• Clinical and Experimental Reproductive Medicine
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• v.34 no.1
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• pp.33-39
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• 2007

Objective: The objective of this study was to investigate whether serum levels of vascular endothelial growth factor (VEGF) measured at ovulation triggering day reflect ovarian response in intrauterine insemination (IUI) cycles. Methods: Forty-nine fertile women who undergoing superovulation and IUI were included. Superovulation was performed using clomiphene citrate (100 mg/d on day 3$\sim$7) in combination with human menopausal gonadotropin (150 IU every other day starting on day 5). Serum samples were obtained on the day of hCG administration and the levels of VEGF-A and estradiol were measured. The numbers of mature follicle $\geq$17 mm in diameter were also counted. Results: Serum VEGF-A levels did not correlate with the numbers of mature follicle count nor serum estradiol levels. Serum estradiol level was positively associated with mature follicle count. Serum VEGF-A levels tended to be lower in women with mature follicle count less than three or women with more than five. Conclusion: Our results indicate that serum VEGF-A levels do not have an association with superovulation outcome in IUI cycles. However, a tendency of lower VEGF-A level in poor and high responder suggests that those with extreme response to superovulation may be related with abnormal angiogenesis. Further studies should be warranted in larger populations.

• Genomics & Informatics
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• v.2 no.1
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• pp.36-44
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• 2004

Astrocytes play supportive roles for neurons in the brain. Recently, they have been accepted to have various functions in the vascular system as well as in the nervous system. We investigated the differential gene expression in rat astrocytes according to the oxygen tension, which is a crucial factor for angiogenesis. A cDNA microarray was performed to find the genes whose expression was sensitive to oxygen tension. We found 26 genes in the astrocyte were found and classified into 4 groups. In order to show the genes' relevancy to angiogenesis, seven of the 26 genes were investigated to see whether they have capabilities of interaction with angiogenesis­related factors in AngioDB. Through this investigation, we found interactions of three proteins with angiogenesis-related factors. These genes were further investigated with a new focus on the vascular endothelial growth factor (VEGF) expression in an astrocyte based on our hypothesis that astrocytes can have effects on endothelial angiogenesis via the release of VEGF. Collectively, we identified several genes whose expressions were dependent on the oxygen concentration of the astrocyte. Furthermore, the relevancy of astrocytes to angiogenesis was investigated using preexisting information of AngioDB, and suggested a possible signaling pathway for VEGF expression in the aspects of brain endothelial angiogenesis by astrocytes.

• Journal of Acupuncture Research
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• v.24 no.5
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• pp.23-32
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• 2007

Objectives : Angiogenesis consists of the proliferation, migration, and differentiation of endothelial cells, and angiogenic factors and matrix protein interactions modulate this process. The aim of this study was to determine whether herbs medicine(KHBJs) could induce angiogenic activity in human umbilical vein endothelial cells(HUVECs). Methods : The angiogenic activity of KHBJs were evaluated by proliferation using BrdU assay, chemotactic migration assay, tube formation assay, and measurement of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor(VEGF) in HUVECs. Also, In order to identify enhance angiogenic activity by activity guided fractionation, the angiogenic activity of fractions of KHBJs such as KHBJB or KHBJR were evaluated in vitro and in vivo Matrigel plug angiogenesis asaay. Results : About 9 KHBJs significantly increased HUVECs proliferation in a dose-dependent manner. In addition, 9 herbs medicine(KHBJs) increased migration and tube-like formation in HUVECs. Interestingly the expression of bFGF and VEGF, an angiogenesis-inducing growth factor, were dose-dependently increased by KHBJs. However, angiogenic activity of fractionated KHBJs(KHBJB or KHBJR) not enhanced more than KHBJs in HUVECs and Matrigel plug in vivo angiogenesis assay. Conclusions : 9 KHBJs significantly induces angiogenesis in in vitro and in vivo. These results suggest that 9 KHBJs potent angiogenic agents and promising drug for the induction of neovascularization.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.257-263
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• 2014

Background: Vascular endothelial growth factor (VEGF), an endothelial cell specific mitogen, has been implicated as a critical factor influencing tumor related angiogenesis. The aim of present study was to evaluate the relationship between VEGF +936C>T and +405C>G polymorphisms of VEGF with risk of breast cancer in Punjab, India. Materials and Methods: We screened DNA samples of 192 sporadic breast cancer patients and 192 unrelated healthy, gender and age matched control individuals for VEGF +936C>T and +405C>G polymorphisms using the PCR-RFLP method. Results: For the VEGF +405C>G polymorphism, we observed significantly increased frequency of GG genotype in cases as compared to controls and strong association of +405GG genotype was observed with three fold risk for breast cancer (OR=3.07; 95%CI 1.41-6.65; p=0.003). For the +936C>T polymorphism, significant associations of CT and combined CT+TT genotypes were observed with elevated risk of breast cancer (p=0.021; 0.023). The combined genotype combinations of GG-CC and GG-CT of +405C>G and +936C>T polymorphisms were found to be significantly associated with increased risk of breast cancer (p=0.04; 0.0064). Conclusions: The findings of the present study indicated significant associations of VEGF +936C>T and +405C>G polymorphisms with increased breast cancer risk in patients from Punjab, North India.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.39
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• pp.8.1-8.8
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• 2017

