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Full-Text Articles in Gastroenterology
The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia
The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia
Dissertations & Theses (Open Access)
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …
Leveraging Single Cell Technologies For The Characterization And Treatment Of Refractory Pancreatic Cancer, Maria Monberg
Leveraging Single Cell Technologies For The Characterization And Treatment Of Refractory Pancreatic Cancer, Maria Monberg
Dissertations & Theses (Open Access)
Heterogeneity is a hallmark of cancer, and the advent of multimodal single-cell technologies has helped uncover heterogeneity in a high-throughput manner in different cancers across varied contexts at an unprecedented resolution. In an effort to improve precision medicine approaches in pancreatic ductal adenocarcinoma (PDAC), a highly lethal malignancy with a mere 11% 5-year survival rate, this dissertation focuses on first questioning the assumptions of the most basic models used to study PDAC via multimodal single-cell characterization methods at multiple levels of biological organization (scCNVseq and snATACseq for DNA assays, scRNAseq for transcriptomics, and paired protein assays such as multiplexed immunofluorescence …