Canine hemangiosarcoma tissues, monolayer- and sphere-cultured cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Canis lupus familiaris
PROVIDER: GSE53219 | GEO | 2014/12/11
SECONDARY ACCESSION(S): PRJNA231157
REPOSITORIES: GEO
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Project description:Cell lines and tumor tissues from canine hemangiosarcoma derived cell lines and hemangiosarcoma tissue samples Identification of three molecular and functional subtypes in canine hemangiosarcoma through gene expression profiling
2014-12-11 | E-GEOD-53219 | biostudies-arrayexpress
Project description:Cell lines and tumor tissues from canine hemangiosarcoma derived cell lines and hemangiosarcoma tissue samples
2014-12-08 | GSE46040 | GEO
Project description:Abnormal function of genes is at the root of most cancers, but heritable cancer syndromes account for a very small minority of all tumors in humans and domestic animals. The majority of cancers are “sporadic,” that is, they are not heritable in the strictest sense. Instead, sporadic cancers occur due to interactions of unknown intrinsic (heritable) and environmental factors that lead to malignant transformation and uncontrolled growth. Identification of heritable risk factors in sporadic human cancers is difficult because individual genetic backgrounds are very heterogeneous. To this end, individual genetic backgrounds of purebred dogs are more homogeneous, and dog breeds show different predilection to develop specific cancers. Here, we used genomic screens based on gene expression profiling to identify sets of genes that may contribute to the development of canine hemangiosarcoma, a relatively common endothelial sarcoma. Specific genes in a single breed (Golden Retrievers) are modulated by (or with) heritable risk traits, showing functional features that appear to modulate tumor behavior. Our results suggest these methods are suitable to identify genes that will enhance our understanding of how these cancers happen, as well as possible treatment targets that will improve outcomes of both human and canine cancer patients. Keywords: Hemangiosarcoma, microarray, heritability, GSEA, canine 10 samples were analysed. 6 Golden Retrievers with hemangiosarcoma, 3 non-Golden Retrievers with hemangiosarcoma, and 1 mixed breed Golden Retriever with hemangiosarcoma. The experiment was designed to find genes associated with breed and hemangiosarcoma to asses genetic make-up on disease susceptibility and/or progression
2009-03-06 | E-GEOD-15086 | biostudies-arrayexpress
Project description:The etiology of hemangiosarcoma remains incompletely understood. Its common occurrence in dogs suggests predisposing factors favor its development in this species. These factors could represent a constellation of heritable characteristics that promote transformation events and/or facilitate the establishment of a microenvironment that is conducive for survival of malignant blood vessel-forming cells. The hypothesis for this study was that characteristic molecular features distinguish hemangiosarcoma from non-malignant endothelial cells, and that such features are informative for the etiology of this disease. We first evaluated mutational events in candidate genes that might drive hemangiosarcoma. Each of 10 tumor and four non-tumor samples had wild type sequence for these genes. Thus, we used gene expression profiling as a global approach to test the hypothesis. Hemangiosarcoma cells clustered separately from non-malignant endothelial cells based on robust signatures that included genes involved in inflammation, angiogenesis, adhesion, invasion, metabolism, cell cycle, signaling, and patterning. The data do not distinguish whether functional or ontogenetic plasticity creates this phenotype, although they suggest that the cells that give rise to hemangiosarcoma modulate their microenvironment to promote tumor growth and survival. Keywords: Hemangiosarcoma, microarray, heritability, GSEA, canine 10 dogs with hemangiosarcoma were compared to 3 dogs without hemangiosarcoma and 21 dogs with other tumors
2010-06-16 | E-GEOD-22129 | biostudies-arrayexpress
Project description:The etiology of hemangiosarcoma remains incompletely understood. Its common occurrence in dogs suggests predisposing factors favor its development in this species. These factors could represent a constellation of heritable characteristics that promote transformation events and/or facilitate the establishment of a microenvironment that is conducive for survival of malignant blood vessel-forming cells. The hypothesis for this study was that characteristic molecular features distinguish hemangiosarcoma from non-malignant endothelial cells, and that such features are informative for the etiology of this disease. We first evaluated mutational events in candidate genes that might drive hemangiosarcoma. Each of 10 tumor and four non-tumor samples had wild type sequence for these genes. Thus, we used gene expression profiling as a global approach to test the hypothesis. Hemangiosarcoma cells clustered separately from non-malignant endothelial cells based on robust signatures that included genes involved in inflammation, angiogenesis, adhesion, invasion, metabolism, cell cycle, signaling, and patterning. The data do not distinguish whether functional or ontogenetic plasticity creates this phenotype, although they suggest that the cells that give rise to hemangiosarcoma modulate their microenvironment to promote tumor growth and survival. Keywords: Hemangiosarcoma, microarray, heritability, GSEA, canine
2010-06-04 | GSE22129 | GEO
Project description:Background The etiology of hemangiosarcoma remains incompletely understood. Its common occurrence in dogs suggests predisposing factors favor its development in this species. These factors could represent a constellation of heritable characteristics that promote transformation events and/or facilitate the establishment of a microenvironment that is conducive for survival of malignant blood vessel-forming cells. The hypothesis for this study was that characteristic molecular features distinguish hemangiosarcoma from non-malignant endothelial cells, and that such features are informative for the etiology of this disease. Methods We first investigated mutations of VHL and Ras family genes that might drive hemangiosarcoma by sequencing tumor DNA and mRNA (cDNA). Protein expression was examined using immunoblotting. Next, we evaluated genome-wide gene expression profiling using the Affymetrix Canine 2.0 platform as a global approach to test the hypothesis. Data were evaluated using routine bioinformatics and validation was done using quantitative real time RT-PCR. Results Each of 10 tumor and four non-tumor samples analyzed had wild type sequences for these genes. At the genome wide level, hemangiosarcoma cells clustered separately from non-malignant endothelial cells based on a robust signature that included genes involved in inflammation, angiogenesis, adhesion, invasion, metabolism, cell cycle, signaling, and patterning. This signature did not simply reflect a cancer-associated angiogenic phenotype, as it also distinguished hemangiosarcoma from non-endothelial, moderately to highly angiogenic bone marrow-derived tumors (lymphoma, leukemia, osteosarcoma). Conclusions The data show that inflammation and angiogenesis are important processes in the pathogenesis of vascular tumors, but a definitive ontogeny of the cells that give rise to these tumors remains to be established. The data do not yet distinguish whether functional or ontogenetic plasticity creates this phenotype, although they suggest that cells which give rise to hemangiosarcoma modulate their microenvironment to promote tumor growth and survival. We propose that the frequent occurrence of canine hemangiosarcoma in defined dog breeds, as well as its similarity to homologous tumors in humans, offers unique models to solve the dilemma of stem cell plasticity and whether angiogenic endothelial cells and hematopoietic cells originate from a single cell or from distinct progenitor cells. This SuperSeries is composed of the SubSeries listed below.
