An antiangiogenic agent (TNP-470) inhibited reoxygenation during fractionated radiotherapy of murine mammary carcinoma.

摘要: Purpose: TNP-470, a synthetic analogue of fumagillin which is natural product Aspergillus fumigatus, has been noted as an angiogenesis inhibitor. Combined effects TNP-470 with fractionated radiotherapy (RT) were investigated using mouse tumor. Methods and Materials: Tumors early generations mammary carcinoma in C3H/He mice. Treatments initiated when tumors reached average diameter 4-5 mm. Tumor response was evaluated by tumor growth (TG) time assay 50% control dose (TCD 50 ) assay. irradiated locally under hypoxic conditions or air. Five radiation doses given the TG assay, whereas single 10 TCD (100 mg/kg) administered subcutaneously twice week during and/or after RT. Results: In significant delay observed alone mg/kg x 2) compared (p < 0.001), indicating that antitumor effect vivo. When RT, no additional observed. However, additive it end difference S between RT combined experiments. Hypoxic fraction calculated from not affected significantly administrating 24 h before On other hand, 10-fraction experiments, (RT air higher than alone, air) 0.005), decreased radiocurability. This negative conditions. Conclusion: The probability unexpected result may be attributable to partial inhibition reoxygenation because TNP-470) alone)