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Matriptase Mediated C-Met Signaling In Breast Cancer, Gina Lynn Zoratti

Wayne State University Dissertations

MATRIPTASE MEDIATED c-MET SIGNALING IN CRITICAL FOR BREAST CANCER PROGRESSION

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GINA ZORATTI

Historically proteases have been associated with tumor progression and metastasis through degradation of the basement membrane. However, in recent years these enzymes have also been shown to play key roles in the activation of growth factors and cytokines, thereby activating pro-oncogenic signaling pathways. Matriptase (MT-SP1, ST14) is an epithelia-specific pericellular protease which has received considerable attention in recent years spurred by the consistent dysregulation of the protease in human epithelial tumors including breast cancer. We have performed both functional and mechanistic studies of matriptase in breast cancer …

Combating Resistance To Epidermal Growth Factor Recpetor Inhibitors In Triple Negative Breast Cancer, Julie Marie Madden

Wayne State University Dissertations

Triple negative breast cancer (TNBC) patients suffer from a highly malignant and aggressive cancer that lacks an effective targeted therapeutic. Although many TNBCs, both in vitro and in vivo, have increased expression of epidermal growth factor receptor (EGFR), EGFR targeted inhibitors, such as gefitinib (GEF), have yet to demonstrate efficacy. Using mass spectrometry to identify pathways that remain activated in the presence of GEF, we found that components of the mTOR signaling pathway remain phosphorylated. While inhibiting mTOR with temsirolimus (TEM) decreased mTOR signaling, EGFR signaling pathways remained activated and the TNBC cell lines continued to proliferate. However, dual treatment …

Pathway Profiling Of Replicative And Induced Senescence, Maggie Purcell

Wayne State University Dissertations

Senescence is a permanent withdrawal from cell cycle that occurs naturally in cells in response to the shortening of telomeres. This natural "clock" serves to limit the number of cell divisions and therefore protects the cell from potentially carcinogenic mutations. However, senescence also occurs in response to external stresses to the cell, which is known as induced senescence. This study compares the mechanisms of natural senescence, a response to the shortening of telomeres during replication, with induced senescence by using various drugs to induce senescence: 5-aza-2-deoxycytidine (a demethylating agent), Adriamycin (a chemotherapeutic drug), and H2O2 (an agent causing oxidative stress). …

Social Cognitive Factors Associated With Verbal Bullying And Defending, Heather L. Carroll

Wayne State University Dissertations

The purpose of the study was to examine defending and verbal bullying and the role of social cognitive variables, including empathy, values, moral disengagement, and efficacy among middle school students. Middle school students (n=282) in grades 6 through 8 in an urban public school district in Michigan participated in the study. Data were collected using a self-report survey format during the 2013-2014 school year. Social cognitive variables were analyzed by grade and gender. Results indicated a statistically significant main effect for gender. Female students reported significantly higher scores for empathy, self-transcendence values and openness to change values, in comparison to …

Falls And Hospitalized Cancer Patients, Rebecca Allan-Gibbs

Wayne State University Dissertations

FALLS AND HOSPITALIZED CANCER PATIENTS

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REBECCA ALLAN-GIBBS, MSN, RN, CNS-BC, AOCNS

May 2014

Advisor: Dr. Patricia Jarosz, PhD, RN

Major: Nursing

Degree: Doctor of Philosophy

Problem: Many hospital fall prevention studies have shown that having a diagnosis of cancer places patients at higher risk for falls/falls with injury when compared to other hospitalized groups of patients. Few studies have focused solely on cancer patients at risk for falls in the hospital setting. Specifically, this study used Dorothea Orem's theory of self-care (Orem, 2001), and Albert Bandura's (2001), social cognitive theory to determine if factors such as age, gender, health …

Isolation And Characterization Of Natural Alpha-Glucosidase Inhibitors From Antioxidant Rich Red Wine Grapes (Vitis Vinifera), Hoda Chaouki Kadouh

Wayne State University Dissertations

Background: Diabetes is currently a global public health problem affecting people at all ages. Dietary antioxidants have been associated with a reduced risk of type 2 diabetes. Grape pomace contains considerable amounts of polyphenols and it has been reported to exhibit an inhibitory activity against alpha- glucosidases. Alpha-glucosidases, in turn, play a major role in controlling starch digestion and therefore postprandial blood glucose, a target for diabetes management.

Objective: This study aims to investigate the anti-diabetes potential of a selection of six grape pomaces and prepare and purify active components in the active variety that specifically inhibit intestinal alpha-glucosidases. The …

Empathy As A Moderator Of Adolescent Bullying Behavior And Moral Disengagement After Controlling For Social Desirability, Amy Zelidman

Wayne State University Dissertations

The purpose of this study was to assess the moderating influence empathy has on the associations between adolescent bullying behavior and moral disengagement after controlling for social desirability (e.g., response bias). 676 students in 7th and 8th grade from a suburban middle school in Southeast Michigan participated in this study in the fall of 2012.

