Digital Commons Network^™

Mitochondria Imaging And Targeted Cancer Treatment, Tinghan Zhao

Dissertations

Mitochondria are essential organelles as the site of respiration in eukaryotic cells and are involved in many crucial functions in cell life. Dysfunction of mitochondrial metabolism and irregular morphology have been frequently found in human cancers. The capability of imaging mitochondria as well as regulating their microenvironment is important both scientifically and clinically. Mitochondria penetrating peptides (MPPs), certain peptides that are composed of cationic and hydrophobic amino acids, are good candidates for mitochondria targeting. Herein, a novel MPP, D-argine-phenylalanine-D-argine-phenylalanine-D-argine-phenylalanine-NH₂ (rFrFrF), is conjugated with a rhodamine-based fluorescent chromophore (TAMRA). The TAMRA-rFrFrF probe exhibits advantageous properties for long-term mitochondria tracking of …

Cancer Risk Prediction With Whole Exome Sequencing And Machine Learning, Abdulrhman Fahad M Aljouie

Dissertations

Accurate cancer risk and survival time prediction are important problems in personalized medicine, where disease diagnosis and prognosis are tuned to individuals based on their genetic material. Cancer risk prediction provides an informed decision about making regular screening that helps to detect disease at the early stage and therefore increases the probability of successful treatments. Cancer risk prediction is a challenging problem. Lifestyle, environment, family history, and genetic predisposition are some factors that influence the disease onset. Cancer risk prediction based on predisposing genetic variants has been studied extensively. Most studies have examined the predictive ability of variants in known …

Burden And Risk Of Non-Aids Defining Cancers In Hiv-Infected Persons Receiving Antiretroviral Therapy, Brittney L. Dickey

Theses & Dissertations

The burden of cancers not previously associated with an HIV infection, called non-AIDS defining cancers (NADCs), have increased in the years since highly active anti-retroviral therapy has been introduced. The studies in this dissertation attempted to quantify this burden via incidence and mortality compared to the general population. Further, an assessment of risk factors and creation of a predictive risk model, a nomogram, were utilized to better understand how factors associated with demographics, lifestyle, and immune response affected risk for an NADC diagnosis once therapy was initiated and HIV better controlled. Standardized incidence and mortality ratios showed that burden of …

Amphiphilic Cell-Penetrating Hybrid Cyclic-Linear Peptides As A Drug Delivery System, Saghar Mozaffari

Pharmaceutical Sciences (PhD) Dissertations

A number of cyclic peptides containing a positively charged ring composed of arginine residues attached to hydrophobic tail made of tryptophan residues through a lysine linker namely [R₅K]W₅, [R₆K]W₅, [R₅K]W₆, [R₇K]W₅, [R₅K]W₇, [R₆K]W₆, and [R₇K]W₇ were synthesized and evaluated as molecular transporters. The peptides were evaluated for their ability to deliver, fluorescence-labeled cell-impermeable negatively charged phosphopeptide (F′-GpYEEI), and fluorescent labeled anti-HIV drugs (F′-FTC and F′-d4T). The results indicated that the presence of positively …

Putting A Face To Cancer, Lenn Robbins

Capstones

About one month after I began my studies at the Craig Newmark Graduate School of Journalism, I was diagnosed with a rare form of cancer, Langerhans Cell Histiocytosis (LCH). Three years and three relapses later, I have my MA, I defiant will to fight this disease and the hope that by chronicling my experience I might help others. If this project helps just one person, it's been worth the ride.

https://lennrobbins.wixsite.com/facetocancer

Synthesis Of Gadolinium-Doxorubicin Prodrug Carrying Functional Nanoceria For The Targeted Drug Delivery And Cancer Treatment, Arth Patel

Electronic Theses & Dissertations

The main focus of this research was the development of a polymer-coated nanoceria (PNC) platform to be used as a drug delivery system. Water-dispersible PNC is synthesized using a water-based alkaline precipitation method. Cerium nitrate hexahydrate and poly (acrylic acid) are used for the preparation of PNC. The synthesized PNC was characterized using ZETA, and UV- Vis characterization techniques. Polyacrylic acid (PAA)-coated cerium oxide nanoparticles fabricated for the targeted combination therapy of TNBC (MDA-MB-231) and MCF-7. Using EDC/NHS chemistry, the surface carboxylic acid groups of nanoceria was designed and synthesized with ICAM-1 antibody to target ICAM-1 overexpressing TNBC. Next, doxorubicin …

