Decreased repopulation as well as increased reoxygenation contribute to the improvement in local control after targeting of the EGFR by C225 during fractionated irradiation
Decreased repopulation as well as increased reoxygenation contribute to the improvement in local control after targeting of the EGFR by C225 during fractionated irradiation
复制标题
DOI：
10.1016/j.radonc.2005.06.032
复制
发表时间：
2005-08-01
影响因子：
5.7
通讯作者：
Baumann, M
中科院分区：
文献类型：
--
作者：
Krause, M;Ostermann, G;Baumann, M
背景与目的：抑制再增殖和增强再氧合已被认为有助于改善局部肿瘤控制后，分次照射结合抑制剂的表皮生长因子受体（EGFR）。本研究在FaDu人鳞状细胞癌中解决了这一假设。对于这种肿瘤模型，以前已经证明了分次照射期间明显的再增殖和不完全复氧。材料与方法：裸鼠FaDu肿瘤用18天18次（18 f/18 d）或36天18次（18 f/36 d）照射。三个戈伊的分数下，无论是在环境或钳夹缺氧条件下。C225或载体在治疗过程中应用四次。分次照射后，通过分级的补充剂量，以获得完整的剂量-反应曲线，局部肿瘤控制。在治疗结束后第120天测定肿瘤控制剂量50%（TCD 50）。
Background and purpose: Inhibition of repopulation and enhanced reoxygenation has been suggested to contribute to improvement of local tumour control after fractionated irradiation combined with inhibitors of the epidermal growth factor receptor (EGFR). The present study addresses this hypothesis in FaDu human squamous cell carcinoma. For this tumour model marked repopulation and incomplete reoxygenation during fractionated irradiation has previously been demonstrated. Furthermore, the anti-EGFR monoclonal antibody C225 has been shown to significantly improve the results of fractionated irradiation in this tumour.Materials and methods: FaDu tumours in nude mice were irradiated with 18 fractions in 18 days (18f/18d) or 18 fractions in 36 days (1 8f/36d). Three Gy fractions were given either under ambient or under clamp hypoxic conditions. C225 or carrier was applied four times during the course of treatment. Fractionated irradiations were followed by graded top-up doses to obtain complete dose-response curves for local tumour control. Tumour control dose 50% (TCD50) was determined at day 120 after end of treatment.Results: Significant repopulation and reoxygenation occurred during fractionated irradiation of FaDu tumours (P-values between 0.028 and