Baumann M, DuBois W, Pu A, Freeman J, Suit H D
Edwin L. Steele Laboratory of Radiobiology, Department of Radiation Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston 02114.
Int J Radiat Oncol Biol Phys. 1992;23(4):803-9. doi: 10.1016/0360-3016(92)90653-y.
The response of xenografts of five human malignant glioma cell lines and two human squamous cell carcinomas to fractionated irradiation was studied. For this, the tumors were transplanted into nude mice which had been further immunosuppressed by 6 Gy whole-body irradiation. Radiation was given as 30 fractions applied under normal blood flow conditions in two sessions per day over 15 days. Absolute and specific tumor growth delay after 48 Gy, and tumor control dose 50% (TCD50) were evaluated. Using local tumor control as experimental endpoint, four out of five malignant gliomas were more resistant to fractionated radiation therapy than the two squamous cell carcinomas. The TCD50s of these four gliomas ranged from 73 Gy to more than 120 Gy, whereas the TCD50s of the squamous cell carcinomas were 51 and 60 Gy. Absolute tumor growth delay correlated well with TCD50, but no correlation was obtained between specific growth delay and TCD50. The response of the human tumor xenografts in vivo did not correlate with the surviving fractions at 2 Gy of the same cell lines in vitro which have been previously obtained in our laboratory. The results suggest that the unique radioresistance observed in malignant gliomas in patients is at least in part reflected in human tumor xenografts. The lack of correlation between the surviving fraction at 2 Gy in vitro and the tumor response in vivo could be a consequence of an immune response by the host, a difference in cell radiation sensitivity between cell lines and xenografted tumors, or of differences of parameters such as hypoxic fraction, rate of repopulation, and cell cycle effects between the different tumor lines studied. It illustrates the difficulties which might be involved in the prediction of the response of individual tumors to radiation therapy based solely on the intrinsic radiosensitivity of the tumor cells as assayed by in vitro assays of colony formation.
研究了五种人类恶性胶质瘤细胞系和两种人类鳞状细胞癌异种移植瘤对分次照射的反应。为此，将肿瘤移植到经6 Gy全身照射进一步免疫抑制的裸鼠体内。在正常血流条件下，分30次给予辐射，每天两次，共15天。评估48 Gy后的绝对和特异性肿瘤生长延迟以及50%肿瘤控制剂量（TCD50）。以局部肿瘤控制作为实验终点，五种恶性胶质瘤中有四种比分型鳞状细胞癌对分次放射治疗更具抗性。这四种胶质瘤的TCD50范围为73 Gy至超过120 Gy，而鳞状细胞癌的TCD50分别为51 Gy和60 Gy。绝对肿瘤生长延迟与TCD50相关性良好，但特异性生长延迟与TCD50之间未获得相关性。人类肿瘤异种移植瘤在体内的反应与先前在我们实验室获得的相同细胞系在体外2 Gy时的存活分数不相关。结果表明，在患者恶性胶质瘤中观察到的独特放射抗性至少部分反映在人类肿瘤异种移植瘤中。体外2 Gy时的存活分数与体内肿瘤反应之间缺乏相关性可能是宿主免疫反应、细胞系与异种移植瘤之间细胞辐射敏感性差异或不同研究肿瘤系之间诸如缺氧分数、再增殖率和细胞周期效应等参数差异的结果。这说明了仅基于通过体外集落形成测定法测定的肿瘤细胞内在放射敏感性来预测个体肿瘤对放射治疗反应可能存在的困难。
