PATIENT-LIKE NUDE-MOUSE METASTATIC MODEL OF ADVANCED HUMAN PLEURAL CANCER
PATIENT-LIKE NUDE-MOUSE METASTATIC MODEL OF ADVANCED HUMAN PLEURAL CANCER
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DOI：
10.1002/jcb.240560104
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发表时间：
1994-09-01
影响因子：
4
通讯作者：
HOFFMAN, RM
中科院分区：
文献类型：
--
作者：
ASTOUL, P;COLT, HG;HOFFMAN, RM
胸膜癌是人类的常见病、多发病。最近，临床试验表明，胸腔内化疗和免疫治疗可能会对早期疾病产生反应。然而，在放射学和胸膜内窥镜检查中，大多数患者被发现有内脏胸膜受累，通常难以治疗，导致预后不良。这项研究的目标是构建一种能反映这种疾病的临床图像的人类壁层和内脏胸膜癌的裸鼠模型。然后，该模型可能会对胸膜癌的药物开发有用。用分化良好的人肺腺癌作为完整组织进行种植。通过我们开发的一种新的开胸手术，10只小鼠接受了壁层-胸膜植入，10只小鼠进行了内脏-胸膜植入。肿瘤生长的症状是通过体重减轻、呼吸窘迫或虚弱来确定的。实际肿瘤的生长和扩散是在尸检时测量的。用Kaplan-Meier法估计各组小鼠的存活曲线，用Log-ranch检验估计各组小鼠中位存活时间的差异。用标准的两样本t检验比较平均鼠体重曲线的斜率。建立胸膜癌模型的成功率为100%。肿瘤生长通过症状学和生存期初步评估：内脏-胸膜和壁膜-胸膜植入组的中位生存期分别为27.9天和31天(P<；0.05)。相应组平均体重曲线斜率的比较表明，内脏-胸膜植入动物的体重下降显著高于壁层-胸膜植入动物(P<；.001)。无论是内脏胸膜植入组还是壁层胸膜植入组，尸检分析都显示肿瘤在所有小鼠体内生长，表现出与临床特征相似的局部和区域扩散。然而，只有内脏胸膜植入的小鼠才能观察到纵隔淋巴结转移。利用组织学上完整的人标本，在裸鼠体内建立了类似病人的人类顶膜-胸膜和内脏-胸膜癌模型。肿瘤症状、生长、扩散和存活率表明，壁胸膜模型和内脏胸膜模型分别代表早期和晚期疾病。这些“像病人一样”的胸膜癌裸鼠模型现在为胸膜癌生物学、病理生理学和治疗学的进一步研究提供了合理的基础。(C)1994年Wiley-Liss，Inc.
Pleural cancer in humans is a frequently occuring tumor. Recently, clinical trials have suggested that chemotherapy and immunotherapy administered intrapleurally may elicit responses in early-stage diseases. However, at radiological and pleural endoscopic evaluation, most of the patients are found to have a visceral pleural involvement that is generally refractory to therapy and leads to a poor prognosis. The goal of this study was to construct a nude mouse model of human parietal- and visceral-pleural cancer that could reflect the clinical picture for this disease. The model could then be useful for drug discovery for pleural cancer. A well-differentiated human lung adenocarcinoma was used as intact tissue for implantation. Ten mice underwent parietal-pleural implantation and ten mice visceral-pleural implantation via a novel thoracotomy procedure we have developed. Symptoms of tumor growth were determined from weight loss, respiratory distress, or debilitation. Actual tumor growth and spread were measured at autopsy. The mouse survival curves of each group were estimated by the Kaplan-Meier method and the difference of the median survival times was assessed by the Log-rank test. The slopes of mean-mouse weight curves were compared using a standard two-sample t-test. A 100% take rate was achieved in constructing the pleural cancer models. Tumor growth was initially assessed by symptomatology and survival: the median survival time was, respectively, 27.9 days and 31 days for visceral-pleural and parietal-pleural implanted groups (P < 0.05). The comparison between the slopes of the mean weight curves of corresponding groups demonstrated that visceral-pleural implanted animals lost significantly more weight than the parietal-pleural implanted animals (P < .001). Both in the visceral- and parietal-pleural implanted groups, post-mortem analysis revealed that tumor grew in all mice demonstrating local and regional spread mimicking clinical features. However, mediastinal lymph node metastases were observed only in mice with visceral pleural implantation. Patient-like models of human parietal-pleural and visceral-pleural cancer were constructed in nude mice using histologically intact human specimens. Tumor symptoms, growth, and spread as well as survival indicated that the parietal-pleural and visceral-pleural models represent, respectively, early- and advanced-stage disease. These ''patient-like'' nude mouse models of pleural cancer now allow a rational basis for further studies of pleural cancer biology,pathophysiology, and therapeutics. (C) 1994 Wiley-Liss, Inc.