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Biological And Proteomic Characterization Of Cornus Officinalis On Human 1.1b4 Pancreatic Β Cells: Exploring Use For T1d Interventional Application, Arielle E. Tawfik

USF Tampa Graduate Theses and Dissertations

Type 1 diabetes (T1D) is an autoimmune disease resulting in the loss of pancreatic β cells and subsequent loss of insulin production. Exogenous insulin coupled with continuous glucose monitoring is the only treatment for T1D. Therefore, novel interventional therapies are needed that can inhibit the autoimmune destruction and increase β cell proliferation and function. Based on initial in vitro studies, traditional Chinese medicine (TCM) extract, Cornus officinalis, may be able to serve in this function. CO has been used for 2 millennia for its glucose regulating potential and has shown efficacy in animal models but rarely studied in the context …

Inhibiting The Interaction Between Grp94 And Myocilin To Treat Primary Open-Angle Glaucoma, Andrew Stothert

USF Tampa Graduate Theses and Dissertations

Glaucoma is a neurodegenerative protein misfolding disorder classified by increases in IOP, damage to retinal ganglion cells (RGCs), optic nerve (ON) head damage, and progressive irreversible blindness. Primary open-angle glaucoma (POAG) is the most common form of glaucoma, constituting over 90% of clinical cases. POAG is observed in patients where normal outflow channels, mainly the trabecular meshwork (TM), are exposed at the angle formed by the iris and cornea. However, due to TM cellular dysfunction, aqueous outflow resistance is increased preventing normal circulation of aqueous humor. Recent studies have shown that in 2-4% of POAG cases, increased intracellular levels of …

Targeting Tau Degradation By Small Molecule Inhibitors For Treatment Of Tauopathies, Mackenzie Martin

USF Tampa Graduate Theses and Dissertations

Tauopathies are neurodegenerative diseases that affect millions of people around the world. Tauopathies include more than 20 neurodegenerative diseases. Some of the most common tauopathies are Alzheimer’s disease (AD), frontotemporal dementia (FTD), chronic traumatic encephalopathy (CTE), Pick’s disease, corticobasal degeneration, progressive supranuclear palsy (PSP), agyrophillic grain disease, and amyotrophic lateral sclerosis (ALS). These diseases can cause significant memory loss, behavioral changes, motor deficits and speech impairments. Tauopathies stem from accumulation of the microtubule associated protein tau (MAPT). Tau stabilizes microtubules and helps with axonal transport. In a disease state tau becomes hyperphosphorylated and truncated leading to its aggregation. More recently …

Potential Targeted Therapeutic Strategies For Overcoming Resistance In Braf Wild Type Melanoma, Vito William Rebecca

USF Tampa Graduate Theses and Dissertations

Melanoma manifests itself from the malignant transformation of melanocytes and represents the deadliest form of skin cancer, being responsible for the disproportionate majority of all skin cancer deaths. The 2002 discovery that 50% of all melanoma patients possess activating BRAF mutations ignited a significant paradigm shift in the way the melanoma field approached research and how patients were treated [1]. The era of targeted therapy had begun and with it came successful targeted BRAF inhibitor therapy regimens, which have accomplished improved clinical benefit (response rate, progression free survival, and overall survival) compared with treatment with chemotherapy in three phase III …

Characterization Of Iron Response In Gynecological Cell Lines, Kyle A. Bauckman

USF Tampa Graduate Theses and Dissertations

Ovarian carcinoma afflicts over 22,000 women each year with a 5 year survival rate of only 18% for stage IV patients [23]. Current treatment options are limited due to high rates of drug resistance and recurrence. Further, the identity of "precursor lesions" which give rise to various subclasses of epithelial ovarian cancer has been evasive. This is due to discovery of the cancer at already an advanced stage. Interestingly, endometriosis a benign but invasive gynecological disease has been described as a "precursor lesion" in the development of specific subtypes of ovarian cancer. Endometriotic cyst development involves the accumulation of "old …

Drug Resistance Mechanisms To Gamma-Secretase Inhibitors In Human Colon Cancer Cells, Cindy R. Timme

USF Tampa Graduate Theses and Dissertations

Colorectal cancer is the third leading cause of cancer-related mortality. Much progress has been achieved in combating this disease with surgical resection and chemotherapy in combination with targeted drugs. However, most metastatic patients develop drug resistance so new modalities of treatment are needed.

Notch signaling plays a vital role in intestinal homeostasis, self-renewal, and cell fate decisions during post-development and is activated in colorectal adenocarcinomas. Under debate is its role in carcinomas and metastatic disease. In theory, blocking Notch activation using gamma-secretase inhibitors (GSIs) may show efficacy alone or in combination with chemotherapy in the treatment of colon cancer.

In …

Molecular Mechanism Of Agc Kinases In Human Malignant, Shaokun Shu

USF Tampa Graduate Theses and Dissertations

The maintenance of normal cell function and tissue homeostasis is dependent on the precise regulation of multiple signaling pathways that control cellular decisions to either proliferate, differentiate, arrest cell growth, or initiate programmed cell death (apoptosis). Cancer arises when clones of mutated cells escape this balance and proliferate inappropriately without compensatory apoptosis. Deregulated cell growth occurs as a result of perturbed signal transduction that modulates or alters cellular behavior or function to keep the critical balance between the rate of cell-cycle progression (cell division) and cell growth (cell mass) on one hand, and programmed cell death (apoptosis, autophagy) on the …