Background: For an effective bone graft for reconstruction of the maxillofacial region, an adequate vascular network will be required to supply blood, osteoprogenitor cells, and growth factors. We previously reported that the secretomes of bone marrow-derived mesenchymal stem cells (MSC-CM) contain numerous growth factors such as insulin-like growth factor (IGF)-1, transforming growth factor $(TGF)-{\beta}1$, and vascular endothelial growth factor (VEGF), which can affect the cellular characteristics and behavior of regenerating bone cells. We hypothesized that angiogenesis is an important step for bone regeneration, and VEGF is one of the crucial factors in MSC-CM that would enhance its osteogenic potential. In the present study, we focused on VEGF in MSC-CM and evaluated the angiogenic and osteogenic potentials of MSC-CM for bone regeneration. Methods: Cytokines in MSC-CM were measured by enzyme-linked immunosorbent assay (ELISA). Human umbilical vein endothelial cells (HUVECs) were cultured with MSC-CM or MSC-CM with anti-VEGF antibody (MSC-CM + anti-VEGF) for neutralization, and tube formation was evaluated. For the evaluation of bone and blood vessel formation with micro-computed tomography (micro-CT) and for the histological and immunohistochemical analyses, a rat calvarial bone defect model was used. Results: The concentrations of IGF-1, VEGF, and $TGF-{\beta}1$ in MSC-CM were $1515.6{\pm}211.8pg/mL$, $465.8{\pm}108.8pg/mL$, and $339.8{\pm}14.4pg/mL$, respectively. Tube formation of HUVECs, bone formation, and blood vessel formation were increased in the MSC-CM group but decreased in the MSC-CM + anti-VEGF group. Histological findings suggested that new bone formation in the entire defect was observed in the MSC-CM group although it was decreased in the MSC-CM + anti-VEGF group. Immunohistochemistry indicated that angiogenesis and migration of endogenous stem cells were much more abundant in the MSC-CM group than in the MSC-CM + anti-VEGF group. Conclusions: VEGF is considered a crucial factor in MSC-CM, and MSC-CM is proposed to be an adequate therapeutic agent for bone regeneration with angiogenesis.

• IMMUNE NETWORK
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• v.24 no.1
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• pp.10.1-10.17
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• 2024

In this review, we will explore the intricate roles of cytokines and vascular endothelial growth factors in autoimmune diseases (ADs), with a particular focus on rheumatoid arthritis (RA) and multiple sclerosis (MS). AD is characterized by self-destructive immune responses due to auto-reactive T lymphocytes and Abs. Among various types of ADs, RA and MS possess inflammation as a central role but in different sites of the patients. Other common aspects among these two ADs are their chronicity and relapsing-remitting symptoms requiring continuous management. First factor inducing these ADs are cytokines, such as IL-6, TNF-α, and IL-17, which play significant roles in the pathogenesis by contributing to inflammation, immune cell activation, and tissue damage. Secondly, vascular endothelial growth factors, including VEGF and angiopoietins, are crucial in promoting angiogenesis and inflammation in these two ADs. Finally, placental growth factor (PlGF), an emerging factor with bi-directional roles in angiogenesis and T cell differentiation, as we introduce as an "angio-lymphokine" is another key factor in ADs. Thus, while angiogenesis recruits more inflammatory cells into the peripheral sites, cytokines secreted by effector cells play critical roles in the pathogenesis of ADs. Various therapeutic interventions targeting these soluble molecules have shown promise in managing autoimmune pathogenic conditions. However, delicate interplay between cytokines, angiogenic factors, and PlGF has more to be studied when considering their complementary role in actual pathogenic conditions. Understanding the complex interactions among these factors provides valuable insights for the development of innovative therapies for RA and MS, offering hope for improved patient outcomes.

