Medicine and Health Sciences Commons^™

Role Of C-Met And Egfr In Acquired Resistance To Parp Inhibitors In Triple-Negative Breast Cancer, Clinton Yam

Dissertations and Theses (Open Access)

Triple-negative breast cancer is associated with a poor prognosis and treatment options are limited. The Poly (ADP-ribose) polymerase (PARP) inhibitors, olaparib and talazoparib, were recently approved for metastatic breast cancer (including triple-negative breast cancer) in patients with a germline BRCA1/2 mutation. Despite impressive response rates of ~60%, the prolongation in median progression-free survival with PARP inhibitors is modest, suggesting the emergence of resistance. We previously demonstrated that c-MET contributes to intrinsic resistance to PARP inhibitors in triple-negative breast cancer. However, whether c-MET plays a role in acquired resistance to PARP inhibitors in triple-negative breast cancer remains unclear. Here, we show …

Oxidative Phosphorylation: A Critical Feature And Novel Therapeutic Target In Melanoma Brain Metastases, Grant Fischer

Dissertations and Theses (Open Access)

We recently showed via RNA-sequencing (RNA-seq) analysis of clinical samples that melanoma brain metastases (MBMs) have higher expression of oxidative phosphorylation (OXPHOS) genes (including PPARGC1A or PGC1α) than patient-matched extracranial metastases (ECMs). Thus, the central hypothesis of this dissertation is that OXPHOS plays a critical role in the pathogenesis of MBMs.

RNA-seq analysis identified increased expression of OXPHOS genes in intracranial (ICr) vs. subcutaneous (SQ) xenografts of 4 different human melanoma cell lines. Increased OXPHOS in the ICr xenografts was confirmed by direct metabolite analysis and [U-¹³C]-glucose tracing analysis. Together, these studies indicate that the brain TME …

The Influence Of The Pep-Pts And Other Metabolic Systems On The Master Virulence Regulator Atxa And To Xin Gene Expression In Bacillus Anthracis, Naomi Bier-Reizes

Dissertations and Theses (Open Access)

AtxA, the master virulence gene regulator in Bacillus anthracis, is a PRD-containing virulence regulator (PCVR) as indicated by the crystal structure, post-translational modifications, and activity of the protein. PCVRs are transcriptional regulators, named for the regulatory domains subject to phosphorylation by the phosphoenolpyruvate phosphotransferase system (PEP-PTS), termed PTS Regulatory Domains (PRD), and for their impact on virulence gene expression. Generally, the phosphorylation of a PCVR regulates protein activity and multimerization. AtxA is phosphorylated at two histidine residues - one in each of its two PRDs. Phosphorylation at position 199 allows for AtxA to positively affect expression of virulence genes, whereas …

Dhhc5 Regulates Beta-Adrenergic Signaling In The Heart Through Palmitoylation Of G Alpha Proteins, Jie Chen

Dissertations and Theses (Open Access)

S-palmitoylation is a reversible posttranslational modification that plays an important role in regulating protein localization, trafficking, and stability. Recent studies have shown that some proteins undergo extremely rapid palmitoylation/depalmitoylation cycles after cellular stimulation supporting a direct signaling role for this posttranslational modification. The work in this dissertation investigated whether β-adrenergic stimulation led to stimulus-dependent palmitoylation of downstream signaling proteins in immortalized and primary cell models. I found that β-adrenergic stimulation led to rapidly increased Gαs and Gαi palmitoylation only in primary cardiomyocytes. The kinetics of palmitoylation was temporally consistent with the downstream production of cAMP and contractile responses. I identified …

Tracking Treatment Response And Resistance To Parp Inhibition (Talazoparib) In Hereditary Pancreatic Cancer., Jennifer Goldstein

Dissertations and Theses (Open Access)

polyADP ribose polymerase (PARP) inhibitors are a class of drugs that block the PARP enzymes, involved in the repair of singe-stranded DNA breaks through the base excision repair pathway. PARP inhibition leads to replication-associated double stranded DNA breaks, which are repaired by homologous recombination (HR). In tumors with HR defects (i.e. BRCA mutants), there is a shift to error-prone DNA repair and subsequent genomic instability and cell death.

