Digital Commons Network^™

Functional Analysis Of Rad6 In Brca1 Wild Type And Brca1 Mutant Triple Negative Breast Cancer Drug Response, Brittany Haynes

Wayne State University Dissertations

TNBCs account for 15-20% of all breast and are unsuitable for common targeted therapies as they lack expression of estrogen, progesterone, and Her2/neu receptors. Cisplatin, a DNA damaging agent, is currently under clinical investigation for treatment of TNBCs and paclitaxel, a mitotic spindle poison, is a first-line treatment option for this disease. While both agents elicit therapeutic benefit BRCA1 mutation status, toxicity, and resistance are limiting factors. Rad6 functions as an E2 ubiquitin conjugating protein and its enzymatic activity is critical for its cellular function. Rad6 is known to play a critical role in the translesion synthesis (TLS) damage response …

Mechanisms Of Hormonal Regulation Of Invasiveness And Metastasis Of Luminal Breast Cancer, Thomas Mcfall

Wayne State University Dissertations

ABSTRACT

MECHANISMS OF HORMONAL REGULATION OF INVASIVENESS AND METASTASIS OF LUMINAL BREAST CANCER

By

THOMAS MCFALL

December 2017

Advisor: Dr. Manohar Ratnam

Major: Cancer Biology

Degree: Doctor of Philosophy

Over 20% of breast cancer cases present with distal metastasis and they are predominantly of luminal subtypes. As luminal breast cancer is relatively indolent, it is believed that progression to metastasis must occur over many years, generally well into post-menopausal years. Unfortunately, very little is known about the mechanisms by which these hormone receptor positive tumors metastasize, likely in part due to their slow metastatic rates in animal model systems as …

Commissioning And Validation Of Analytical And Monte Carlo Based Dose Calculation Algorithms For Proton Spot Scanning, Jatinder Saini

Wayne State University Dissertations

Purpose: Accurate dose calculation is one of the most necessary components of radiation therapy. While the commercially available photon dose calculation algorithm offerings have improved considerably in last decade, proton dose calculations are still performed using the analytical dose calculation algorithms. The goal of this work is to validate a newly available commercial Monte Carlo (MC) dose calculation algorithm using measurements and simulations in GATE software. A secondary goal is to compare and contrast the performance of analytical algorithm against MC algorithm. Finally, GATE simulations are used to evaluate a newly available ceramic marker for ocular melanoma proton therapy.

Methods: …

Arab American Adolescents’ Bullying Experiences And Effects On Their Perceived Stress And Health, Maha Albdour

Wayne State University Dissertations

This study is intended to examine the bullying experience among Arab American adolescents and effects on their perceived stress and health. Adolescents who are vulnerable or marginalized might be at higher risk for bullying. Arab American adolescents have not been included in research studies examining bullying and described as the invisible population.

The Neuman System Model, which focuses on wellness of adolescents in relation to environmental stress, guided this study. Bullying is a tension producing stressor, operationally defined as repeated attacks or intimidation that cause fear, distress or harm and perceived power imbalance between bully and victim. Perceived stress is …

Middle School And High School Students Who Stutter: A Qualitative Investigation Of School Experiences, Tiffany Cobb

Wayne State University Dissertations

ABSTRACT

MIDDLE SCHOOL AND HIGH SCHOOL STUDENTS WHO STUTTER: A QUALITATIVE INVESTIGATION OF SCHOOL EXPERIENCES

by

TIFFANY COBB

MAY 2017

Advisor: Dr. Derek Daniels

Major: Speech-Language Pathology

Degree: Doctor of Philosophy

Purpose: The purpose of this study was to explore and further understand the ways in which middle school and high school students perceive their school experiences within the school environment.

