Abstract
BackgroundPatient-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.MethodsWe 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.ResultsTumor 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.ConclusionWe 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.
Highlights
Patient-derived xenografts (PDX) have a biologically stable in tumor architecture, drug responsiveness, mutational status and global gene-expression patterns
Schematic outline of the generation of four different types of cancer PDX models and the growth and death of PDX model mice We analyzed 21 GBM, 11 lung cancers (LC), 54 gastric cancers (GC) and 21 colorectal cancers (CRC) from the hospital (Fig. 1c), and put the brief information about patients’ number, gender and WHO grade in Table 1, detailed clinical pathology reports were shown at Additional file 1: Table S1, Additional file 2: Table S2, Additional file 3: Table S3, Additional file 4: Table S4
When the tumor volume grew to 500 mm3 within 8 months, PDX model was considered to be successful
Summary
Patient-derived xenografts (PDX) have a biologically stable in tumor architecture, drug responsiveness, mutational status and global gene-expression patterns. Afterwards, in vivo models based on a limited number of cancer cells previously isolated from tumors and selected prior to implantation in animals have been used extensively in tumor biology research or evaluation of anticancer drugs [6, 7]. Patient-derived xenograft (PDX) models of human tumor tissues obtained directly from the patients and transplanted into immunecompromised mice have gained popularity in cancer research. These models better resemble the heterogeneity of human tumors [2, 9,10,11]. PDX models have been shown to predict clinical responses to chemotherapeutic drugs more accurately than other platforms, which centralize the role of PDX models in a new generation of personalized cancer therapy [12, 13]
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