2010-08-24 | GSE23760 | GEO
Project description:Abnormal function of genes is at the root of most cancers, but heritable cancer syndromes account for a very small minority of all tumors in humans and domestic animals. The majority of cancers are “sporadic,” that is, they are not heritable in the strictest sense. Instead, sporadic cancers occur due to interactions of unknown intrinsic (heritable) and environmental factors that lead to malignant transformation and uncontrolled growth. Identification of heritable risk factors in sporadic human cancers is difficult because individual genetic backgrounds are very heterogeneous. To this end, individual genetic backgrounds of purebred dogs are more homogeneous, and dog breeds show different predilection to develop specific cancers. Here, we used genomic screens based on gene expression profiling to identify sets of genes that may contribute to the development of canine hemangiosarcoma, a relatively common endothelial sarcoma. Specific genes in a single breed (Golden Retrievers) are modulated by (or with) heritable risk traits, showing functional features that appear to modulate tumor behavior. Our results suggest these methods are suitable to identify genes that will enhance our understanding of how these cancers happen, as well as possible treatment targets that will improve outcomes of both human and canine cancer patients. Keywords: Hemangiosarcoma, microarray, heritability, GSEA, canine
2009-03-07 | GSE15086 | GEO
Project description:Transcriptome analysis of hemangiosarcoma samples were performed to assess EGFR and PLAUR/uPAR expression profiles and compare to human tumors from TCGA. Abstract Sarcomas differ from carcinomas in their mesenchymal origin. Therapeutic advancements have come slowly so alternative drugs and models are urgently needed. These studies report a new drug for sarcomas that simultaneously targets both tumor and tumor neovasculature. eBAT is a bispecific angiotoxin consisting of truncated, deimmunized Pseudomonas exotoxin fused to epidermal growth factor (EGF) and the amino terminal fragment (ATF) of urokinase. Here, we study the drug in an in vivo “ontarget” companion dog trial since eBAT effectively kills canine hemangiosarcoma (HSA) and human sarcoma cells in vitro. We reasoned the model has value due to the common occurrence of spontaneous sarcomas in dogs and a limited lifespan allowing for rapid accrual and data collection. Splenectomized dogs with minimal residual disease were given one cycle of eBAT followed by adjuvant doxorubicin in an adaptive dose-finding, phase I- II study of 23 dogs with spontaneous, stage I-II, splenic HSA. eBAT improved 6-month survival from <40% in a comparison population to ~70% in dogs treated at a biologically active dose (50 μg/kg). Six dogs were long-term survivors, living >450 days. eBAT abated expected toxicity associated with EGFR-targeting, a finding supported by mouse studies. Urokinase plasminogen activator receptor (uPAR) and EGFR are targets for human sarcomas, so thorough evaluation is crucial for validation of the dog model. Thus, we validated these markers for human sarcoma targeting in the study of 212 human and 97 canine sarcoma samples. Our results support further translation of eBAT for human patients with sarcomas and perhaps other EGFR-expressing malignancies.
2017-02-23 | GSE95183 | GEO
Project description:Splenic masses are common in older dogs and may be malignant, benign, or non-neoplastic; yet diagnosis preceding splenectomy and histopathology remains elusive. MicroRNAs (miRNAs) are 18-25 nucleotide, single stranded, non-coding RNAs that play a role in post-transcriptional regulation. MicroRNAs in tumor samples have been used to diagnose tumors, provide prognostic information, and aid in targeted treatments in human medicine, but have not been extensively evaluated in veterinary medicine. The objective of this study was to determine differential expression of microRNAs (miRNAs) between canine splenic hemangiosarcoma, canine splenic nodular hyperplasia, and normal canine spleens by use of RNA-sequencing. Eighteen miRNAs were found to be significantly differentially expressed between hemangiosarcoma and nodular hyperplasia only. The five of these with the largest fold change were mir-193a, mir-450a, mir-503, mir-542, and mir-876. Four miRNA were significantly differentially expressed between hemangiosarcoma and nodular hyperplasia and also hemangiosarcoma and normal spleen (mir-126, mir-150, mir-203, and mir-452). Findings of this study show that miRNA expression profiles are different between canine splenic hemangiosarcoma, nodular hyperplasia, and normal spleens. This is a preliminary study with findings of clinical relevance, as masses of the spleen cannot be diagnosed pre-operatively in most cases. Canine splenic masses are relatively common, and validation these findings is warranted for potential use as a diagnostic test.
2016-09-29 | GSE81113 | GEO
Project description:Kdm2b promotes cell viability by enhancing DNA damage response in canine hemangiosarcoma
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