• Journal of Microbiology and Biotechnology
• /
• v.11 no.4
• /
• pp.543-551
• /
• 2001

The vascular endothelial growth factor (VEGF), or VEGF-A, is intimately involved in both physiological and pathological forms of angiogenesis. VEGF-A is now recognized as the founding member of a family of growth factors that has expanded to include VEGF-B, VEGF-C, VEGF-D, VEGF-E, and placental growth factor (PIGF). This family of cytokines binds differentially to at least three receptor tyrosine kinases, however, the extent to which family members other than VEGF-A contribute to physiological and pathological angiogenesis remains unclear. Issues that are of relevance include uncertainty regarding the consequences of signaling through VEGF - RI in particular, and the ability of some family members to heterodimerize, leading to the possibility ofheterodimeric receptor complexes. Structural characterization is one approach that can be used to address these issues, however, the vast majority of previous structure-function studies have only focused on VEGF-A. While these studies may provide some clues regarding the structural basis of the interaction of other family members with their receptors, studies using the ligands themselves are clearly required if highly specific interactions are to be revealed. With the recent progress toward refolding and purifying substantial' quantities of other VEGF family members, such structural studies are now possible. Here, these ~ssues are addressed with a particular emphasis on VEGF-B and its receptors.

• Biotechnology and Bioprocess Engineering:BBE
• /
• v.9 no.3
• /
• pp.201-206
• /
• 2004

Vascular endothelial growth factor (VEGF), plays a key role in angiogenesis. Many endogenous factors can affect angiogenesis in endothelial cells. VEGF is known to be a strong migration, sprouting, survival, and proliferation factor for endothelial cells during angiogenesis in endothelial cells. Searching for novel genes involved in VEGF signaling during angiogenesis, we carried out differential display polymerase chain reaction on RNA from VEGF-stimulated human umbilical vein endothelial cells (HUVECs). In this study, follistatin (FS) differentially expressed in VEGF-treated HUVECs, compared with controls. Addition of VEGF (10ng/L) produced an approximately 11.8-fold increase of FS mRNA. F5 or VEGF produced approximately 1.8- or 2.9-fold increases, respectively, in matrix metalloproteinase-2 (MMP-2) secretion for 12h, compared to the addition of a control buffer. We suggest that VEGF may affect the angiogenic effect of HUVECs, through a combination of the direct effects of VEGF itself, and the indirect effects mediated via induction of FS in vitro.

• Journal of Life Science
• /
• v.34 no.2
• /
• pp.128-137
• /
• 2024

This review discusses the pivotal role of vascular endothelial growth factors (VEGF) in angiogenesis and lymphangiogenesis, vital processes influencing vascular permeability, endothelial cell recruitment, and the maintenance of tumor-associated blood and lymphatic vessels. VEGF exerts its effects through tyrosine-kinase receptors, VEGFR-1, VEGFR-2, and VEGFR-3. This VEGF-VEGFR system is central not only to cancer but also to diseases arising from abnormal blood vessel and lymphatic vessel formation. In the context of cancer, VEGF and its receptors are essential for the development of tumor-associated vessels, making them attractive targets for therapeutic intervention. Various approaches, such as anti-VEGF antibodies, receptor antagonists, and VEGF receptor function inhibitors, are being explored to interfere with tumor growth. However, the clinical efficacy of anti-angiogenic agents remains uncertain and necessitates further refinement. The article also highlights the physiological role of VEGFs, emphasizing their involvement in endothelial cell functions, survival, and vascular permeability. The identification of five distinct VEGFs in humans (VEGF-A, VEGF-B, VEGF-C, VEGF-D, and PLGF) is discussed, along with the classification of VEGFRs as typical receptor tyrosine kinases with distinct signaling systems. The family includes VEGFR-1 and VEGFR-2, crucial in tumor biology and angiogenesis, and VEGFR-3, specifically involved in lymphangiogenesis. Overall, this review has provided a comprehensive overview of VEGF and VEGFR, detailing their roles in various diseases, including cancer. This is expected to further facilitate the utilization of VEGF and VEGFR as therapeutic targets.

