Digital Commons Network^™

Shape Memory Alloy Capsule Micropump For Drug Delivery Applications, Youssef Mohamed Kotb

Theses and Dissertations

Implantable drug delivery devices have many benefits over traditional drug administration techniques and have attracted a lot of attention in recent years. By delivering the medication directly to the tissue, they enable the use of larger localized concentrations, enhancing the efficacy of the treatment. Passive-release drug delivery systems, one of the various ways to provide medication, are great inventions. However, they cannot dispense the medication on demand since they are nonprogrammable. Therefore, active actuators are more advantageous in delivery applications. Smart material actuators, however, have greatly increased in popularity for manufacturing wearable and implantable micropumps due to their high energy …

Microwave Imaging Technique For Breast Cancer Detection, Nure Alam Chowdhury

Theses and Dissertations

Breast cancer is a global problem, and it is inevitable to detect cancerous cells at early stages. In recent years, microwave imaging technology has been widely applied in biomedical applications for its non-ionizing radiation. In this study, we design a micro-strip patch antenna with an inverted T-type notch in the partial ground to detect tumor cells inside the human breast. The size of the current antenna is small enough (18 mm × 21 mm × 1.6 mm) to distribute around the breast phantom. The operating frequency has been observed from 6–14 GHz with a minimum return loss of −61.18 dB …

The Role Of The Cdk8 Kinase Module In Maintaining Proteostasis, Stephen Willis

Theses and Dissertations

The underlying etiology of numerous disease states results from perturbations in the maintenance of cellular proteostasis. Carcinogenesis relies on these perturbations to foster uncontrolled cell growth and eventual metastases, while neurodegenerative diseases are a consequence of such perturbations. Control of these processes occurs at numerous molecular levels, commonly starting with transcription. A key transcriptional complex that is involved is the CDK8 Kinase Module (CKM). The CKM is conserved from yeast to man, forming a tetrameric complex consisting of MED12, MED13, CDK8, and CCNC. The CKM has not only been implicated in a variety of cancers but also in a spectrum …

Cancer Treatment By Targeting Hdac4 Translocation Induced By Microsecond Pulsed Electric Field Exposure: Mechanistic Insights Through Kinases And Phosphatases, Zahra Safaei

Theses and Dissertations

Epigenetic modifications, arising from sub-cellular shifts in histone deacetylase (HDAC) activity and localization, present promising strategies for diverse cancer treatments. HDACs, enzymes responsible for post-translational histone modifications, induce these epigenetic changes by removing acetyl groups from ε-N-acetyl-lysine residues on histones, thereby suppressing gene transcription. Within the HDAC group, class IIa HDACs are notable for their responsiveness to extracellular signals, bridging the gap between external stimuli, plasma membrane, and genome through nuclear-cytoplasmic translocation. This localization offers two significant mechanisms for cancer treatment: nuclear accumulation of HDACs represses oncogenic transcription factors, such as myocyte-specific enhancer factor 2C (MEF2C), triggering various cell death …

Go Big Or Go Flat: Life Satisfaction After Mastectomy With Or Without Reconstruction, Susan T. Smith

Theses and Dissertations

Prior research on psychosocial functioning after mastectomy has focused on comparing women with different types of reconstruction to women who “remained flat.” We found that women who remained “flat by choice” had the highest overall psychosocial functioning, followed by the reconstructed group and lastly, by “flat without choice" women.

