Transcription profiling of human PEGylated interferon-a2b treatment of one sensitive and two resistant osteosarcoma xenografts established in nude mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Christoph Muller
PROVIDER: E-TABM-707 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:We generated novel patient derived xenograft (PDX) and cell line -derived xenograft models for pancreatic ductal adenocarcinoma (PDAC) which reflect different molecular subtypes. Pancreatic ductal adenocarcinoma is currently the tumor with the fourth highest mortality rate. Recently, subtypes of PDAC have been reported by Collisson et al (Nat. Med. 17(4) 2011. DOI: 10.1038/nm.2344). However current fetal calf serum (FCS) cultured cell lines do not accurately model these subtypes. We thus generated novel serum-free cell lines derived from primary patient xenografts. We here analyse the gene-expression profiles of the xenografts and the derived cell lines. We show that indeed three different subtypes can be separated in our models based on gene-expression data. Further, we identify upregulation of a drug-detoxification pathway specifically in xenografts and cell lines of one of the subtypes. These models and data will help to better understand inter-patient heterogeneity in PDAC and identify novel drug targets and diagnostic markers.
2016-01-12 | E-MTAB-4029 | biostudies-arrayexpress
Project description:ERG overexpression is the most frequent molecular alteration in prostate cancer. We analyzed different stages of prostate cancer to identify genes that were coexpressed with ERG overexpression. In primary prostate tumors, it was shown that TDRD1 expression was the strongest correlated gene with ERG overexpression and we suggest TDRD1 as a direct ERG target gene. 6 Prostate cancer cell lines and 11 prostate cancer xenografts are included in this study. Each sample was analyzed once.
2013-02-11 | E-GEOD-41407 | biostudies-arrayexpress
Project description:Adenoid cystic carcinoma (ACC) is one of the most common malignancies that arise in the salivary glands, with an incidence of 4.5 per 1,000,000. It can also arise in glandular tissue closely related to salivary glands in the lacrimal gland, nasal passages and tracheobronchial tree, as well as in glands of the breast and vulva. At all of these sites, it is characterized by a distinctive histology of basaloid epithelial cells arranged in cribriform or tubular patterns, usually demonstrating abundant hyaline extracellular matrix secretion and some degree of myoepithelial differentiation. ACC is generally a slow-growing tumor characterized by a protracted clinical course, usually well over 5 years in duration, marked by regional recurrence, distant metastasis and/or spread along peripheral nerves. A recurrent chromosomal translocation, t(6;9)(q23;p21), has been identified in ACC, and recently it has been discovered that in a majority of ACC the MYB gene on chromosome 6 is fused to the 3’ terminus of the NFIB gene on chromosome 9, creating a fusion gene product resulting in increased MYB-related transcriptional activation. Recently it has been determined that most cell lines with attribution of ACC derivation are either contaminants of other cell lines or do not have the characteristic MYB-NFIB translocation. Also, there are no animal models of this histologically and genetically defined tumor type. To address the paucity of experimental and pre-clinical models systems of ACC, we have for several years been establishing xenograft tumor lines from clinical samples of ACC. We describe our experience with these models and their characterization here. Analysis of 12 xenografts of human adenoid cystic carcinoma (ACC) along with 10 samples of ACC directly from humans. Note, that 12 of these samples are paired primary ACC & xenograft ACC from the same individual (6 pairs in total).
2011-05-03 | E-GEOD-28996 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-02-11 | E-GEOD-41410 | biostudies-arrayexpress
Project description:Nude mice were allografted with medulloblastoma tumors derived from Ptch+/-HIC+/- transgenic mouse and treated with vehicle or NVP-LDE225. RNA was prepared from tumours from vehicle or NVP-LDE225 treated nude mice allografted with medulloblastoma tumors derived from Ptch+/-HIC+/- transgenic mouse and hybridized on the Affymetrix Mouse Genome 430A 2.0 RNA expression microarray.
2010-09-29 | E-GEOD-22005 | biostudies-arrayexpress
Project description:Nude mice were allografted with medulloblastoma tumors derived from Ptch+/-p53-/- transgenic mouse and treated with vehicle or NVP-LDE225. RNA was prepared from tumours from vehicle or NVP-LDE225 treated nude mice allografted with medulloblastoma tumors derived from Ptch+/-p53-/- transgenic mouse and hybridized on the Affymetrix Mouse Genome 430A 2.0 RNA expression microarray.
