Tumor tissue vessel development has often been compared with embryonic vessel development, and vessel development between zebrafish and mammalian systems are very similar at the molecular level. Using antibodies against specific vascular antigens, Phase I research will investigate the response of zebrafish vessels to angiogenic inhibitors, and develop a whole animal angiogenesis ELISA for drug screening. In current methods used to study angiogenesis, tissue manipulation makes drug screening difficult. Zebrafish is an ideal whole animal model for drug screening because embryos can be generated and maintained inexpensively and are amenable to automated analysis. Drug delivery is simple, and drug and toxicity effects are easily detected because the embryos are transparent. Rapid embryonic development also facilitates rapid detection of drug effects. In addition, a number of genes involved in vertebrate angiogenesis have been shown to have the same function in zebrafish.
By providing a rapid method for screening durgs for effects on angiogenic vessel formation, the zebrafish assay will facilitate the drug development process for a variety of diseases, including cancer. Therapeutics approaches for cancer are numerous and generate in excess of $10B in worldwide revenue. Assays that streamline the drug development and clinical process are in high demand.
| Seng, Wen Lin; Eng, Kurt; Lee, Jenny et al. (2004) Use of a monoclonal antibody specific for activated endothelial cells to quantitate angiogenesis in vivo in zebrafish after drug treatment. Angiogenesis 7:243-53 |