• Tuberculosis and Respiratory Diseases
• /
• v.50 no.2
• /
• pp.171-181
• /
• 2001

Background : Angiogenesis is an essential process for the growth and metastatic ability of solid tumors. One of the key factors known to be capable of stimulating tumor angiogenesis is the vascular endothelial growth factor (VEGF). The serum VEGF concentration has been shown to be a useful parameter related to the clinical features and prognosis of lung cancer and has been recently applied to a the malignant pleural effusion showing a correlation with the biochemical parameters. The VEGF has been shown to play a role in the inflammatory diseases, but rarely in the tuberculosis (TB). The serum and pleural fluid VEGF levels were measured in patients with lung cancer and TB. Their relationship with the clinical and laboratory parameters and repeated measurement 3 months after various anticancer treatments were evaluated to assess the utility of the VEGF as a tumor marker. Methods : Using a sandwich enzyme-linked immunosorbent assay, the VEGF conoentration was measured in both sera and pleural effusions collected from a total of 85 patients with lung cancer, 13 patients with TB and 20 healthy individuals. Results : The serum VEGF levels in patients with lung cancer ($619.9{\pm}722.8pg/ml$) were significantly higher than those of healthy controls ($215.9{\pm}191.1pg/ml$), However, there was no significant difference between the VEGF levels in the lung cancer and TB patients. The serum VEGF levels were higher in large cell and undifferentiated carcinoma than in squamous cell carcinoma and adenocarcinoma. The serum VEGF levels of lung cancer patients revealed no significant relationship with the various clinical parameters. The VEGF concentrations in the malignant effusion ($2,228.1{\pm}2,103.0pg/ml$) were significantly higher than those in the TB effusion ($897.6{\pm}978.8pg/ml$). In the malignant pleural effusion, the VEGF levels revealed significant correlation with the number of red blood cells (r=0.75), the lactate dehydrogenase (LDH)(r=0.70), and glucose concentration (r=-0.55) in the pleural fluid. Conclusion : The serum VEGF levels were higher in the lung cancer patients. The VEGF levels were more elevated in the malignant pleural effusion than in the tuberculous effusion. In addition, the VEGF levels in the pleural fluid were several times higher than the matched serum values suggesting a local activation and possible etiologic role of VEGF in the formation of malignant effusions. The pleural VEGF levels showed a significant correlation with the numbers of red blood cells, LDH and glucose concentrations in the pleural fluid, which may represent the tumor burden.

• YAKHAK HOEJI
• /
• v.45 no.1
• /
• pp.71-77
• /
• 2001

We recently developed a high efficiency expression vectors pCK, which drives a high level of gene expression in the skeletal muscles of mice. In this study, we investigated the pharmacokinetics and biodistribution of pCK-VEGF expressing human VEGF165 after intravenous or intramuscular administration. The quantity of pCK-VEGF in the tissues of mice was measured by the PCR method which has a detection limit of approximately 1 pg of the exogenously added plasmid. In the case of intravenous administration, the half life of the pCK-VEGF plasmid in the bloodstream was 1.68 min. After intra-muscular administration, the half life of pCK-VEGF plasmid in the bloodstream was 6.78 min. At 90 min post-administration, 30% of the injected pCK-VEGF was found at the site of injection, where it persisted for up to 8 hours. Less than 1.6% of the injected pCK-VEGF plasmid DNA was detected in highly vascularized tissues such as the lung, kidney; and liver at 90 min post-administration, but the plasmid was undetectable at later time points. These results suggested that intramuscularly administrated pCK-VEGF persisted for longer periods of time in muscles than in other tissues and that direct intra-muscular injection of pCK-VEGF might be useful for local therapeutic angiogenesis.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.7
• /
• pp.3089-3097
• /
• 2012

Background and Aims: Vascular endothelial growth factor (VEGF) is a potential prognostic biomarker for patients with resected gastric cancer. However, its role remains controversial. The objective of this study was to conduct a systematic review and meta-analysis of published literature. Methods: Relevant literature was identified using Medline and survival data from published studies were collected following a methodological assessment. Quality assessment of eligible studies and meta-analysis of hazard ratio (HR) were performed to review the correlation of VEGF overexpression with survival and recurrence in patients with gastric cancer. Results: Our meta-analysis included 44 published studies with 4,794 resected patients. VEGF subtype for the prediction of overall survival (OS) included tissue VEGF (HR=2.13, 95% CI 1.71-2.65), circulating VEGF (HR=4.22, 95% CI 2.47-7.18), tissue VEGF-C (HR=2.21, 95% CI 1.58-3.09), tissue VEGF-D (HR=1.73, 95% CI 1.25-2.40). Subgroup analysis showed that HRs of tissue VEGF for OS were, 1.78 (95% CI 0.90-3.51) and 2.31 (95% CI 1.82-2.93) in non-Asians and Asians, respectively. The meta-analysis was also conducted for disease free survival (DFS) and disease specific survival (DSS). Conclusion: Positive expression of tissue VEGF, circulating VEGF, VEGF-C and VEGF-D were all associated with poor prognosis in resected gastric cancer. However, VEGF demonstrated no significant prognostic value for non-Asian populations. Circulating VEGF may be better than tissue VEGF in predicting prognosis.