Results showed male respondents were more likely than female respondents to (a) report engaging in all forms of traditional bullying behavior overall, including physical, verbal, and social bullying and (b) report higher rates of physical victimization and moral disengagement. Female respondents were more likely to …

Evaluation Of Presynaptic Dopamine Dynamics After: Toluene Inhalation Or Trkb Receptor Activation, Aaron Kwaku Apawu

Wayne State University Dissertations

Dopamine (DA) neurons in the striatum mediate several functions of the brain and have been linked to a host of neurological disorders including Parkinson's disease and addiction, both of which occur as a result of dysfunction in the DA system. In the present study, our first objective was to understand how the striatal DA system adapts to acute and repeated administration of inhalant toluene. The use of toluene as inhalant, like other drugs of abuse, is known to perturb DA neurotransmission in the brain reward pathway. However, the exact mechanism underling toluene's influence on striatal DA neurotransmission is unknown. The …

An Exploration Of The Use Of Objects In The Creation, Maintenance, And Social Performance Of Self Among People With Alzheimer's Disease And Related Disorders, Jayne Marie Yatczak

Wayne State University Dissertations

In the United States individuals with Alzheimer's disease and related disorders (ADRD) are faced with multiple threats to their social lives and to their sense of self. Such threats include the assumption that our sense of self is entirely dependent upon cognition and memory, elements that become impaired in AD (Kontos 2006) and images of Alzheimer's disease as the death before death (Behuniak 2011). The move to a long term care setting with its simultaneous stripping away of possessions that supply one with personal identity also poses such a threat. Although, individuals with ADRD who move to long term care …

Metabolic Syndrome In Obese African American Adolescents, Yulyu Yeh

Wayne State University Dissertations

Limited research regarding metabolic syndrome (MetS) has been conducted in obese African American adolescents (OAAA) using the International Diabetes Federation IDF criteria. MetS is a constellation of risk factors that increase the risk for chronic diseases and is defined as presence of any 3 or more of the 5 criteria: fasting glucose 100mg/dl, waist circumference 90th percentile, triglycerides 150 mg/dl, blood pressure (BP) 130/85 mmHg and HDL < 40mg/dl. The aim of this study was to assess the incidence of MetS in OAAA by using the IDF criteria and the relationship with diet, fast food consumption, nutrition knowledge, home food environment (HFE), and serum calcium, leptin, 1,25-dihydroxy vitamin D (1, 25 D3) levels. One hundred and fifty one OAAA (mean age: 14.3 ± 1.4 years, 65.6% girls, mean BMI: 37.4±7.2 kg/m2) in a metropolitan area took part in this study. Anthropometric data and fasting blood samples were collected. Participants completed a set of questionnaires regarding diet, fast food consumption, and nutrition knowledge. HFE was completed by the care givers. The MetS rate for OAAA was 61.6% and boys had higher MetS than girls (73.1%, 55.6% respectively). OAAA without MetS had higher serum calcium and 1,25 D3 level but no significant difference were found in food consumption, nutrition knowledge, and HFE. Total cholesterol /HDL ratio and Insulin resistance increased the odds of MetS by 55% and 10% and 1,25 D3 decrease the odds of MetS by 2%. Even though high fast food consumption, lack of nutrition knowledge and poor food environment were negatively associated with obesity, they didn't contribute to MetS. Increase serum vitamin D and calcium level might be beneficial to reduce MetS in OAAA population.

Alterations In The Mouse Striatum Following Acute And Repeated Ethanol Exposure, Brooke D. Newman

Wayne State University Dissertations

Brain-derived neurotrophic factor (BDNF) is an important neuromodulator that has implicated in regard to several neurological disorders, including alcohol addiction. BDNF is also an important modulator of dopamine (DA), a neurotransmitter that is heavily implicated in addiction with one of the DA rich brain regions being referred to as the reward center of the brain. One of the focuses in alcohol dependence research includes determining risk factors that make an individual more susceptible to becoming dependent. BDNF has been of interest as a risk factor due to its involvement in ethanol consumption and addiction evidenced in a vast number of …

Longitudinal Change In Regional Cortices And Fluid Intelligence, Peng Yuan

Wayne State University Dissertations

Fluid intelligence (Gf) and crystalized intelligence (Gc) are two factors of the general intelligence. They have distinct age-related trajectories of change. Jung and Haier proposed Parieto-Frontal Integration Theory (P-FIT, 2007) to account for the inter-person variance in reasoning intelligence. Some brain regions such as prefrontal, parietal, temporal and anterior cingulate cortices were included in the P-FIT model and were hypothesized to be involved in fluid reasoning task. Therefore, in the current study, we examined latent growth curves (LGC) of longitudinal change in Gf, Gc, prefrontal cortex, parietal cortex, anterior cingulate, temporal cortex and primary visual cortex. Forty-six healthy middle-aged and …