School has an important impact on the social development of children (Milsom, 2006). Learning is not done individually as classrooms are inherently social places. This suggests that students do not learn alone, but rather in the presence of many …

Assessing Parent Invovlment In Applied Behavior Analysis Treatment For Children With Autism, Krista Marie Clancy

Wayne State University Dissertations

The purpose of this study was to compare two groups of parents whose children participated in ABA on their levels of stress, self-efficacy, treatment acceptability, and parents’ level of involvement in their children’s treatment, and to assess variables that may explain variance in parent involvement. Parents in the treatment group participated in a voluntary parent training (n=18) and the comparison group were parents who elected not to participate in the voluntary training (n=22). This was a quasi-experimental design study where parents and their therapists completed a survey regarding parents’ involvement in their children’s treatment programs. Additional parent measures collected as …

Brain Connectivity After Concussion, Armin Iraji

Wayne State University Dissertations

Mild traumatic brain injury (mTBI) accounts for over one million emergency visits in the United States each year. While most mTBI patients have normal findings in clinical neuroimaging, alterations in brain structure and functional connectivity have frequently been reported. In this study, we investigated the large-scale brain structural and functional connectivity using diffusion MRI and resting-state fMRI data. Data from 40 mTBI patients was acquired at the acute stage (within 24 hrs after injury). 35 patients returned for data acquisition at a follow-up (4-6 weeks after injury). Data was also collected from a cohort of 58 healthy subjects, 36 of …

Understanding The Mechanism Of Oxidative Stress Generation By Oxidized Dopamine Metabolites: Implications In Parkinson's Disease, Nihar Mehta

Wayne State University Dissertations

Oxidation of dopamine to toxic metabolites is considered to be one of the prime factors involved in the death of dopaminergic neurons in Parkinson’s disease. Some dopamine oxidation products have the capability to redox cycle in the presence of molecular oxygen, further contributing to oxidative stress. Therefore, our aim here was to study the redox cycling of dopamine oxidized metabolites and elucidate the underlying mechanism by which they cause oxidative stress.

Redox reactions involve transfer of one or more electrons between two compounds

resulting in either oxidation or reduction. In redox cycling, a compound undergoes

alternate oxidation and reduction, transferring …

Clinical Applications Of Advanced Rotational Radiation Therapy, Adrian Nalichowski

Wayne State University Dissertations

Purpose: With a fast adoption of emerging technologies, it is critical to fully test and understand its limits and capabilities. In this work we investigate new graphic processing unit (GPU) based treatment planning algorithm and its applications in helical tomotherapy dose delivery. We explore the limits of the system by applying it to challenging clinical cases of total marrow irradiation (TMI) and stereotactic radiosurgery (SRS). We also analyze the feasibility of alternative fractionation schemes for total body irradiation (TBI) and TMI based on reported historical data on lung dose and interstitial pneumonitis (IP) incidence rates.

Methods and Materials: An anthropomorphic …

Anti-Cancer Effects Of Tocotrienols In Nsclc, Lichchavi Raj Raj

Wayne State University Dissertations

Lung cancer is one of the leading causes of death among cancers, with non-small cell lung cancer (NSCLC) accounting for 80-85% of all lung cancers and a five-year survival rate of 5 % at stage IIIB. Delta-tocotrienol (δT) including other tocotrienol isomers has been shown to exhibit anti-tumor activity via inhibition of different signaling pathways in tumors including NSCLC. Previously we reported that δT reduced cell invasion via inhibition of the Notch-1 and NF-κb pathway.

Matrix metallopeptidase 9 (MMP9) dependent cell migration and invasion are key processes in cancer metastasis. Hence, its suppression is a promising strategy for cancer therapeutics. …

Measuring The Effectiveness Of Benefit-Provisioning And Cost-Inflicting Mate Retention Tactics Through Relationship Outcomes, Tara Delecce

Wayne State University Dissertations

Mate retention has received much less research attention compared to mate choice and attraction. Even the research that has been done on mate retention often only aims to identify what constitutes as mate retention tactics. In the current studies, the effectiveness of mate retention strategies is explored by measuring relationship outcomes of tactics unlike previous research that measures effectiveness through perceptions of relationship satisfaction. In Study 1, individuals who have experienced a nonmarital breakup reported on their own and their ex-partners’ mate retention tactics before the breakup to see which ones predicted the outcome of relationship dissolution. Tests for moderation …