Infection Of Mitochondria In Damselfish Neurofibromatosis: Impacts On Mitochondrial Function And Dna Levels, Merly Laura Ovares

Open Access Dissertations

Damselfish neurofibromatosis (DNF) is a type of cancer affecting Stegastes partitus (Bicolor damselfish) on Florida reefs. The agent which causes the disease, termed the damselfish virus-like agent (DVLA), is the only known agent to replicate within mitochondria of animal cells. Determining the effects DVLA has on mitochondrial function and DNA levels are of importance to further understand DNF, as well as which mechanisms of mitochondrial function are directly affected by DVLA which may cause cancer. Experiments analyzed DNA levels of both DVLA and mitochondria (mtDNA), as well as mitochondrial-mediated metabolism on healthy and tumor tissues. Cell lines were also analyzed …

A Comprehensive Investigation Of Mth1 As A Novel Therapeutic Target In Ras-Driven Cancers., Govindi Jayanika De Alwis Samaranayake

Open Access Dissertations

The nucleotide pool is significantly more susceptible to oxidative damage induced by reactive oxygen species (ROS) compared to genomic DNA, due to DNA being more protected by the double helix and nucleosome packing. The NUDIX pyrophosphatase, MutT Homolog 1 (MTH1), maintains nucleotide pool integrity by hydrolyzing oxidized purines thus preventing their genomic incorporation. If incorporated into DNA the accumulation of these oxidized purines can lead to DNA strand breaks, genomic instability, and ultimately cell death. Our prior work has shown that MTH1 is critical in facilitating multiple pro-tumorigenic phenotypes in oncogenic RAS-mutated cancer cells, with its depletion leading to decreased …

Evaluating The Utility Of Protein Biomarker, S100a7, And Diagnostic Test, Straticyte, In Predicting The Progression Of Oral Dysplasia, Lachlan Mclean

Electronic Thesis and Dissertation Repository

Five-year survival of oral cancer has remained relatively unchanged despite advancements in treatment, mostly because diagnosis is often made at an advanced stage of disease. The progression of dysplasia to oral cancer often follows a stepwise progression. Histopathology is considered the ‘gold standard’ for diagnosing dysplasia and lesions at a high risk of progression to oral cancer, but lends itself to subjectivity. The protein biomarker, S100A7, in oral dysplasia and squamous cell carcinoma has shown some predictive value for the transformation of dysplasia to cancer. Straticyte, a diagnostic test utilizing S100A7 to predict the probability of progression of oral dysplasia …

Cervical Cancer Prevention And Control In Haitian Women Living In South Florida And The Central Plateau Of Haiti, Rhoda K. Moise

Open Access Dissertations

The cervical cancer burden in Haiti is among the highest in the world, despite being a largely preventable disease through primary (i.e., vaccination against Human papillomavirus (HPV), the principal cause of cervical cancer), and secondary (i.e., routine cervical cancer screening) prevention strategies. Haitian women likely face multiple barriers to disease prevention though knowledge of these barriers remains limited, particularly from a multilevel, transnational orientation. This dissertation aims to fill this gap. Guided by the PEN-3 model and the tenets of Community Engaged Research, the three associated papers rely on mixed methodologies to articulate the complex interplay between socio-cultural, environmental, political, …

Exploration Of Ataxia Telangiectasia And Rad3-Related’S (Atr’S) Role In Cell Death Regulation: Implications In Development, Cancer, And Stroke, Brian Cartwright

Electronic Theses and Dissertations

From gametogenesis until death an organism’s genome is under constant bombardment from endogenous and exogenous sources of DNA damage. To maintain genomic integrity amid this damage, cells have evolved responses which allow them to either preserve viability for recovery or initiate self-destructive pathways depending on the severity of DNA damage. One protein involved in initiating and carrying out these responses is the protein kinase ataxia telangiectasia and Rad3-related (ATR). ATR is known primarily for its regulatory role in initiating the checkpoint-signaling cascade following DNA damage and replicative stress. These signaling events lead to cell cycle arrest, DNA repair, or apoptosis …