In 2014, Olaparib became the first FDA-approved PARP inhibitor for the treatment of BRCA-mutant ovarian cancer. In the phase III POLO (Pancreas cancer OLaparib Ongoing) trial presented at the American Society …

Bilirubin Nanoparticle As An Anti-Inflammatory Therapy For Graft Versus Host Disease, Sumedha Pareek

Dissertations and Theses (Open Access)

Graft versus host disease (GvHD) caused by alloreactive donor lymphocytes is a fatal complication of hematopoietic stem cell transplant (HSCT). Myeloablative conditioning regimen, consisting of chemotherapy and/or radiation, given prior to HSCT can cause tissue damage. This non-specific tissue damage triggers cross-presentation of alloantigens to the donor immune cells, causing recruitment of leukocytes and production of inflammatory cytokines. Targeting this inflammation without affecting the anti-leukemia effects of HSCT, continues to be one of the biggest challenge in finding a therapy for GvHD. Bilirubin is a tetrapyrrole pigment, found in the blood, with natural anti-oxidative and anti-inflammatory properties. Using mouse models …

Role Of Nudt21 Mediated Alternative Polyadenylation And Hyaluronan In The Development Of Pulmonary Hypertension, Scott Dale Collum

Dissertations and Theses (Open Access)

Pulmonary hypertension (PH) is a progressive disease with serious effects on quality of life and life expectancy of patients. PH is a complex disease that likely develops due to multiple influences, and no curative treatments exist for this disease. It has been shown that alternative polyadenylation (APA) due to depletion of Nudix Hydrolase 21(NUDT21) is involved in several disease states including the chronic lung disease idiopathic pulmonary fibrosis (IPF). Additionally, hyaluronan, an extracellular matrix glycosaminoglycan has been associated with PH. The role and mechanism of NUDT21 and hyaluronan have not yet been described in this disease. My results reveal that …

Investigations Of The Structure-Function Relationship In Kainate Receptors Using FöRster Resonance Energy Transfer, Douglas Litwin

Dissertations and Theses (Open Access)

Kainate receptors belong to the family of ion channels known as the ionotropic glutamate receptors. Ionotropic glutamate receptors mediate the majority of excitatory synaptic transmission, modulate the release of presynaptic glutamate, and facilitate dendrite formation. Kainate receptors are unique among the ionotropic glutamate receptors in being modulated by sodium ions. They have also been implicated in the development of higher learning and epilepsy. In recent years a wealth of structural data has become available for the AMPA and NMDA classes; however, the structural characterization of kainate receptors has been limited. The work in this dissertation utilizes luminescence resonance energy transfer …

Modeling Cancer Using Li-Fraumeni Syndrome Patient-Derived Induced Pluripotent Stem Cells, Ruoji Zhou

Dissertations and Theses (Open Access)

Li-Fraumeni syndrome (LFS) is an autosomal dominant disease caused by germline mutations in the gene TP53, which predispose individuals to a wide range of malignancies, including osteosarcoma and breast cancer. In the previous study, our group developed a novel disease model platform by reprograming LFS patients' fibroblasts to induced pluripotent stem cells (iPSCs), and further differentiate these iPSCs into mesenchymal stem cells (MSCs) then to osteoblasts (OBs), the cells from which osteosarcomas originate. Interestingly, LFS iPSC-derived osteoblasts recapitulated the osteosarcoma phenotype, creating “a bone tumor in a dish”. This “tumor in a dish” platform proved that LFS is an …

Quantifying Uncertainty In A Measurement-Based Assessment Of Relative Biological Effectiveness In Carbon Ion Radiotherapy, Shannon Hartzell

Dissertations and Theses (Open Access)

One of the largest inconsistencies in dose delivered during carbon ion therapy is due to uncertainties in relative biological effectiveness (RBE), a value that is calculated via one of several clinically implemented algorithms. This study investigates the uncertainty in measured microdosimetric parameters for RBE calculation by the Microdosimetric Kinetic Model (MKM), Repair Misrepair Fixation model (RMF), and Local Effect Model I (LEM) using a Tissue Equivalent Proportional Counter (TEPC).

