• BMB Reports
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• v.41 no.4
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• pp.278-286
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• 2008

Angiogenesis, the formation of blood vessels, is essential for preparing a closed circulatory system in the body, and for supplying oxygen and nutrition to tissues. Major diseases such as cancer, rheumatoid arthritis, and atherosclerosis include pathological angiogenesis in their malignant processes, suggesting anti-angiogenic therapy to be a new strategy for suppression of diseases. However, until the 1970s, the molecular basis of angiogenesis was largely unknown. In recent decades, extensive studies have revealed a variety of angiogenic factors and their receptors, including vascular endothelial growth factor (VEGF)-VEGFRs, Angiopoietin-Tie, Ephrin-EphRs and Delta-Notch to be the major regulators of angiogenesis in vertebrates. VEGF and its receptors play a central role in physiological as well as pathological angiogenesis, and functional inhibitors of VEGF and VEGFRs such as anti-VEGF neutralizing antibody and small molecules that block the tyrosine kinase activity of VEGFRs have recently been approved for use to treat patients with colorectal, lung, renal and liver cancers. These drugs have opened a novel field of cancer therapy, i.e. anti-angiogenesis therapy. However, as yet they cannot completely cure patients, and cancer cells could become resistant to these drugs. Thus, it is important to understand further the molecular mechanisms underlying not only VEGF-VEGFR signaling but also the VEGF-independent regulation of angiogenesis, and to learn how to improve anti-angiogenesis therapy.

• The Korean Journal of Nuclear Medicine
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• v.38 no.2
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• pp.171-174
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• 2004

Angiogenesis, the formation of new capillaries from existing vessels, increases oxygenation and nutrient supply to ischemic tissue and allows tumor growth and metastasis. As such, angiogenesis targeting provides a novel approach for cancer treatment with easier drug delivery and less drug resistance. Therapeutic anti-angiogenesis has shown impressive effects in animal tumor models and are now entering clinical trials. However, the successful clinical introduction of this new therapeutic approach requires diagnostic tools that can reliably measure angiogenesis in a noninvasive and repetitive manner. Molecular imaging is emerging as an exciting new discipline that deals with imaging of disease on a cellular or genetic level. Angiogenesis imaging is an important area for molecular imaging research, and the use of radiotracers offers a particularly promising technique for its development. While current perfusion and metabolism radiotracers can provide useful information related to tissue vascularity, recent endeavors are focused on the development of novel radioprobes that specifically and directly target angiogenic vessels. Presently available proges include RGD sequence containing peptides that target ${\alpha}_v\;{\beta}_3$ integrin, endothelial growth factors such as VEGF or FGF, metalloptoteinase inhibitors, and specific antiangiogenic drugs. It is now clear that nuclear medicine techniques have a remarkable potential for angiogenesis imaging, and efforts are currently continuing to develop new radioprobes with superior imaging properties. With future identification of novel targets, design of better probes, and improvements in instrumentation, radiotracer angiogenesis imaging promises to play an increasingly important role in the diagnostic evaluation and treatment of cancer and other angiogenesis related diseases.

• BMB Reports
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• v.41 no.12
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• pp.833-839
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• 2008

Angiogenesis in tumors is driven by multiple growth factors that activate receptor tyrosine kinases. An important driving force of angiogenesis in solid tumors is signaling through vascular endothelial growth factor (VEGF) and its receptors (VEGFRs). Angiogenesis inhibitors that target this signaling pathway are now in widespread use for the treatment of cancer. However, when used alone, inhibitors of VEGF/VEGFR signaling do not destroy all blood vessels in tumors and do not slow the growth of most human cancers. VEGF/VEGFR signaling inhibitors are, therefore, used in combination with chemotherapeutic agents or radiation therapy. Additional targets for inhibiting angiogenesis would be useful for more efficacious treatment of cancer. One promising target is the signaling pathway of hepatocyte growth factor (HGF) and its receptor (HGFR, also known as c-Met), which plays important roles in angiogenesis and tumor growth. Inhibitors of this signaling pathway have been shown to inhibit angiogenesis in multiple in vitro and in vivo models. The HGF/c-Met signaling pathway is now recognized as a promising target in cancer by inhibiting angiogenesis, tumor growth, invasion, and metastasis.

• Proceedings of the KSME Conference
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• 2007.05b
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• pp.2951-2954
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• 2007

Tumor hemodynamics in vascular state is numerically simulated using pressure node solution. The tumor angiogenesis pattern in our previous study is used for the geometry of vessel networks. For tumor angiogenesis, the equation that governed angiogenesis comprises a tumor angiogenesis factor (TAF) conservation equation in time and space, which is solved numerically using the Galerkin finite element method. A stochastic process model is used to simulate vessel formation and vessel. In this study, we use a two-dimensional model with planar vessel structure. Hemodynamics in vessel is assumed as incompressible steady flow with Newtonian fluid properties. In parent vessel, arterial pressure is assigned as a boundary condition whereas a constant terminal pressure is specified in tumor inside. Kirchhoff's law is applied to each pressure node to simulate the pressure distribution in vessel networks. Transient pressure distribution along with angiogenesis pattern is presented to investigate the effect of tumor growth in tumor hemodynamics.

