• Journal of Microbiology and Biotechnology
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• 제11권4호
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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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• 제21권4호
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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.

• 대한방사성의약품학회지
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• 제4권2호
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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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• 제1권1호
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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.

• 생명과학회지
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• 제34권2호
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• pp.128-137
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• 2024

이 리뷰 논문에서는 혈관 투과성, 내피세포 모집, 종양관련 혈관 및 림프관의 유지 등에서 핵심적인 과정인 angiogenesis와 lymphangiogenesis에 있어서 vascular endothelial growth factors (VEGF)가 이행하는 중요한 역할에 대해 재조명하고자 한다. VEGF는 tyrosine-kinase receptor인 VEGFR-1, VEGFR-2, VEGFR-3를 통해 그 역할을 이행하며, 이러한 VEGF-VEGFR 시스템은 암에서뿐만 아니라 비정상적인 혈관 및 림프관 형성으로 인해 야기되는 다른 질병들에 있어서도 핵심적인 요소로 각광받고 있다. 암의 측면에서 보았을 때, VEGF와 그 수용체는 종양관련 혈관 및 림프관을 형성하는 과정에서 필수적이라는 점에서 치료적인 타겟으로 이목을 끌고 있다. 때문에 암세포의 성장을 방해하기 위한 항VEGF 항체, 수용체 길항체, 수용체 기능 억제제 등과 같은 여러 가지 시도들이 있었지만, 아직까지 그 임상효과가 불확실하며 더 많은 연구들이 필요한 실정이다. 이 논문에서는 VEGF의 생리적 역할을 VEGF-A, VEGF-B, VEGF-C, VEGF-D, PLGF에 따라 나누어 설명하면서 VEGF/VEGFR 시스템의 중요성을 강조한다. VEGFR-1과 VEGFR-3은 각각 angiogenesis와 lymphangiogenesis에 핵심적인 인자이며, VEGFR-2의 경우 두 가지 모두를 일으킨다. 전반적으로 이 리뷰는 현재까지 밝혀진 암을 포함한 다양한 질병에서의 VEGF와 VEGFR의 역할에 대해 상세히 설명하고자 하였다. 이를 통해 치료 표적으로서 VEGF와 VEGFR의 활용이 더욱 촉진될 것으로 기대된다.

• Journal of Microbiology and Biotechnology
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• 제18권1호
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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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• 제31권1호
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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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• 제19권1호
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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.

• 대한한의학방제학회지
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• 제11권2호
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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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• 제17권12호
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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.