Project description:Characterization of 68 cell lines derived from human sarcoma and 5 normal counterpart cells, including drug sensitivity testing, gene expression profiling and microRNA expression profiling have been completed. Data and tools for searching these data will be made publicly available through the NCI Developmental Therapeutics Program. The raw data (.cel files ) are provided through the GEO website. Sarcoma represents a variety of cancers at arise from cells of mesenchymal origin and have seen limited treatment advances in the last decade. Drug sensitivity data coupled with the transcription and microRNA profiles of a cohort of sarcoma cell lines may help define novel treatment paradigms.

2015-08-01 | GSE68591 | GEO

Characterization of an Oxaliplatin Sensitivity Predictor in a preclinical Murine Model of Colorectal Cancer

Project description:Despite advances in contemporary chemotherapeutic strategies, long term survival still remains elusive for patients with metastatic colorectal cancer. A better understanding of the molecular markers of drug sensitivity to match therapy with patient is needed to improve clinical outcomes. In this study, we used in vitro drug sensitivity data from the NCI-60 cell lines together with their Affymetrix microarray data to develop a gene expression signature to predict sensitivity to oxaliplatin. In order to validate our oxaliplatin sensitivity signature, Patient-Derived Colorectal Cancer Explants (PDCCEs) were developed in NOD-SCID mice from resected human colorectal tumors. Analysis of gene expression profiles found similarities between the PDCCEs and their parental human tumors, suggesting their utility to study drug sensitivity in vivo. The oxaliplatin sensitivity signature was then validated in vivo with response data from 14 PDCCEs treated with oxaliplatin and was found to have an accuracy of 92.9% (Sensitivity=87.5%; Specificity=100%). Our findings suggest that PDCCEs can be a novel source to study drug sensitivity in colorectal cancer. Furthermore, genomic-based analysis has the potential to be incorporated into future strategies to optimize individual therapy for patients with metastatic colorectal cancer. Fourty-two human tumors and murine explants of colorectal origin, both primary colon and of various metastatic sites, were processed for total RNA. The samples included RNA from 14 patient samples in addition to RNA from Patient-Derived Colorectal Cancer Explant (PDCCEs) generated from these 14 patient samples. The PDCCEs were processed as fresh frozen whole tumor in addition to formalin-fixed paraffin-embedded (FFPE) tumors.

2012-02-17 | E-GEOD-28691 | biostudies-arrayexpress

microRNA expression profiling of human sarcoma cell lines (~68) in the Molecular Pharmacology Branch, DTP, DCTD NCI collection of human cell lines

Project description:Characterization of ~68 cell lines derived from human sarcoma and 5 normal counterpart cells, including drug sensitivity testing, gene expression profiling and microRNA expression profiling have been completed. Data and tools for searching these data will be made publicly available through the NCI Developmental Therapeutics Program. The raw data (RCC files) are provided through the GEO website. Sarcoma represents a variety of cancers at arise from cells of mesenchymal origin and have seen limited treatment advances in the last decade. Drug sensitivity data coupled with the transcription and microRNA profiles of a cohort of sarcoma cell lines may help define novel treatment paradigms. For each cell line, microRNA expression was measured on nCounter miRNA Expression Arrays (Nanostring Technologies), providing multiplexed, digital detection and counting of 800 human microRNA's. Please note that there are 2 replicates included in the study: A-204-rep1 and A-204-rep2, ES-4-rep1 and ES-4-rep2 resulting total 77 samples.

2015-08-01 | E-GEOD-69470 | biostudies-arrayexpress

Distal chromosome 6q harbors a haploinsufficient tumor suppressor gene that regulates PI3K signaling in glioblastoma

Project description:Glioblastoma is a universally fatal disease characterized by remarkable molecular heterogeneity. Prognostic biomarkers in glioblastoma have implications for patient management and drug development but are currently limited. In this study, we analyzed exome-wide human glioblastoma somatic copy number alteration data and discovered cytoband 6q27 as an independent poor prognostic marker across multiple glioblastoma datasets. We then combined CRISPR-Cas9 data, human spatial transcriptomic data, and human and mouse RNA sequencing data to nominate PDE10A as a potential haploinsufficient tumor suppressor in the 6q27 region. Mouse glioblastoma modeling using the RCAS/tv-a system confirmed that Pde10a suppression induced an aggressive glioma phenotype in vivo. Cell culture analysis showed that decreased Pde10a expression led to increased Pi3k/Akt signaling, a response blocked by selective Pi3k inhibitors. Single nucleus RNA sequencing from our mouse gliomas in vivo, in combination with cell culture validation showed that Pde10a suppression was associated with a proneural to a mesenchymal transition that exhibited increased cell adhesion and decreased cell migration. PDE10A loss was associated with unmethylated MGMT promoter status in human glioblastoma and resistance to temozolomide and radiation therapy in vitro. Our results indicate that patients with glioblastoma harboring PDE10A loss have worse outcomes, increased resistance to standard-of-care therapy, and potentially increased sensitivity to PI3K inhibition.

2024-09-19 | GSE243575 | GEO

Human expression data from Glioblastoma cell malignancy and drug sensitivity are affected by the cell of origin.

Project description:The cell of origin in glioblastoma is not formally proven but generally accepted to be a neural stem cell or glial precursor cell. In addition, there is also limited knowledge about the functional consequences of the cell of origin for glioblastoma development and response to therapy. We have investigated the role of cell of origin in glioblastoma by inducing glioblastomas of defined cell of origin using PDGFB in the brains of adult mice. Gene expression was analysed from cultured mouse glioblastoma cells and a mouse cell origin gene signature was extracted that we used in a cluster analysis on gene expression data from patient-derived glioblastoma cell lines.

2017-01-23 | GSE91392 | GEO

Mouse expression data from Glioblastoma cell malignancy and drug sensitivity are affected by the cell of origin.

2017-01-23 | GSE91391 | GEO