Characterizing Stress Granule Regulation By Pas Kinase, Ataxin-2 And Ptc6 And Investigating The Lifespan Of Covid-19 Virus On Currency, Colleen R. Newey

Theses and Dissertations

The protein Ataxin-2 is a known positive regulator of stress granules in humans, mice and yeast (known as yeast PBP1). Due to the role that stress granules play in diseases including Amyotrophic Lateral Sclerosis (ALS) and cancer, this thesis investigates the role of Ataxin-2 and its protein binding partners in stress granule development and its effects on various metabolic phenotypes of the cell. PAS kinase is a sensory protein kinase, conserved from yeast to man, which regulates respiration and lipid biosynthesis. Our lab discovered that PAS kinase phosphorylates and activates Ataxin-2 in yeast, and that PAS kinase overexpression enhances localization …

The Genetic Associations Of Circadian Rhythm And Sleep Disorder Traits With Risk Of Monoclonal Gammopathy Of Undetermined Significance And Multiple Myeloma, Brittany Crawford

Theses and Dissertations

Background: Circadian rhythm disruption and sleep have been widely studied for their roles in immunity and cancer development. Evidence for an association of circadian rhythm and sleep traits with multiple myeloma (MM) risk is inconclusive. No studies have investigated these traits in relation to monoclonal gammopathy of undetermined significance (MGUS). Given that MGUS precedes almost all MM cases, investigating sleep and circadian rhythm in relation to both MM and MGUS is necessary. The purpose of this dissertation was to explore the genetic influences of circadian rhythm and sleep traits on the risk of MGUS and MM. Methods: Data were leveraged …

Magnetic Softness Tuned Superparamagnetic Nanoparticles For Highly Efficient Cancer Theranostics, Jie Wang

Theses and Dissertations

Magnetic resonance imaging (MRI)-guided magnetic nanofluid hyperthermia (MNFH) using iron oxide based superparamagnetic nanoparticles (SPNPs) has recently attracted considerable attention as a treatment modality for cancer theranostics, because MRI-guided MNFH can allow for diagnosis, therapeutics, and prognosis simultaneously using the same administrated magnetic nanofluid agent. However, several primary limiting factors: (1) insufficient AC magnetic heating induction (specific loss power/intrinsic loss power, SLP/ILP) at the biologically safe and physically tolerable range of AC magnetic field (H_AC,safe: f_appl × H_appl < 3.0 ~ 5.0×10⁹ A·m^-1·s^-1), (2) low _r2- relaxivity directly related to the low resolution of …

Metaproteomics Profiling Of Gut Microbiota In Pediatric Acute Lymphoblastic Leukemia Patients, Shahd Ezz El Din

Theses and Dissertations

The gut microbiota is the collection of microorganisms that harbor the human gastrointestinal tract. The relation of microbiota and cancer is an emerging field as several studies have linked the gut microbiota to cancer. Such findings opened the door towards a new era of studies aiming to reveal the role of the microbiota in cancer initiation and progression. Although several metagenomic studies have provided insights into the gut microbial composition in health and diseased state, the microbial functional characteristics is still poorly understood. With current advances in mass spectrometry, comprehensive understanding of microbiota proteome became possible. In this vein, the …

Atomistic Assessment Of Drug-Phospholipid Interactions Consequent To Cancer Treatment: A Study Of Anthracycline Cardiotoxicity, Yara Elsayed Ahmed

Theses and Dissertations

Despite being one of the most effective chemotherapeutic agents developed to date, Anthracyclines are notorious for their cardiotoxicity. Their clinical use is frequently limited both in dosage and in prescription due to the severe cardiac damage they cause. The mechanism of anthracycline-induced cardiotoxicity is not yet fully understood. However, it is hypothesized that interactions with the myocardial membrane play an important role in imparting cardiotoxicity. In this study, we use molecular dynamics simulations and density functional theory calculations to study the anthracycline drug molecules and the interactions that they have with the myocardial membrane. We construct a myocardial membrane model …

Dad Talk: Father-Child Communication When A Parent Has Cancer, Elizabeth A. Reed

Theses and Dissertations

Most individuals are impacted by a cancer diagnosis, in fact 54% of Americans say they or someone in their immediate family has been diagnosed with cancer at some point (CBS Interactive, 2017). While most Americans have a family member with cancer, most research has been done to understand the mother-daughter relationship during such a time. Unfortunately, there is little research regarding father-child communication during a cancer diagnosis, and father-child communication is understudied. The father-child dyad is an important relationship that impacts a child throughout their lives (Fellers & Schrodt, 2021). To further understand these relationships and how cancer may impact …