In Vivo Metabolic And Vascular Response To Hypoxia In Twist Knockdown Murine Breast Cancer, Brandon Sturgill

Graduate Theses and Dissertations

Twist transcription factor is often overexpressed in aggressive tumors. Although needed in early embryonic development for organogenesis, Twist is known to induce an epithelial to mesenchymal transition in cells. In cancer, epithelial to mesenchymal transitions can lead to increased motility and invasiveness. It has also been linked to metabolic reprogramming and increased metastatic risk. Furthermore, metabolic preferences can increase proliferation, enhance metastatic potential, and influence the site of metastasis. We hypothesize that Twist directly affects the metabolism of cancer cells. We expect to see in vivo what we have seen in vitro; Twist overexpression should promote a shift away from …

Preparation Of Folic Acid-Carbon Dots-Doxorubicin Nanoparticles As Targeting Tumor Theranostics, Samson Dada

Electronic Theses and Dissertations

Carbon dots (CDs) have attracted much attention as an excellent gene/drug delivery and biological imaging agent for early cancer theranostics. In this study, we prepared two series of nanoparticles (NPs), which are composed of (CDs) with a targeting agent, folic acid (FA), and a chemotherapeutic agent Doxorubicin (Dox). All the NPs and their intermediates were characterized using ultraviolet-visible spectroscopy (UV-vis), fluorescence spectroscopy, and Fourier transform-infrared spectroscopy (FT-IR). The drug loading capacity (DLC) and drug loading efficiency (DLE) of two series of FA-CDs-Dox were assessed using UV-vis absorption spectroscopy at the wavelength of 485 nm. Both showed good DLE and DLC …

Investigation Of Phosphoserine Aminotransferase 1(Psat1) In Breast Cancer Progression., Stephanie Metcalf

Electronic Theses and Dissertations

This dissertation describes my research into the involvement of phosphoserine aminotransferase 1 (PSAT1) in breast cancer progression; specifically, in triple negative breast cancer (TNBC) metastasis and endocrine resistance in estrogen receptor positive breast cancer (ER+BC). Breast cancer is the most common tumor diagnosis among women. While the overall 5-year survival for breast cancer is reaching 90%, the 5-year survival for metastatic disease is only 22%. Metastasis and endocrine resistance combined can affect over 50% of patients. One of the proteins and pathways implicated in both metastasis and endocrine resistance in breast cancer is phosphoserine aminotransferase 1 (PSAT1) and the serine …

Dietary Advanced Glycation End-Products (Ages) And Breast Cancer Risk And Survival, Omonefe Opeyemi Omofuma

Theses and Dissertations

Introduction: Advanced glycation end-products (AGEs) are implicated in the pathogenesis of chronic diseases including cancer. AGEs are produced endogenously and are also consumed from foods. High amounts of AGEs are found in animal products and processed foods, and AGE formation is accelerated during cooking at high temperatures. Using data from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), we assigned and quantified NƐ-carboxymethyl-lysine (CML)-AGE content in food and investigated the association between dietary AGE intake and breast cancer (BrCa) risk. We assessed whether the risk was modified by race/ethnicity, obesity status, fruit and vegetable intake, BrCa invasiveness …

Evidence For P53-Mediated Induction Of Wrap53a In Response To Dna Damage, Anne Shelton Hucks

Theses and Dissertations

p53 is a powerful tumor suppressor mutated in approximately half of all cancers. Its mRNA is stabilized post-transcriptionally via complementary base pairing with the transcript of its antisense gene, WRAP53α; without this interaction, p53 protein cannot accumulate enough to carry out its many functions related to apoptosis, cell cycle arrest, and DNA damage repair. Previous studies have shown that WRAP53α is induced in response to DNA damage. The purpose of this study was to determine which transcription factors might be responsible for this induction. After identifying three putative p53 binding sites on the WRAP53α promoter, we used chromatin immunoprecipitation …

Elucidating The Mechanism Of Bone Morphogenetic Protein (Bmp) -Mediated Sox2 Downregulation In Ovarian Cancer, Zainab Motolani Shonibare