• Journal of Radiopharmaceuticals and Molecular Probes
• /
• v.4 no.2
• /
• pp.106-114
• /
• 2018

Angiogenesis is the new blood vessel formation process and has known to a fundamental event of tumor growth and metastasis. Especially, vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) are the crucial regulators of angiogenesis in tumor. VEGF-A is one of the VEGF family and binds to endothelial cell specific VEGFR1 and VEGFR2, which are associated with tumor growth and tumor angiogenesis. $VEGF_{121}$ is more tumorigenic isomer of VEGF-A. Targeted VEGF or VEGFR molecular imaging has been widely used to enable diagnosis and monitoring of proliferation and development of angiogenic tumors. Therefore, in this review, we have focused on the radioligands with $VEGF_{121}$ for angiogenesis of tumor.

• YAKHAK HOEJI
• /
• v.45 no.1
• /
• pp.108-115
• /
• 2001

We have recently reported the development of a high efficiency expression vector, pCK, which can drive a high level of gene expression in mouse skeletal muscle. In this study, we tested the therapeutic potential of pCK expressing human VEGF165, pCK-VEGF in the rabbit ischemic hind limb model. To determine the optimal dose of plasmid DNA, various concentrations of pCK-CAT were injected into the muscle of a rabbit hind limb and the levels of CAT activity were determined. It was found that the expression level of the exogenously added gene became stable between 250 and 1,000 $\mu$g. Based on this result, we tested whether intramuscular transfer of 500$\mu$g of pCK-VEGF could actually modulate collateral vessel development in a rabbit ischemic hind limb model. It was found that relative to the control group injected with the pCK lacking the VEGF sequence, single intramuscular doses (500$\mu$g) of pCK-VEGF produced statistically significant augmentation of collateral vessels as determined by the angiographic vessel count, maximal blood flow by Doppler flowmeter and the number of capillaries by histology. These results suggest that a single 500$\mu$g-delivery of pCK-VEGF is potent enough to induce sufficient angiogenic activity and achieve therapeutic benefit on this rabbit model.

• Radiation Oncology Journal
• /
• v.24 no.1
• /
• pp.37-43
• /
• 2006

Purpose: We wanted to determine the clinical characteristics and prognosis according to the VEGF expression in stage II cervical carcinoma patients treated with definitive radiotherapy. Materials and Methods: We enrolled 31 patients who were diagnosed with cervical cancer from 1995 to 2003 at Samsung Medical Center and their paraffin block tissue samples were available for study. The median age of the patients was 65 years. The mean tumor size was 4.1 cm $(range:\;1.2{\sim}8.2cm)$. Seven patients (22.6%) were suspected of having pelvic lymph node metastasis. An external beam irradiation dose of 45-56.4 Gy was administered to the whole pelvis with a 15 MV linear accelerator, and an additional 24 Gy was given to point A by HDR intracavitary brachytherapy. VEGF staining was defined as positive when more than 10% of the tumor cells were stained. The median follow-up duration was 58 months. Results: A positive VEGF expression was observed in 21 patients (67.7%), There was no significant correlation between the VEGF expression and pelvic lymph node metastasis, tumor size and the response of radiotherapy. During follow-up, 7 patients had recurrence. The complete response rate was not significant between the VEGF(-) and VEGF(+) tumors. However, the VEGF(+) tumors showed a significantly higher recurrence rate in comparison with the VEGF(-) tumors (p=0.040), The three year disease-free survival rates were 100% and 66.7%, respectively, for patients with VEGF(-) or VEGF(+) tumor (p=0.047), Conclusion: The VEGF expression was a significant factor for recurrence and disease-free survival. However, the significance of the VEGF expression is still controversial because of the various definitions of VEGF expression and the mismatches of the clinical data in the previous studies.

• Journal of Life Science
• /
• v.23 no.9
• /
• pp.1177-1182
• /
• 2013

Trichinella spiralis (T. spiralis) has been reported to induce angiogenesis and a supply of nutrients and to act as a reliable waste disposal system by induction of the expression of the angiogenic molecule vascular endothelial cell growth factor (VEGF) during nurse cell formation. However, the mechanism underlying the induction of VEGF in nurse cells by T. spiralis has not yet been defined. Some research has pointed to the possibility of hypoxia in nurse cells, but whether hypoxia occurs in infected muscle or nurse cells has not been studied. It is also a matter of debate whether hypoxia induces the expression of VEGF and subsequent angiogenesis in infected muscle. Recent studies showed that thymosin ${\beta}4$, a potent VEGF-inducing protein, was expressed at a very early stage of muscle infection by T. spiralis, suggesting that VEGF is induced at an early stage in nurse cells. Furthermore, hypoxia was not detected in any nurse cell stage but was detected in inflammatory cells. The findings suggest that induction of angiogenesis by VEGF in T. spiralis-infected nurse cells is mediated by thymosin ${\beta}4$ and unrelated to hypoxia.