Rofstad E K
Institute for Cancer Research, Norwegian Radium Hospital, Montebello.
J Natl Cancer Inst. 1992 Oct 7;84(19):1517-24. doi: 10.1093/jnci/84.19.1517.
Human tumor xenografts in athymic mice are often used to study the efficacy of cancer treatments, but it is not known whether the xenografts accurately reflect the treatment responsiveness of the original tumors.
To assess the validity of tumor xenografts as specific models of neoplastic disease, a soft-agar colony assay was used to compare the sensitivity of cells from surgical tumor specimens and derivative xenograft lines to various radiation and heat treatments in vitro.
Xenograft lines were established from melanomas and from carcinomas of the bladder, breast, cervix, and colon. Single-cell suspensions from the original tumors and the corresponding tumor xenografts were subjected to treatments that measured inherent radiation sensitivity, split-dose radiation repair capacity, low-dose-rate radiation sensitivity, inherent heat sensitivity, capacity for development of thermotolerance, and sensitivity to step-down heating (treatment at 43.5 degrees C followed by treatment at 41.5 degrees C). Cell survival curves were plotted for each treatment, and a two-tailed Student's t test was used to search for statistically significant correlations between the curves.
Although cells from different surgical tumor specimens varied widely in their sensitivity to radiation and heat treatments, there was always a statistically significant correlation (P < .05) between the sensitivity of cells from the surgical specimens and the corresponding tumor xenografts.
These observations strongly suggest that intrinsic properties of human tumor cells generally are retained during serial heterotransplantation. Thus, human tumor xenograft lines may be valuable tools in studies aimed at identifying cellular properties of importance for the clinical treatment sensitivity of human cancer. This does not necessarily mean, however, that the treatment responsiveness of the xenografts in vivo mirrors the clinical treatment responsiveness of the tumors in patients.
无胸腺小鼠体内的人肿瘤异种移植常用于研究癌症治疗的疗效，但尚不清楚异种移植是否能准确反映原发肿瘤的治疗反应性。
为评估肿瘤异种移植作为肿瘤疾病特定模型的有效性，采用软琼脂集落试验在体外比较手术肿瘤标本和衍生异种移植系的细胞对各种辐射和热处理的敏感性。
从黑色素瘤以及膀胱、乳腺、宫颈和结肠癌建立异种移植系。对来自原发肿瘤和相应肿瘤异种移植的单细胞悬液进行处理，以测量其固有辐射敏感性、分次剂量辐射修复能力、低剂量率辐射敏感性、固有热敏感性、热耐受发展能力以及对逐步降温加热（43.5℃处理后再进行41.5℃处理）的敏感性。为每种处理绘制细胞存活曲线，并使用双尾学生t检验寻找曲线之间具有统计学意义的相关性。
尽管来自不同手术肿瘤标本的细胞对辐射和热处理的敏感性差异很大，但手术标本的细胞敏感性与相应肿瘤异种移植的细胞敏感性之间始终存在统计学显著相关性（P <.05）。
这些观察结果强烈表明，人肿瘤细胞的固有特性在连续异种移植过程中通常得以保留。因此，人肿瘤异种移植系可能是旨在确定对人类癌症临床治疗敏感性具有重要意义的细胞特性的研究中的有价值工具。然而，这并不一定意味着异种移植在体内的治疗反应性反映了患者肿瘤的临床治疗反应性。