2010-09-29 | E-GEOD-22006 | biostudies-arrayexpress
Project description:Hes6 is a transcription co-factor that is associated with stem cell characteristics in neural tissue, but its role in cancer remains uncertain. Here we show that Hes6 is controlled by c-Myc and the AR and can drive castration resistance in xenografts of the androgen-dependent LNCaP prostate cancer cell line model. Hes6 activates a cell cycle enhancing transcriptional network that maintains tumour growth in the absence of circulating androgen but with maintained nuclear AR. We demonstrate interaction between E2F1, the AR and Hes6 and show the co-dependency of these factors in the castration-resistant setting. In the clinical setting, we have discovered a Hes6-associated signature that predicts poor outcome in prostate cancer, which could be pharmacologically targeted. LNCaP-LM (luciferase expressing) cells with stable Hes6-overexpression and empty vector controls injected dorso-subcutaneously into NOD SCID gamma (NSG) mice. Mice were castrated when average graft size reached 100mm3 . Mice were culled after 12 weeks growth and grafts harvested.
2014-04-17 | E-GEOD-36433 | biostudies-arrayexpress
Project description:Breast cancer research is hampered by difficulties in obtaining and studying primary human breast tissue, and by the lack of in vivo preclinical models that reflect patient tumor biology accurately. To overcome these limitations, we propagated a cohort of human breast tumors grown in the epithelium-free mammary fat pad of SCID/Beige and NOD/SCID/IL2γ-receptor null (NSG) mice, under a series of transplant conditions. Both models yielded stably transplantable xenografts at comparably high rates (~23% and ~19%, respectively). Of the conditions tested, xenograft take rate was highest in the presence of a low-dose estradiol pellet. Overall, 32 stably transplantable xenograft lines were established, representing unique 25 patients. Most tumors yielding xenografts were “triple-negative” (ER-PR-HER2+) (n=19). However, we established lines from three ER-PR-HER2+ tumors, one ER+PR-HER2-, one ER+PR+HER2- and one “triple-positive” (ER+PR+HER2+) tumor. Serially passaged xenografts show biological consistency with the tumor of origin, are phenotypic stability across multiple transplant generations at the histological, transcriptomic, proteomic, and genomic levels, and show comparable treatment responses. Xenografts representing 12 patients, including two ER+ lines, showed metastasis to the mouse lung. These models thus serve as a renewable, quality-controlled tissue resource for preclinical studies investigating treatment response and metastasis. The study was designed to determine how stable patient-derived xenografts are across multiple transplant generations in mice, and to determine how closely xenografts established with pre-treatment samples cluster with xenografts established with post-treatment samples. Overall, pre-treatment and post-treatment samples derived from the same patient cluster together, and multiple transplant generations of xenografts derived from an individual patient cluster together.
2013-05-30 | E-GEOD-46106 | biostudies-arrayexpress
Project description:Pancreatic adenocarcinoma (PDAC) is one of the most lethal human malignancies and a major health problem. Patient-derived tumor xenografts (PDTXs) have been increasingly used as a prime approach for preclinical studies despite being insufficiently characterized as a model of the human disease and its diversity. Extensive multiomics characterization of these PDTXs have demonstrated their utility as a suitable model for preclinical studies, representing the diversity of the primary cancers. We performed a multi-factorial integrative analysis of genome-wide ChIP-seq on multiple histone modifications, as well as RNA-seq on subcutaneous PDTXs from 24 PDAC samples obtained either surgically or using diagnostic biopsies (endoscopic ultrasound guided fine needle aspirate). In the dataset, ChIP-seq for five distinct histone marks (H3K4me1, H3K27ac, H3K4me3, H3K27me3, and H3K9me3) and RNA-seq was carried out to generate new knowledge on the epigenetic landscapes underlying the heterogeneity of PDAC tissues grown in this manner. <br>Note: Sample phenotypes have been updated on 2020-09-11 to correct the swapped labels between \"classical\" and \"basal\" phenotypes.
2018-05-29 | E-MTAB-5639 | biostudies-arrayexpress
Project description:In this study we performed gene transcription analysis of parental MACF7 cell and MCF7 engineered to overexpress oncoprotein RAF1. We demonstrate that overexpression of RAF1 leads to development of ivasive phenotype. Total RNA was extracted from culturued cells or from nude mice xenografts.
2011-10-14 | E-GEOD-29884 | biostudies-arrayexpress