Using Video Games For Decreasing Pain Caused By Acute Painful Crisis In Adolescents With Sickle Cell Pain, Talal Ali

Wayne State University Dissertations

Purpose: The most common symptom of sickle cell disease is pain, which occurs as the cells clump compromising further blood flow to distal organs. Despite the advancement in pain management, many children and adolescents' pain remains under treated. The purpose of this study is measure the effectiveness of a videogame as a developmentally appropriate non-pharmacological modality on pain in adolescents 12-21 years of age with sickle cell crisis.

Methods: A one-group repeated measure quasi-experimental design was used to evaluate the effectiveness of using videogames on pain in a sample of adolescents 12-21 years of age. Using a repeated measures design …

Cervical Remodeling/Ripening At Term And Preterm Delivery: The Same Mechanism Initiated By Different Mediators And Different Effector Cells, Juan Miguel Gonzalez Velez

Wayne State University Dissertations

Premature cervical remodeling/ripening is believed to contribute to preterm delivery (PTD), the leading cause of perinatal morbidity and mortality. Despite considerable research, the causes of term and PTD remain unclear, and there is no effective treatment for PTD. We tested the hypothesis that complement activation plays a role in cervical remodeling and PTD. We studied cervical remodeling at term.

We studied two mouse models of inflammation-induced PTD. The first model was induced by vaginal administration of lipopolysaccharide (LPS)and the second one by administration of progesterone antagonist RU486. Increased cervical C3 deposition and macrophage infiltration and increased serum C3adesArg and C5adesArg …

Dendrimer Based Nanotherapeutics For Ocular Drug Delivery, Siva Pramodh Kambhampati

Wayne State University Dissertations

PAMAM dendrimers are a class of well-defined, hyperbranched polymeric nanocarriers that are being investigated for ocular drug and gene delivery. Their favorable properties such as small size, multivalency and water solubility can provide significant opportunities for many biologically unstable drugs and allows potentially favorable ocular biodistribution. This work exploits hydroxyl terminated dendrimers (G4-OH) as drug/gene delivery vehicles that can target retinal microglia and pigment epithelium via systemic delivery with improved efficacy at much lower concentrations without any side effects.

Two different drugs Triamcinolone acetonide (TA) and N-Acetyl Cysteine (NAC) conjugated to G4-OH dendrimers showed tailorable sustained release in physiological relevant …

Development And Initial Psychometric Testing Of The Perceived Racism Shifting Survey (Prss), Saran Hollier

Wayne State University Dissertations

ABSTRACT

DEVELOPMENT AND INITIAL PSYCHOMETRIC TESTING OF THE PERCEIVED RACISM SHIFTING SURVEY (PRSS)

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SARAN T. HOLLIER, MSN, RN

May, 2015

Advisor: Dr. Rosalind Peters

Major: Nursing

Degree: Doctor of Philosophy

Perceived racism experienced from those of a different race (intergroup), and those of the same race (intragroup), is a stressor that may be contributing to health disparities among African Americans. As a result, coping strategies are necessary for African Americans to navigate in both a "Black" and "White" world. Hence, African Americans may use "shifting" as a way to cope with inter- and intragroup racism. Shifting has been defined …

The Role Of Pdgf C And Its Splice Variant In Breast Cancer, Alyssa Bottrell

Wayne State University Dissertations

The PDGF family consists of four members; while PDGF A and B are secreted as active dimers, PDGF C and D are secreted as latent dimers that undergo serine protease-mediated extracellular proteolytic activation. Gene expression analysis of breast cancer cell lines showed that PDGF C expression is associated with Basal B subtype breast cancer cells which have cancer stem cell-like characteristics. Furthermore, PDGF C expression is associated with triple-negative (estrogen receptor-, progesterone receptor- and HER2/neu-negative) breast cancer cells, a challenging type of breast cancer to treat. During the course of our study, we discovered a splice variant of PDGF C …

Blast-Induced Tinnitus: A Combined Behavioral, Memri, And Electrophysiology Study, Jessica Pengyun Ouyang

Wayne State University Dissertations

ABSTRACT

BLAST-INDUCED TINNITUS: A COMBINED BEHAVIORAL, MEMRE, AND ELECTROPHYSIOLOGY STUDY

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JESSICA OUYANG

May 2014 Advisor: Drs. Steve Cala & Jinsheng Zhang

Major: Physiology

Degree: Doctor of Philosophy

Tinnitus and hearing loss are the frequent auditory-related co-morbidities of blast trauma. The etiology of blast-induced tinnitus is also muddled by brain mechanisms associated with emotional and cognitive problems such as anxiety, memory loss, and depression. We set out to develop a realistic and ecologically valid model to address changes of cognitive status and psychological state that are associated with blast- induced tinnitus. In this study, 19 adult rats were randomly divided …