Microdosimetric spectra, kinetic energy spectra, and dose fragment contributions were calculated using Monte Carlo (GEANT IV) for monoenergetic and SOBP carbon beams of clinical energy. From microdosimetric spectra, lineal energy values …

Dissecting The Roles Of Human Smc Complexes In Transcription Regulation And Chromatin Organization, Ruoyu Wang

Dissertations and Theses (Open Access)

Metazoans utilize a constellation of distal regulatory elements to control gene transcription, and therefore they have to forge highly complex chromatin loops to spatially bridge these regulatory elements and genes in the three-dimensional (3D) genome. However, the hierarchy of chromatin contacts and their underlying mechanisms are not well-understood. SMC complexes including Cohesin complex and Condensin complex has been widely proposed to organize 3D genome structure, and further regulate metazoans’ gene transcription. Here, we aim to dissect the direct functions of SMC complexes (both Cohesin and Condensin) in transcriptional regulation and 3D genome organization, by utilizing an inducible protein degradation system. …

P53r245w Mutation Elicits Metastatic Phenotype In Pten Deficient Prostate Cancer, Ky Pham

Dissertations and Theses (Open Access)

Trp53 mutations are the most frequent genetic alterations in prostate cancer and are associated with more aggressive disease and worse overall survival. The majority of Trp53 mutations in prostate cancer are missense mutations, resulting in amino acid substitutions with profound effect. In addition to the loss of wild type function, missense mutations in Trp53 result in a gain-of-function (GOF) phenotype. This GOF phenotype confers biologic advantages to the tumor cells, enabling them to metastasize and invade distant organs. In this study, we generated mice carrying a conditional prostate-specific p53R245W mutant and Pten deletion to access the role of this common …

Fasting Reduces Intestinal Radiotoxicity Enabling Dose-Escalated Radiotherapy For Pancreatic Cancer, Marimar De La Cruz Bonilla

Dissertations and Theses (Open Access)

Surgical resection is the only potentially curative treatment for pancreatic cancer, but only 15-20% of patients have resectable tumors. In unresectable cases, stereotactic body radiotherapy (SBRT) may be used to give tumor-directed radiotherapy (RT). Unfortunately, this can cause severe gastrointestinal (GI) toxicity due to proximity of the pancreatic head to the duodenum. Protecting the intestine from the toxic side-effects of radiation may enable dose-escalation that could achieve more effective local control of disease. We and others have previously shown that a fast of 24 hours protects mice from lethal doses of the DNA-damaging agent etoposide. In this study, we demonstrate …

Investigating The Role Of Cd109 In Pancreatic Ductal Adenocarcinoma, Mennatallah Shaheen

Dissertations and Theses (Open Access)

Pancreatic Ductal Adenocarcinoma (PDAC) is the 3rd leading cause of cancer death in the US. We performed loss of function genomic screening on a cohort of four patient derived PDAC cell populations and our data shows a cell surface receptor CD109 to be a common vulnerability, the biologic role of which in PDAC is yet unstudied and largely unknown. We hypothesized that CD109 expression provides PDAC cells with a survival advantage, and promotes cancer progression through activation of downstream signaling. We believe therefore that targeting CD109 could improve PDAC patients’ survival. Here we report that CD109 plays a role in …

Gcn5 Loss Impacts Myc-Driven Cancer In Mice And Human Cells, Aimee Farria

Dissertations and Theses (Open Access)

GCN5 is the catalytic subunit in the acetyltransferase module of SAGA and ATAC, multiprotein complexes involved in the modification of histone and nonhistone proteins. GCN5 is most recognized as a co-activator of gene transcription. The SAGA complex is recruited to chromatin by transcription factors such as MYC and E2F1 where GCN5 acetylates H3K9 leading to a more open and accessible chromatin structure. Previous research has demonstrated that GCN5 also acetylates MYC, a protein that amplifies the expression of cancer-promoting genes and is frequently dysregulated in cancer, increasing its stability. Our lab has found there is a significant overlap in the …

Molecular Consequences Of High Taz Expression In Gliomas, Visweswaran Ravikumar

Dissertations and Theses (Open Access)

Diffuse high grade gliomas are complex and lethal neoplasms of the adult central nervous system that are driven by a range of genetic and epigenetic alterations. Molecular classification of these tumors has identified different transcriptional subtypes, the most notable being Proneural (PN) and Mesenchymal (MES) classes. The most aggressive forms of the disease have a Mesenchymal expression signature, with reported PN-to-MES transition occurring with tumor progression. Master regulatory analysis has identified the transcriptional co-activator TAZ (WWTR1) as a major driver of the MES transition. Overexpression of this single protein in glioma stem cells has been shown to drive a transition …

Louisiana’S Statewide Implementation And Dissemination: Lessons Learned, Opportunities And Recommendations, Evidence To Practice, Cep Briefs

Policy & Position Papers

No abstract provided.

