Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pancreatic cancer organoids recapitulate disease and allow personalized drug screening

ABSTRACT: We report derivation of 30 Patient-Derived Organoid lines (PDOs) from tumors arising in the pancreas and distal bile duct. PDOs recapitulate tumor histology and contain genetic alterations typical for pancreatic cancer. In vitro testing of a panel of 76 therapeutic agents revealed sensitivities currently not exploited in the clinic. The PRMT5 inhibitor EZP015556, shown to target MTAP negative tumors, was validated as such, but also appeared to constitute an effective therapy for a subset of MTAP+ tumors. Taken together, the work presented here provides a platform to identify novel therapeutics to target pancreatic tumor cells using PDOs.

PROVIDER: EGAS00001003369 | EGA |

REPOSITORIES: EGA

ACCESS DATA

Json Xml

Similar Datasets

Regional differences in human biliary tissues and corresponding in vitro derived organoids

Project description:RNA-Sequencing was performed on mechanically dissociated, epithelial-enriched samples, of human extrahepatic biliary tissue from Gallbladder, Common Bile Duct, and Pancreatic Duct tissues. Sequencing was also performed on in vitro cultures of Organoid cell lines at passage 5 that were derived from human Gallbladder, Common Bile Duct, Pancreatic Duct, or Intrahepatic Bile Ducts.

2019-01-20 | E-MTAB-7569 | biostudies-arrayexpress

Integrated Genomic Analysis of Periampullary Tumors

Project description:<p>Adenocarcinomas arising in the complex environment of the ampulla of Vater constitute a histopathological heterogenous group, presumably originating from the different epithelial cellular constituents present at the site: pancreas, bile duct, and intestinal duodenum. These tumors have been described in many different ways: intra-ampullary, periampullary, intra-ampullary papillary-tubular neoplasm, ampullary-ductal, periampullary-duodenal, and ampullary-not otherwise specified. These varied classifications reflect the difficulty in classifying these tumors into specific groups. Only the tumors clearly localized in the bile duct or duodenum are identified as distal cholangiocarcinomas (CAC) or duodenal adenocarcinomas (DUOAC). The current classification is based on macroscopic features that may distinguish the epithelium of origin, microscopic features, clinicopathological criteria, histopathology and expression of differential markers. This classification is subjective and prone to inter-observer variability and significantly impacts on treatment selection and therapeutic development.</p> <p>In order to define subtypes of periampullary cancer with clinical relevance, we performed whole exome sequencing and copy number analysis of 160 cancers arising in the periampullary region, 62 of these clearly arising from either the bile duct (n = 44), or the duodenum (n = 18) and 98 periampullary cancers (AMPAC) where the epithelium of origin could not be clearly defined.</p>

| phs000895 | dbGaP

Comparison of gene expression similarity between mouse extrahepatic bile duct and pancreatic duct epithelia and organoids prepared from these epithelia.

Project description:By RNA sequencing we found that extrahepatic bile duct organoids and pancreatic duct organoids have similar gene expression signatures compared with duct epithelia.

2023-06-06 | GSE196394 | GEO

Single cell RNA-seq defines novel heterogeneity within the pancreatic ductal tree

Project description:Lineage tracing using genetically engineered mouse models has become an essential tool for investigating cell-fate decisions of progenitor cells and biology of mature cell types, with respect to physiology and disease progression. To study disease development, an inventory of an organ’s cell types and understanding of physiologic function is paramount. Here, we performed single-cell RNA sequencing to examine heterogeneity of murine pancreatic duct cells, pancreatobiliary cells, and intrapancreatic bile duct cells. We isolated duct cells within the murine pancreas using the DBA lectin sorting strategy that labels all pancreatic duct cell types. Our data contest the paradigm suggested by previous single cell studies that murine pancreatic duct cells are homogenous. We describe an epithelial mesenchymal transitory axis among our two subpopulations of pancreatic duct cells and identify SPP1 as a regulator of this phenotype and human duct cell de-differentiation. Our results further define functional heterogeneity of pancreatic duct subpopulations by elucidating a role for Geminin in accumulation of DNA damage in the setting of chronic pancreatitis. Our findings implicate diverse functional roles for subpopulations of pancreatic duct cells in disease progression and establish a comprehensive road map of murine pancreatic duct cell, pancreatobiliary cell, and intrapancreatic bile duct cell homeostasis.

