Kringle 1-5 Reduces Growth of Malignant Gliomas in Rats
Malignant gliomas is a highly vascularized and invasive tumor. The prognosis is still extremely poor despite advances in the cancer therapy. The growth and spread of gliomas within the host tissue depends upon their ability to stimulate new vessel formation, the angiogenesis, to get nutrients and remove waste products. Therefore, blocking the action of angiogenic factors, or utilizing angiogenic suppressors to inhibit angiogenesis, constitute a new strategy to suppress tumor growth. A representative drug is Avastin (Bevacizumab). It has been proved by FDA to treat patients with recurrent glioblastoma. It is a protein that acts against vessel growth factor. However, there are many vessel growth factors and Avastin only target one of them. Therefore the inhibition effect for vessel growth can be compensated by other angiogenic factors. Other disadvantages such as drug resistance and increased vascular cooption of the host vasculature have been reported. Kringle 1-5 (K1-5), discovered by Cao, is also a protein aimed on the vessels. Compared with Avastin, K1-5 acts directly on endothelial cells and leads endothelial cell death. The tumor inhibition effect of K1-5 was proven in a murine hepatocellular carcinoma model. In this chapter the therapeutic effect of K1-5 in malignant gliomas was discussed. We demonstrated that K1-5 is effective in the treatment of malignant gliomas. It is effective not only in the inhibition of vascular growth but also in limiting tumor invasiveness and improving tumor hypoxia, and then lead to a longer survival.
KeywordsVascular Endothelial Growth Factor Malignant Glioma Intensity Modulate Radiation Therapy Tumor Hypoxia Recurrent Glioblastoma
The authors thank Professor Y. Cao for providing K1-5 and his valuable advice; Professor Henrich Cheng and Yang-Hsin Shih for their support during the work.
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