Budach W, Budach V, Stuschke M, Dinges S, Sack H
Dept. of Radiation Oncology, West German Tumor Center, University of Essen, Germany.
Int J Radiat Oncol Biol Phys. 1993 Jan 15;25(2):259-68. doi: 10.1016/0360-3016(93)90347-x.
The response to irradiation of five human xenograft cell lines--a malignant paraganglioma, a neurogenic sarcoma, a malignant histiocytoma, a primary lymphoma of the brain, and a squamous cell carcinoma--were tested in nude mice. All mice underwent 5 Gy whole body irradiation prior to xenotransplantation to minimize the residual immune response. The subcutaneous tumors were irradiated at a tumor volume of 120mm3 under acutely hypoxic conditions with single doses between 8 Gy and 80 Gy depending on the expected radiation sensitivity of the tumor line. Endpoints of the study were the tumor control dose 50% (TCD50) and the regrowth delay endpoints growth delay, specific growth delay, and the tumor bed effect corrected specific growth delay. Specific growth delay and corrected specific growth delay at 76% of the TCD50 was used in order to compare the data to previously published data from spheroids. The lowest TCD50 was found in the lymphoma with 24.9 Gy, whereas the TCD50 of the soft tissue sarcomas and the squamous cell carcinoma ranged from 57.8 Gy to 65.6 Gy. The isoeffective dose levels for the induction of 30 days growth delay, a specific growth delay of 3, and a corrected specific growth delay of 3 ranged from 15.5 Gy (ECL1) to 37.1 Gy (FADU), from 7.2 Gy (ENE2) to 45.6 Gy (EPG1) and from 9.2 Gy (ENE2) to 37.6 Gy (EPG1), respectively. The corrected specific growth delay at 76% of the TCD50 was correlated with the number of tumor rescue units per 100 cells in spheroids, which was available for three tumor lines, and with the tumor doubling time in xenografts (n = 5). The TCD50 values corresponded better to the clinical experience than the regrowth delay data. There was no correlation between TCD50 and any of the regrowth delay endpoints. This missing correlation was most likely a result of large differences in the number of tumor rescue units in human xenografts of the same size.
在裸鼠中测试了五种人类异种移植细胞系——恶性副神经节瘤、神经源性肉瘤、恶性组织细胞瘤、原发性脑淋巴瘤和鳞状细胞癌——对辐射的反应。所有小鼠在异种移植前均接受5戈瑞的全身照射，以尽量减少残留的免疫反应。根据肿瘤细胞系预期的放射敏感性，在急性缺氧条件下，当皮下肿瘤体积达到120立方毫米时，给予8戈瑞至80戈瑞的单次剂量照射。研究的终点是50%肿瘤控制剂量（TCD50）以及再生长延迟终点，即生长延迟、特异性生长延迟和肿瘤床效应校正后的特异性生长延迟。为了将数据与之前发表的球体数据进行比较，采用了TCD50的76%时的特异性生长延迟和校正后的特异性生长延迟。在淋巴瘤中发现最低的TCD50为24.9戈瑞，而软组织肉瘤和鳞状细胞癌的TCD50范围为57.8戈瑞至65.6戈瑞。诱导30天生长延迟、特异性生长延迟为3以及校正后的特异性生长延迟为3的等效剂量水平分别为15.5戈瑞（ECL1）至37.1戈瑞（FADU）、7.2戈瑞（ENE2）至45.6戈瑞（EPG1）以及9.2戈瑞（ENE2）至37.6戈瑞（EPG1）。TCD50的76%时的校正后特异性生长延迟与每100个球体中的肿瘤挽救单位数量相关（该数据适用于三种肿瘤细胞系），也与异种移植中的肿瘤倍增时间相关（n = 5）。TCD50值比再生长延迟数据更符合临床经验。TCD50与任何再生长延迟终点之间均无相关性。这种缺失的相关性很可能是由于相同大小的人类异种移植中肿瘤挽救单位数量存在巨大差异所致。