Comparing Efficiency, Empowerment, And Satisfaction Between Individual And Group Genetic Counseling For Prostate Cancer, Sarah Marie Dickman

Theses and Dissertations

A hereditary cause for prostate cancer can be identified in 5-17% of cases, which can impact treatment and cancer screening recommendations for patients and their families. Increased demand for genetic testing has necessitated consideration of alternative genetic counseling service delivery models to meet needs. Studies have shown that group genetic counseling increases efficiency while maintaining the same patient benefits as individual genetic counseling, but research has mainly focused on patients who were assigned female at birth (AFAB). The purpose of this study was to evaluate the utility of group genetic counseling for prostate cancer by assessing participants’ satisfaction and feelings …

Evaluating Health Awareness In Cancer Genetics Amongst The Black And African American Community In South Carolina, Annika Jaliya Gadson

Theses and Dissertations

Historically minoritized individuals are underrepresented in genomic research which limits the ability to fully understand genetic variation within the population (Sirugo et al., 2019). This creates bias that questions the effectiveness of guidelines for genetic testing, predictive risk values, and medical management. Disparities in cancer genetics may be attributed to historical events that have cultivated mistrust in research and medicine, institutional bias, provider skepticism in patient reporting of medical symptoms, and limited access to genetic testing (Saulsberry et al., 2013). More exploration is needed to better understand how to increase access and awareness of cancer genetic services to Black and …

Protacs – A Novel And Rapidly Developing Field Of Targeted Protein Degradation, Hannah R. Gatley

Theses and Dissertations

There is a continued need for new technology and strategies for tackling cancer and other diseases, and within the current century a novel therapeutic strategy has emerged in the realm of targeted protein degradation called Proteolysis-Targeting Chimeras (PROTACs). This technology specifically targets and degrades disease-causing proteins via the ubiquitin-proteasome system, and has seen an explosion of research and intrigue in both academia and industry over the past two decades. The diversity of PROTAC classes based on the E3 ligase recruiting ligand and the target protein allows for a universal molecular structure that can be customized for a specific target and …

Profiles Of Family Functioning In Pediatric Hematology-Oncology Patients: Longitudinal Associations With Child Well-Being, Sydney Sumrall

Theses and Dissertations

This study aims to assess 1) patterns of family functioning and 2) longitudinal associations between family functioning patterns and well-being in a vulnerable cohort of children with chronic illness. Caregivers of hematology (16.4%) and oncology (83.6%) patients ages 7-20 (N=55; M_age = 13.3 [SD = 2.7]; 52.7% female; 45.5% non-Latinx White, 38.2% Black or African American, 12.7% Latinx, 1.8% Asian, and 1.8% multi-racial,) reported on family functioning via the Family Assessment Device. Cluster analyses identified three mutually exclusive clusters: one high adaptive group, one moderate adaptive group, and one maladaptive group. Group membership was not significantly …

Synthesis Of Bioactive Heterocycles, Shaila Akter Shetu

Theses and Dissertations

The Discovery of a variety of heterocyclic drugs for the treatment of cancer and other diseases (e.g, neglected tropical diseases) is a medical breakthrough and inspiring for the research community as a whole. A wide range of natural, semi-synthetic, and synthetic anticancer drugs are synthesized using various methods. Among them, β -lactams stand out as a novel class of antibiotics that has different types of biological as well as anti-cancer properties. β -lactam has become a premier and active research subject towards the development of revolutionary anti-cancer drugs. In recent years, a large amount of investigations have been done to …

Xenobiotic Exposures On Women’S Reproductive Health, Maria Zubizarreta Mcclam

Theses and Dissertations

Environmental and chemical exposures are continually introduced into our bodies. The female reproductive cycle is complex and particularly sensitive to toxic substances. A recent rise in infertility and reproductive diseases and cancers make reproductive toxicity a public health concern. The overall purpose of this dissertation is to explore how environmental and chemical exposures impact women’s reproductive health and overall wellbeing. To do this, a variety of topics related to women’s reproductive health are explored, including how environmental exposures can impact reproduction, methods for studying reproductive dysfunctions, fertility preservation among cancer patients, and the overall wellbeing of female cancer patients.

