical evidence of any significant association with overall breast cancer risk (OR_{BB vs. bb}?=?1.00, 95 % CI?=?0.93–1.07, P?=?0.999; OR_{BB + Bb vs. bb}?=?1.00, 95 % CI?=?0.95–1.05, P?=?0.999; OR_{BB vs. Bb + bb}?=?1.03, 95 % CI?=?0.96-1.09, P?=?0.984; OR_{allele B vs. allele b}?=?1.01, 95 % CI?=?0.97–1.05, P?=?0.998; OR_{Bb vs. bb}?=?0.99, 95 % CI?=?0.92–1.06, P?=?0.992). In further stratified analyses by ethnicity and control source, no significant association was revealed. This study suggests that the -634G/C polymorphism does not appear to represent a risk factor for breast cancer.     

Vascular endothelial growth factor in ovarian cancer

Tumor growth requires nutrients and oxygen. Both nutrients and oxygen are provided via the vasculature. Thus, when a tumor increases in volume, new blood vessels must form and invade the expanding tumor. This process, called angiogenesis, has theoretical significance in the context of ovarian cancer for two reasons. First, the process of angiogenesis and vessel regression occurs in a tightly controlled way as part of normal ovarian function. This suggests that at least some ovarian cells are primed to produce the paracrine stimulus needed for new blood vessel growth and that, on tranformation, this capability is present early in tumor development. Second, the characteristically large size of ovarian tumors indicates that angiogenesis is mandatory to sustain the tumor. In this article, we review the experimental and clinical correlative data that support the hypothesis that ovarian cancers are highly angiogenic. Because a critical component of angiogenesis is the paracrine and autocrine production of vascular endothelial cell growth factor, there is substantial focus on this topic.     

Vascular endothelial growth factor in esophageal cancer

Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis of many solid malignancies. The influence of angiogenesis and VEGF expression on progression and recurrence of esophageal cancer has been investigated over the last years. This article reviews the prognostic significance of VEGF expression, microvessel density (MVD), and lymphangiogenic factors in squamous cell carcinoma (SCC), Barrett's dysplasia, and adenocarcinoma (AC) of the esophagus, their predictive value for treatment response to chemo-radiotherapy and new anti-angiogenic treatment strategies.     

Vascular endothelial growth factor and prognosis in patients with node-negative breast cancer

Vascular endothelial growth factor (VEGF) has emerged as one of the most important angiogenic growth factors from experimental in vitro and in vivo studies. In the present study, we investigated the relationship between VEGF expression and microvessel density (MVD) and defined their prognostic relevance on a series of 242 patients with node-negative breast cancer, using immunohistochemical methods. In parallel, estrogen and progesterone receptors were quantitatively assessed using the dextran-charcoal technique and cell proliferation was evaluated as S-phase cell fraction according to (3)H-thymidine-labeling index (TLI). The percentage of VEGF-expressing cells varied from 0-95% in the different tumors and was unrelated to menopausal status, tumor size or steroid receptor status. Conversely, a significant inverse relation was observed with patient age or tumor cell proliferation, albeit with very poor correlation coefficients. A significant relation was observed between VEGF expression and MVD (r(s) = 0.55, p < 0.001). Clinical outcome analyzed as a function of high and low VEGF expression showed slight differences in terms of both disease-free survival (DFS) and overall survival (OS) that never reached statistical significance. Moreover, the trend was paradoxically in favor of patients with highly VEGF-expressing tumors. Finally, DFS and OS curves, when analyzed as a function of VEGF expression or MVD, were superimposable. In conclusion, our study did not highlight a prognostic relevance of VEGF expression in patients with node-negative breast cancer, as already observed for MVD.     

Vascular endothelial growth factor and insulin-like-growth factors in prostate cancer.

To study the levels of vascular endothelium growth factor (VEGF), insulin-like growth factor of type I and II (IGF-I and IGF-II), prostate-specific antigen (PSA) and their correlations in prostatic cancer (PC) and benign prostatic hyperplasia (BPH), we examined 38 PC patients (mean age 66.6 +/- 5.5 years) and 80 BPH patients (mean age 60.3 +/- 2.5 years). Serum concentrations of VEGF, IGF-I and IGF-II were measured using kits made by R&D (USA), PSA by Boehringer Mannheim (Germany). Sensitivity and specificity of the tests were analysed by plotting the curves. The serum VEGF concentration in PC patients was 518.9 +/- 60.7 pkg/ml, in BPH patients--267.9 +/- 99.9 pkg/ml (p < 0.001). The IGF-I and IGF-II it was 178 +/- 19 and 136 +/- 9 ng/ml (p < 0.05), 400 +/- 31 and 351 +/- 23 ng/ml (p < 0.05), respectively. The ratio of growth factor concentration to PSA concentration in the blood serum in BPH patients was higher than in PC patients (p < 0.01). Sensitivity and specificity of PSA (4 ng/ml) made up 85.7 and 57%, VEGF (151.5 pg/ml)--76.2 and 57.6%, IGF-I (157 ng/ml)--57.6 and 50%; IGF-II (392 ng/ml)--57.5 and 50%, respectively. Sensitivity and specificity VEGF/PSA was 85.7 and 70%; IGF-I/PSA--84.2 and 75%; IGF-II/PSA--84.2 and 79.6%, respectively. Thus, the ratio of concentrations of IGF-I, IGF-II and VEGF to PSA level in blood serum has high sensitivity and specificity for PC detection. Clinical implications of serum levels of VEGF, IGF-I and IGF-II for prediction of PC course and detection is to be elicited.     