The Effects Of Bone Marrow Adipocytes On Metabolic Regulation In Metastatic Prostate Cancer, Jonathan Diedrich

Wayne State University Dissertations

Bone is a preferential site of metastasis from prostate cancer (PCa). Although there have been many advances in therapeutic options for patients suffering from metastatic PCa, this disease remains incurable with an estimated five-year survival of 33%. To design effective therapeutic interventions for metastatic PCa, it is essential that we elucidate the molecular mechanisms responsible for tumor cell adaptation to and the ability to thrive within the bone metastatic niche. Age and obesity, conditions that increase adipocyte numbers in bone marrow, are risk factors for skeletal metastases from PCa; therefore, our laboratory is focused on the interactions between marrow adipocytes …

Rituals Reproducing Race: African American Women's Feminine Hygiene Practices, Shared Experiences, And Power, Angela K. Guy-Lee

Wayne State University Dissertations

This dissertation is an exploration of the role African American women’s feminine hygiene practices, namely vaginal douching, plays in the creation and reproduction of race. Compared to their white and Latina counterparts, African American women are the most likely to engage in this practice. Vaginal douching is associated with myriad reproductive and sexual health problems. These problems include but are not limited to recurrent yeast infections, bacterial vaginosis, disrupting healthy vaginal microbiomes, and spontaneous preterm birth; of which African American women experience disproportionately. Although racial differences in vaginal douching are well documented, little is known about the impetus for African …

Pet Imaging Of Early Therapeutic Response In Solid Tumors, Stephanie J. Blocker

Wayne State University Dissertations

An important pillar of precision medicine for oncology is the ability to identify patients who respond to treatment early into their therapy. Positron emission tomography (PET) allows physicians and researchers to measure changes in tumor behavior prior to noticeable differences in morphology.

Objective: Determine the utility of multiple tracers for PET in assessing early changes in tumor activity that result from treatment.

Methods: Two tracers for PET were studied. 64Cu-labeled liposomes were used to assess changes in liposome delivery two solid colon tumors early into treatment with bevacizumab (Bev). 18F-FMAU thymidine analog (1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)thymine), was utilized to detect early response to …

New Mechanism Based Approaches For Treating Prostate Cancer, Rayna Rosati

Wayne State University Dissertations

Prostate cancer (PC) is generally dependent on the androgen signaling axis for tumor growth. PC is managed by androgen deprivation therapy (ADT). The tumors then frequently progress by restoring ADT-resistant AR signaling through mechanisms such as intratumoral androgen synthesis, overexpression of AR, expression of splice variants of AR and alteration in the balance of AR co-regulators. This stage of progression is termed castrate recurrent prostate cancer (CRPC). Moreover, ADT has many major undesirable acute and chronic side effects on various normal tissues. Therefore a more strategic therapy approach is one that would disrupt a functional arm of AR signaling critical …

Neuropharmacological Investigation Of Stress And Nicotine Self-Administration Among Current Cigarette Smokers, Eric Woodcock

Wayne State University Dissertations

ABSTRACT

NEUROPHARMACOLOGICAL INVESTIGATION OF STRESS AND NICOTINE SELF-ADMINISTRATION AMONG CURRENT CIGARETTE SMOKERS

by

ERIC ANDREW WOODCOCK

August 2017

Advisor: Dr. Mark K. Greenwald

Major: Neuroscience (Translational)

Degree: Doctor of Philosophy

Nicotine use, especially cigarette smoking, is a significant public health problem. Existing pharmacotherapies attenuate nicotine craving and withdrawal symptoms. However, the majority of patients relapse within the first year of treatment. Treatment studies indicate a commonly cited precipitant to smoking relapse is stress. Pharmacotherapies do not attenuate, and may exacerbate, the effects of acute stress. Experimental studies (preclinical and clinical) indicate that acute stress potentiates drug-seeking behavior across drugs of …

