ScRNA-seq of pediatric glioblastoma patient-derived xenografts
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ABSTRACT:
PROVIDER: PRJNA482625 | ENA |
REPOSITORIES: ENA
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Project description:scRNA-seq of patient-derived xenografts.
2019-03-15 | GSE117599 | GEO
Project description:In this study, pediatric ALL patient-derived xenografts (PDXs) inherently resistant to glucocorticoids were cultured in vitro. The study aims to determine discrepancy in gene expressions between different xeno strains.
2015-10-24 | GSE74299 | GEO
Project description:In this study, pediatric ALL patient-derived xenografts (PDXs) inherently resistant to glucocorticoids were cultured in vitro. The study aims to determine discrepancy in gene expressions between different xeno strains. The same xenograft was innoculated into 3 mice. Spleen-harvest xenograft samples were analyzed using microarray.
2015-10-24 | E-GEOD-74299 | biostudies-arrayexpress
Project description:Glioblastoma (GBM) patient-derived orthotopic xenografts (PDOXs) were derived from organotypic spheroids obtained from patient tumor samples. To detect whether gene expression profiles of GBM patient tumors are retained in PDOXs, we performed genome-wide transcript analysis by human-specific microarrays . In parallel, we analyzed GBM cell cultures and corresponding intracranial xenografts from stem-like (NCH421k, NCH644) and adherent GBM cell lines (U87, U251). PDOXs show a better transcriptomic resemblance with patient tumors than other preclinical models. The major difference is largely explained by the depletion of human-derived non-malignant cells.
2020-07-01 | GSE134470 | GEO
Project description:Thoracic patient-derived xenografts
| PRJNA339191 | ENA
Project description:Brain tumors are the leading cause of cancer-related death in children. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of pediatric brain cancer are limited and hard to establish. We present a protocol that enables efficient generation, expansion and biobanking of pediatric brain cancer organoids. Utilizing our protocol, we have established patient-derived organoids (PDOs) from ependymomas, medulloblastomas, low-grade glial tumors and patient-derived xenograft organoids (PDXOs) from medulloblastoma xenografts. PDOs and PDXOs recapitulate histological features, DNA methylation profiles and intratumor heterogeneity of the tumors from which they were derived. We also showed that PDOs can be xenografted. Most interestingly, when subjected to the same routinely applied therapeutic regimens, PDOs respond similarly to the patients. Taken together, our study highlights the potential of PDOs and PDXOs for research and translational applications for personalized medicine.
2023-12-01 | GSE247380 | GEO
Project description:Glucocorticoids are critical components of combination chemotherapy regimens in pediatric acute lymphoblastic leukemia (ALL). The pro-apoptotic BIM protein is an important mediator of glucocorticoid-induced apoptosis in normal and malignant lymphocytes, while the anti-apoptotic BCL2 confers resistance. The signaling pathways regulating BIM and BCL2 expression in glucocorticoid-treated lymphoid cells remain unclear. In this study, pediatric ALL patient-derived xenografts (PDXs) inherently sensitive or resistant to glucocorticoids were exposed to dexamethasone in vivo. In order to understand the basis for differential in vivo glucocorticoid sensitivity of PDXs, microarray analysis of gene expression was carried out on 5 each of dexamethasone-sensitive and resistant PDXs . This provided a global understanding of dexamethasone-induced signaling cascades in ALL cells in vivo, and especialy identified the genes that are involved in transducing the apoptotic signal, upstream of BIM/BCL2 dynamic interactions.
2014-05-20 | GSE57795 | GEO
Project description:Tumor microtubes (TMs) connect glioma cells to a network with considerable relevance for tumor progression and therapy resistance. The determination of TM-interconnectivity in individual tumors has been challenging and the impact on patient survival unresolved. Here, a connectivity signature from single-cell RNA-sequenced (scRNA-Seq) xenografted primary glioblastoma (GB) cells has been established using a dye uptake methodology, confirmed with recording of cellular calcium epochs and validated with clinical correlations. Astrocyte-like and mesenchymal-like GB cells have the highest connectivity signature scores in scRNA-sequenced patient-derived xenografts and patient samples. In large GB cohorts, network connectivity correlated with the mesenchymal subtype and dismal patient survival. CHI3L1 has been identified and validated as a robust molecular marker of connectivity with functional relevance. The connectivity signature allows novel insights into brain tumor biology, provides a proof-of-principle that tumor cell TM-connectivity is relevant for patients’ prognosis, and serves as a robust prognostic biomarker.
2023-11-27 | PXD044001 | Pride
Project description:Glucocorticoids are critical components of combination chemotherapy regimens in pediatric acute lymphoblastic leukemia (ALL). The pro-apoptotic BIM protein is an important mediator of glucocorticoid-induced apoptosis in normal and malignant lymphocytes, while the anti-apoptotic BCL2 confers resistance. The signaling pathways regulating BIM and BCL2 expression in glucocorticoid-treated lymphoid cells remain unclear. In this study, pediatric ALL patient-derived xenografts (PDXs) inherently sensitive or resistant to glucocorticoids were exposed to dexamethasone in vivo. In order to understand the basis for differential in vivo glucocorticoid sensitivity of PDXs, microarray analysis of gene expression was carried out on 5 each of dexamethasone-sensitive and resistant PDXs . This provided a global understanding of dexamethasone-induced signaling cascades in ALL cells in vivo, and especialy identified the genes that are involved in transducing the apoptotic signal, upstream of BIM/BCL2 dynamic interactions. ALL xenograft cells were inoculated by tail-vein injection into NOD/SCID mice, and engraftment was monitored weekly. When >70% %huCD45+ engraftment in the peripheral blood was apparent, which occurred 8-10 weeks post-transplantation, mice were treated with either dexamethasone (15 mg/kg) or vehicle control by intra-peritoneal (IP) injection, and culled at 8 hours following the treatment. Cell suspensions of spleens were prepared and mononuclear cells enriched to >97% human by density gradient centrifugation. RNA was extracted using the RNeasy Mini Kit (QIAGEN, Valencia, CA, USA), and RNA samples with integrity number (RIN) > 8.0 were amplified and hybridized onto Illumina HumanWG-6 v3 Expression BeadChips (6 samples/chip). All chips (with associated reagents) were purchased from Illumina, and scanned on the Illumina BeadArray Reader according to the manufacturer’s instructions. Microarray data were analyzed using the online modules in GenePattern. 10 xenografts were derived from patients of 5 dexamethasone-good responder and 5 dexamethasone-poor responder. Each xenograft was innoculated into 5-6 mice, and treated with dexamethasone (15 mg/kg) or vehicle control. In total spleen-harvest xenograft samples from 58 mice were analyzed using microarray.
2014-05-20 | E-GEOD-57795 | biostudies-arrayexpress
Project description:Proteomics reveal protein stability after xenotransplantation in murine models. Tryptic peptide digests from patient mononuclear cells were analyzed by Data Independent Acquisition (DIA) mass spectrometry. High-pH fractionation was performed on a pool of samples, followed by data dependent acquisition (DDA) mass spectrometry analysis. Spectral information from DDA and DIA data were used to generate a sample-specific library for targeted analysis to identify and quantify proteins. We present a global landscape of protein stability in paired patients and patient-derived xenografts, pediatric leukemic cell lines, and normal individuals.
2019-12-02 | MSV000084646 | MassIVE