Theses and Dissertations

Sex determining region Y-box 2 (Sox2) is a transcription factor essential for maintaining self-renewal and pluripotency of undifferentiated embryonic stem cells. Sox2 is involved in multiple processes of cancer cells, however, regulation of Sox2 expression and the consequences of that regulation in cancer remains elusive. Previously, we demonstrated that BMP9/GDF2 is significantly reduced in expression in ovarian cancer (OVCA) cells, methylated in patient tumors and, promoted anoikis resistance in both breast and OVCA cell lines. In an attempt to identify genes downstream of BMP9 that may provide anoikis resistance, transcriptomics was performed leading to the identification of Sox2, a developmental …

Anti-Cancer Effects Of Oleocanthal And Extra Virgin Olive Oil, Limor Goren

Dissertations, Theses, and Capstone Projects

Oleocanthal is a phenolic compound found in varying concentrations in extra virgin olive oil. Oleocanthal has been shown to be active physiologically, benefiting several diseased states by conferring anti-inflammatory and neuroprotective benefits. Recently, we and other groups have demonstrated its specific and selective toxicity toward cancer cells; however, the mechanism leading to cancer cell death is still disputed. The current study demonstrates that oleocanthal induced damage to cancer cells’ lysosomes leading to cellular toxicity in vitro. Non-cancer cells were significantly less affected. Lysosomal membrane permeabilization following oleocanthal treatment in various cell lines was assayed via three complementary methods. Additionally, …

Examining Financial Stress And Coping Among U.S. Cancer Patients And Survivors: Quantitative Analyses Of Survey Data., Meredith J. Doherty

Dissertations, Theses, and Capstone Projects

Financial hardship, a growing problem for cancer patients and survivors, is associated with increased pain and symptom burden, reduced quality of life and psychological wellbeing, poor treatment adherence, and early mortality. Nearly one in three cancer patients reports that cancer caused some financial stress or strain. Emerging research has begun to explore the coping strategies used by cancer-affected individuals to manage the direct and indirect costs associated with cancer and its treatment. This dissertation seeks to answer three research questions: (1) what are the measurable characteristics of different cost-coping strategies? (2) what behavioral, institutional, and social factors are associated with …

The Role Of Kidney Injury Molecule-1 In The Metastasis Of Renal Cell Carcinoma, Jasper Lee

Electronic Thesis and Dissertation Repository

Over 30% of patients with renal cell carcinoma (RCC) present with metastases, with median survival of 2 years. Kidney injury molecule 1 (KIM-1) is a cell-surface glycoprotein expressed by >90% of RCC tumours. Preliminary data mined from The Cancer Genome Atlas RNA-sequencing database indicates that KIM-1 overexpression predicts overall survival in patients. Here we sought to determine if tumour KIM-1 plays a role in RCC cell extravasation and metastasis to the lungs. In vitro invasion and in vivo metastasis assays were performed to investigate the metastatic potential of KIM-1-expressing cells, and RNA-seq was conducted to identify differentially expressed genes between …

Mechanosensitive Epithelial Cell Scattering And Migration On Layered Matrices, Christopher Michael Walter

McKelvey School of Engineering Theses & Dissertations

Epithelial cells form multi-layered tissue scaffolding that makes up every organ in the body. Along with epithelial cells, the basement membrane (BM) and connective tissue are composed of various proteins that sculpt the organs and protect them from foreign macromolecules. Epithelial cells respond to various cues, both chemical and mechanical, from their surrounding matrices to aid in maintenance and repair of these layers through degradation and deposition of extracellular matrix (ECM) proteins. In cancer progression, epithelial cells lose their normal function of supporting tissue structure and instead adopt more aggressive behaviors through an epithelial-to-mesenchymal transition (EMT) of their cellular traits. …

Functional Investigation Of The Role Of The Retinoblastoma Protein In Genome Stability, Aren E. Marshall

Electronic Thesis and Dissertation Repository

Genome instability is an enabling characteristic of cancerous cells. It has recently been discovered that the retinoblastoma protein (pRB), typically known for its role in cell cycle regulation, also aids in the maintenance of genome stability. Intriguingly, mutations to the pRB gene, RB1, can arise late in tumorigenesis in cancer cells whose cell cycle regulation is already compromised by another mutation. This suggests that pRB’s functions in genome stability could underlie cancer relevant characteristics that are independent of its ability to negatively regulate proliferation. The overall aim of this thesis is to characterize the different means through which pRB …

