Irradiated nude rat model for orthotopic human lung cancers.
Irradiated nude rat model for orthotopic human lung cancers.
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发表时间：
1991-06
期刊：
影响因子：
11.2
通讯作者：
R. Howard;H. Chu;B. Zeligman;T. Marcell;P. Bunn;T. McLemore;D. Mulvin;M. Cowen;M. Johnston
中科院分区：
文献类型：
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作者：
R. Howard;H. Chu;B. Zeligman;T. Marcell;P. Bunn;T. McLemore;D. Mulvin;M. Cowen;M. Johnston
开发用于人类肺癌生物学和临床前研究的改良动物模型非常重要，因为肺癌是美国癌症死亡的主要原因。为了确定 Rowett 裸鼠是否可以作为这种疾病的原位（器官特异性）模型，将裸鼠（CR：NIH-RNU）在接受或不接受 500 拉德的先前伽玛射线照射的情况下，将来自 3 个人类肺癌系的 10（7）个培养细胞植入支气管内。未经照射，NCI-H460大细胞未分化癌的摄取率为54%，而NCI-H125腺鳞癌和A549腺癌的摄取率分别为7%和33%；辐照将利用率分别提高到 100%、83% 和 90%。在受辐射的大鼠中，肿瘤年龄与体重测量结果显示，所有三种肿瘤均逐渐生长，生长速率依次为：NCI-H460大于A549大于NCI-H125，平均肿瘤大小分别需要大约3、5和9周，才能超过500毫克。小细胞癌细胞系 NCI-H345 仅被植入受辐射的大鼠体内，导致肿瘤生长更缓慢。组织病理学研究表明，所有模型肿瘤类型都具有与细胞系来源的临床肿瘤一致的组织学特征。每种肿瘤类型都有不同的生长模式，一些 A549 和 NCI-H125 衍生的肿瘤转移至对侧肺和/或区域淋巴结。没有证据表明受辐射的荷瘤大鼠出现免疫排斥反应。未受辐射、没有肉眼肿瘤的植入大鼠表现出细支气管周围单核细胞浸润，伴或不伴纤维化，表明先前存在免疫排斥。这 4 种人类肺癌细胞系在受辐射裸鼠体内的成功原位生长表明，该模型可用于人类肺癌的生物学和临床前研究，无论是在完整的大鼠中还是通过荷瘤肺的离体灌注。
The development of improved animal models for biological and preclinical studies of human lung cancer is important because lung cancer is the leading cause of cancer death in the United States. To determine whether the Rowett nude rat could serve as an orthotopic (organ-specific) model of this disease, nude rats (CR: NIH-RNU), with and without 500 rads of prior gamma-irradiation, were implanted intrabronchially with 10(7) cultured cells from 3 human lung cancer lines. Without irradiation, the NCI-H460 large-cell undifferentiated carcinoma had a 54% take-rate, whereas the NCI-H125 adenosquamous carcinoma and A549 adenocarcinoma had take-rates of 7 and 33%, respectively; irradiation increased the respective take-rates to 100, 83, and 90%. In irradiated rats, tumor age versus weight measurements showed progressive growth for all three tumors, with growth rates in the order: NCI-H460 greater than A549 greater than NCI-H125, requiring approximately 3, 5, and 9 weeks, respectively, for average tumor sizes to exceed 500 mg. The small-cell carcinoma cell line NCI-H345 was implanted only into irradiated rats and resulted in more slowly growing tumors. Histopathological study showed all model tumor types to have histological characteristics consistent with the clinical tumors from which the cell lines were derived. Each tumor type had a different growth pattern, with some of the the A549- and NCI-H125-derived tumors metastasizing to contralateral lung and/or regional lymph nodes. There was no evidence for immunological rejection in irradiated, tumor-bearing rats. Nonirradiated, implanted rats without gross tumor exhibited peribronchiolar mononuclear cell infiltration with or without fibrosis, suggesting prior immunological rejection. The successful orthotopic growth of these 4 human lung cancer cell lines in irradiated nude rats suggests that this model could be useful for biological and preclinical studies of human lung cancer, both in intact rats and via ex vivo perfusion of their tumor-bearing lungs.