Radiation response and cure rate of human colon adenocarcinoma spheroids of different size: The significance of hypoxia on tumor control modelling
Radiation response and cure rate of human colon adenocarcinoma spheroids of different size: The significance of hypoxia on tumor control modelling
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DOI：
10.1016/s0360-3016(00)01533-9
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发表时间：
2001-03-15
影响因子：
7
通讯作者：
Nahum, AE
中科院分区：
文献类型：
--
作者：
Buffa, FM;West, C;Nahum, AE
目的：评价泊松肿瘤控制概率模型的合理性以及低氧对肿瘤治疗的影响。方法与材料：将人结肠腺癌细胞株WiDR培养成不同直径的多细胞球体，观察300千伏X射线外束照射后细胞存活率和球体愈合情况。细胞存活数据采用两室模型和氧扩散模型进行拟合。结果：只有直径大于500微米的球体才能观察到缺氧。对于小球体，放射敏感性和克隆形成数的REP估计与实验得出的值显示出很好的一致性。对于大型球体，尽管对放射敏感性的tcp估计与测量值相当，但对克隆形成数的估计明显低于实验计数。照射前大球体的复氧导致对克隆形成细胞数量的ICP值的估计与实测值一致。结论：在没有缺氧的情况下，根据测量的放射敏感性和克隆形成数，TCP模型可以准确地预测治愈。当存在低氧时，能够在原位再生的细胞数量比最初存活下来的克隆细胞数量要少得多。由于这抵消了降低的放射敏感性，低氧对治愈的重要性不如细胞存活分析预测的那样重要。这一发现表明，慢性缺氧可能不会直接限制放射治疗的成功。(C)2001年爱思唯尔科学公司。
Purpose: To evaluate the adequacy of a Poisson tumor control probability (tcp) model and the impact of hypoxia on tumor cure.Methods and Materials: A human colon adenocarcinoma cell line, WiDr, was grown as multicellular spheroids df different diameters, Measurements were made of cell survival and spheroid cure following 300-kV X-ray external beam irradiation in air and nitrogen. Cell survival data were fitted using a two-compartment and an oxygen diffusion model. Spheroid cure data were fitted using the icp model.Results: Hypoxia was seen only for spheroids greater than 500 mum in diameter. For small spheroids rep estimates of radiosensitivity and clonogenic number showed excellent agreement with experimentally derived values. For large spheroids, although tcp estimates of radiosensitivity were comparable with measurements, estimates of the clonogenic number were considerably lower than the experimental count. Reoxygenation of large spheroids before irradiation resulted in the icp estimates of the number of clonogenic cells agreeing with measured values.Conclusions: When hypoxia was absent, the tcp model accurately predicted cure from measured radiosensitivity and clonogen number. When hypoxia was present, the number of cells capable of regrowth in situ was considerably lower than the number of clonogenic cells that initially survived irradiation. As this counteracted the decreased radiosensitivity, hypoxia was less important for cure than predicted from cell survival assays. This finding suggests that chronic hypoxia may not Limit directly the success of radiation therapy. (C) 2001 Elsevier Science Inc.