Project description:mRNA expression profiling of pancreatic cancer, comparing adjacent normal tissue, patient tumour and first generation patient derived xenograft tumours Fresh tumour samples for human pancreatic adenocarcinoma patients were implanted in SCID mice. 70% of these pancreatic ductal adenocarcinoma patients grew as PDX tumours, confirmed by histopathology. Frozen samples from F1 PDX tumours could be later successful passaged in SCID mice to F2 PDX tumours. The human origin of the PDX was confirmed using human specific antibodies; however, the stromal component was replaced by murine cells. Cell lines were successfully developed from three PDX tumours. RNA was extracted from 8 PDX tumours and where possible, corresponding primary tumour and adjacent normal tissues. mRNA profiles of tumour vs F1 PDX and normal vs tumour were compared by Affymetric microarray analysis
Project description:Analysis of primary PDAC cells established from Pdx-1CreAPCL/+p53L/L and Pdx-1Crep53L/L mice. APC haploinsufficiency combined with P53 loss in the pancreas drives MCN progression in mice. Results provide insight into molecular mechanisms invloved in the MCN formation of Pdx-1Cre APCL/+P53L/L mice. Pdx-1CreAPC+/LP53L/L PDAC cell lines and 2 Pdx-1CreP53L/L ductal cell lines were analyzed.
Project description:OCT-embedded PDAC tissues were assessed for stromal and tumour epithelial regions which were both laser-capture microdissected from 33 patients. Integration of these proteomic profiles with transcriptomic data lead to the identification of two spatially confined tumour microenvironment programs: deserted and reactive.
Project description:Analysis of primary PDAC cells established from Pdx-1CreAPCL/+p53L/L and Pdx-1Crep53L/L mice. APC haploinsufficiency combined with P53 loss in the pancreas drives MCN progression in mice. Results provide insight into molecular mechanisms invloved in the MCN formation of Pdx-1Cre APCL/+P53L/L mice.
Project description:<p>Cancer, including head and neck squamous cell carcinoma (HNSCC), induces changes to metabolism that drive the disease. Regional metabolomics can help to understand metabolic variation across the tumour including changes near the tumour core, where hypoxia is likely more pronounced. We apply ultra-high performance liquid chromatography-mass spectrometry metabolomics to regionally distinct patient tissue samples: tumour edge, tumour core and adjacent non-tumour. Statistical, correlation and pathway enrichment analyses were performed. Markers of hypoxia or pseudohypoxia—lactate, succinate, fumarate, and the lactate:pyruvate ratio—were elevated in both core and edge tumour regions relative to adjacent tissue, with a trend toward stronger changes in the core. One-carbon metabolites were altered in HNSCC, including tumour-associated increases of S-adenosylmethionine (SAM) and SAM metabolites (S-adenosylhomocysteine, polyamines, methylated nucleosides, dimethylarginine, trimethylysine and 1-methylnicotinamide). Histidine, tryptophan, choline and folate appear metabolically connected to one-carbon metabolism in HNSCC: histidine, L-kynurenine (tryptophan metabolite), some purine metabolites (including deoxyguanosine, deoxyinosine) and choline were elevated in tumour tissue; while histidine/SAM, L-kynurenine/deoxyguanosine, L-kynurenine/deoxyinosine and folate/methionine were correlated in tumour tissue only. Tumour edge and core exhibited similar one-carbon metabolic changes relative to non-tumour, but the magnitude of change was generally greater in the core reflecting location dependent variation of SAM metabolism in HNSCC.</p>
Project description:Pancreatic adenocarcinoma (PDAC) is one of the most lethal human malignancies and a major health problem. Patient-derived xenografts (PDX) are appearing as a prime approach for preclinical studies despite being insufficiently characterized as a model of the human disease and its diversity. We generated subcutaneous PDX from PDAC samples obtained either surgically or using diagnostic biopsies (endoscopic ultrasound guided fine needle aspirate). The extensive multiomics characterization of the xenografts demonstrated that PDX is a suitable model for preclinical studies, representing the diversity of the primary cancers. We generated subcutaneous PDX from PDAC samples obtained either surgically or using diagnostic biopsies (endoscopic ultrasound guided fine needle aspirate). The variable 'MultiOmicsClassification' indicates the resulting sample's group. 'CIMPclass' is the CpG island methylator phenotype as estimated from the methylation arrays analysis. In this dataset, Illumina Infinium HumanCode-24 BeadChips SNP arrays were used to analyze the DNA xenografts samples from pancreatic ductal adenocarcinoma.
Project description:Pancreatic adenocarcinoma (PDAC) is one of the most lethal human malignancies and a major health problem. Patient-derived xenografts (PDX) are appearing as a prime approach for preclinical studies despite being insufficiently characterized as a model of the human disease and its diversity. We generated subcutaneous PDX from PDAC samples obtained either surgically or using diagnostic biopsies (endoscopic ultrasound guided fine needle aspirate). The extensive multiomics characterization of the xenografts demonstrated that PDX is a suitable model for preclinical studies, representing the diversity of the primary cancers. this dataset, describe the RNA sequencing data used in the multiomics study.