Vascular Endothelial Growth Factor In Carcinomas Research Articles

HIF-1α in Epidermis: Oxygen Sensing, Cutaneous Angiogenesis, Cancer, and Non-Cancer Disorders

Besides lung, postnatal human epidermis is the only epithelium in direct contact with atmospheric oxygen. Skin epidermal oxygenation occurs mostly through atmospheric oxygen rather than tissue vasculature, resulting in a mildly hypoxic microenvironment that favors increased expression of hypoxia-inducible factor-1α (HIF-1α). Considering the wide spectrum of biological processes, such as angiogenesis, inflammation, bioenergetics, proliferation, motility, and apoptosis, that are regulated by this transcription factor, its high expression level in the epidermis might be important to HIF-1α in skin physiology and pathophysiology. Here, we review the role of HIF-1α in cutaneous angiogenesis, skin tumorigenesis, and several skin disorders.

Vascular Endothelial Growth Factor (VEGF) and Microvessel Density in Squamous Cell Carcinomas of the Larynx: an Immunohistochemical Study

The distribution of vascular endothelial growth factor (VEGF), one of the most important angiogenic factors, and microvessel density (MVD) were assessed in laryngeal carcinomas by means of immunohistochemistry. Correlation of VEGF with MVD and clinical parameters (T stage, N stage, histological grading, survival, recurrence-free interval) was also examined. VEGF expression was evaluated semi-quantitatively and was observed in varying intensity (i) in tumour cells, (ii) in the stromal department as diffuse, sometimes strong reactivity, especially in close proximity to tumour masses and (iii) in macrophages and endothelial cells. Normal epithelium presented no VEGF reactivity except in the immediate vicinity of tumour transformation. Forty percent of our specimens exhibited substantial VEGF reactivity, whereas 20% showed no staining in tumour cells and stroma. These results could be positively correlated with MVD. Moreover, high-graded carcinomas revealed higher VEGF expression, but there was no association of tumour stage or lymph node status with VEGF or MVD. There was a trend in the survival and recurrence analysis towards a higher risk of disease relapse and shorter survival time for patients with enhanced VEGF expression. Apart from tumour cells, macrophages seem to be a substantial source of VEGF in carcinomas. This observation supports the concept of a pivotal role of these cells in tumour defence-in our case, promoting tumour formation by contributing to neovascularization. VEGF was also found in the connective tissue, where it seems to be bound on collagens and probably builds a reservoir for rapid enzymatic mobilization.

In oesophageal squamous cell carcinoma vascular endothelial growth factor is associated with p53 mutation, advanced stage and poor prognosis.

Vascular endothelial growth factor (VEGF) affects malignant tumours by promoting angiogenesis. The tumour-suppressor gene p53 has been thought to regulate VEGF. We investigated the effect of VEGF on oesophageal carcinoma and the connection between VEGF and p53. One hundred and nine resected oesophageal squamous cell carcinomas were examined. VEGF expression was analysed by immunohistochemical staining. Sixty-five tumours (59.6%, 65 out of 109) were classified as VEGF positive. A significant correlation was found between the VEGF expression and both the depth of invasion (P = 0.0001) and lymph node metastasis (P < 0.0001). With regard to p53, we compared the expression of VEGF with the mutation of p53, examined using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct sequencing in tumour samples obtained from 36 patients who we have reported previously. The VEGF expression was significantly correlated to p53 mutation (P = 0.0291). To evaluate the angiogenesis, microvascular density (MVD) was counted, and endothelial cells were stained immunohistochemically using anti-CD34 monoclonal antibody against 29 cases with invasion limited to the submucosal layer. The average MVD had a tendency to correlate to VEGF expression (P = 0.1626). The prognoses of patients with VEGF-positive primary tumours were significantly worse than for those with VEGF-negative primary tumours (P = 0.0077). We have assumed that VEGF contributes to aggressive characteristics in oesophageal carcinomas and that VEGF expression might be affected by p53 status.

Linomide blocks angiogenesis by breast carcinoma vascular endothelial growth factor transfectants.

The blocking of angiogenesis provides a novel therapeutic target to inhibit tumour spreading. In this study, we investigated the effect of linomide on angiogenesis induced in vivo by highly angiogenic breast carcinoma cells. The rabbit cornea was used to assess neovascular growth in the absence of a tumour mass. MCF-7 cells stably transfected with the cDNA encoding for vascular endothelial growth factor 121 (VEGF121) (V12 clone) were used to elicit a potent VEGF-dependent corneal angiogenesis. After tumour cell implant, albino rabbits received 100 mg kg(-1) day(-1) linomide for 5 consecutive days. Daily observation of neovascular progression indicated that linomide blocked angiogenesis. The antiangiogenic effect of linomide was apparent within 48 h from the beginning of the treatment and was both angiosuppressive and angiostatic. The block of neovascular growth lasted over 10 days from treatment suspension, and preformed vessels, which had regressed, remained dormant, suggesting the persistence of unfavourable conditions for capillary progression. Linomide (50-200 microg ml[-1]) was not cytotoxic in vitro on resting capillary endothelial cells but blocked endothelial cell replication induced by VEGF. Our data indicate that linomide can efficiently and persistently block VEGF-dependent angiogenesis in vivo in the absence of a growing tumour mass. These data suggest that linomide could be a chemopreventive drug in breast cancer patients and a valuable tool in clinical settings in which metastatic spreading occurs in the absence of a detectable tumour mass.