Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA241099 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Patient-derived xenograft models are considered to represent the heterogeneity of human cancers and might be more relevant preclinical models to evaluate effective therapeutic agents. Our consortium joins efforts to extensively develop and characterize a new collection of patient-derived colorectal cancer models. From 86 unsupervised surgical colon sample collection, 54 tumors were successfully xenografted in immunodeficient mice and rats, representing 35 primary tumors, 5 peritoneal carcinosis and 14 metastases. Our histological and molecular characterization of patient tumors, first passage on mice and later passages includes the sequence of key genes involved in CRC (ie APC, KRAS, TP53), CGH array and transcriptomic analysis. This comprehensive characterization demonstrates that our collection recapitulates the clinical situation regarding the histopathological and molecular diversity of colorectal cancers. Moreover, patient tumors and corresponding models are clustering together which gives the opportunity to look for relevant signatures and comparison studies between clinical and preclinical data. Hence, we performed pharmacological monotherapy studies with standard of care for colon cancer (5-FU, oxaliplatin, irinotecan, cetuximab). Through this extensive in vivo analysis, we have compared the molecular profile with the drug sensitivity of each tumor models, and run an equivalent of a cetuximab phase II clinical trial in a preclinical setting. Our results confirm the key role of KRAS mutation in the cetuximab resistance and demonstrate that such collection could bring benefit to evaluate novel targeted therapeutic strategies and potentially help the stratification strategy for cancer patients according to molecular marker. This set correspond to 82 CGH profiles, with 7 samples from patient tumor and 75 samples from mouse xenograft at different passages P0 to P9. All hybridizations are performed with Human CGH 244K Agilent arrays (amadid 014693) in dual color with Human DNA Promega (sex matched) as reference. ID for biosources without an -Px suffix correspond to tumor patients. ID with a suffix correspond to xenograft with 0 for the first passage.
2012-07-27 | E-MTAB-991 | biostudies-arrayexpress
Project description:Patient-derived xenograft models are considered to represent the heterogeneity of human cancers and might be more relevant preclinical models to evaluate effective therapeutic agents. Our consortium joins efforts to extensively develop and characterize a new collection of patient-derived colorectal cancer models. From 86 unsupervised surgical colon sample collection, 54 tumors were successfully xenografted in immunodeficient mice and rats, representing 35 primary tumors, 5 peritoneal carcinosis and 14 metastases. Our histological and molecular characterization of patient tumors, first passage on mice and later passages includes the sequence of key genes involved in CRC (ie APC, KRAS, TP53), CGH array and transcriptomic analysis. This comprehensive characterization demonstrates that our collection recapitulates the clinical situation regarding the histopathological and molecular diversity of colorectal cancers. Moreover, patient tumors and corresponding models are clustering together which gives the opportunity to look for relevant signatures and comparison studies between clinical and preclinical data. Hence, we performed pharmacological monotherapy studies with standard of care for colon cancer (5-FU, oxaliplatin, irinotecan, cetuximab). Through this extensive in vivo analysis, we have compared the molecular profile with the drug sensitivity of each tumor models, and run an equivalent of a cetuximab phase II clinical trial in a preclinical setting. Our results confirm the key role of KRAS mutation in the cetuximab resistance and demonstrate that such collection could bring benefit to evaluate novel targeted therapeutic strategies and potentially help the stratification strategy for cancer patients according to molecular marker. This set correspond to 82 CGH profiles, with 7 samples from patient tumor and 75 samples from mouse xenograft at different passages P0 to P9. All hybridizations are performed with Human CGH 244K Agilent arrays (amadid 014693) in dual color with Human DNA Promega (sex matched) as reference. ID for biosources without an -Px suffix correspond to tumor patients. ID with a suffix correspond to xenograft with 0 for the first passage.
