Angiogenesis, inhibitors

MG M24 M24.002 Methionyl aminopeptidase 2 Target of the potent angiogenesis inhibitors fumagillin and ovalicin... 

Reliable markers are needed to monitor the activity of antiangiogenic dtugs. Circulating endothelial cells and their progenitor subset are a potential candidate, as is MRI dynamic measurement of vascular permeability/ flow in response to angiogenesis inhibitors, but neither has been clinically validated. 

FIGURE 9 Influence of angiogenesis inhibitors on blood vessel growth. Several inhibitors of angiogenesis were released from PTA-SA 50 50 in vivo. The effect of these agents on the growth of blood vessels around the VX2 carcinoma implanted into rabbit corneas was then determined as described in the text. 

KAPIOTIS S, HERMAN M, HELD I, SEELOS C, EHRINGER H, GMEINER B M, (1997) Genistein, the dietary-derived angiogenesis inhibitor, prevents LDL oxidation and protects endothelial... 

Erdmann et al. (2000) report the fabrication of devices for the localized delivery of salicylic acid from the poly(anhydride-co-ester)s mentioned in Section II.C. A unique feature of this drug delivery system is that the drug compound is part of the polymer backbone. Devices were implanted intraorally and histopathology was reported (Erdmann et al., 2000). Chasin et al. (1990) review fabrication and testing of implantable formulations for other drugs including angiogenesis inhibitors for treatment of carcinomas and bethanechol for the treatment of Alzheimer s disease. 

Park, M. et al., Tetra-arsenic oxide, a novel orally administrable angiogenesis inhibitor, Int. J. Oncol., 22, 1271, 2003. 

Lefkove B, Govindarajan B, Arbiser JL. (2007) Fumagillin An anti-infective as a parent molecule for novel angiogenesis inhibitors. Expert Rev Anti Infect Ther 5 573-579. 

Endothelial cells can also be prepared from tissue from other species. Capillary endothelial cells of bovine origin are used quite frequently, because these cells are rather sensitive to treatment with angiogenesis inhibitors such as angiostatin and endostatin (Griffioen et al., unpublished results). It should be noted however, that species-dependent responses to drugs can occur. 

The corneal pocket assay and the window preparations are designed to measure vessel formation after addition of stimulators. These assays can for instance be used for the study of angiogenic potential of human tumours. These models are also suitable for pre-clinical testing of angiogenesis inhibitors. 

Fig. 8.1 Structures of thalidomide, EM-12 and their metabolites which are all angiogenesis inhibitors and teratogens or potential teratogens.

Genistein (64), an isoflavone found in plants of the family Legu-minosae, is an inhibitor of several protein tyrosine kinases (PTK) and is currently in phase II clinical trials for its potential as an angiogenesis inhibitor. Genistein also has been utilized as a probe to identify binding sites for PTKs by observing the effect it demonstrates on cyclic-nucleotide-gated channels. ... 

Development of Angiogenesis Inhibitors to Vascular Endothelial Growth Factor Receptor 2 for Cancer Therapy... 

Keywords Angiogenesis Angiogenesis inhibitor VEGF VEGFR KDR ... 

Identification of the active component of Neovastat may elucidate its specific mode of acfion and potentially limit the side effects identified at the present time. This is particularly pertinent if, as expected, life-long administration is required, because the effects of chronic exposure and interactions between Neovastat and other therapies are not yet known. The positive safety profile and fhe oral administration route of Neovastat, however, are advantages in comparison with current therapies and some angiogenesis inhibitors. Thus, should antiangiogenic therapy become a mainstream therapy, Neovastat could play a substantial role in the treatment of cancer. 

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