• Proceedings of the KSME Conference
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• 2002.08a
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• pp.709-710
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• 2002

Cancer angiogenesis is simulated using a two dimensional model. Governing equation of angiogenesis is a TAE (Tumor angiogenesis factor) conservation equation in time and space. A stochastic process model is utilized to simulate vessel formation, proliferation, and migration to a cancer pellet. Numerical results are presented especially in case of growing cancer.

• BMB Reports
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• v.36 no.1
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• pp.120-127
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• 2003

The formation of new blood vessels, angiogenesis, is an essential process during development and disease. Angiogenesis is well known as a crucial step in tumor growth and progression. Angiogenesis is induced by hypoxic conditions and regulated by the hypoxia-inducible factor 1 (HIF-1). The expression of HIF-1 correlates with hypoxia-induced angiogenesis as a result of the induction of the major HIF-1 target gene, vascular endothelial cell growth factor (VEGF). In this review, a brief overview of the mechanism of angiogenesis is discussed, focusing on the regulatory processes of the HIF-1 transcription factor. HIF-1 consists of a constitutively expressed HIF-1 beta(HIF-1β) subunit and an oxygen-regulated HIF-1 alpha(HIF-1α) subunit. The stability and activity of HIF-1α are regulated by the interaction with various proteins, such as pVHL, p53, and p300/CBP as well as by post-translational modifications, hydroxylation, acetylation, and phosphorylation. It was recently reported that HIF-1α binds a co-activator of the AP-1 transciption factor, Jab-1, which inhibits the p53-dependent degradation of HIF-1 and enhances the transcriptional activity of HIF-1 and the subsequent VEGF expression under hypoxic conditions. ARD1 acetylates HIF-1α and stimulates pVHL-mediated ubiquitination of HIF-1α. With a growing knowledge of the molecular mechanisms in this field, novel strategies to prevent tumor angiogenesis can be developed, and form these, new anticancer therapies may arise.

• Korean Journal of Oriental Medicine
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• v.4 no.1 s.4
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• pp.129-138
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• 1998

Angiogenesis, the formation of new blood vessels, is considered to be involved in many pathological symptoms such as diabetic retinopathy, arthritis, inflammation and solid tumour. In particular, it is thought that angiogenesis is critical for development and growth of solid tumour. Recent study shows that there is a highly significant association of microvessel density with overall survival and relapse-free survival in patients with breast tumour In this study, the inhibition effect of angiogenesis of traditional herbs used for the treatment of cancer was examined. It was found out that the extract of Agaricus blazei by boiling water is a possible inhibitor of angiogenesis. It inhibited normal developmental angiogenesis In the chorioallantoic membrane of chick embryos and also inhibited capillary-like tube formation by endotherial cells on matrigel in vitro. These results suggest that Agaricus blazei can be a potent angiogenesis inhibitor.

• Biomolecules & Therapeutics
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• v.31 no.4
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• pp.456-465
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• 2023

Cervical tumors represent a prevalent form of cancer affecting women worldwide; current treatment options involve surgery, radiotherapy, and chemotherapy. Angiogenesis, the process of new blood vessel formation, is a crucial factor in cervical tumor growth. The molecular mechanisms underlying the effects of the liver kinase B1 (LKB1/STK11) tumor suppressor protein on tumor angiogenesis have not been elucidated. Therefore, we investigated the role of LKB1 in cervical tumor angiogenesis both in vitro and in vivo in this study. Our results demonstrated that LKB1 inhibited cervical tumor angiogenesis by suppressing the expression of angiogenesis-related factors such as vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1α. LKB1 directly affected both carcinoma and vascular endothelial cells, resulting in a significant reduction in tumor growth and angiogenesis. Furthermore, LKB1 was found to bind to VEGF receptor 2 (VEGFR-2) and target the VEGFR-2-mediated protein kinase B/mechanistic target of rapamycin signaling pathway in endothelial cells, thereby reducing cervical tumor growth and angiogenesis. Our study provides new insights into the molecular mechanisms underlying the anti-tumor and anti-angiogenic effects of LKB1 in cervical cancer. These findings will help develop new therapeutic strategies for cervical cancer.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.1
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• pp.43-51
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• 2011

Natural products in Chonnam, Korea were screened via anti-angiogenesis experiments, and 1 candidate product was identified, Corni fructus, which exerted dose-dependent inhibitory effects against angiogenesis, adipogenesis, and cell adhesion. C. fructus extract (CFE) exhibits an angiogenesis inhibitory effect superior to that of the EGCG from green tea leaves. The expression level of angiogenesis and adipogenesis-related signal molecules in the western blotting was reduced by increasing the amount of added CFE. Moreover, a diet supplemented with CFE was deemed more effective in inducing weight loss in LB mice than a representative synthetic diet drug, orlistat, which incidently caused the side effect of denuding the mice of their hair. These results indicate that C. fructus may prove to be a useful anti-adipogenic compound, and these in vitro results may be reflected later under in vivo conditions.

• Journal of Microbiology and Biotechnology
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• v.18 no.2
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• pp.377-382
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• 2008

Interleukin-2 plays a significant role in T cell proliferation. Here, we report the role of IL-2 in angiogenesis. IL-2 increased the ROS level and phosphorylation of Akt in human umbilical vein endothelial cells (HUVECs). IL-2 increased angiogenesis in an animal model and tube formation in HUVECs. The effect of IL-2 on angiogenesis and tube formation was mediated by ROS and Akt. This is the first report that IL-2 promotes angiogenesis.