The …

Understanding The Complexities Of Anemia In Chronic Inflammatory Diseases From Diagnosis To Treatment, Naomi Rae Flindt

Theses and Dissertations

Iron is an essential nutrient for energy and DNA replication. Its homeostasis is commonly perturbed by chronic inflammatory mechanisms. Chronic inflammation upregulates a cytokine, hepcidin, that degrades the iron export protein ferroportin. Without a way to export iron into the bloodstream iron availability in blood becomes depleted. Iron depletion in the blood stream hinders erythropoiesis and is termed anemia. Herein I investigate and inhibit the mechanism of hepcidin activation. Inhibition of hepcidin activation has released iron from tissues and alleviated anemic conditions in a cancer model. I have laid the foundation to investigate this pathway in a 3D spheroid model. …

Mechanisms And Impact Of Hypoxia Regulated Inhibins In Cancer, Ben Allen Horst

Theses and Dissertations

Inhibins are heterodimeric ligands within the TGFβ superfamily, comprised of an α-subunit (INHA) and a β-subunit (either INHBA or INHBB) with emergent roles in cancer. Inhibins are biomarkers of disease burden and prognosis in a subset of cancers and utilize the coreceptors betaglycan (TGFBR3) and endoglin (ENG) for physiological or pathological outcomes. Previously, we found inhibin promotes angiogenesis in ovarian cancer however no mechanism of regulation for inhibin expression in cancer has been established. Hypoxia, a driver of tumor growth and metastasis, regulates angiogenic pathways that are targets for vessel normalization and ovarian cancer management. …

Long Non-Coding Rna Pvt1 – An Exploratory Study In Ovarian And Endometrial Cancer, Kevin Tabury

Theses and Dissertations

Gynecological cancers, ovarian and endometrial cancer, are still leading causes of cancer-related death in women worldwide. Early detection methods as well as treatment resistance remain a challenge. Long non-coding RNAs (lncRNAs) are emerging as therapeutic targets with diagnostic and prognostic potential with lncRNA PVT1 being one of them.

Here I test and demonstrate the role of PVT1 in ovarian cancer growth and metastasis. PVT1 is amplified and overexpressed in ovarian cancer and has predictive value for survival and response to targeted therapeutics. We find that expression of PVT1 is regulated by tumor cells in response to cellular stress, particularly loss …

Using Geospatial Analysis To Evaluate Relationships Between Cancer Incidence And Social Factors In Brooklyn, Ny, Sheena Philogene

Theses and Dissertations

This study explored the spatial distribution of cancer incidence in Brooklyn, NY. Using publicly available data, the relationships between cancer incidence and factors linked to cancer were investigated. Furthermore, the study explored the value of using large amounts of data with GIS techniques to quickly analyze geographic trends for cancer.

Evaluation Of Bmi, Diet Quality, Alcohol Intake, And Physical Activity In Cancer Survivors: Is There An Association With Primary Source Of Nutrition Advice?, Zachary J. Heindl

Theses and Dissertations

Objective: The purpose of this study was to determine if cancer survivors are meeting nutrition and physical activity recommendations presented by the ACS. The association between a survivor’s primary source of nutrition advice and these factors was also assessed. Method: A sample of 132 cancer survivors was recruited through social media. Inclusion criteria included: United States citizenship, at least 18 years of age, and diagnosis of cancer or malignancy by a health care professional. A one-time, self-administered survey was distributed via Qualtrics. The Dietary Screener Questionnaire was utilized to determine average daily consumption of fruits and vegetables and the weekly …

