Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA208530 | ENA |
REPOSITORIES: ENA
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Project description:Pancreatic ductal adenocarcinoma (PDAC) has one of the worst prognoses of any human malignancy and there are few human cellular models of disease progression. When human PDAC cells are injected into immunodeficient animals, they create tumors of the late stage from which they were derived. We hypothesized that if human pancreatic cancer cells were converted to pluripotency and then allowed to differentiate back into pancreas, the developmental progression would recapitulate early stages of the cancer. To that end, we have generated isogenic matched sets of induced pluripotent stem (iPS) cell-like lines from epithelial cells of human pancreatic tumors and from histologically normal epithelial cells at the resected pancreatic margins. Notably, when injected into immunodeficient mice, at low or high passages, a human pancreatic cancer iPS-like line, but not the corresponding margin iPS-like line, slowly generates intra-epithelial neoplasia (PanIN) ductal structures that typically reflect the early stages of human pancreatic cancer. The PanIN-like ducts can be isolated and cultured. They secrete protein products reflective of PanINs and provide new insights into underlying regulatory networks. An additional iPS-like line from histologically normal cells at a pancreatic resection margin, but containing a mutation that predisposes to PDAC, does not generate PanIN ductal structures. These studies demonstrate that iPS technology can be exploited to recapitulate early progression events of a human epithelial cancer. Study includes a single experiment (#10): a tumor-adjacent pancreatic tissue control (10N); tumor tissue (10C); IPS-transformed tissue control (10N12); and IPS-transformed tumor tissue (10C22).
2013-06-20 | E-GEOD-47985 | biostudies-arrayexpress
Project description:Pancreatic ductal adenocarcinoma (PDAC) has one of the worst prognoses of any human malignancy and there are few human cellular models of disease progression. When human PDAC cells are injected into immunodeficient animals, they create tumors of the late stage from which they were derived. We hypothesized that if human pancreatic cancer cells were converted to pluripotency and then allowed to differentiate back into pancreas, the developmental progression would recapitulate early stages of the cancer. To that end, we have generated isogenic matched sets of induced pluripotent stem (iPS) cell-like lines from epithelial cells of human pancreatic tumors and from histologically normal epithelial cells at the resected pancreatic margins. Notably, when injected into immunodeficient mice, at low or high passages, a human pancreatic cancer iPS-like line, but not the corresponding margin iPS-like line, slowly generates intra-epithelial neoplasia (PanIN) ductal structures that typically reflect the early stages of human pancreatic cancer. The PanIN-like ducts can be isolated and cultured. They secrete protein products reflective of PanINs and provide new insights into underlying regulatory networks. An additional iPS-like line from histologically normal cells at a pancreatic resection margin, but containing a mutation that predisposes to PDAC, does not generate PanIN ductal structures. These studies demonstrate that iPS technology can be exploited to recapitulate early progression events of a human epithelial cancer.
2013-06-20 | GSE47985 | GEO
Project description:Whole transcriptome RNA sequencing (RNA-seq) of human induced pluripotent stem cell lines from three independent donors at seven islet developmental stages: definitive endoderm (DE), primitive gut tube (GT), posterior foregut (PF), pancreatic endoderm (PE), endocrine progenitors (EP), endocrine-like cells (EN), and beta-like cells (BLC).
| EGAD00001003807 | EGA
Project description:To further development of our lncRNA and mRNA expression approach to pancreatic ductal adenocarcinoma(PDAC), we have employed lncRNA and mRNA microarray expression profiling as a discovery platform to identify lncRNA and mRNA expression in pancreatic ductal adenocarcinoma.Human pancreatic ductal adenocarcinoma tissues and normal pancreatic tissues from PDAC donors and other duodenum diseases donors. analyze mRNA and lncRNA expression in pancreatic ductal adenocarcinoma (PDAC) by microarray platform
2014-11-18 | E-GEOD-57144 | biostudies-arrayexpress
Project description:The aggressiveness of pancreatic ductal adenocarcinoma (PDAC) is affected by a tumor microenvironment (TME). In this study, to recapitulate PDAC TME ex vivo, we cocultured patient-derived PDAC cells with mesenchymal and vascular endothelial cells derived from human induced-pluripotent stem cells (hiPSCs) to create a fused pancreatic cancer organoid (FPCO) in air–liquid interface. FPCOs were further induced to resemble two distinct parts of a PDAC tissue. Owing to various types of cancer associated fibroblasts (CAFs) derived from hiPSCs, the TME consisted of abundant extracellular matrix proteins, which likely conferred strong drug resistance to PDAC cells in one type of FPCOs. Because of re-proliferation capacity of PDAC cells after anticancer drug treatment, the other FPCO is the first culture system for investigating PDAC recurrence. Introducing hiPSC technology, we have created, for the first time, the PDAC organoids representing the heterogeneity of PDAC tissue, a potential platform for screening anticancer drugs.
2023-11-13 | GSE243647 | GEO
Project description:The aggressiveness of pancreatic ductal adenocarcinoma (PDAC) is affected by a tumor microenvironment (TME). In this study, to recapitulate PDAC TME ex vivo, we cocultured patient-derived PDAC cells with mesenchymal and vascular endothelial cells derived from human induced-pluripotent stem cells (hiPSCs) to create a fused pancreatic cancer organoid (FPCO) in air–liquid interface. FPCOs were further induced to resemble two distinct parts of a PDAC tissue. Owing to various types of cancer associated fibroblasts (CAFs) derived from hiPSCs, the TME consisted of abundant extracellular matrix proteins, which likely conferred strong drug resistance to PDAC cells in one type of FPCOs. Because of re-proliferation capacity of PDAC cells after anticancer drug treatment, the other FPCO is the first culture system for investigating PDAC recurrence. Introducing hiPSC technology, we have created, for the first time, the PDAC organoids representing the heterogeneity of PDAC tissue, a potential platform for screening anticancer drugs.
2023-11-13 | GSE243649 | GEO
Project description:Pancreatic ductal adenocarcinoma
| PRJNA432344 | ENA
Project description:Pancreatic ductal adenocarcinoma, caused by activating mutation in K-Ras, is an aggressive malignancy due to its early invasion and matastasis. Ral GTPases, negatively regulated by RalGAP, are activated downstream of Ras and play a crucial role in development and progression of pancreatic ductal adenocarcinoma. However, the underlying mechanisms remain unclear. We used microarrays to detail the global programme of gene expression underlying the human pancreatic ductal adenocarcinoma cell line, MIA PaCa-2 with RalGAPβ deficiency or not, and identified distinct classes of Ral activation-related mRNA.
2023-04-24 | GSE223382 | GEO
Project description:To further develop our understanding of the gene expression signature of pancreatic ductal adenocarcinoma Gene expression signatures in macrodissected resected pancreatic ductal adenocarcinoma specimens
2014-03-14 | E-GEOD-55643 | biostudies-arrayexpress