Inhibition of angiogenesis in vitro and in vivo: comparison of the relative activities of triflavin, an Arg-Gly-Asp-containing peptide and anti-α vβ 3 integrin monoclonal antibody (original) (raw)
Related papers
2013
Abstract................................................................................ 238 I. General aspects of angiogenesis........................................................... 238 A. Introduction......................................................................... 238 B. Function of endothelial cells in normal physiology....................................... 239 C. Molecular control of angiogenesis...................................................... 239 1. Initiation of the angiogenic response................................................ 239 2. Endothelial cell migration and proliferation.......................................... 240
Anti-angiogenesis and angioprevention: mechanisms, problems and perspectives
Cancer Detection and Prevention, 2003
The recognition that angiogenesis is a key early event in tumor progression and metastasis has led to the development of new strategies for cancer therapy. The generation of a new blood vessel network under physiological conditions is regulated by the concerted action of activators and inhibitors. Perturbation of this balance, as it occurs in solid tumor growth and metastasis, appears to be a critical point in tumorigenesis. This has led to the "angiogenic switch" hypothesis: the point at which a tumor acquires the potential to induce angiogenesis is a critical step towards malignancy. Based on experimental evidence, prevention of blood vessel development appears to be the mechanism of action of many successful chemopreventive drugs of natural or synthetic origin: a novel concept that we termed "angioprevention". The hypothesis that anti-angiogenesis is at the basis of tumor prevention also suggests that many anti-angiogenic drugs could be used for chemoprevention in higher risk populations or in early intervention. There is a growing body of experimental evidence that anti-angiogenic strategies will contribute to the future therapy of cancer, several compounds with anti-angiogenic properties are now under clinical investigation including anti-inflammatory coumpounds, as inflammation may play a key role in angiogenesis. We must persevere in the development of novel, powerful and safer angiogenesis inhibitors and in the use of anti-angiogenic drugs in combination with other natural or synthetic anti-cancer agents in a biological therapy strategy.
IBC’s 6th Annual Conference on Angiogenesis: Novel Therapeutic Developments
Expert Opinion on Investigational Drugs, 2001
Angiogenesis is a process that is dependent upon coordinate production of angiogenesis stimulatory and inhibitory (angiostatic) molecules. Any imbalance in this regulatory circuit may lead to the development of a number of angiogenesis-mediated diseases. Angiogenesis is a multi-step process including activation, adhesion, migration, proliferation and transmigration of endothelial cells across cell matrices to or from new capillaries and from existing vessels. Angiogenesis is a process involved in the formation of new vessels by sprouting from pre-existing vessels. In contrast, vessel rudiments are sorted by a process termed vasculogenesis. Endothelial heterogeneity and organ specificity might contribute to differences in the response to different anti-angiogenic mechanisms (cultured EC versus microvascular EC isolated from different tissues). Under normal physiological conditions in mature organisms, endothelial cell turnover or angiogenesis is extremely slow (from months to years). However, angiogenesis can be activated for a limited time in certain situations such as wound healing and ovulation. In certain pathological states, such as human metastasis (oncology) and ocular neovascularisation, disorders including diabetic retinopathy and age-related macular degeneration (ophthalmology), there is excessive and sustained angiogenesis. Hence, understanding the mechanisms involved in the regulation of angiogenesis could have a major impact in the prevention and treatment of pathological angiogenic processes. Additionally, endothelial cells play a major role in the modelling of blood vessels. The interplay of growth factors, cell adhesion molecules, matrix proteases and specific signal transduction pathways either in the maintenance of the quiescent state or in the reactivation of endothelial cells is critical in physiological and pathological angiogenic processes.
Recent advances in cancer research highlighted the importance of target-specific drug discovery. In view of these advances, the most important mechanism in tumour growth is its ability to stimulate the formation of blood capillaries around itself called tumour-driven angiogenesis. Hence targeting the angiogenesis, inhibits the growth of blood vessels around it and responsible for death of the tumour due to starvation and accumulation of toxic waste. The therapy, thus, indirectly cytotoxic to the tumour cells by targeting newly developing blood vessels. In this review, we summarised the various antiangiogenic agents with their clinical uses and current status.
Angiogenesis as a therapeutic target
Nature, 2005
The major signalling pathways in tumour angiogenesis VEGF/VEGF receptors Angiogenesis is a fundamental developmental and adult physiological process, requiring the coordinated action of a variety of growth factors and cell-adhesion molecules in endothelial and mural cells (reviewed in this issue by Coultas, Chawengsaksophak and Rossant, p. 937). So far, VEGF-A and its receptors are the best-characterized signalling pathway in developmental angiogenesis 1,8,9. Loss of a single VEGF-A allele results in embryonic lethality 1,8,9. This pathway also has an essential role in reproductive and bone angiogenesis 8. Much research has also established the role of VEGF-A in tumour angiogenesis 8,10. VEGF-A binds to two receptor tyrosine kinases (RTK), VEGFR-1 (Flt-1) and VEGFR-2 (KDR, Flk-1) (reviewed in ref. 10). Of the two, it is now generally agreed that VEGFR-2 is the major mediator of the mitogenic, angiogenic and permeability-enhancing effects of VEGF-A. The significance of VEGFR-1 in the regulation of angiogenesis is more complex. Under some circumstances, VEGFR-1 may function as a 'decoy' receptor that sequesters VEGF and prevents its interaction with VEGFR-2 (ref. 10). However, there is growing evidence that VEGFR-1 has significant roles in haematopoiesis and in the recruitment of monocytes and other bonemarrow-derived cells that may home in on the tumour vasculature and promote angiogenesis 11-13. In addition, VEGFR-1 is involved in the induction of matrix metalloproteinases (MMPs) 14 and in the paracrine release of growth factors from endothelial cells 15. Thus the VEGFR-1selective ligands VEGF-B and placental-like growth factor (PlGF) may also have a role in these processes. Furthermore, in some cases VEGFR-1 is expressed by tumour cells and may mediate a chemotactic signal, thus potentially extending the role of this receptor in cancer growth 16. VEGF-A gene expression is upregulated by hypoxia 17. The transcription factor hypoxia inducible factor (HIF), which operates in concert with the product of the von Hippel-Lindau (VHL) tumour suppressor gene, has a major role in such regulation. Under normoxic conditions, the VHL protein targets HIF for ubiquitination and degradation 17. In situ hybridization studies demonstrate that VEGF-A messenger
IJPSM, 2018
Angiogenesis was first identified as an important process in tumor survival and sustenance in the 1980’s, but the therapeutic potential of anti-angiogenic agents was only realized and implemented into clinical practice in early 2000. It is well recognized that tumors selectively recruit vasculature which serves to provide a survival advantage, while also permitting escape from natural defense mechanisms. Research into modification of this process of neovascularization, using anti-angiogenic agents, has shown that tumor cell death can be significantly accelerated, especially in combination with cytotoxic chemotherapy. We discuss the research that has been conducted in elucidating the process of angiogenesis in the tumor micro-environment, and the possible pharmacological interventions to achieve clinical benefit with tumor responses.