• Biomedical Science Letters
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• v.20 no.4
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• pp.209-220
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• 2014

Vascular endothelial growth factor (VEGF) is a key factor involved in the induction of angiogenesis and has become an attractive target for anti-angiogenesis therapies. The purpose of this study was to elucidate the anti-angiogenic activity of Rubus coreanus Miquel water extract (RCME). Rubus coreanus Miquel has long been employed as a traditional medicine, and recent studies have demonstrated that it has measureable biological activities. Thus, we investigated for the first time the effect of RCME on angiogenesis and its underlying signaling pathways. The effects of RCME were tested on in vitro models of angiogenesis, namely, proliferation, migration, invasion and tube formation of human umbilical vein endothelial cells as well as an ex vivo model of vessel sprouting from the rat aorta in response to VEGF. We observed that VEGF-induced angiogenesis was strongly suppressed by RCME treatment compared to that of the control group. Moreover, we found that RCME inhibited VEGF-induced activation of matrix metalloproteinases and phosphorylation of extracellular signal-regulated kinase and p38, and also effectively inhibited phosphorylation of VEGF receptor 2. These results indicated that RCME inhibits angiogenesis by suppressing phosphorylation of the VEGF receptor and may be useful for the treatment of angiogenesis-dependent diseases such as cancer and diabetic retinopathy.

• Biomolecules & Therapeutics
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• v.22 no.1
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• pp.1-9
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• 2014

Vascular endothelial growth factor (VEGF)-VEGF receptor (VEGFR) system has been shown to play central roles not only in physiological angiogenesis, but also in pathological angiogenesis in diseases such as cancer. Based on these findings, a variety of anti-angiogenic drugs, including anti-VEGF antibodies and VEGFR/multi-receptor kinase inhibitors have been developed and approved for the clinical use. While the clinical efficacy of these drugs has been clearly demonstrated in cancer patients, they have not been shown to be effective in curing cancer, suggesting that further improvement in their design is necessary. Abnormal expression of an endogenous VEGF-inhibitor sFlt-1 has been shown to be involved in a variety of diseases, such as preeclampsia and aged macular degeneration. In addition, various factors modulating angiogenic processes have been recently isolated. Given this complexity then, extensive studies on the interrelationship between VEGF signals and other angiogenesis-regulatory systems will be important for developing future strategies to suppress diseases with an angiogenic component.

• Journal of Gastric Cancer
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• v.17 no.1
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• pp.1-10
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• 2017

Gastric cancer (GC) has high mortality owing to its aggressive nature. Tumor angiogenesis plays an essential role in the growth, invasion, and metastatic spread of GC. The aim of this work was to review the angiogenic biomarkers related to the behavior of GC, documented in the literature. A search of the PubMed database was conducted with the MeSH terms: "Stomach neoplasms/blood [MeSH] or stomach neoplasms/blood supply [MeSH] and angiogenic proteins/blood [Major]". A total of 30 articles were initially collected, and 4 were subsequently excluded. Among the 26 articles collected, 16 examined the role of vascular endothelial growth factor (VEGF), 4 studied endostatin, 3 investigated angiopoietin (Ang)-2, 2 studied the Ang-like protein 2 (ANGTPL2), and 1 each examined interleukin (IL)-12, IL-8, and hypoxia inducible factor. Regarding VEGF, 6 articles concluded that the protein was related to lymph node metastasis or distant metastases. Five articles concluded that VEGF levels were elevated in the presence of GC and decreased following tumor regression, suggesting that VEGF levels could be a predictor of recurrence. Four articles concluded that high VEGF levels were correlated with poor prognosis and lower survival rates. Ang-2 and ANGTPL2 were elevated in GC and associated with more aggressive disease. Endostatin was associated with intestinal GC. VEGF is the most extensively studied angiogenic factor. It is associated with the presence of neoplastic disease and lymph node metastasis. It appears to be a good biomarker for disease progression and remission, but not for diagnosis. The data regarding other biomarkers are inconclusive.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2491-2494
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• 2014

Objective: To explore the mechanism and significance of tumor angiogenesis by observing changes of microvessel density (MVD) and expression of vascular endothelial growth factor (VEGF) in residual tumor tissues after cryoablation. Materials and Methods: A total of 18 nude mice xenograft models with transplanted lung adenocarcinoma cell line A549 were established and randomly divided into 3 groups when the maximum diameter of tumor reached 1 cm: control, cisplatin (DDP) and cryoablation. The nude mice were sacrificed after 21-d cryoablation to obtain the tumor tissues. Then immunohistochemistry was applied to determine MVD and the expression of VEGF in tumor tissues. Results: The tumor volumes of control group, DDP group and cryoablation group were $1.48{\pm}0.14cm^3$, $1.03{\pm}0.12cm^3$ and $0.99{\pm}0.06cm^3$ respectively and the differences were significant (P<0.01), whereas MVD values were $21.1{\pm}0.86$, $24.7{\pm}0.72$ and $29.2{\pm}0.96$ (P<0.01) and the positive expression rates of VEGF were $36.2{\pm}1.72%$, $39.0{\pm}1.79%$ and $50.8{\pm}2.14%$ (P<0.01), respectively, showing that MVD was proportional to the positive expression of VEGF (r=0.928, P<0.01). Conclusions: Cryoablation can effectively inhibit tumor growth, but tumor angiogenesis significantly increases in residual tumors, with high expression of VEGF playing an important role in the residual tumor angiogenesis.