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Department of Neurosurgery, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan

Hisae Hori and Noriko Yamaguchi

Department of Molecular Pathogenesis, Division of Adult Disease, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan

Tsiridis et al. presented an unusual case of avascular necrosis in the peripheral bone, which was later found to be combined with a glioblastoma in the brain. They suspected the avascular necrosis was caused by an endogenous inhibitor of angiogenesis, such as endostatin or transforming growth factor ß, secreted from the glioblastoma tissue. Their hypothesis is very attractive. However, it is necessary to show data supporting a direct causal relationship between a glioblastoma and avascular necrosis of the peripheral bone. Detection of the tissue levels or serum levels of endostatin or transforming growth factor ß could support the hypothesis. Although we showed increased levels of tissue endostatin in glioblastomas (1) , we unfortunately did not examine the levels of endostatin in the serum for these patients. Furthermore, there have been no reports in which glioblastomas or other tumors secreting high levels of endostatin are combined with avascular necrosis of the peripheral bone (2 , 3) . With regard to the systemic effects of antiangiogenic therapies suggested by Tsiridis et al., no side effects such as avascular necrosis of the peripheral bone have been reported in a Phase I clinical trial of recombinant endostatin (4) . However, this case report by Tsiridis et al. will promote further careful survey for the systemic effects of antiangiogenic factors in tumors secreting high levels of endostatin as well as in clinical application of recombinant endostatin.

Received 9/15/03; accepted 9/22/03.

REFERENCES

1. Morimoto T., Aoyagi M., Tamaki M., Yoshhino Y., Hori H., Duan L., Yano T., Shibata M., Ohno K., Hirakawa K., Yamaguchi N. Increased levels of tissue endostatin in human malignant gliomas. Clin. Cancer Res., 8: 2933-2938, 2002.[Abstract/Free Full Text]
2. Feldman A. L., Tamarkin L., Paciotti G. F., Simpson B. W., Linehan W. M., Yang J. C., Fogler W. E., Turner E. M., Alexander H. R., Jr., Libutti S. K. Serum endostatin levels are elevated and correlate with serum vascular endothelial growth factor levels in patients with stage IV clear cell renal cancer. Clin. Cancer Res., 6: 4628-4634, 2000.[Abstract/Free Full Text]
3. Feldman A. L., Pak H., Yang J. C., Alexander H. R., Jr., Libutti S. K. Serum endostatin levels are elevated in patients with soft tissue sarcoma. Cancer (Phila.), 91: 1525-1529, 2001.
4. Thomas J. P., Arzoomanian R. Z., Alberti D., Marnocha R., Lee F., Friedl A., Tutsch K., Dresen A., Geiger P., Pluda J., Fogler W., Schiller J. H., Wilding G. Phase I pharmacokinetic and pharmacodynamic study of recombinant human endostatin in patients with advanced solid tumors. J. Clin. Oncol., 21: 223-231, 2003.[Abstract/Free Full Text]

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