Molecular Studies On The Anti-Tumor Effects Of Metal-Based Complexes: Involvement Of The Ubiquitin-Proteasome And Apoptotic Pathways, Sara M. Schmitt

Wayne State University Dissertations

The ubiquitin-proteasome pathway is crucial to normal cellular function, and as such, has been extensively investigated as a potential target for cancer therapeutics. Many compounds have been tested for their proteasome inhibitory ability, including various small peptide aldehydes, and, following the success of cisplatin, several metal-containing complexes. The efficacy of these compounds in preclinical studies ultimately resulted in the development and approval of the first-in-class proteasome inhibitor bortezomib, the use of which, unfortunately, has been hindered by toxicity and resistance. These limitations have led to a massive push toward designing and developing new, less toxic proteasome inhibitors for clinical use. …

Accumulation Of Subcortical Iron As A Modifier Of Volumetric And Cognitive Decline In Healthy Aging: Two Longitudinal Studies, Ana Marie Daugherty

Wayne State University Dissertations

Accumulation of non-heme iron in the brain has been theorized as a cellular mechanism underlying global neural and cognitive decline in normal aging and neurodegenerative disease. Relatively few studies of brain iron in normal aging exist and extant studies are almost exclusively cross-sectional. Here, I estimated iron content via T2* and measured volumes in several brain regions in two independent samples of healthy adults. The first sample (N = 89) was measured twice with a two-year delay; and the second sample (N = 32) was assessed four times over a span of 7 years. Latent models estimated change in iron …

Coping Similarity And Psychosocial Risk Factors In Couples With Chronic Pain, Amy M. Williams

Wayne State University Dissertations

Chronic pain is an important public health problem that is associated with a host of negative individual and relationship outcomes. Chronic pain is a chronic stressor that both the individual in pain and their spouse must cope with. The current study examined how pain coping similarity within the couple predicted not only patient adjustment, but also spouse adjustment in a longitudinal study. Participants were 108 heterosexual couples in which one partner had chronic pain. The participants completed measures at 3 time points at 6 month intervals. Both the patient and spouse individually completed questionnaires pertaining to their marriage, mood, pain …

Proximate And Evolutionary Insights Into The Epigenetics Of Posttraumatic Stress Disorder, Levent Sipahi

Wayne State University Dissertations

Posttraumatic stress disorder (PTSD) is an important medical and social condition. Although the vast majority of individuals are exposed to traumatic events within their lifetime, a minority subsequently develop diagnosable PTSD. What underlies differential risk and resiliency in the face of trauma is an ongoing research and clinical question with implications for prevention and treatment. Recent work has revealed a putative role of epigenetic variation and modification - most notably DNA methylation - in the etiology of PTSD. That DNA methylation is stable, yet modifiable in response to lived experiences, makes it a strong candidate to mechanistically explain the ontogeny …

Linking Molecular, Electrical And Anatomical Properties Of Human Epileptic Brain, Shruti Bagla

Wayne State University Dissertations

Epilepsy is a common neurological disorder of recurrent unprovoked seizures. It affects almost 1% of the world population. Although there is a wide range of anti-epileptic drugs (AEDs) available, they only treat the seizure symptoms and do not cure the disease itself. The poor role of AEDs can be attributed to the lack of knowledge of exact mechanisms and networks that produce epileptic activities in the neocortex. At present, the best cure for epilepsy is surgical removal of electrically localized epileptic brain tissue. Surgically removed brain tissue presents an excellent opportunity to discover the molecular and cellular basis of human …

Tmprss2-Erg Regulation Of Androgen Biosynthetic Enzyme Expression, Dht Synthesis, And Androgen Receptor Activation In Prostate Cancer, Katelyn Ann Powell

Wayne State University Dissertations

Intratumoral androgen synthesis in prostate cancer (PCa) contributes to the development of castration-resistant prostate cancer (CRPC). Several enzymes responsible for androgen biosynthesis have been shown to be overexpressed in CRPC, thus, contributing to CRPC in a castrated environment. Although intratumoral androgen synthesis is thought to contribute to the development and progression of CRPC, currently little is known regarding the regulation of androgen biosynthetic enzyme gene expression in PCa. The TMPRSS2-ERG transcription factor has been shown to be present in primary PCa tumors as well as CRPC tumors. The hypothesis was investigated that TMPRSS2-ERG fusions regulate androgen biosynthetic enzyme (ABE) gene …