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Project description:The lack of model systems limits the preclinical testing of novel therapies to address Wilms tumor patient groups with poor outcomes. Therefore, we established 45 heterotopic Wilms tumor patient-derived xenografts (WTPDX) in CB17 scid-/- mice that capture the biological heterogeneity of Wilms tumor (WT). These WTPDX include six showing diffuse anaplasia, nine from patients who went on to experience disease relapse, and thirteen from patients with bilateral disease. WTPDX retained the genetic alterations and the global transcriptomic and methylation profile of corresponding primary WT. In addition, favorable histology WTPDX were chemosensitive, while unfavorable histology WTPDX were resistant to conventional chemotherapy with vincristine, actinomycin-D, and doxorubicin. This WTPDX library is a unique scientific resource that retains the spectrum of biological heterogeneity present in WT and provides an essential tool for the testing of novel targeted therapies in the era of precision medicine.
2019-02-14 | GSE110697 | GEO
Project description:The lack of model systems limits the preclinical testing of novel therapies to address Wilms tumor patient groups with poor outcomes. Therefore, we established 45 heterotopic Wilms tumor patient-derived xenografts (WTPDX) in CB17 scid-/- mice that capture the biological heterogeneity of Wilms tumor (WT). These WTPDX include six showing diffuse anaplasia, nine from patients who went on to experience disease relapse, and thirteen from patients with bilateral disease. WTPDX retained the genetic alterations and the global transcriptomic and methylation profile of corresponding primary WT. In addition, favorable histology WTPDX were chemosensitive, while unfavorable histology WTPDX were resistant to conventional chemotherapy with vincristine, actinomycin-D, and doxorubicin. This WTPDX library is a unique scientific resource that retains the spectrum of biological heterogeneity present in WT and provides an essential tool for the testing of novel targeted therapies in the era of precision medicine.
2019-02-14 | GSE110696 | GEO
Project description:Comparing Wilms tumor primary samples to patient-derived xenografts
| PRJNA434302 | ENA
Project description:Gene expression data comparing Wilms tumor primary samples to patient-derived xenografts
| PRJNA434301 | ENA
Project description:DNA methylation data comparing Wilms tumor primary samples to patient-derived xenografts
| PRJNA434304 | ENA
Project description:The lack of model systems has limited the preclinical discovery and testing of therapies for Wilms tumor (WT) patients who have poor outcomes. Herein, we establish 45 heterotopic WT patient-derived xenografts (WTPDX) in CB17 scid-/- mice that capture the biological heterogeneity of Wilms tumor (WT). Among these 45 total WTPDX, 6 from patients with diffuse anaplastic tumors, 9 from patients who experienced disease relapse, and 13 from patients with bilateral disease are included. Early passage WTPDX show evidence of clonal selection, clonal evolution and enrichment of blastemal gene expression. Favorable histology WTPDX are sensitive, whereas unfavorable histology WTPDX are resistant to conventional chemotherapy with vincristine, actinomycin-D, and doxorubicin given singly or in combination. This WTPDX library is a unique scientific resource that retains the spectrum of biological heterogeneity present in WT and provides an essential tool to test targeted therapies for WT patient groups with poor outcomes.
| S-EPMC6925259 | biostudies-literature
Project description:Patient-derived xenograft (PDX) models have been recognized as being more suitable for predicting therapeutic efficacy than cell-culture models. However, there are several limitations in applying PDX models in preclinical studies, including their availability-especially for cancers such as gastric cancer-that are not frequently encountered in Western countries. In addition, the differences in morphology between primary, PDX, and tumor cell line-derived xenograft (CDX) models have not been well established. In this study, we aimed to establish a series of gastric cancer PDXs and cell-lines from a relatively large number of gastric cancer patients. We also investigated the clinicopathological factors associated with the establishment of PDX and CDX models, and compared the histology between the primary tumor, PDX, and CDX that originated from the same patient. We engrafted 232 gastric cancer tissues into immune-deficient mice subcutaneously and successfully established 35 gastric cancer PDX models (15.1% success rate). Differentiated type adenocarcinomas (DAs, 19.4%) were more effectively established than poorly differentiated type adenocarcinomas (PDAs, 10.8%). For establishing CDXs, the success rate was less influenced by histological differentiation grade (DA vs. PDA, 12.1% vs. 9.8%). In addition, concordance of histological differentiation grade between primary tumors and PDXs was significant (p < 0.01), while concordance between primary tumors and CDXs was not. Among clinicopathological factors investigated, pathological nodal metastasis status (pN) was significantly associated with the success rate of PDX establishment. Although establishing cell lines from ascites fluid was more efficient (41.2%, 7/17) than resected tissues, it should be noted that all CDXs from ascites fluid had the PDA phenotype. In conclusion, we established 35 PDX and 32 CDX models from 249 gastric cancer patients; among them, 21 PDX/CDX models were established from the same patients. Our findings may provide helpful insights for establishing PDX and CDX models not only from gastric but from other cancer types, as well as select preclinical models for developing new therapeutics.
