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ゼブラフィッシュによる発生毒性試験とサリドマイド

》第85回薬理学会年会で発表します

                     
2012/03/14

○演題番号:  O1C2-3-2
○発表日:   2012年3月14日(水) 11:12 - 11:24
○会場:    Room C-2


Pharmacogenomics of Tumor Angiogenesis in Novel Human Cancer XenoTransplantation Model

Junya Kuroyanagi 1), Noriko Umemoto 1), Beibei Zhang 1), Yasuhito Shimada 1)2)3)4), Yuhei Nishimura 1)2)3)4), Toshio Tanaka 1)2)3)4)

1) Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine,
2) Department of Bioinformatics, Mie University Life Science Research Center
3) Mie University Medical Zebrafish Research Center
4) Department of Omics Medicine, Mie University Industrial Technology Innovation Institute

Angiogenesis plays an important role in tumor growth and metastasis. Most tumors release angiogenesis regulating factors, and neovasculature occurs when there are predominating positive signaling from regulators of angiogenesis. The use of agents that can inhibit angiogenesis has indicated that antiangiogenic therapy can be a promising therapeutic approach in clinical cancer treatment. We identified tumor angiogenesis in zebrafish which is one of powerful models to define gene relevant to human malignant disease because of the ease of gene manipulation and large scale pharmacological screens. We transplanted plural human cancer cells to zebrafish and analysis the tumor angiogenesis in vivo. Then, we performed DNA microarray analysis to reveal the transcriptome profile of tumor angiogenesis. The pathways identified by the transcriptome analysis included several genes that are known to be involved in angiogenesis in human and rodent models, such as including EGF, HGF and TGF- &beta pathways. In addition, we discovered several novel target clusters which promote tumor angiogenesis. In summary, we clarified the transcriptome profiles and therapeutic target gene of the tumor angiogenesis using zebrafish model of human cancer transplantation.