Cancer In Louisiana: 2012-2016, Volume 34, Louisiana Tumor Registry, Lauren Maniscalco, Carla Rosales, Christina Lefante, Mei-Chin Hsieh, Yong Yi, Lisa Pareti, Brent Mumphrey, Mary Anne Lynch, Xiao-Cheng Wu, Jiadi Liu, William Mi, Pratibha Shrestha

Policy & Position Papers

Mission:

To collect and report complete, high-quality, and timely population-based cancer data in Louisiana to support cancer research, control, and prevention.

Vision:

To reduce suffering and death from cancer using information collected by the Louisiana Tumor Registry.

History:

Cancer registration in Louisiana began in 1947 at the Charity Hospital Tumor Registry in New Orleans. In 1974, as part of its Surveillance, Epidemiology and End Results (SEER) Program, the National Cancer Institute provided funds for a population-based cancer incidence and survival registry covering Jefferson, Orleans, and St. Bernard parishes. Five years later, the Louisiana Tumor Registry (LTR) was transferred to the …

Effects Of Neuromuscular Fatigue Resulting From Repeat Sprint Exercise Among Trained Cyclists On Measures Of Strength And Power Performance, Robert B. Blaisdell

Electronic Theses and Dissertations

The purpose of this dissertation is to better understand the role of repeated-sprint ability (RSA) and resulting fatigue in cyclists; how it relates to measures of aerobic power and strength and power performance indices- due to the nature of cycling competitions and the necessity of RSA for success.

The first part of this dissertation attempted to elucidate the relationship between RSA and aerobic power and strength/ power measures in competitive cyclists. The purpose was to potentially illustrate the importance of the inclusion of strength and power training in the training regimen of cyclists. The findings showed several statistically significant relationships …

Temperature Influence On Insecticide Resistance In Aedes Aegypti And Aedes Albopictus Mosquitoes From South Texas, Wendy Soledad Salinas

Theses and Dissertations

Aedes aegypti and Aedes albopictus are vectors for several emerging arboviruses including Zika, chikungunya and dengue. Both mosquitoes are found along the Rio Grande River in South Texas, along the border between Mexico and the United States of America. These mosquito species typically reside near human settlements. A preventative measure public health official use to help halt the spread of diseases is by controlling vector population with the use of insecticides, but as temperature vary, and with the constant exposure to commonly used insecticides, mosquitoes from South Texas may be developing a resistance to the insecticides. Resistance to insecticides may …

Nasopharyngeal Carcinoma In Pregnancy: Management Approach Case Report At Moi Teaching And Referral Hospital, Eldoret-Kenya, Philip Tonui, Elly B. Odongo, Andrew Cheruiyot, Sahara Shurie, Elkanah Omenge

Obstetrics and Gynaecology, East Africa

Nasopharyngeal carcinoma is an uncommon tumour, which raises management dilemma in pregnant women. The condition has a considerable effect on the pregnancy outcome, considering the risk of preterm delivery. This paper reports a case of 26 years old Gravida 7 Para 6 admitted at 28 weeks of gestation with epistaxis, hematemesis and a neck mass. The head CT scan showed a right paranasal space soft tissue mass with bony destruction and bilateral cervical adenopathy, consistent with neoplastic carcinoma. Histopathological examination confirmed the diagnosis of nasopharyngeal carcinoma. Deterioration of the patient’s condition, necessitated emergency caesarean delivery at 32 weeks to accommodate …

Intervention Principles In Pediatric Health Care: The Difference Between Physicians And The State., D. Robert Macdougall

Publications and Research

According to various accounts, intervention in pediatric decisions is justified either by the best interests standard or by the harm principle. While these principles have various nuances that distinguish them from each other, they are similar in the sense that both focus primarily on the features of parental decisions that justify intervention, rather than on the competency or authority of the parties that intervene. Accounts of these principles effectively suggest that intervention in pediatric decision making is warranted for both physicians and the state under precisely the same circumstances. This essay argues that there are substantial differences in the competencies …

August 2019, Swosu Bulldog Wellness Committee

SWOSU BULLDOG WELLNESS

National Immunization Month

We all need shots (vaccines) to help protect us from serious diseases. This protection is called immunization and it is in place to help keep our community safe. Shots can prevent serious diseases like the flu, measles, and pneumonia. It’s important to know which shots you need and when to get them.

Unilateral Enophthalmos., Grace L. Su, Sara E. Lally, Carol L. Shields

Wills Eye Hospital Papers

No abstract provided.

