Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1251859 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR33190814_1.fastq.gz | Fastqsanger.gz | |||
| SRR33190814_2.fastq.gz | Fastqsanger.gz | |||
| SRR33190815_1.fastq.gz | Fastqsanger.gz | |||
| SRR33190815_2.fastq.gz | Fastqsanger.gz | |||
| SRR33187388.fastq.gz | Fastqsanger.gz |
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Project description:This study aims to investigate the regulatory influence of the host microenvironment on tumor growth during the establishment of patient-derived xenograft (PDX) models of human lung cancer in athymic nude mice. By serially passaging tumor tissues from primary clinical specimens through generations P0 to P3, we examined how the immunodeficient but NK cell-competent microenvironment of athymic nude mice affects tumor adaptation and progression. Whole transcriptome (RNA-seq) profiling was used to identify changes in gene expression related to immune signaling and stromal interaction across passages. This project provides important insights into the role of the murine host microenvironment, particularly innate immune responses, in shaping the development and evolution of human lung cancer in PDX models, and supports future translational studies using PDX systems as clinically relevant tools for cancer research.
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Project description:Engraftment of primary pancreas ductal adenocarcinomas (PDAC) in mice to generate patient derived xenograft (PDX) models is a promising platform to for biological and therapeutic studies in this disease. However, these models are still incompletely characterized. Here, we measured the impact of the murine environment on the gene expression of the engrafted human tumoral cells. We have analyzed gene expression profiles from 35 new PDX models and compared them with previously published microarray data from PDAC and hepatocellular carcinoma (HCC). Our results showed that PDX models derived from PDAC, or HCC, were clearly different to the cell lines derived from the same cancer tissues. Indeed, PDAC- and HCC-derived cell lines are indistinguishable one from the other based in their gene expression profiles. In contrast, the transcriptomes of PDAC and HCC PDX models are clearly different and more similar to their original tumor than to PDX models from the other tumor type. Interestingly, the main differences between pancreatic PDX models and human PDAC is the expression of genes involved in pathways related with extracellular matrix interactions and cell cycle regulation likely reflecting the adaptations of the tumors to the new environment. Furthermore, most of these differences are detected in the first passages after the tumor engraftment, indicating early phases of the adaptation process. In conclusion, different from conventional cancer cell lines, PDX models of PDAC retain similar gene expression profiles of PDAC. Expression changes are mainly related to genes involved in stromal pathways likely reflecting the adaptation to new environments. We also provide evidence of the stability of gene expression patterns over subsequent passages. We have analyzed gene expression profiles from 35 new PDX models and compared them with previously published in GEO microarray data. We used PDX models, primary tumors and cell lines from PDAC and hepatocellular carcinoma. All these public data were re-process in order to compare with our 35 samples
2014-04-22 | E-GEOD-51798 | biostudies-arrayexpress
Project description:Sezary syndrome (SS) is a rare, aggressive leukemic variant of cutaneous T cell lymphoma (CTCL) that lacks adequate therapeutic options and representative small animal models. Here we demonstrate that IL-15 is a critical CTCL growth and survival factor. Importantly, a genetically engineered immunodeficient mouse model expressing human IL-15 uniquely supported the growth of patient derived Sezary cells relative to conventional immunodeficient mouse strains. Patient derived xenograft (PDX) SS models recapacitated the pathologic features of the human disease, including skin infiltration and spread of leukemic cells to the periphery, and maintained the dependence on human IL-15 upon serial in vivo passaging. Detailed molecular characterization of the engrafted cells by single cell transcriptome analysis revealed tissue specific regulation of gene expression and distinct clonal engraftment patterns. Overall, we document an important dependence of Sezary cell survival and proliferation on IL-15 signaling and the utility of the humanized IL-15, immunodeficient mice for SS PDX model generation. Furthermore, these studies advocate for the thorough molecular understanding of the resultant PDX models to maximize their translational impact.
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Project description:Sezary syndrome (SS) is a rare, aggressive leukemic variant of cutaneous T cell lymphoma (CTCL) that lacks adequate therapeutic options and representative small animal models. Here we demonstrate that IL-15 is a critical CTCL growth and survival factor. Importantly, a genetically engineered immunodeficient mouse model expressing human IL-15 uniquely supported the growth of patient derived Sezary cells relative to conventional immunodeficient mouse strains. Patient derived xenograft (PDX) SS models recapacitated the pathologic features of the human disease, including skin infiltration and spread of leukemic cells to the periphery, and maintained the dependence on human IL-15 upon serial in vivo passaging. Detailed molecular characterization of the engrafted cells by single cell transcriptome analysis revealed tissue specific regulation of gene expression and distinct clonal engraftment patterns. Overall, we document an important dependence of Sezary cell survival and proliferation on IL-15 signaling and the utility of the humanized IL-15, immunodeficient mice for SS PDX model generation. Furthermore, these studies advocate for the thorough molecular understanding of the resultant PDX models to maximize their translational impact.
2023-09-29 | GSE227326 | GEO
Project description:Patient-derived xenograft (PDX) models represent an essential tool for the preclinical evaluation of novel targeted therapies and their combinations. In this project, we molecularly characterized a comprehensive panel of glioma PDX models with well conserved molecular and pathological features over multiple passages. PDX samples were subjected to next generation sequencing (NGS). Characterization of cancer-relevant features including driver mutations or cellular processes was performed using mutational and gene expression data in order to identify potential biomarker or treatment targets in glioblastoma. In summary, we reported a newly established and molecularly characterized panel of glioma PDX models with high relevance for translational preclinical research.
