• Title, Summary, Keyword: angiogenesis

Search Result 850, Processing Time 0.063 seconds

Vascular endothelial growth factor-dependent and -independent regulation of angiogenesis

  • Shibuya, Masabumi
    • BMB Reports
    • /
    • v.41 no.4
    • /
    • pp.278-286
    • /
    • 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.

Molecular Nuclear imaging of Angiogenesis (혈관신생 분자핵의학 영상)

  • Lee, Kyung-Han
    • The Korean Journal of Nuclear Medicine
    • /
    • v.38 no.2
    • /
    • pp.171-174
    • /
    • 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.

The hepatocyte growth factor/c-Met signaling pathway as a therapeutic target to inhibit angiogenesis

  • You, Weon-Kyoo;McDonald, Donald M.
    • BMB Reports
    • /
    • v.41 no.12
    • /
    • pp.833-839
    • /
    • 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.

Novel Anti-Angiogenic Activity in Rubus coreanus Miquel Water Extract Suppresses VEGF-Induced Angiogenesis

  • Kim, Eok-Cheon;Kim, Hye Jin;Kim, Tack-Joong
    • Biomedical Science Letters
    • /
    • v.20 no.4
    • /
    • pp.209-220
    • /
    • 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.

Numerical Research about Asymmetric Growth of Cancer, Angiogenesis and Hemodynamics (암의 비대칭적 성장, 혈관생성 및 혈류역학에 대한 수치적 연구)

  • Kim, Y.S.;Shim, E.B.
    • Proceedings of the KSME Conference
    • /
    • /
    • pp.2951-2954
    • /
    • 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.

  • PDF

Computational analysis of cancer angiogenesis using two dimensional model (2차원 모델을 이용한 암의 혈관생성에 대한 수치적 연구)

  • Shim Eun Bo;Ko Hyung Jong;Deisboeck Thomas
    • Proceedings of the KSME Conference
    • /
    • /
    • pp.709-710
    • /
    • 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.

  • PDF

Hypoxia-induced Angiogenesis during Carcinogenesis

  • Choe, Gyu-Sil;Bae, Mun-Gyeong;Jeong, Ju-Won;Mun, Hyo-Eun;Kim, Gyu-Won
    • BMB Reports
    • /
    • v.36 no.1
    • /
    • pp.120-127
    • /
    • 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.

Antiangiogenic and Antitumor Activities of the Cryptic Fragments with Kringle Architecture

  • Joe, Young-Ae;Kim, Myung-Rae;Shim, Byoung-Shik;Oh, Dae-Shik;Hong, Sung-Hee;Hong, Yong-Kil
    • Biomolecules & Therapeutics
    • /
    • v.11 no.4
    • /
    • pp.205-213
    • /
    • 2003
  • Various angiogenesis inhibitors target vascular endothelial cells and block tumor angiogenesis. Angiostatin is a specific endogenous angiogenesis inhibitor in clinical trials, which contains only the first four triple loop structures, known as kringle domains. Its generated by proteolytic cleavage of its parent molecule plasminogen, which itself does not exhibit antiangiogenic activity. Kringle domains from prothrombin, apolipoprotein, hepatocyte growth factor, urokinase and tissue-type plasminogen activator also elicit anti-angiogenic or antitumor activities in several model systems, albeit low amino acid sequence identity between angiostatin and each individual kringle. However, the differential effects of each kringle domain on endothelial cell proliferation, and migration observed in these kringle domains, suggest that the amino acid sequence of the primary structure is still important although kringle architecture is essential for anti-mlgiogenic activity. If it is further studied as to how amino acid sequence and kringle architecture contributes in anti-angiogenic activity, with studies on underlying mechanisms of anti-angiogenesis by kringle-based angiogenesis inhibitors, it will provide basis for the development of new potent anti-angiogenesis inhibitors and improvement of the efficacy of angiogenesis inhibitors.

Endothelial miR-26a regulates VEGF-Nogo-B receptor-mediated angiogenesis

  • Jo, Ha-neul;Kang, Hyesoo;Lee, Aram;Choi, Jihea;Chang, Woochul;Lee, Myeong-Sok;Kim, Jongmin
    • BMB Reports
    • /
    • v.50 no.7
    • /
    • pp.384-389
    • /
    • 2017
  • The Nogo-B receptor (NgBR) is necessary for not only Nogo-B-mediated angiogenesis but also vascular endothelial growth factor (VEGF) -induced angiogenesis. However, the molecular mechanisms underlying the regulatory role of the VEGF-NgBR axis in angiogenesis are not fully understood. Here, we report that miR-26a serves as a critical regulator of VEGF-mediated angiogenesis through directly targeting NgBR in endothelial cells (ECs). Stimulation of ECs by VEGF increased the expression of NgBR and decreased the expression of miR-26a. In addition, miR-26a decreased the VEGF-induced migration and proliferation of ECs. Moreover, miR-26a overexpression in ECs decreased the VEGF-induced phosphorylation of the endothelial nitric oxide synthase (eNOS) and the production of nitric oxide, which is important for angiogenesis. Overall, these data suggest that miR-26a plays a key role in VEGF-mediated angiogenesis through the modulation of eNOS activity, which is mediated by its ability to regulate NgBR expression by directly targeting the NgBR 3'-UTR.

Studies on Angiogenesis Inhibition Activity of Traditional Herb Extract (한약재의 신생혈관생성 억제 활성에 관한 연구)

  • Jeon, Won-Kyung;Lee, Tae-Hee;Yoon, Yoo-Sik;Kim, Yeon-Ok;Sung, Hyun-Jea
    • Korean Journal of Oriental Medicine
    • /
    • v.4 no.1
    • /
    • pp.129-138
    • /
    • 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.

  • PDF