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

• Genomics & Informatics
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• v.21 no.4
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• pp.44.1-44.10
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• 2023

Tumor hypoxia, oxygen deprivation state, occurs in most cancers and promotes angiogenesis, enhancing the potential for metastasis. The vascular endothelial growth factor (VEGF) family genes play crucial roles in tumorigenesis by promoting angiogenesis. To investigate the malignant processes triggered by hypoxia-induced angiogenesis across pan-cancers, we comprehensively analyzed the relationships between the expression of VEGF family genes and hypoxic microenvironment based on integrated bioinformatics methods. Our results suggest that the expression of VEGF family genes differs significantly among various cancers, highlighting their heterogeneity effect on human cancers. Across the 33 cancers, VEGFB and VEGFD showed the highest and lowest expression levels, respectively. The survival analysis showed that VEGFA and placental growth factor (PGF) were correlated with poor prognosis in many cancers, including kidney renal cell and liver hepatocellular carcinoma. VEGFC expression was positively correlated with glioma and stomach cancer. VEGFA and PGF showed distinct positive correlations with hypoxia scores in most cancers, indicating a potential correlation with tumor aggressiveness. The expression of miRNAs targeting VEGF family genes, including hsa-miR-130b-5p and hsa-miR-940, was positively correlated with hypoxia. In immune subtypes analysis, VEGFC was highly expressed in C3 (inflammatory) and C6 (transforming growth factor β dominant) across various cancers, indicating its potential role as a tumor promotor. VEGFC expression exhibited positive correlations with immune infiltration scores, suggesting low tumor purity. High expression of VEGFA and VEGFC showed favorable responses to various drugs, including BLU-667, which abrogates RET signaling, an oncogenic driver in liver and thyroid cancers. Our findings suggest potential roles of VEGF family genes in malignant processes related with hypoxia-induced angiogenesis.

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

• Journal of Gastric Cancer
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• v.1 no.1
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• pp.10-16
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• 2001

Purpose: The p53 protein is a tumor supressor gene, and its mutation is associated with biologic aggressiveness. CD44v6, one of the CD44 family, is a cell surface glycoprotein that plays a role in cancer invasion and metastasis. Vascular endothelial growth factor (VEGF) is another recently identified growth factor with significant angiogenic properties. The purpose of this study was to investigate p53, CD44v6, and VEGF expressions to determine whether degree of expression was related to pathological parameters such as Lauren's classification, depth of invasion, and lymph node metastasis. Materials and Methods: Immunohistochemical stains of p53, CD44v6, and VEGF in formalin-fixed paraffin-embedded tissue sections of 125 gastric adenocarcinomas were done. Results: The overall expression rates of p53, CD44v6, and VEGF were $54.4\%$ (68/125), $36.8\%$ (46/125), and $48.0\%$ (60/125), respectively. The p53, not CD44v6 and VEGF was higher in intestinal-type gastric carcinomas by Lauren's classification. The expressions of p53, CD44v6, and VEGF were statistically correlated with depth of tumor invasion. The expression of CD44v6 was higher in the lymph node metastatic group than in the negative group. The p53 expression was significantly associated with VEGF expression. Conclusions: These data suggest that the expressions of p53, CD44v6, and VEGF are biologically related to malignancy. The p53 and CD44v6 expressions are independent; however, p53 gene mutation is one of the contributing factors to VEGF expression in gastric adenocarcinoma.

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

• Journal of Microbiology and Biotechnology
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• v.18 no.1
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• pp.183-187
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• 2008

Vascular endothelial growth factors (VEGFs) are a family of proteins that mediate angiogenesis. $VEGF_{165}$ is a VEGF-A isoform and has been extensively studied owing to its potential use in therapeutic angiogenesis. This study established Chinese hamster ovary (CHO) cells overexpressing recombinant human $VEGF_{165}$ $(rhVEGF_{165})$ protein. The production rate of the established CHO cells was over 80mg/l of $rhVEGF_{165}$ protein from a 7-day batch culture process using a 7.5-l bioreactor with a 5-l working volume and serum-free medium. The $rhVEGF_{165}$ protein was purified to homogeneity from the culture supernatant using a two-step chromatographic procedure that resulted in a 48% recovery rate. The purified $rhVEGF_{165}$ protein was a glycosylated homodimeric protein with a higher molecular weight (MW) than the protein expressed from insect cells, suggesting that the glycosylation of the $rhVEGF_{165}$ protein in CHO cells differed from that in insect cells. The purified $rhVEGF_{165}$ protein in this study was functionally active with a half-maximal effective concentration of 3.8ng/ml and specific activity of $2.5{\times}10^5U/mg$.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.31 no.1
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• pp.27-34
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• 2009