Changes In Physical Activity And Relationships To Submaximal Exercise Capacity And Cardiac Function During Breast Cancer Therapy, Moriah P. Bellissimo

Theses and Dissertations

Background: Breast cancer (BC) survivors are at high risk for heart failure due to curative cancer therapies. In non-cancer populations, physical activity is a first line treatment for preventing cardiovascular disease. This study examined whether more physical activity was associated with better submaximal exercise capacity and cardiac function during the first three months of cancer therapy.

Methods: Participants included 223 women with stage I-III BC before therapy and after three months of undergoing treatment and 126 controls. Leisure time physical activity was reported using the Godin Sheppard leisure time exercise questionnaire. Cardiac function was assessed by cardiac magnetic resonance, and …

Human Papillomavirus 16 E2 Regulates Host Cell Pathways Important For Cancer Progression And Treatment Sensitivity Which May Contribute To Cancer Outcomes, Christian Fontan

Theses and Dissertations

Human papillomaviruses (HPVs) are causative agents in around 5% of all cancers, including cervical and oropharyngeal. A feature of HPV cancers is their better clinical outcome compared with non-HPV anatomical counterparts. In turn, the presence of E2 predicts a better clinical outcome in HPV-positive cancers; the reason(s) for the better outcome of E2-positive patients is not fully understood.

Previously, we demonstrated that HPV16 E2 regulates host gene transcription that is relevant to the HPV16 lifecycle in N/Tert-1 cells. One of the genes repressed by E2 and the entire HPV16 genome in N/Tert-1 cells is TWIST1. In these studies, we demonstrate …

Novel Microfabricated Systems To Elucidate The Role Of Anisotropic Stiffness In The Tumor Microenvironment, Jiten Narang

Theses and Dissertations

Cancer is the second leading cause of death in women and late stage (metastatic) cancers have abysmal survival rates compared to early stage regional cases (27% vs 86%). As a tumor grows, the surrounding extracellular matrix (ECM) is reorganized into a dense, collagen rich matrix. The new matrix of aligned collagen fibers provides unique mechanical cues such as anisotropic stiffness and contact guidance. Matrix turnover also constricts local vasculature and restricts delivery of key nutrients and signaling molecules to malignant cells to outside the tumor creating a chemotactic gradient from outside to inside. In this work, we developed a novel …

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 …

The Joint Influence Of Social Support And Coping On Anxiety In Aya Cancer Survivors, Genevieve Durso

Theses and Dissertations

Background Adolescent and young adult (AYA) cancer survivors experience unique psychosocial needs during remission. Cancer-related anxiety is endemic amongst AYA survivors and can impede upon the survivor’s life post-cancer treatment. Independent of one another, confiding in a social support system and frequent engagement in coping mechanisms benefit those throughout the cancer experience, leading to more positive psychosocial outcomes. Hypothesis The dual utilization of one’s social support network and coping mechanisms would reduce cancer-related anxiety in AYA cancer survivors. Methods This study’s data was derived from a prior study conducted at Memorial Sloan Kettering Cancer Center, consisting of 128 adolescent and …

Handgrip Strength In Cancer Survivors: 2011-2014 National Health And Nutrition Examination Survey, Ayla Monet Kibler

Theses and Dissertations

Cachexia, or a loss of muscle mass, has been identified as a potential indicator of cancer survival rates. Previous explorations in research have connected muscular strength to muscle loss and cancer survivorship, but nationally generalizable findings are limited. PURPOSE: To investigate handgrip strength in cancer survivors using the National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of US adults. METHODS: The analysis included 368 males and 425 females from the 2011-2014 NHANES dataset. Cancer survivor information (type of cancer and age of diagnosis) was determined by questionnaire. Cancer types were grouped into the following: skin cancers, reproductive …

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 …