Vascular endothelial growth factor

Vascular endothelial growth factor (VEGF) is a hypoxia-inducibleangiogenesis and vascular permeability factor which is expressedin high amounts in perinecrotic palisading cells inhuman glioblastomas. In vitro VEGF gene expression isenhanced approximately ten times by hypoxia. Current evidencesuggests, that hypoxia is also the driving forcefor VEGF gene expression in glioblastoma cells invivo and represents the most important trigger fortumor angiogenesis and edema. Our approaches to inhibittumor angiogenesis and edema formation in glioblastoma patientswill concentrate on the disruption of VEGF/VEGF receptorsignal transduction pathway in vivo.     

Vascular endothelial growth factor and breast cancer risk

Vascular endothelial growth factor (VEGF) is a key factor in angiogenesis and is important to carcinogenesis. Previous studies relating circulating levels of VEGF to breast cancer have been limited by small numbers of participants and lack of adjustment for confounders. We studied the association between serum VEGF and breast cancer in an unmatched case–control study of 407 pre- and postmenopausal women (n = 203 cases, n = 204 controls). Logistic regression was used to model the breast cancer risk as a function of natural log transformed VEGF levels adjusted for age, Gail score, education, physical activity, history of breastfeeding, serum testosterone, and hormone therapy (HT) use. The majority of the population was postmenopausal (67.6%) and the average age was 56 years; age and menopausal status were similar among cases and controls. Geometric mean VEGF levels were non-significantly higher in cases (321.4 pg/ml) than controls (291.4 pg/ml; p = 0.21). In a multivariable model, the odds of breast cancer was 37% higher for women with VEGF levels ≥314.2 pg/ml compared to those with levels below 314.2 pg/ml, albeit not significantly (p = 0.16). There was no interaction between VEGF and menopausal status (p = 0.52). In this case–control study, VEGF was not significantly associated with breast cancer risk in pre- and postmenopausal women.     

Vascular endothelial growth factor and bevacitumab in breast cancer

Cancer development requires neovascularization. The level of angiogenic activity in breast cancer has been shown to be a determinant of disease progression and survival. Vascular endothelial growth factor (VEGF) is a one of the most essential pro-angiogenic growth factors expressed by most cancer-cell types and certain tumor stromal cells. Blocking the action of VEGF appears to be a promising anti-angiogenic approach to treat multiple types of solid tumors including breast cancer, and clinical trials using agents which target VEGF were launched beginning in the late 1990s. The effort reached fruition in 2005 with the first report of a large, prospective randomized trial of anti-VEGF therapy in patients with metastatic breast cancer (MBC), which demonstrated the benefit of adding the monoclonal antibody bevacizumab to the chemotherapeutic agent paclitaxel. The success of this trial provided proof of principle that inhibition of angiogenesis has the potential to enhance the effectiveness of treatment of this disease. Adjuvant therapy trials are in development with bevacizumab and numerous other anti-VEGF agents are now being tested in patients with breast cancer in various settings. Nevertheless, since bevacizumab monotherapy has minimal activity, a question for future therapeutic development of these agents in breast cancer relates to the interaction between anti-angiogenic strategies and cytotoxic therapies. Further research is still needed for complete understanding of the exact role of VEGF and angiogenesis in health and disease, to take best advantage and avoid the adverse effects of anti-angiogenic therapy.     