Changes In Psychological, Morphological, And Performance Characteristics In Preparation For A National Weightlifting Competition, Donald Marsh

Electronic Theses and Dissertations

The primary aim of this study was to examine the time course of change in muscle morphology and vertical jump performance in weightlifters preparing for a national competition. The secondary aim of this study is to examine how perceived recovery and stress state corresponds with alterations in training load leading up to competition. Eleven Olympic Training Site weightlifters completed a 4-week peaking phase for a national competition. Body mass, stress and recovery psychometric measures, and unloaded/loaded (20kg) squat jump height (SJH) were measured weekly and at the competition site. Vastus lateralis cross-sectional area (CSA), muscle thickness (MT) and pennation angle …

General Anesthetic Induction Sequence High Fidelity Simulation: Determining Efficacy Among Novice Student Registered Nurse Anesthetists, Alex Wilkie, Steven Urbick, Kenn B Daratha

Books, Presentations, Posters, Etc.

Background High Fidelity Simulation (HFS) is used across multiple health professions. Despite the wide variety of clinical experiences that Student Registered Nurse Anesthetists (SRNA) possess prior to training, the induction sequence to a General Anesthetic (GA) is a daunting task. Although the efficacy of HFS has been widely studied within undergraduate nursing programs, there are no studies published determining the efficacy of HFS on SRNA training. The purpose of this study was to determine the efficacy of simulation training amongst entry-level SRNA’s and examine any individual participant factors that may influence clinical performance within HFS.

Methods • Human subjects were …

Association Of Copy Number Variations With Chronic Hepatitis B In Chinese Population, Fang Niu

Capstone Experience: Master of Public Health

With one third of the Hepatitis B virus (HBV) infection population of the world, chronic Hepatitis B (CHB) has become a top burden in China. CHB is a lifelong infection with HBV which can cause serious health problems, like cirrhosis, liver cancer or even death. HBV infection is known to result in various clinical conditions, including asymptomatic HBV carriers to chronic hepatitis and primary hepatocellular carcinoma. Several studies have shown that host genetic susceptibility could be an important factor that determines these various outcomes of HBV infection. Many Single Nucleotide Polymorphisms (SNPs) and Copy Number Variations (CNVs) have been associated …

Comorbidity Profile Of Head And Neck Cancer Patients With And Without Depression, Michaela Frenzel

Capstone Experience: Master of Public Health

This population-based retrospective study used SEER-Medicare data from 2002-2010 to assess depression, comorbidity, and substance use in the elderly head and neck cancer population. Out of 3,533 head and neck cancer patients, 10.6% had depression diagnoses two years prior to cancer diagnosis, 8.9% were newly diagnosed with depression within one year after cancer diagnosis, and 44.5% of those with preexisting depression had an additional depression diagnosis within one year following cancer diagnosis. Comorbid conditions (p<0.0001) and substance use (p=0.0017) showed associations with depression prior to cancer diagnosis yet, no significant associations with incidence of depression in this head and neck cancer population. This study affirms the need for continual depression screenings in head and neck cancer patients and suggests the need for increased research into the burden of comorbid conditions and substance use within the head and neck cancer population.

The Lived Experience Of Psychological Occupational Stress In Early Childhood Education, Brooke Fletcher

Capstone Experience: Master of Public Health

Early childhood education (ECE) programs have been recognized by the Institute of Medicine and the Administration for Children and Families as excellent interventions to alleviate the long-term negative effects of poverty in the United States, but the quality of intervention provided and outcomes for the target population are adversely hindered by high occupational stress burdens for ECE teachers. According to Sheridan, Edwards, Marvin, and Knoche, the models used to address this concern are not empirically supported for specific applicability to ECE nonprofit settings. There is a need for deeper understanding of the lived experiences of ECE teachers, including the psychological …

Evaluation Of Family Inc.'S Home Visitation Program, Brooke A. Linnenbrink

Capstone Experience: Master of Public Health

FAMILY, Inc. is a nonprofit that provides public health and family support services to women, children, and families in Pottawattamie and Mills counties. It's home visitation program provides health education information to families in the communities that are expecting a child or have a child less than five years of age. This project looked at FAMILY, Inc.’s database regarding the health of children enrolled in their home visitation program and use that information to help develop health education tools as they prepare to expand their programming to include Early Head Start (EHS). Currently FAMILY uses the Parents as Teachers curriculum, …