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Project description:Patient-derived xenograft (PDX) models represent an essential tool for the preclinical evaluation of novel targeted therapies and their combinations. In this project, we molecularly characterized a comprehensive panel of RCC PDX models with well conserved molecular and pathological features over multiple passages. PDX samples were subjected to next generation sequencing (NGS). Characterization of cancer-relevant features including driver mutations or cellular processes was performed using mutational and gene expression data in order to identify potential biomarker or treatment targets in RCC. In summary, we reported a newly established and molecularly characterized panel of RCC PDX models with high relevance for translational preclinical research.
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Project description:Engraftment of primary pancreas ductal adenocarcinomas (PDAC) in mice to generate patient derived xenograft (PDX) models is a promising platform to for biological and therapeutic studies in this disease. However, these models are still incompletely characterized. Here, we measured the impact of the murine environment on the gene expression of the engrafted human tumoral cells. We have analyzed gene expression profiles from 35 new PDX models and compared them with previously published microarray data from PDAC and hepatocellular carcinoma (HCC). Our results showed that PDX models derived from PDAC, or HCC, were clearly different to the cell lines derived from the same cancer tissues. Indeed, PDAC- and HCC-derived cell lines are indistinguishable one from the other based in their gene expression profiles. In contrast, the transcriptomes of PDAC and HCC PDX models are clearly different and more similar to their original tumor than to PDX models from the other tumor type. Interestingly, the main differences between pancreatic PDX models and human PDAC is the expression of genes involved in pathways related with extracellular matrix interactions and cell cycle regulation likely reflecting the adaptations of the tumors to the new environment. Furthermore, most of these differences are detected in the first passages after the tumor engraftment, indicating early phases of the adaptation process. In conclusion, different from conventional cancer cell lines, PDX models of PDAC retain similar gene expression profiles of PDAC. Expression changes are mainly related to genes involved in stromal pathways likely reflecting the adaptation to new environments. We also provide evidence of the stability of gene expression patterns over subsequent passages.
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Project description:Osteosarcoma (OS) and Ewing’s sarcoma (EW) are the two most common pediatric solid tumors, after brain tumors. Multimodal treatments have significantly improved prognosis in localized disease but outcome is still poor in metastatic patients, for whom therapeutic options are often inadequate. Preclinical drug testing to identify promising treatment options that match the molecular make-up of these tumors is hampered by the lack of appropriate and molecularly well-characterized patient-derived models. To address this need, a panel of patient-derived xenografts (PDX) was established by subcutaneous implantation of fresh, surgically resected OS and EW tumors in NSG mice. Tumors were re-transplanted to next mice generations and fragments were collected for histopathological and molecular characterization. A model was considered established after observing stable histological and molecular features for at least three passages. To evaluate the similarity of the model with primary tumor, we performed a global gene expression profiling and tissue microarrays (TMA), to assess tumor specific biomarkers on tissues from OS/EW tumors and their PDXs (1st and 3rd passage). Moreover, we verified the feasibility of these models for preclinical drug testing. We implanted 61 OS and 29 EW samples: 14/38 (37%) primary OS and 9/23 (39%) OS lung metastases successfully engrafted; while among EW, 5/26 (19%) primary samples and 1/3 (33%) metastases were established. Comparison between patient samples and PDXs, highlighted that histology and genetic characteristics of PDXs were stable and maintained over passages. In particular, correlative analysis between OS and EW samples and their PDXs was extremely high (Pearson’s r range r=0.94-0.96), while patient-derived primary cultures displayed reduced correlation with human samples (r=0.90-0.93), indicating that in vitro adaptation superimpose molecular alterations that create genetic diversion from original tumors. No significant differentially expressed gene profile was observed from the comparison between EW samples and PDXs (fold change > 2, adjusted p <0.05 at paired t-test). In OS, the comparison between OS patient-derived tumors and PDX indicated differences in 397 genes, mostly belonging to immune system functional category. This is in line with the idea that human immune cells are gradually replaced by murine counterparts upon engraftment in the mouse. As proof-of concept, two EW PDX and one OS PDX have been treated with conventional and innovated drugs to test their value in terms of drug-sensitivity prediction. Overall, our study indicated that PDX models maintained the histological and genetic markers of the tumor samples and represent reliable models to test sensitivity to novel drug associations.
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Project description:Purpose: The goal of this study is to establish and molecularly characterize non-small cell lung cancer (NSCLC) organoids. Generation of NSCLC organoids would provide additional preclinical models for drug screening and biomarker discovery. Methods: Patient lung tumors and previously established patient-derived xenografts (PDX) were processed to generate organoids. Total RNA was extracted and subjected to RNA-seq to examine the gene expression similarity between patient/PDX/organoid of the same model using t-SNE clustering. Results: Through RNA-sequencing, we generated TPM values of patient, PDX and organoid samples of 5 models. t-SNE analysis showed that the patient/PDX/organoid of the same models clustered together. The lung adenocarcinoma samples formed a separate cluster from the squamous cell carcinoma samples based on gene expression. Conclusions: Our study introduces the establishment of NSCLC organoids and demonstrates the gene expession similarity of the organoid model to its corresponding PDX and patient sample.
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