| Research Abstract |
It is generally accepted that hepatocellular carcinoma (hepatoma) is charactered by its marked tumor angiogenesis, and formation of new blood vessels is critical for the growth of the tumor. It was expected that the inhibition of neovascularization with some anti-angiogenic factor would suppress the development of hepatoma, and lead to its selective therapy. TNP-470, a semisynthetic analogue of fumagillin, had been shown to be a potent angiogenesis inhibitor with relatively few side-effects. In this study, the effect of TNP-470 on the growth of hepatoma was examined using woodchucks, experimental animals of primary hepatocellular carcinoma, to assess its therapeutic possibility.
[Materials and Methods] TNP-470 was given to woodchucks by following three methods. (1) Focal injection : The woodchuck having two hepatoma nearly same size (30mm in diameter) was selected. One was in left lobe and another was in right lobe. respectively, To the left-lobe tumor, TNP-470 was injected at the dose
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of 20mg in 5% glucose solution with ultrasonographic guide once a week On the other hand, to the right-lobe tumor 5% glucose solution alone was injected in a same manner. (2) Systemic administration : To the other woodchuck having hepatoma, 10mm in diameter, in right lobe, TNP-470 was administered intra-muscularly at the dose of 30mg in 5% glucose solution twice a week. (3) Selective hepatic artery infusion : Hepatic angiography of woodchuck having two hepatoma was performed, and TNP-470 was infused intra-arterially through cathetel at the dose of 20mg in miglyol solution.
[Results] (1) The growth of left-lobe tumor treated with TNP-470 had been inhibited, and the size of tumor had remained 30mm in diameter during 12 weeks, in contrast to the right-lobe one which had grown more than 50mm in size (2) The tumor size had remained 10mm in diameter during 16 weeks. When TNP-470 was discontinued, however, the tumor began to grow rapidly. (3) Hepatic angiogram performed three weeks later showed mass reduction of each tumor.
[Conclusion] These results described above suggest that anti-angiogenic factor can be one of promising antitumor agent. Less
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