2021-02-28 | GSE159343 | GEO

Differential gene expression profiling of cultured neu-transformed versus spontaneously-transformed rat cholangiocytes and of corresponding cholangiocarcinomas

Project description:Characterization of preclinical models of intrahepatic cholangiocarcinoma progression that reliably recapitulate altered molecular features of the human disease. Here, we performed comprehensive gene expression profiling of cholangiocarcinoma tumors arising from bile duct inoculation of different grade malignant rat cholangiocytes. Tumors arising from bile duct inoculation of spontaneously-transformed low grade malignant rat BDE1 cholangiocytes (BDEsp cells) compared to tumors arising from the inoculation of high grade malignant erbB-2/neu- transformed BDE1 cholangiocytes (BDEneu cells) into the livers of syngeneic rats.

2012-06-20 | E-GEOD-38834 | biostudies-arrayexpress

Development of blood biomarkers that distinguish pancreatic cancer from biliary tract cancer

Project description:We have developed a method for diagnosing pancreatic cancer and bile duct cancer based on miRNA expression information in the circulating blood. 2565 miRNAs in 426 serum samples were analyzed.

2023-06-30 | GSE212211 | GEO

Genomic profiling identifies GATA6 as a candidate oncogene amplified in pancreatobiliary cancer

Project description:Pancreatobiliary cancers have among the highest mortality rates of any cancer type. Discovering the full spectrum of molecular genetic alterations may suggest new avenues for therapy. To catalogue genomic alterations, we carried out array-based genomic profiling of 31 exocrine pancreatic cancers and 6 distal bile duct cancers, expanded as xenografts to enrich the tumor cell fraction. We identified numerous focal DNA amplifications and deletions, including in 19% of pancreatobiliary cases gain at cytoband 18q11.2, a locus uncommonly amplified in other tumor types. The smallest shared amplification at 18q11.2 included GATA6, a transcriptional regulator previously linked to normal pancreas development. When amplified, GATA6 was overexpressed at both the mRNA and protein level, and strong immunostaining was observed in 25 of 54 (46%) primary pancreatic cancers compared to 0 of 33 normal pancreas specimens surveyed. GATA6 expression in xenografts was associated with specific microarray gene-expression patterns, enriched for GATA binding sites and mitochondrial oxidative phosphorylation activity. siRNA mediated knockdown of GATA6 in pancreatic cancer cell lines with amplification led to reduced cell proliferation, cell cycle progression, and colony formation. Our findings indicate that GATA6 amplification and overexpression contribute to the oncogenic phenotypes of pancreatic cancer cells, and implicate GATA6 as a lineage-specific oncogene in pancreatobiliary cancer, with implications for novel treatment strategies. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Tissue type: cancer xenograft from diff tissues Keywords: Logical Set cDNA microarrays from the Stanford Functional Genomics Facility were used to perform gene expression profiling on 28 out of 31 of the exocrine pancreatic cancer and all 6 distal bile duct cancer xenografts. Using regression correlation

2008-07-18 | E-GEOD-11152 | biostudies-arrayexpress

Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor

Project description:Decreased bile secretion in rodents by either ligation of the common bile duct or induction of cirrhosis causes changes in the small intestine, including bacterial overgrowth and translocation across the mucosal barrier. Oral administration of bile acids inhibits these effects. The genes regulated by FXR in ileum suggested that it might contribute to the enteroprotective actions of bile acids. To test this hypothesis, mice were administered either GW4064 or vehicle for 2 days and then subjected to bile duct ligation (BDL) or sham operation. After 5 days, during which GW4064 or vehicle treatment was continued, the mice were killed and their intestines were analyzed for FXR target gene expression. Mice were treated with or without FXR ligand GW4064 for 2 days prior to bile duct ligation surgery and for 5 days after surgery. After 5 days the mice were sacrificed and the ileum collected and processed for gene expression analysis. Gene expression in the ilium from each sample group was assayed in duplicate using Affymetrix Mouse Genome 430A 2.0 Gene Chips.

2012-09-12 | E-GEOD-40821 | biostudies-arrayexpress

Methylation analysis of normal and tumor bile duct samples

Project description:Genome wide DNA methylation profiling of normal and tumor bile duct samples. The Illumina HumanMethylation450 BeadChip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in 138 tumor bile duct samples and 4 normal bile duct samples.

2017-07-03 | GSE89803 | GEO

Human bile cholangiocyte organoids originate from the extrahepatic bile duct and can repair bile duct scaffolds in vitro

Project description:Cholangiocyte organoids provide a powerful tool for characterizing bile duct epithelium and expanding cholangiocytes for tissue engineering purposes. However, this involves invasively obtained tissue-biopsies via surgery which is not preferential and limits the patient-specific capacities of these cultures. To overcome this, organoid culture were initiated from minimal invasive bile-samples obtained during routine clinical procedures. Characterization revealed that these bile-cholangiocyte organoids originate from the extrahepatic bile duct and are capable to repopulate human extrahepatic bile duct scaffolds. With this, bile duct tissue engineering as well as personalized disease modelling is in sight.

2020-11-19 | GSE156519 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data