Project description:DNA copy number profiling of 32 glioblastoma orthotopic xenografts Descriptive experiment, comparison of 39 glioblastoma tumors as orthotopic xenografts flow sorted for anueploidy
Project description:This SuperSeries is composed of the following subset Series: GSE38814: Glioblastoma Orthotopic Xenograft Transcriptome GSE38815: Glioblastoma Xenograft Comparative Genomic Hybridization Arrays Refer to individual Series
Project description:Frequent discrepancies between preclinical and clinical results of anti-cancer agents demand a reliable translational platform that can precisely recapitulate the biology of human cancers. Another critical unmet need is the ability to predict therapeutic responses for individual patients. Toward this goal, we have established a library of orthotopic glioblastoma (GBM) xenograft models using surgical samples of GBM patients. These patient-specific GBM xenograft tumors recapitulate histopathological properties and maintain genomic characteristics of parental GBMs in situ. Furthermore, in vivo irradiation, chemotherapy, and targeted therapy of these xenograft tumors mimic the treatment response of parental GBMs. We also found that establishment of orthotopic xenograft models portends poor prognosis of GBM patients and identified the gene signatures and pathways signatures associated with the clinical aggressiveness of GBMs. Together, the patient-specific orthotopic GBM xenograft library represent the preclinically and clinically valuable “patient tumor’s phenocopy” that represents molecular and functional heterogeneity of GBMs. Gene expression profiling experiments were conducted for 58 human glioblastoma samples using Affymetrix Human Gene 1.0 ST arrays according to manufacturer's protocol.
Project description:Frequent discrepancies between preclinical and clinical results of anti-cancer agents demand a reliable translational platform that can precisely recapitulate the biology of human cancers. Another critical unmet need is the ability to predict therapeutic responses for individual patients. Toward this goal, we have established a library of orthotopic glioblastoma (GBM) xenograft models using surgical samples of GBM patients. These patient-specific GBM xenograft tumors recapitulate histopathological properties and maintain genomic characteristics of parental GBMs in situ. Furthermore, in vivo irradiation, chemotherapy, and targeted therapy of these xenograft tumors mimic the treatment response of parental GBMs. We also found that establishment of orthotopic xenograft models portends poor prognosis of GBM patients and identified the gene signatures and pathways signatures associated with the clinical aggressiveness of GBMs. Together, the patient-specific orthotopic GBM xenograft library represent the preclinically and clinically valuable “patient tumor’s phenocopy” that represents molecular and functional heterogeneity of GBMs. aCGH experiments were performed for a human glioblastoma tissue (sample ID: PC-NS08-559) and the matching xenograft tumor tissue using the Agilent Human Whole Genome CGH 244K microarray according to manufacturer's protocol (2-color).
Project description:A reliable animal model that can mimic the GBM intracranial infiltration and Blood-brain barrier (BBB) interaction is necessary for effective therapeutics development. Here, we report a zebrafish-based orthotopic GBM xenograft model, in which GBM cells from different species and even patients, can robustly propagate and faithfully reproduce their histological characteristics. Single-cell RNA-seq indicates a transcriptomic adaption of GBM xenografts to infiltrative phenotype within the zebrafish brains. We also provide evidence that the BBB in zebrafish larva is molecularly and functionally intact and can interact with GBM cells in similar ways as in mammals, which together enables this model to accurately identify BBB penetrating drugs. Using GBM patients’ samples, we further generate zebrafish patient-derived orthotopic xenografts (z-PDOX) and proof-of-concept experiments indicate the short-term temozolomide response in z-PDOX can predict the long-term prognosis of corresponding GBM patients. These together illustrate the value of zebrafish GBM model in drug discovery and precision medicine.
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.