The 936C>T polymorphism of the gene for vascular endothelial growth factor is associated with 18F-fluorodeoxyglucose uptake

Background: Positron emission tomography (PET) is a an important technology for detection and staging of breast cancer. The method is based upon assessment of glucose metabolism using the 18F-fluorodeoxyglucose (18F-FDG) as glucose analog. A strong variability of 18F-FDG uptake by breast cancer tissue has been reported, the reason for which is not fully understood but may involve vascular density and integrity. A 936C>T polymorphism in the gene for the vascular endothelial growth factor (VEGF) has been associated with VEGF plasma levels and breast cancer risk.Methods: To analyze the role of this polymorphism for 18F-FDG uptake in breast cancer patients, we determined the VEGF genotype in 37 patients in whom PET was performed for detection of metastases. An 18F-FDG uptake score of 1 (low uptake), 2 (medium uptake) or 3 (high uptake) was assigned to each patient.Results: VEGF CC, CT and TT genotypes were found in 28, 8 and 1 patient. Uptake score of 1 was found in three patients, score 2 in 12 patients and score 3 in 22 patients. VEGF genotype was significantly associated with FDG uptake score (ϲ test, p=0.007). The number of 936-T alleles correlated with a lower 18F-FDG uptake score (Spearman correlation test, p=0.032).Conclusion: In the present study the common VEGF 936C>T polymorphisms had a major impact on 18F-FDG uptake in breast cancer patients. If this result can be confirmed in following studies, it might have strong relevance for the use of PET as diagnostic tool.     

Vascular endothelial growth factor, platelet-derived endothelial cell growth factor and angiogenesis in non-small-cell lung cancer

High microvessel density, an indirect measure of angiogenesis, has been shown to correlate with increased tumour size, lymph node involvement and poor prognosis in non-small-cell lung cancer (NSCLC). Tumour cell vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) expression correlate with angiogenesis and a poor outcome in this disease. In a retrospective study VEGF and PD-ECGF expression and microvessel density were evaluated immunohistochemically in surgically resected specimens (T1-3, N0-2) from 223 patients with operable NSCLC using the VG1, P-GF.44C and JC70 monoclonal antibodies respectively. High VEGF immunoreactivity was seen in 104 (46.6%) and PD-ECGF in 72 (32.3%) cases and both were associated with high vascular grade tumours (P= 0.009 and P= 0.05 respectively). Linear regression analysis revealed a weak positive correlation between VEGF and PD-ECGF expression in cancer cells (r= 0.21; P = 0.002). Co-expression of VEGF and PD-ECGF was not associated with a higher microvessel density than VEGF or PD-ECGF only expressing tumours. Furthermore a proportion of high vascular grade tumours expressed neither growth factor. Univariate analysis revealed tumour size, nodal status, microvessel density and VEGF and PD-ECGF expression as significant prognostic factors. Tumour size (P < 0.02) and microvessel density (P < 0.04) remained significant on multivariate analysis. In conclusion, VEGF and PD-ECGF are important angiogenic growth factors and have prognostic significance in NSCLC. Furthermore the study underlines the prognostic significance of microvessel density in operable NSCLC.     

Vascular endothelial growth factor in node-positive breast cancer patients treated with adjuvant tamoxifen

In 212 postmenopausal women with node-positive oestrogen receptor-positive (ER(LBA)) breast cancer subjected to radical surgery and adjuvant tamoxifen, the risk of 6-year relapse increased with increasing values of intratumoral vascular endothelial growth factor (VEGF) in patients whose tumours had a low/intermediate ER(LBA) content compared to patients with high-ER(LBA) tumours. These findings indicate that tumour progression, activated or sustained by high VEGF levels, may be counteracted in high-ER(LBA) cancers by tamoxifen, which in contrast fails to contrast the metastatic potential in low-ER(LBA) tumours.     

VEGFR-3在肿瘤淋巴管转移中的作用

VEGFR-3主要在成熟组织的淋巴管内皮细胞上表达,肿瘤分泌的VEGF-C、VEGF-D与之结合后可诱导淋巴管内皮细胞增殖和迁移,刺激淋巴管的新生,介导肿瘤淋巴道的转移.通过竞争性抑制VEGFR-3的信号转导可有效阻止肿瘤淋巴管的转移,最终达到提高治疗肿瘤的作用.     

Vascular endothelial growth factor in patients with hepatocellular carcinoma

The main aims of this study were to analyze the significance of serum vascular endothelial growth factor (VEGF) levels in the development of hepatocellular carcinoma, and the effect of transcatheter arterial embolization treatment on the production of VEGF. Serum VEGF levels in hepatocellular carcinoma were significantly higher than in liver cirrhosis (P<0.01) but not significantly different from normal controls. Serum VEGF levels in cirrhosis decreased gradually as the Pugh-Child grade increased in severity. In hepatocellular carcinoma serum VEGF levels were not related to the tumor stage or serum levels of the tumor markers, cr-fetoprotein and des-gamma-carboxy prothrombin. In 18 patients who underwent transcatheter arterial embolization, serum VEGF increased gradually and reached a peak at day 7, although serum interleukin-6 and hepatocyte growth factor levels peaked at days 1-3 and then decreased. VEGF levels were elevated significantly in patients who did not respond to transcatheter arterial embolization treatment as compared to those who responded to this treatment (P<0.05). Serum VEGF levels may be useful in the assessment of hepatocellular carcinoma patients and may indicate responsiveness to transcatheter arterial embolization.