Effects Of Visit Frequency On Swallowing Function During Organ Preservation For Head And Neck Cancer, Mathew Blaine Vansant

LSU Doctoral Dissertations

Chemoradiotherapy is not without risk of injury to the muscles and nerves associated with swallowing function. Current research supports the use of prophylactic behavioral swallowing exercise in the HNC population, however, wide variations in swallowing treatment methodologies exist and no optimal SLP-patient visit frequency has been established. In addition, poor patient adherence to swallowing exercise appears prevalent. The current study explored the impact of speech language pathologist (SLP)-patient contact time, adherence to prophylactic behavioral swallowing exercises, and explored effects of exercise intensity on immediate post-radiation swallowing outcomes. Groups included a high frequency group (5 weekly SLP-patient visits, n = 15), …

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

Dissertations & 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 …

The Effects Of Hand Holding On Cancer Patients Level Of Anxiety: A Single-Case Study, West Loveland

Graduate Theses and Dissertations

The purpose of this dissertation was to explore how the anxiety levels of non-Hodgkin’s lymphoma patients receiving chemotherapy are affected while holding hands with a secure attachment. This study utilized three experimental single-case designs: participant one measured under a B-design, participant two measured under a B-A design, and participant three measured under an A-B design. Each participant’s anxiety was assessed during six chemotherapy treatments and one meeting with their primary oncologist to discuss the prognosis of their cancerous disease. Results visually indicate a greater effect on anxiety reduction during treatment when the intervention is utilized compared to only having a …

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

Capstone Experience

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.

Melanoma, Dianna Lauer

Nursing Student Class Projects (Formerly MSN)

There are many types of skin cancer prevalent in the world today. The three most common types of skin cancer are basal cell carcinoma, squamous cell carcinoma, and melanoma (Watson et al, 2015). In the words of Hawryluk & Tsao (2014), “Melanoma is an aggressive malignancy borne of melanocytes, the pigment-generating cells of the skin”. Melanoma is known to cause the most deaths of the three main skin cancers and has many risk factors. The personal risk factors include, “family history, multiple moles, fair skin, blue eyes, red hair, and freckles” (Watson et al, p.e92, 2015). There are risk factors …

Human Papillomavirus (Hpv) And Cervical Cancer, Stephanie Gregorc

Nursing Student Class Projects (Formerly MSN)

Human papillomavirus (HPV) is one of the most common sexually transmitted diseases with more than 100 types. The American Cancer Society (2019) reports, “Most men and women who have ever had sexual contact will get HPV at some time in their lives.” Certain strands are more detrimental than others, however it is important to understand how it spreads and ways to minimize its occurrence. Preventative actions are available to women, such as pap smear screenings, which can allow for early identification and treatment of abnormalities. As an advanced practicing nurse, it is essential to provide education to women surrounding HPV, …

Cervical Cancer, Katie Redmon

Nursing Student Class Projects (Formerly MSN)

Cervical Cancer is a major health concern worldwide for women. Human papillomavirus (HPV) is one of the major health risk factors known to causing cervical cancer. Early prevention and detection are key to preventing the cancer. There are vaccinations to prevent HPV and ways to detect abnormal cells by having a Papanicolaou cytology (Pap) test. The underlying signs and symptoms, pathophysiology, and implications for nursing care are discussed within the poster.

Synthesis Of New Aliphatic Pseudo-Branched Polyester Co-Polymers For Biomedical Applications, Zachary Shaw

Electronic Theses & Dissertations

In this study, a hyperbranched polyester co-polymer was designed using a proprietary monomer and diethylene glycol or triethylene glycol as monomers. The synthesis was carried out using standard melt polymerization technique and catalyzed by p-Tolulenesulfonic acid. The progress of the reaction was monitored with respect to time and negative pressure, with samples being subjected to standard characterization protocols. The resulting polymers were purified using the solvent precipitation method and characterized using various chromatographic and spectroscopic methods including GPC, MALDI-TOF, and NMR. We have observed polymers with a molecular weight of 29,643 kDa and 33,996 kDa, which is ideal to be …