| S-EPMC6627523 | biostudies-literature
Project description:Various in vitro and in vivo experimental models have been used for the discovery of genes and pathways involved in melanoma and other types of cancer. However, in many cases, the results from various tumor models failed to be validated successfully in clinical studies. Limited information is available on how closely these models reflect the in vivo physiological conditions. In this study, a comprehensive genomics approach was used to systematically compare the expression patterns of snap frozen samples obtained from patients with primary melanoma, lymph node metastasis, and distant metastases, and compare these patterns to those of their corresponding cell lines and tumor xenografts in nude mice. The GE Healthcare 20k human genome array was used and the expression data was normalized and analyzed using GeneSpring 7.2 software. Based on the expression analysis, the correlation rate between the snap frozen primary patient samples vs. derived cell lines was 66%, with 1687 differentially expressed genes. The correlation rate between the snap frozen primary patient samples and the tumor xenografts was 75%, with 1,374 differentially expressed genes, and the correlation rate comparing tumor xenografts to derived cell lines ranged between 58% and 84%. These results demonstrated significant gene expression differences between tumor materials with different in vitro and in vivo growth microenvironments. Such studies can help us to distinguish between genes up- or down-regulated as a result of the microenvironment and those stably expressed independently of the tumor milieu. With the extensive use of cell lines and xenografts in cancer research, the information obtained using our approach may help to better interpret results generated from different tumor models by understanding common differences, as well as similarities at the gene expression level, information that may have important practical and biological implications.
| S-EPMC3226839 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-01-04 | GSE93109 | GEO
Project description:BackgroundBecause patient-derived xenografts (PDXs) are grown in immunodeficient mouse strains, PDXs are regarded as lacking an immune microenvironment. However, whether patients' immune cells co-exist in PDXs remains uncharacterized.MethodsWe cultured small pieces of lung PDX tissue in media containing human interleukin-2 and characterized the proliferated lymphocytes by flow cytometric assays with antibodies specific for human immune cell surface markers. Presence of immune cells in PDXs was also determined by immunohistochemical staining.ResultsHuman tumor-infiltrating lymphocytes (TILs) were cultured from nine of 25 PDX samples (36%). The mean time of PDX growth in immunodeficient mice before obtaining TILs in culture was 113 days (range 63-292 days). The TILs detected in PDXs were predominantly human CD8+ T cells, CD4+ T cells, or CD19+ B cells, depending on cases. DNA fingerprint analysis showed that the TILs originated from the same patients as the PDXs. Further analysis of two PDX-derived CD8+ T cells showed that they were PD-1-, CD45RO+, and either CD62L+ or CD62L-, suggesting they were likely memory T cells. Immunohistochemical staining showed that human T cells (CD8+ or CD4+), B cells (CD19+), and macrophages (CD68+) were present in stroma or intraepithelial cancer structures and that human PD-L1 was expressed in stromal cells. Moreover, the patient-derived immune cells in PDX can be passaged to the F2 generation and may migrate to spleens of PDX-bearing mice.ConclusionsPatient-derived immune cells co-exist in early passages of PDXs in some lung cancer PDX models. The CD8+ cells from PDXs were likely memory T cells. These results suggest that PDXs can be used for evaluating the functionality of immune components in tumor microenvironments.
| S-EPMC6260563 | biostudies-literature