Analysis Of The Secondary Neurodegenerative Consequences Of Primary Oligodendrocyte Stress Through The Use Of The Novel Obiden Mouse Model, Daniel Zdzislaw Radecki

Wayne State University Dissertations

The work of this project was to develop, test and characterize a potential novel mouse model of the neurodegenerative disease Multiple Sclerosis (MS). Historically, MS has been identified as a primary autoimmune disease of the central nervous system (CNS). However, treatments based on this view have met with limited success, and in most cases, fail to prevent progression of MS from mild to moderate and severe forms. Original observations regarding axonal and neuronal pathology in the white and gray matter of the CNS were rediscovered in the 1990s. These observations indicated that even in the absence of the immune system, …

Online Health Information Gathering And Health Service Utilization By Emergency Department Patients With Acute, Non-Urgent Illness Symptoms, Joanne Yastik

Wayne State University Dissertations

ABSTRACT

ONLINE HEALTH INFORMATION GATHERING AND HEALTH SERVICE UTILIZATION BY EMERGENCY DEPARTMENT PATIENTS WITH ACUTE, NON-URGENT ILLNESS SYMPTOMS

by

JOANNE M. YASTIK

May 2017

Advisor: Dr. Deborah Schutte

Major: Nursing

Degree: Doctor of Philosophy

Statement of the Problem: The influence of the Internet on our global society cannot be overstated. One of the most utilized areas on the Internet is the quest for health information (Bouche & Migeot, 2008; Goldman & Macpherson, 2006; Warner & Procaccino, 2007, Seckin, 2014). To date, little is known on how this information is being used or whether there is a link between online health …

Estimating The Variables Of The Nonlinear Dynamical Theory Of Acute Cell Injury, Fika Tri Anggraini

Wayne State University Dissertations

This Dissertation is the first to estimate the variables D and S of the nonlinear theory of acute cell injury in hippocampal regions CA1 and CA3 using a rat model of global brain ischemia and reperfusion (I/R). D was estimated by quantifying protein aggregates using ubiquitin Western blotting. S was estimated by quantifying changes in polysomal mRNAs as measured by microarray chips. D and S time courses were sampled at 0.5, 8, 16, 24, 48, and 72 hrs of reperfusion after 10 min brain ischemia. CA1 dies and CA3 survives. The theory predicts D will be larger in CA1 and …

Change In Processing Speed And Its Associations With Cerebral White Matter Microstructure, Muzamil Arshad

Wayne State University Dissertations

The decline of cognition with age is one of the most feared aspects of aging, while the slowing of responses, or reduced processing speed, is one of the most reliable aspects of aging. Slowing of processing has been hypothesized to affect other domains of cognition as well. Despite the well-known slowing-age relationship and central position processing speed plays in theories of cognitive aging the neurobiological mechanisms which underpin slowing is unclear. If we could identify the biology associated with processing speed we could then attempt to develop interventions to mitigate the effects of age on those variables. In turn we …

Preparing To Parent: Mindfulness In Expectant Parents Exposed To Adversity, Laurel Marie Hicks

Wayne State University Dissertations

Expectant parents who have been exposed to psychosocial risk encounter deleterious psychological (Ashley et al., 2016), and physiological (V. H. Pereira, Campos, & Sousa, 2017) effects. This not only affects the parent-to-be, but also may affect the developing fetus (E. P. Davis et al., 2011) and is linked to poorer infant development (Lefmann & Combs-Orme, 2014). However, not all risk-exposed individuals experience this, many are resilient and still thrive in the face of adversity. Understanding potential risk and resiliency factors in expectant parents is advantageous, so tailored interventions can be devised to improve outcomes. One potential resiliency factor, mindfulness, is …

