Project description:Analysis of myofibroblast ablation at the gene expression level of PDAC tumors. Total RNA optained from pancreas of PDAC mice with and without aSMA myofibroblast ablated In addition, late stage aSMA ablated mice were treated with anti-CTLA4 treatment
Project description:We analyzed chromatin accessibility genome wide in EZH2KO and control cells derived from PDAC tumors of KrasG12D/PEC-IkkαΔPEC PDAC model mice to gain insight how the ablation of EZH2 affects the accessibility of genes involved in PDAC tumorigenesis.
Project description:KRAS* is required for PDAC tumor mantainence. To dissect the molecular mechanisms that regulated by KRAS* in PDAC tumors, we conducted RNA-seq analysis of KRAS*-expressing iKPC PDAC tumors and iKPC tumors after KRAS* extinction for 24 hours.
Project description:Pancreatic ductal adenocarcinoma is an aggressive disease with a dismal five-year survival of 5%. Gene expression profiling has been instrumental for subtype classification in cancer, highlighting fundamental differences in tumors at the molecular level. Over the last years, multiple genomics studies have led to the classification of PDAC into two major subtypes: classical and basal-type. The classical subtype expresses higher levels of endodermal lineage specifiers, including HNF4A, GATA6, FOXA2, FOXA3 than the basal-type. The basal-type confers a worse prognosis, raising the possibility that loss of these lineage specifiers might enhance the malignant potential of PDAC. We found that the lineage specifier HNF4a plays a key role in maintaining a transcriptional network that characterizes the classical subtype, restraining growth in different PDAC models. Additionally, we demonstrated that HNF4a controls PDAC cell identity and proliferation, and represses the expression of SIX family members, two mesodermal lineage specifiers highly expressed in basal-type.
Project description:We investigated differences between CD90- myCAFs and CD90+ myCAFs flow-sorted from murine PDAC tumors derived from the orthotopic transplantation of PDAC KPC T-LOH organoids
Project description:RBFOX2 is an RNA binding protein that directs alternative splicing. In this study, we characterized RBFOX2-mediated alternative splicing in pancreatic cancer (PDAC) In this dataset, we assayed gene-level and exon-level expression differences in pancreatic cancer cell lines replete and depleted for RBFOX2 expression and in 8 pairs of orthotopic pancreas tumors and related liver metastases generated from human 4039 or Panc1 cell lines replete or depleted for RBFOX2.
Project description:Metastatic pancreatic adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the United States, with a 5-year survival rate of only 11%, necessitating identification of novel treatment paradigms. Tumor tissue specimens from patients with PDAC, breast cancer, and other solid tumor malignancies were collected and tumor cells were enriched using laser microdissection (LMD). Reverse phase protein array (RPPA) analysis was performed on enriched tumor cell lysates to quantify a 32-protein/phosphoprotein biomarker panel comprising known anticancer drug targets and/or cancer-related total and phosphorylated proteins, including HER2Total, HER2Y1248, and HER3Y1289. RPPA analysis revealed significant levels of HER2Total in PDAC patients at abundances comparable to HER2-positive (IHC 3+) and HER2-low (IHC 1+ /2+ , FISH-) breast cancer tissues, for which HER2 screening is routinely performed. These data support a critical unmet need for routine clinical evaluation of HER2 expression in PDAC patients and examination of the utility of HER2-directed antibody-drug conjugates in these patients.
Project description:In this dataset, we included expression data obtained from 30 resected human PDAC tumors, to examine what genes are differentially expressed in different cohorts that might lead to various outcomes The two cohorts we have are defined as short term survivors (STS) with median survival of >3 month and <1 year postsurgery, and long term survivors (LTS) with overall survival of >3 years postsurgery.
Project description:We investigated changes in CAFs and epithelial cells flow-sorted from PDAC tumors derived from the orthotopic transplantation of PDAC T-LOH KPC organoids in C57BL/6J mice following 2-week treatment with Neratinib compared to vehicle