Angiogenesis is essential for solid tumor growth and progression. Among the pro-angiogenetic factors, vascular endothelial growth factor(VEGF), also known as vascular permeability factor, is the most important as a mitogen for vascular endothelium. The VEGF family of molecules currently consists of six growth factors, VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, and placenta growth factor(PlGF). Over-expression of PlGF is associated with angiogenesis under pathological conditions such as ischemia, inflammation, and cancer. Hence, the goal of this study is to identify the correlation of clinicopathlogical factors and the up-regulation of PlGF expression in oral squamous cell carcinoma. We studied the immunohistochemical staining of PlGF, PlGF gene expression and a real time quantitative RT-PCR in 20 specimens of 20 patients with oral squamous cell carcinoma. The results were as follows. 1. In the immunohistochemical study of poorly differentiated and invasive oral squamous cell carcinoma, the high level staining of PlGF was observed. And the correlation between immunohistopathological PlGF expression and histological differentiation of specimens was significant (Pearson correlation analysis, significance [r] >0.6, P < .05). 2. In the PlGF gene RT-PCR analysis, PlGF expression was more in tumor tissue than in adjacent normal tissue. Paired-samples analysis determined the difference of PlGF mRNA expression level between the cancer tissue and the normal tissue (Student's t - test, P < .05) These findings suggest that up-regulation of the PlGF gene may play a role in progression and local metastasis in invasive oral squamous cell carcinoma.

• Genomics & Informatics
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• v.19 no.1
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• pp.6.1-6.10
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• 2021

Vascular endothelial growth factor (VEGF) is expressed at elevated levels by most cancer cells, which can stimulate vascular endothelial cell growth, survival, proliferation as well as trigger angiogenesis modulated by VEGF and VEGFR (a tyrosine kinase receptor) signaling. The angiogenic effects of the VEGF family are thought to be primarily mediated through the interaction of VEGF with VEGFR-2. Targeting this signaling molecule and its receptor is a novel approach for blocking angiogenesis. In recent years virtual high throughput screening has emerged as a widely accepted powerful technique in the identification of novel and diverse leads. The high resolution X-ray structure of VEGF has paved the way to introduce new small molecular inhibitors by structure-based virtual screening. In this study using different alkaloid molecules as potential novel inhibitors of VEGF, we proposed three alkaloid candidates for inhibiting VEGF and VEGFR mediated angiogenesis. As these three alkaloid compounds exhibited high scoring functions, which also highlights their high binding ability, it is evident that these alkaloids can be taken to further drug development pipelines for use as novel lead compounds to design new and effective drugs against cancer.

• Herbal Formula Science
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• v.11 no.2
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• pp.173-184
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• 2003

Objectives: This study investigates the effects of Salviae miltiorrhizae Radix, Carthami Flos on Brain ischemia of the rats induced from the Occlusion of Lt. Common Carotid Artery. Methods: I observed effects using light microscopes and examined tissue of parietal lobe and hippocampus and VEGF-immunoreactive cells. Results: A small number of VEGF-immunoreactive cells are observed in the control group. VEGF-immunoreactive cells in Salviae miltiorrhizae Radix-administered group were slightly increased compared with control group. VEGF-immunoreactive cells in Carthami Flos-administered group were significantly increased compared with control group. Neurons of parietal lobe and pyramidal cells of hippocampus in the control group were greatly damaged.(neuronal densitity, form of dendrite and axon) On the other hand, neurons of parietal lobe and pyramidal cells of hippocampus in Salviae miltiorrhizae Radix-administered group were less damaged. Neurons of parietal lobe and pyramidal cells of hippocampus in Carthami Flos-administered group were significantly less damaged compared with control group. Conclusion : Salviae miltiorrhizae Radix, Carthami Flos can effect on stimulating angiogenesis and reducinging the damage of neurons in the rats induced from the Occlusion of Lt. Common Carotid Artery.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5303-5307
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• 2016

Objective: Brain tumors cause great mortality and morbidity worldwide, and success rates with surgical treatment remain very low. Several recent studies have focused on introduction of novel effective medical therapeutic approaches. Genistein is a member of the isoflavonoid family which has proved to exert anticancer effects. Here we assessed the effects of genistein on the expression of MMP-2 and VEGF in low and high grade gliomas in vitro. Materials and Methods: High and low grade glioma tumor tissue samples were obtained from a total of 16 patients, washed with PBS, cut into small pieces, digested with collagenase type I and cultured in DMEM containing 10% FBS. When cells reached passage 3, they were exposed to genistein and MMP-2 and VEGF gene transcripts were determined by quantitative real time PCR (qRT-PCR). Results: Expression of MMP-2 demonstrated 580-fold reduction in expression in low grade glioma cells post treatment with genistein compared to untreated cells (P value= 0.05). In cells derived from high grade lesions, expression of MMP-2 was 2-fold lower than in controls (P value> 0.05). Genistein caused a 4.7-fold reduction in VEGF transcript in high grade glioma cells (P value> 0.05) but no effects were evident in low grade glioma cells. Conclusion. Based on the data of the present study, low grade glioma cells appear much more sensitive to genistein and this isoflavone might offer an appropriate therapeutic intervention in these patients. Further investigation of this possibility is clearly warranted.