Essays On Health And Labor Market Outcomes, Maryam Jafari Bidgoli

Wayne State University Dissertations

This dissertation examines the relationship between health and labor market outcomes using the 1996-2010 longitudinal RAND Health and Retirement Study (HRS). First, it estimates the relationship between health and labor supply using a simultaneous equation model, treating health as endogenous. The effect of health may be overestimated because people may adjust their non-employment status by their health conditions (justification hypothesis). By using a full information maximum likelihood method, we can conduct a true test of exogeneity on the health variable, taking into account the correlation between two labor supply and health equations’ time-varying error components (unobserved heterogeneity). The results confirm …

This Is Us Saying Who We Are: Speaking The Rhetoric Of Mental Disability, Renuka Uthappa

Wayne State University Dissertations

People with mental disabilities, or what are sometimes referred to as “mental illnesses,” face stigma when they interact with the public. To fight this stigma, the members of a small, grassroots, advocacy organization known as the Speakers Bureau travel to high school and college classrooms narrating their experiences with mental disability. They do so to replace culturally circulating stereotypes regarding such disability with more accurate and positive images. This dissertation is an auto-ethnographic exploration of the rhetoric of the Speakers Bureau. Through rhetorical analysis of members’ classroom speeches, of interviews with each speaker, and of the speaker’s self- assessment of …

Functions Of Atr/Mec1 In Meiosis And The Cell Cycle, Layne Weatherford

Wayne State University Dissertations

Mec1 is a protein kinase in S. cerevisiae that is critical for the DNA damage checkpoint response, and is the yeast orthologue of the human ATR protein. Cancer cells rely on ATR to arrest the cell cycle and allow sufficient time to repair DNA damage before proceeding through the cell cycle, and ATR inhibitors have been developed as possible anti-cancer agents. DBF4 is the regulatory subunit of DBF4-dependent kinase (DDK) that regulates initiation of DNA replication and is overexpressed in a number of different cancer types. To better understand ATR and DBF4 function, we took advantage of yeast genetics to …

Postpartum Depression And Acculturation Among U.S. Immigrant Women Of Arabic Descent, Dalia Alhasanat

Wayne State University Dissertations

Purpose and Background/Significance: Postpartum depression (PPD) affects 12-20% of U.S. mothers. The PPD rates for women of Arabic descent are even higher (up to 37%). Higher acculturative stress and acculturation and lack of social support have been related to higher risk for PPD symptoms among immigrant women. No published research has investigated the relationship between acculturative stress, social support, and/ or acculturation and PPD symptoms among U.S. immigrant women of Arabic descent. Therefore, the purpose of this dissertation research was to examine the impact of acculturative stress, social support, and acculturation on PPD symptoms among these women. The specific aims …

Sleep Disturbance And The Immunological Acute Phase Response In Hospitalized Post-Operative Adults., Jean Dorothy Humphries

Wayne State University Dissertations

Abstract

Sleep Disturbance and the Immunological Acute Phase Response

in Postoperative Hospitalized Adults

Abstract

The purpose of this study was to examine the subjective and objective (actigraphy) sleep patterns, the immunological acute phase response of IL1-β and TNF-α, and the physiological stress response of cortisol and systolic blood pressure in post-operative abdominal surgical patients. Nineteen subjects, 10 men and 9 women, mean age 45.63 years (SD = 11.44) were enrolled between April 2015 and March 2016. All subjects were elective major invasive abdominal surgery patients. Laparoscopic surgery occurred in 10 patients and incisional surgery occurred in 9 patients. This descriptive …

Clinicopathology And Molecular Determinants Underlying Benign Breast And Breast Cancer Lesions, Andreana Holowatyj Holowatyj

Wayne State University Dissertations

Despite converging incidence rates for breast cancers by race, disparities in mortality persist where black women suffer from poorer prognosis compared to white counterparts. To understand the clinical, demographic, and molecular characteristics underlying these disparities, we examined differences among patients with breast cancer to understand the role of human epidermal growth factor receptor 2 (HER2) status, age, and race/ethnicity among women diagnosed with hormone receptor-positive breast cancer, and disparities in surgical therapy among female patients with early stage young-onset breast cancer. Benign breast disease, another known risk factor for breast cancer, includes a histological spectrum of lesions, could contribute to …