Establishment and evaluation of four different types of patient-derived xenograft models.
Establishment and evaluation of four different types of patient-derived xenograft models.
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DOI：
10.1186/s12935-017-0497-4
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发表时间：
2017
影响因子：
5.8
通讯作者：
Huang R
中科院分区：
文献类型：
--
作者：
Ji X;Chen S;Guo Y;Li W;Qi X;Yang H;Xiao S;Fang G;Hu J;Wen C;Liu H;Han Z;Deng G;Yang Q;Yang X;Xu Y;Peng Z;Li F;Cai N;Li G;Huang R
患者来源的异种移植物（PDX）在肿瘤结构、药物反应性、突变状态和整体基因表达模式方面具有生物学稳定性。迄今为止，已经建立了许多PDX模型，然而，在所建立的模型中关于肿瘤形成和肿瘤生长速率的彻底表征仍然是一项具有挑战性的任务。本研究旨在为成功有效地建立PDX模型提供更详细的信息。我们移植了来自108名中国患者的四种不同类型的实体瘤，包括胶质母细胞瘤（GBM）21例，肺癌（LC）11例，胃癌（GC）54例和结直肠癌（CRC）21例，并将肿瘤组织连续传代三代。本文报道了PDX模型小鼠的成瘤率、成瘤时间、肿瘤生长曲线和死亡率。我们还报告了患者癌组织和PDX模型之间HLA-A、CD 45、Ki 67、GFAP和CEA蛋白表达的H&E染色和免疫组织化学。肿瘤形成率在随后的肿瘤代中显著增加。胃癌和结直肠癌的生存率明显高于结直肠癌和胆囊癌。至于反映肿瘤生长速度的肿瘤形成所需的时间，表明肿瘤生长速度总是随着代数的增加而增加。肿瘤生长曲线也说明了这一规律。同样地，PDX小鼠的存活率随着GC和CRC的代数增加而逐渐提高。PDX模型中细胞增殖（Ki 67+）较患者肿瘤中细胞增殖（Ki 67+）多，与肿瘤生长速率的结果一致。组织学发现证实了患者癌症组织和PDX模型之间相似的组织学结构和分化程度，并通过GraphPad Prism 5.0进行了统计分析。我们成功地建立了四种不同类型的PDX模型，我们的结果丰富了目前对PDX模型建立的认识，并可能有助于不同类型PDX模型应用的扩展。本文的在线版本（10.1186/s12935-017-0497-4）包含补充材料，可供授权用户使用。
Patient-derived xenografts (PDX) have a biologically stable in tumor architecture, drug responsiveness, mutational status and global gene-expression patterns. Numerous PDX models have been established to date, however their thorough characterization regarding the tumor formation and rates of tumor growth in the established models remains a challenging task. Our study aimed to provide more detailed information for establishing the PDX models successfully and effectively. We transplanted four different types of solid tumors from 108 Chinese patients, including 21 glioblastoma (GBM), 11 lung cancers (LC), 54 gastric cancers (GC) and 21 colorectal cancers (CRC), and took tumor tissues passaged for three successive generations. Here we report the rate of tumor formation, tumor-forming times, tumor growth curves and mortality of mice in PDX model. We also report H&E staining and immunohistochemistry for HLA-A, CD45, Ki67, GFAP, and CEA protein expression between patient cancer tissues and PDX models. Tumor formation rate increased significantly in subsequent tumor generations. Also, the survival rates of GC and CRC were remarkably higher than GBM and LC. As for the time required for the formation of tumors, which reflects the tumor growth rate, indicated that tumor growth rate always increased as the generation number increased. The tumor growth curves also illustrate this law. Similarly, the survival rate of PDX mice gradually improved with the increased generation number in GC and CRC. And generally, there was more proliferation (Ki67+) in the PDX models than in the patient tumors, which was in accordance with the results of tumor growth rate. The histological findings confirm similar histological architecture and degrees of differentiation between patient cancer tissues and PDX models with statistical analysis by GraphPad Prism 5.0. We established four different types of PDX models successfully, and our results add to the current understanding of the establishment of PDX models and may contribute to the extension of application of different types of PDX models. The online version of this article (10.1186/s12935-017-0497-4) contains supplementary material, which is available to authorized users.
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影响因子：
82.9
作者：
Gao, Hui;Korn, Joshua M.;Sellers, William R.
通讯作者：
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影响因子：
5.7
作者：
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11.2
作者：
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影响因子：
4.7
作者：
Morgan KM;Riedlinger GM;Rosenfeld J;Ganesan S;Pine SR
通讯作者：
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