| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
The purpose of this study was to investigate dynamic changes in the tumor microenvironment (tumor blood flow, vascular permeability, clearance, and interstitial fluid pressure) induced after a single dose of X-ray irradiation in a variant of Yoshida sarcoma, LY80, and to clarify the therapeutic significance of intercepting tumor blood flow (TBF) after irradiation. Radiation (10 Gy) was administered locally to tumors of anesthetized rats. A combretastatin derivative which intercepts TBF and disrupts tumor vessels, AC7700, was administered i.v. (10 mg/kg/ml). At 24 h after irradiation, TBF began to increase and showed an increase of 2-2.5 times at 72-96 h. All parameters used to assess the tumor microenvironment consistently showed improvement of tumor microcirculation. Apparently, improvement of this tumor microcirculation contributes to cancer recurrence. At all investigated times after irradiation, AC7700 stopped TBF completely and irreversibly. AC7700 administration after irradiation markedly enhanced of antitumor efficacy. Such a combination might have important therapeutic benefit, even in tumors which are insensitive to either treatment alone. We conclude that destruction of tumor microcirculatory function after irradiation is important for suppressing tumor growth. It is particularly for preventing cancer recurrence.
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