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Establishment and evaluation of four different types of patient-derived xenograft models

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机构: [1]Guangdong Pharmaceut Univ, Sch Basic Courses, Guangzhou 510006, Guangdong, Peoples R China; [2]Guangdong Lab Anim Monitoring Inst, Guangdong Key Lab Anim Lab, 11 Fengxin Rd,Sci City, Guangzhou 510663, Guangdong, Peoples R China; [3]Southern Med Univ, Zhujiang Hosp, Dept Neurosurg, Guangzhou 510282, Guangdong, Peoples R China; [4]Southern Med Univ, Nanfang Hosp, Dept Gen Surg, 1838 Baiyun Rd North, Guangzhou 510080, Guangdong, Peoples R China; [5]Sun Yat Sen Univ, Canc Ctr, Dept Thorac Surg, Guangzhou 510030, Guangdong, Peoples R China; [6]Guangdong Med Univ, Guangdong Key Lab Res & Dev Nat Drug, Zhanjiang 524003, Guangdong, Peoples R China; [7]Sun Yat Sen Univ, Guangdong Inst Gastroenterol, Guangdong Prov Key Lab Colorectal & Pelv Floor Di, Guangzhou 510150, Guangdong, Peoples R China; [8]Sun Yat Sen Univ, Affiliated Hosp 6, Guangzhou 510150, Guangdong, Peoples R China
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关键词: Patient derived xenograft (PDX) Glioblastoma (GBM) Lung cancer (LC) Gastric cancer (GC) Colorectal cancer (CRC)

摘要:
Background: 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. Methods: 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. Results: 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. Conclusion: 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.

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出版当年[2017]版:
大类 | 3 区 医学
小类 | 4 区 肿瘤学
最新[2023]版:
大类 | 2 区 医学
小类 | 3 区 肿瘤学
第一作者:
第一作者机构: [1]Guangdong Pharmaceut Univ, Sch Basic Courses, Guangzhou 510006, Guangdong, Peoples R China; [2]Guangdong Lab Anim Monitoring Inst, Guangdong Key Lab Anim Lab, 11 Fengxin Rd,Sci City, Guangzhou 510663, Guangdong, Peoples R China;
通讯作者:
通讯机构: [2]Guangdong Lab Anim Monitoring Inst, Guangdong Key Lab Anim Lab, 11 Fengxin Rd,Sci City, Guangzhou 510663, Guangdong, Peoples R China; [4]Southern Med Univ, Nanfang Hosp, Dept Gen Surg, 1838 Baiyun Rd North, Guangzhou 510080, Guangdong, Peoples R China;
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