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首页> 外文期刊>Radiotherapy and oncology: Journal of the European Society for Therapeutic Radiology and Oncology >Decreased repopulation as well as increased reoxygenation contribute to the improvement in local control after targeting of the EGFR by C225 during fractionated irradiation.
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Decreased repopulation as well as increased reoxygenation contribute to the improvement in local control after targeting of the EGFR by C225 during fractionated irradiation.

机译：在分次照射过程中，C225靶向EGFR后，种群减少和复氧增加有助于局部控制的改善。

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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 (18f/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 <0.001). Application of C225 significantly decreased TCD50 for 18f/36d under ambient conditions (P=0.04). Bootstrap analysis revealed decreased repopulation and increased reoxygenation after application of C225 (P=0.06 for the combined effect). This was further corroborated by a significant effect of C225 on the 'repopulated' dose under ambient conditions which is influenced by both, reoxygenation and repopulation (P=0.012). CONCLUSIONS: Our study provides evidence that both decreased repopulation as well as increased reoxygenation contribute to the improvement of local control after targeting of EGFR by C225 during fractionated irradiation of FaDu tumours.
机译：背景与目的：有人提出抑制再种群和增强复氧作用有助于改善分次照射后结合表皮生长因子受体（EGFR）抑制剂对局部肿瘤的控制作用。本研究解决了FaDu人鳞状细胞癌中的这一假设。对于这种肿瘤模型，先前已经证明了在分次照射过程中明显的再填充和不完全的复氧。此外，已显示抗EGFR单克隆抗体C225显着改善了该肿瘤中分级照射的结果。材料与方法：在18天内（18f / 18d）或18天内在36天内（18f / 36d）用18份辐照裸鼠的FaDu肿瘤。在环境条件下或在钳位缺氧条件下给出三个Gy分数。在治疗过程中，四次使用C225或载体。分次照射后，按分级补充剂量以获得局部肿瘤控制的完整剂量反应曲线。在治疗结束后第120天确定50％的肿瘤对照剂量（TCD50）。结果：FaDu肿瘤分次照射期间发生明显的再填充和复氧（P值在0.028和<0.001之间）。在环境条件下，使用C225显着降低18f / 36d的TCD50（P = 0.04）。引导分析表明，应用C225后，种群减少和复氧增加（综合作用P = 0.06）。 C225对环境条件下“再填充”剂量的显着影响进一步证实了这一点，该条件受复氧和再填充两者的影响（P = 0.012）。结论：我们的研究提供证据表明，在FaDu肿瘤的分次照射过程中，C225靶向EGFR后，再种群减少以及再氧合增加均有助于改善局部控制。

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