An antiangiogenic agent (TNP-470) inhibited reoxygenation during fractionated radiotherapy of murine mammary carcinoma
Abstract
TNP-470, a synthetic analogue of fumagillin which is a natural product of Aspergillus fumigatus, has been noted as an angiogenesis inhibitor. Combined effects of TNP-470 with fractionated radiotherapy (RT) were investigated using a mouse tumor. Tumors were early generations of mammary carcinoma in C3H/He mice. Treatments were initiated when tumors reached an average diameter of 4-5 mm. Tumor response was evaluated by tumor growth (TG) time assay and 50% tumor control dose (TCD50) assay. Tumors were irradiated locally under hypoxic conditions or in air. Five fractionated radiation doses were given in the TG time assay, whereas a single dose or 10 fractionated doses were given in the TCD50 assay. TNP-470 (100 mg/kg) was administered subcutaneously twice a week during and/or after RT. In the TG time assay, significant delay of tumor growth was observed by TNP-470 alone (100 mg/kg x 2) compared with control tumors (p < 0.001), indicating that TNP-470 alone has an antitumor effect in vivo. When TNP-470 was administered during fractionated RT, no additional delay of tumor growth was observed. However, additive effects of TNP-470 was noted when it was given after the end of fractionated RT. In the TCD50 assay, no significant differenc...Continue Reading
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