2012-07-27 | E-MTAB-992 | biostudies-arrayexpress
Project description:Prostate cancer discovery and translational research are hampered by a lack of preclinical models which accurately reproduce the biological heterogeneity observed in patients. Accordingly, we have established a bank of transplantable patient-derived prostate tumor xenograft lines, using subrenal capsule grafting of human tumor tissue into immuno-deficient mice. This panel includes the first lines generated from primary prostate cancer tissue, and also new lines from metastatic tissue. Critically, the lines retained salient features of the original patient tumors, including histopathology, clinical marker expression, chromosomal aberration and gene expression profiles. Furthermore, they span major histopathological and molecular subtypes of prostate cancer, capturing diverse inter- and intra-tumoral heterogeneity. Host castration led to the development of castrate-resistant tumors, including the first model of complete neuroendocrine transdifferentiation. This publicly-available resource provides novel tools to advance mechanistic understanding of disease progression and response to therapy, and delivers clinically-relevant model systems for evaluation of preclinical drug efficacy. 3 primary tumors and 21 xenograft tumors
2013-01-12 | E-GEOD-41188 | biostudies-arrayexpress
Project description:Prostate cancer discovery and translational research are hampered by a lack of preclinical models which accurately reproduce the biological heterogeneity observed in patients. Accordingly, we have established a bank of transplantable patient-derived prostate tumor xenograft lines, using subrenal capsule grafting of human tumor tissue into immuno-deficient mice. This panel includes the first lines generated from primary prostate cancer tissue, and also new lines from metastatic tissue. Critically, the lines retained salient features of the original patient tumors, including histopathology, clinical marker expression, chromosomal aberration and gene expression profiles. Furthermore, they span major histopathological and molecular subtypes of prostate cancer, capturing diverse inter- and intra-tumoral heterogeneity. Host castration led to the development of castrate-resistant tumors, including the first model of complete neuroendocrine transdifferentiation. This publicly-available resource provides novel tools to advance mechanistic understanding of disease progression and response to therapy, and delivers clinically-relevant model systems for evaluation of preclinical drug efficacy. 3 primary tumors and 22 xenograft tumors
2013-01-12 | E-GEOD-41192 | biostudies-arrayexpress
Project description:Mouse models have been developed to investigate colorectal cancer etiology and evaluate new anti-cancer therapies. While genetically engineered and carcinogen-induced mouse models have provided important information with regard to the mechanisms underlying the oncogenic process, xenograft models remain the standard for the evaluation of new chemotherapy and targeted drug treatments for clinical use. However, it remains unclear if drug efficacy data obtained from xenograft models translate into clinically-relevant treatment modalities. In this study, we have generated a panel of 28 patient-derived colorectal cancer explants (PDCCEs), an extension of our previous work, by direct transplantation of human colorectal cancer (CRC) tissues into NOD-SCID mice. A comprehensive histological and molecular evaluation of PDCCEs and their corresponding patient tumor demonstrates that PDCCEs maintain histological features and global biology through multiple passages. Furthermore, we demonstrate that in vivo sensitivity of PDCCEs to oxaliplatin can predict patient outcomes. Our findings suggest that PDCCEs maintain similarity to the patient tumor from which they are derived and can serve as a reliable preclinical model that can be incorporated into future strategies to optimize individual therapy for patients with CRC. 28 human primary colorectal and 37 mouse derived colorectal explant tumors
2012-06-06 | E-GEOD-35144 | biostudies-arrayexpress
Project description:We established a large panel of preclinical models of human RCC directly from patients, faithfully reproducing the biological features of the original tumor. RCC tissues were collected for 8 years from 336 patients undergoing surgery, xenografted subcutaneously in nude mice, and serially passaged into new mice up to 13 passages. Tissue samples from the primary tumor and tumors grown in mice through passages were analyzed at the histology, genetic and for of them at the molecular levels for biological tissue stability. We established a large panel of 30 RCC models and 5 them of the clear cell type (clear cell renal cell carcinoma, CCC) were characterized at the mRNA expression level. We used Affymetrix whole genome microarrays to analyze the stability of the PDX models comparing the primary tumor (P0) with the subsequent passages in mice (P1 â¦).
