Radiation Treatment Timing and Dose Delivery: Effects on Bladder Cancer Cells in 3D in Vitro Culture
Radiation Treatment Timing and Dose Delivery: Effects on Bladder Cancer Cells in 3D in Vitro Culture
复制标题
放射治疗时机和剂量输送：体外 3D 培养对膀胱癌细胞的影响
作者：
L. Bodgi;J. Al;T. Araji;J. Bou;J. Azzi;R. Challita;C. Feghaly;H. Bahmad;T. Eid;F. Geara;Y. Zeidan;W. Abou
虽然根治性膀胱切除术仍然是膀胱癌的主要治疗选择，越来越多的证据支持使用基于辅助放疗的膀胱保留策略。这突出了需要更好地了解膀胱癌对不同类型治疗的放射敏感性。本研究的目的是分析治疗时间、剂量和分次对生长的三维（3D）膀胱癌球的数量和大小的影响，并评估线性二次模型描述3D培养细胞反应的能力。采用基于3D MatrigelTM的培养物来富集来自三种人膀胱癌细胞系RT 4、T24和UM-UC-3的癌症干细胞（CSC）。在铺板后的不同时间点进行三次单剂量辐射处理，并评估球体数量和尺寸。采用抗CD 44免疫荧光、克隆形成试验和抗γ H2 AX染色分析细胞系的放射敏感性。球的放射敏感性取决于接种后的处理时间。目前的线性二次剂量分割模型被证明高估了3D模型中的放射敏感性。我们的研究结果显示了治疗时机对膀胱癌球体放射反应的重要性。我们还证明，膀胱癌球更耐剂量分割比从理论线性二次模型的估计。
While radical cystectomy remains the primary treatment of choice for bladder cancer, increased evidence supports the use of bladder-preservation strategies based on adjuvant radiotherapy. This highlights the need for a better understanding of bladder cancer radiosensitivity to different types of treatment deliveries. The purpose of this study is to analyze the effect of treatment time, dose and fractionation on the number and sizes of grown three-dimensional (3D) bladder cancer spheres, and to assess the capacity of the linear-quadratic model in describing the response of cells cultured in 3D. 3D MatrigelTM-based cultures were employed to enrich for cancer stem cells (CSCs) from three human bladder cancer cell lines, RT4, T24 and UM-UC-3. Three single dose radiation treatments were performed at different time points after plating, and sphere number and sizes were assessed. Anti-CD44 immunofluorescence, clonogenic assay and anti-γH2AX staining were also performed to analyze the cell lines’ radiosensitivity. The radiosensitivity of spheres was dependent on the treatment timing after plating. Current linear quadratic dose fractionation models were shown to over-estimate radiosensitivity in 3D models. Our results showed the importance of treatment timing on the radio-response of bladder cancer spheres. We also demonstrated that bladder cancer spheres are more resistant to dose-fractionation than the estimation from the theoretical linear-quadratic model.
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影响因子：
3.4
作者：
CURTIS, SB
通讯作者：
CURTIS, SB
影响因子：
14
作者：
DelNero P;Lane M;Verbridge SS;Kwee B;Kermani P;Hempstead B;Stroock A;Fischbach C
通讯作者：
Fischbach C
影响因子：
5.7
作者：
PETERS, LJ
通讯作者：
PETERS, LJ
DOI：
10.1016/0360-3016(82)90517-x
发表时间：
1982-01-01
影响因子：
7
作者：
THAMES, HD;WITHERS, HR;FLETCHER, GH
通讯作者：
FLETCHER, GH