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Articles 1 - 7 of 7
Full-Text Articles in Oncology
Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation And Progression, Janine M. Deblasi
Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation And Progression, Janine M. Deblasi
USF Tampa Graduate Theses and Dissertations
NRF2 is a redox-responsive transcription factor the directs the antioxidant program and several critical metabolic processes. Mutations in NRF2 or its negative regulator KEAP1 occur in up to one third of non-small cell lung cancers (NSCLCs) and are often associated with resistance to therapy and poor outcomes. In the present studies, murine alleles of the Keap1 and Nrf2 mutations found in human NSCLC were developed and I comprehensively investigated their impact on tumor initiation and progression. I observed that chronic Nrf2 stabilization by Keap1 loss-of-function or Nrf2 activating mutation was not sufficient to cause lung tumor initiation, even when p53 …
Histone Deacetylase 8 Is A Novel Therapeutic Target For Mantle Cell Lymphoma And Preserves Natural Killer Cell Cytotoxic Function, January M. Watters
Histone Deacetylase 8 Is A Novel Therapeutic Target For Mantle Cell Lymphoma And Preserves Natural Killer Cell Cytotoxic Function, January M. Watters
USF Tampa Graduate Theses and Dissertations
This study demonstrates for the first time that HDAC8 function is critical for MCL survival, and abrogating its activity in human primary NK cells does not interfere with NK IgG antibody directed ADCC therapies ex vivo. Human NK cells, isolated from healthy donors, are highly resistant to HDAC8 inhibitor treatment with PCI-34051. Even at the highest concentration, 20uM, no toxicity was observed. Conversely, MCL cell lines representative of the aggressive MCL subtype, classical MCL, were especially sensitive to PCI-34051, an HDAC8 selective inhibitor, treatment. Blocking HDAC8 activity and/or abrogating expression through shRNA silencing induced significant DNA damage, hyperacetylation of SMC3, …
Evolution Of Targeted Therapy Resistance In Eml4-Alk Positive Non-Small Cell Lung Cancer, Robert Vander Velde
Evolution Of Targeted Therapy Resistance In Eml4-Alk Positive Non-Small Cell Lung Cancer, Robert Vander Velde
USF Tampa Graduate Theses and Dissertations
Targeted therapies have emerged as potent treatments that lead to the remission of many tumors. However, they rarely cure cancers in advanced, metastatic settings. This is due to the evolution of resistance, which in turn can be ascribed to the survival of small subpopulations of tolerant and/or resistant cells. Here we investigated the evolution of resistance to EML4-ALK inhibitors in non-small cell lung cancer (NSCLC) and demonstrated that resistance evolves gradually, from unique pre-treatment sub-populations, as multiple resistance mechanisms accumulate in a Darwinian fashion. Despite accumulating multiple changes, cells evolved, in parallel, toward similar inhibitor specific phenotypes. Evolving cells have …
Understanding The Influence Of The Cancer Microenvironment On Metabolism And Metastasis, Shonagh Russell
Understanding The Influence Of The Cancer Microenvironment On Metabolism And Metastasis, Shonagh Russell
USF Tampa Graduate Theses and Dissertations
Cancer is a complex and heterogeneous disease. Not only is there considerable variability between different cancer types, but there is enormous variability between and within patients who have the same type of cancer. Within tumors, there are multiple cell types, including cancer cells, stromal cells, and immune cells. The tumor microenvironment often induces the healthy cells to become pro-tumorigenic. Cell metabolism is exquisitely sensitive to changes in the tumor microenvironment and can be measured to infer the aggressiveness of cancer and predict response to therapy. In this dissertation, we aim to understand how the microenvironment, specifically low pH, affects the …
Gene Expression Profiling And The Role Of Hsf1 In Ovarian Cancer In 3d Spheroid Models, Trillitye Paullin
Gene Expression Profiling And The Role Of Hsf1 In Ovarian Cancer In 3d Spheroid Models, Trillitye Paullin
USF Tampa Graduate Theses and Dissertations
Ovarian cancer is the most lethal gynecological cancer, with over 200,000 women diagnosed each year and over half of those cases leading to death. These poor statistics are related to a lack of early symptoms and inadequate screening techniques. This results in the cancer going undetected until later stages when the tumor has metastasized through a process that requires the epithelial to mesenchymal transition (EMT). In lieu of traditional monolayer cell culture, EMT and cancer progression in general is best characterized through the use of 3D spheroid models. In this study, we examine gene expression changes through microarray analysis in …
Matrix Metalloproteinase Genes Are Transcriptionally Regulated By E2f Transcription Factors: A Link Between Cell Cycle Control And Metastatic Progression, Jacqueline Lea Johnson
Matrix Metalloproteinase Genes Are Transcriptionally Regulated By E2f Transcription Factors: A Link Between Cell Cycle Control And Metastatic Progression, Jacqueline Lea Johnson
USF Tampa Graduate Theses and Dissertations
The RbµE2F transcriptional regulatory pathway plays a critical role in the cell cycle. Rb is inactivated through multiple waves of phosphorylation, mediated mainly by cyclin D and cyclin E associated kinases. Once Rb is inactivated, cells can enter Sµphase. Collectively, three Rb family members and ten E2F proteins coordinate every additional stage of the cell cycle, from quiescence to mitosis. However the RbµE2F pathway is frequently altered in cancer. Aside from cell proliferation, the RbµE2F pathway regulates other essential cellular processes including apoptosis, cell differentiation, angiogenesis and DNA damage repair pathways, but its role in invasion and cancer progression is …
Targeting Α4 Integrin Containing Complexes In Multiple Myeloma Using Peptidomimetics, Michael Foster Emmons
Targeting Α4 Integrin Containing Complexes In Multiple Myeloma Using Peptidomimetics, Michael Foster Emmons
USF Tampa Graduate Theses and Dissertations
In our previous work we demonstrated that the integrin antagonist, HYD1, induced necrotic cell death in myeloma cell lines in vitro and in vivo as a single agent. In order to further delineate biomarkers of response to HYD1 we developed an isogenic drug resistant variant named H929-60. We show that the acquisition of resistance towards HYD1 correlates with reduced expression of the cleaved α4 integrin subunit and beta 1 integrin. Moreover, we demonstrate that HYD1 interacts with α4 integrin in myeloma cells. Consistent with reduced VLA-4 expression, the resistant variant showed ablated functional binding to fibronectin, VCAM-1 and the bone …