2016-06-29 | E-GEOD-83820 | biostudies-arrayexpress
Project description:Preclinical models are essential for advancing therapeutic strategies in hepatocellular carcinoma (HCC), an aggressive disease with poor survival outcomes. Here, we established genetically defined HCC models by ex vivo CRISPR editing of porcine hepatocytes. Hepatocytes were isolated from Yucatan minipigs and subjected to combinations of 2-4 gene alterations, including CRISPR-mediated knockout of tumor suppressor genes (TP53, PTEN, CDKN2A, AXIN1), with or without c-myc overexpression. Edited hepatocytes were expanded in culture, and those harboring at least three gene alterations formed tumors in SCID mice that recapitulated human HCC histologically. Clonal derivatives from the cell pools generated mouse xenograft tumors with distinct liver cancer histological features. Transcriptomic profiling of the cell models and xenograft tumors revealed activation of cell cycle pathways and similarity with human HCC. Further, autologous intrahepatic implantation of edited hepatocytes into pigs produced tumors with prominent immune infiltration, establishing an immune-competent large-animal model of HCC. Collectively, this HCC modeling platform provides insights into cooperative gene alterations underlying HCC pathogenesis and enables preclinical testing of systemic and locoregional therapies in a clinically relevant large-animal context.
2025-12-01 | GSE311743 | GEO
Project description:We established a large panel of preclinical models of human RCC directly from patients, faithfully reproducing the biological features of the original tumor. RCC tissues were collected for 8 years from 336 patients undergoing surgery, xenografted subcutaneously in nude mice, and serially passaged into new mice up to 13 passages. Tissue samples from the primary tumor and tumors grown in mice through passages were analyzed at the histology, genetic and for of them at the molecular levels for biological tissue stability. We established a large panel of 30 RCC models and 5 them of the clear cell type (clear cell renal cell carcinoma, CCC) were characterized at the mRNA expression level.
2016-06-29 | GSE83820 | GEO
Project description:Chronic liver diseases are worldwide on the rise. Due to the rapidly increasing incidence, in particular in Western countries, non-alcoholic fatty liver disease (NAFLD) is gaining importance. As the disease progresses it can develop into hepatocellular carcinoma. Lipid accumulation in hepatocytes has been identified as the characteristic structural change in NAFLD development, but the molecular mechanisms responsible for disease development remained unresolved. Here, we uncover a strong downregulation of the PI3K-AKT pathway and an upregulation of the MAPK pathway in primary hepatocytes from a preclinical model fed with a Western diet (WD). Dynamic pathway modeling of hepatocyte growth factor (HGF) signal transduction combined with global proteomics identifies that an elevated basal MET phosphorylation rate is the main driver of altered signaling leading to increased proliferation of WD-hepatocytes. Model-adaptation to patient-derived hepatocytes reveals a patient-specific variability in basal MET phosphorylation, which correlates with the outcome of patients after liver surgery. Thus, dysregulated basal MET phosphorylation could be an indicator for the health status of the liver and thereby inform on the risk of a patient to suffer from liver failure after surgery.
2025-03-24 | BIOMD0000001102 | BioModels
Project description:This dataset contains RNA-seq profiles of patient-derived xenograft (PDX) tumors established from human ovarian clear cell carcinoma (OCCC). Tumor tissues were collected without any therapeutic treatment and used to generate xenografts in immunodeficient mice. Total RNA was extracted from the PDX tumors and sequenced on the Illumina NovaSeq 6000 platform using 150 bp paired-end reads. These data represent the baseline transcriptomic landscape of OCCC tumors and may serve as a resource for studying tumor biology and preclinical model characterization.
2025-12-15 | GSE298088 | GEO