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Full-Text Articles in Medicine and Health Sciences
Molecular Drivers Of Bladder Cancer Motility, Bryan Wehrenberg
Molecular Drivers Of Bladder Cancer Motility, Bryan Wehrenberg
Dissertations & Theses (Open Access)
Bladder cancer (BC) progression is measured by the degree of tumor cell invasion into the bladder wall and dissemination to distant sites. The study of BC cell motility will both enable development of anti-invasion therapeutics to limit progression of early-stage disease and improve our understanding of the metastatic process which drives patient mortality in BC. BCs display a great deal of intertumoral heterogeneity, and can be divided into basal and luminal subtypes, which are biologically and clinically distinct entities. Here, I examine the invasion phenotypes of BC as a function of both subtype and epithelial to mesenchymal transition (EMT) status. …
Inhibition Of Urothelial Carcinoma By Type I Interferon Activation Of The Innate And Adaptive Immune Response, Devin Plote
Inhibition Of Urothelial Carcinoma By Type I Interferon Activation Of The Innate And Adaptive Immune Response, Devin Plote
Dissertations & Theses (Open Access)
Bacillus Calmette-Guerin (BCG) is the first line therapy for bladder cancer patients with non-invasive disease. However, roughly 40% of patients exhibit no response, tumor recurrence or tumor progression following BCG treatment. Type I interferon (IFN-I) has potent anti-tumor effects against urothelial carcinoma (UC) and may be an alternative treatment option for patients who do not respond to BCG standard of care. However, the mechanisms that mediate the IFN-I-stimulated immune responses against UC are not fully elucidated. Herein, we evaluated the anti-tumor mechanisms of IFN-I in UC by use of adenoviral interferon-α (Ad-IFNα/Syn3) in human patients, and poly(I:C) or lentiviral IFNa …
Strategies To Sensitize Bladder Cancer Cells To Small Molecule Inhibitors Targeting The Pi3k Pathway, Giovanni Nitti
Strategies To Sensitize Bladder Cancer Cells To Small Molecule Inhibitors Targeting The Pi3k Pathway, Giovanni Nitti
Dissertations & Theses (Open Access)
After many years of cancer research, it is well accepted by the scientific community that the future cure for this disease lies in a personalized therapeutic approach. Anticipating therapeutic outcome based on the genetic signature of a tumor has become the new paradigm. The PI3K pathway represents an ideal target for bladder cancer, as many of the key proteins of this pathway are altered or mutated in this particular type of cancer. Several small molecule inhibitors have been developed to target this pathway, but their efficacy has been shown to be heterogeneous among different cell lines and mostly cytostatic but …
Mechanisms Underlying The Heterogeneous Sensitivities Of Cancer Cells To Proteasome Inhibitors, Matthew C. White
Mechanisms Underlying The Heterogeneous Sensitivities Of Cancer Cells To Proteasome Inhibitors, Matthew C. White
Dissertations & Theses (Open Access)
The mechanisms underlying cellular response to proteasome inhibitors have not been clearly elucidated in solid tumor models. Evidence suggests that the ability of a cell to manage the amount of proteotoxic stress following proteasome inhibition dictates survival. In this study using the FDA-approved proteasome inhibitor bortezomib (Velcade®) in solid tumor cells, we demonstrated that perhaps the most critical response to proteasome inhibition is repression of global protein synthesis by phosphorylation of the eukaryotic initiation factor 2-α subunit (eIF2α). In a panel of 10 distinct human pancreatic cancer cells, we showed marked heterogeneity in the ability of cancer cells to induce …