Medicine and Health Sciences Commons^™

The Development Of Novel Cdk8 And Cdk19 Inhibitors And Degraders As Potential Anti-Cancer Agents, Li Zhang

Theses and Dissertations

CDK8 and its homolog CDK19 are essential for transcription regulation and their dysregulation has been identified in numerous diseases, especially in cancers. CDK8 and CDK19 have been implicated in cancer development through their kinase activity and kinase independent functions. Despite the existing CDK8/19 inhibitors, there is still a need to develop novel CDK8/19 inhibitors with improved potency and PK profile. It is also necessary to develop CDK8/19 degraders that are able to eliminate the kinase-independent functions. Although two CDK8-degrading PROteolysis Activating Chimeras (PROTACs) have been reported, they have limited CDK8 degradation efficacy and no effect on CDK19. PROTACs with improved …

Investigating Bmp7 Expression In Glioblastoma Multiforme, Yajaira Janett Macias

Theses and Dissertations

The PI3K/AKT/mTOR pathway regulates important cell processes such as growth, survival, motility, inflammation, proliferation, and apoptosis. In Glioblastoma multiforme (GBM) the PI3K/AKT/mTOR pathway is aberrant as it is almost always active. This results in the deregulation of downstream molecules and ultimately leads to cancer progression and maintenance in GBM tumors. In this study, we used RNA-sequencing to identify differentially expressed genes (DEGs) in U87MG GBM cells treated with NVP-BEZ235, a dual inhibitory drug targeting PI3K and mTOR. A total of 7,803 differentially expressed genes were identified via RNA-seq. GEPIA2 online tool was used to assess differential gene expression …

A Multilevel And Spatial Analysis Of Oral And Pharyngeal Cancer In South Carolina, Deborah M. Hurley

Theses and Dissertations

Objective: Disparities in the distribution of oral and pharyngeal cancer exist worldwide. This is also true in the United States and in South Carolina. Differences exist in oral and pharyngeal cancer stage and survival by race and sex, with higher incidence rates for Whites but higher proportions of late-stage cancer and lower survival for Blacks. This study was conducted to evaluate whether any differences exist in the spatial distribution of oral and pharyngeal cancer stage at diagnosis and survival, and to evaluate the association of income inequality, material deprivation and other measures of social determinants of health (contextual risk factors) …

Design And Synthesis Of Macrocyclic Peptide Braf-Wt Dimerization Inhibitors For The Treatment Of Metastatic Melanoma, Chad Mulloy Beneker

Theses and Dissertations

In cases of metastatic melanoma, BRAF is frequently mutated to the V600E oncoprotein causing uncontrolled cell proliferation driven by the MAPK-ERK pathway. There are several BRAF inhibitors, such as vemurafenib, which are FDA approved, but patients treated with these Type-I kinase inhibitors frequently observe relapse under mutant RAS and BRAF-wt conditions due to paradoxical activation. The mechanism of this resistance occurs through binding of the inhibitor to BRAF-wt initiating conformational changes which leads to BRAF dimerization. Once in the dimerized state, the inhibited monomer induces allosteric transactivation of the second monomer. This drug-induced activation of BRAF in cells with mutant …

A Multilevel Mixed Methods Examination Of Treatment Nonadherence Among Rural Cancer Survivors, Bonny Morris

Theses and Dissertations

While mortality rates have been decreasing over the last 40 years, cancer remains a leading cause of death in the United States. Over 1.7 million people were diagnosed with cancer in 2019, and there were more than 600,000 cancer deaths. Of the 15 million cancer survivors in the US, nearly 3 million reside in rural areas and experience 3% higher cancer incidence and 10% higher cancer mortality compared to their nonrural counterparts. During 2006-2015, the annual age-adjusted mortality rates for all cancer sites combined decreased at a slower pace in rural areas versus nonrural areas (-1.0% vs -1.6% per year, …

Using The Memorial Sloan Kettering Frailty Index To Identify Patients At High Risk For Postoperative Intensive Care Unit Admission, Specialized Advanced Care Unit Admission, And 30-Day Readmission, Timothy J. Donoghue

Theses and Dissertations

Frailty is roughly defined as an accumulation of physiological, emotional, cognitive, and social deficits that impair a person’s response to stressful events. A frailty diagnosis has been associated with poor outcomes following surgical procedures. Cancer surgical patients aged 65 or older represent a vulnerable population susceptible to being frail and the potential associated complications that can accompany frailty. Measuring frailty is an objective risk assessment that identifies increased risk better than age or American Society of Anesthesiologists Physical Status (ASA-PS) score such that frailty can independently predict poor surgical outcomes.

Frailty is not specifically a result of having cancer, disability, …