Medicine and Health Sciences Commons^™

Targeting The Colchicine Binding Site On Tubulin To Overcome Multidrug Resistance And Anticancer Efficacy Of Selective Survivin Inhibitors, Kinsle E. Arnst

Theses and Dissertations (ETD)

Tubulin inhibitors are widely used as chemotherapeutic agents, and their successis attributed to their ability to target microtubule dynamics and disrupt critical cellular functions including cell signaling, motility, intracellular trafficking, and mitosis. Interference with microtubule dynamics consequently disrupts mitotic progression and ultimately leads to apoptosis, validating microtubule dynamics as an excellent target for anticancer agents. While this class of drug has proven to be effective against many cancer types, the clinical efficacy of current tubulin inhibitors is often limited by the development of multidrug resistance. The most common form of resistance to these agents arises from the overexpression of drug …

The Role Of Tumor Suppressor Dear1 In The Acquisition Of Mammary Stem/Progenitor Cell Properties, Uyen Le

Dissertations & Theses (Open Access)

Breast cancer is the most commonly diagnosed cancer in women in America. Ductal carcinoma in situ (DCIS), one of the earliest pre-invasive forms of invasive ductal carcinoma (IDC), has a 30-50% risk of progressing to IDC. Understanding the mechanisms regulating progression from DCIS to IDC would help identify biomarkers to stratify patients at higher risk of progression or metastasis. Cumulative literature suggests the earliest phase of dissemination from the primary tumor is driven by the epithelial-mesenchymal transition (EMT) program. DEAR1 is a tumor suppressor gene which is mutated, undergoes loss of heterozygosity in breast cancer, and is downregulated in DCIS …

Roles Of Cytosolic Nucleic Acid Sensors In Cancer And Infection, Qifan Zhu

Theses and Dissertations (ETD)

Pattern recognition receptors are innate immune sensors that recognize pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) with crucial roles in host defense against microbial infection, autoimmune diseases and cancer. Cytosolic nucleic acids including DNA and RNA originate from pathogens or self-cells, which form major groups of PAMPs and DAMPs. A range of nucleic acid sensors have evolved to sense various types of nucleic acids. How different DNA-sensing pathways regulate microbial infection and cancer is the focus of this dissertation.

Stimulator of IFN genes (STING) is a cytosolic innate immune sensor for cyclic dinucleotides that also serves a dual …

Characterization Of Cancer Incidence In Chronic Kidney Disease Patients: A Single Center Study, 2008 – 2018, Jagadeesh Puvvula

Capstone Experience

Background: Chronic kidney disease (CKD) is an established risk factor for cardiovascular disease, but the significance of lower Glomerular filtration rate on incidence and mortality from cancer is uncertain. There is evidence that cancer risk and cancer mortality may be increased in individuals with End Stage Renal Disease (ESRD) requiring dialysis or after renal transplantation but whether less severe kidney disease is associated with cancer remains poorly understood.

Some studies indicate that these associations do appear to be organ specific. It has been reported that reduced renal function is associated with an increased risk of cancers of the kidney and …

The Role Of Cdk8 In Metastatic Growth Of Colon Cancer, Jiaxin Liang

Theses and Dissertations

Unresectable hepatic metastases of colon cancer poorly respond to existing therapies and are a major cause of colon cancer lethality. Transcription- regulating Mediator kinase CDK8, an early clinical stage drug target, is amplified or overexpressed in many colon cancers and CDK8 expression correlates with shorter patient survival. Here we show that CDK8 inhibition does not generally suppress proliferation of CDK8-overexpressing colon cancer cells but nevertheless CDK8 knockdown by shRNA or CDK8 kinase inhibition by a selective small-molecule drug candidate suppresses metastatic growth of mouse and human colon cancer cells in the liver. This effect is due at least in part …

Equipment To Address Infrastructure And Human Resource Challenges For Radiotherapy In Low-Resource Settings, Rachel Mccarroll

Dissertations & Theses (Open Access)

Millions of people in low- and middle- income countries (LMICs) are without access to radiation therapy and as rate of population growth in these regions increase and lifestyle factors which are indicative of cancer increase; the cancer burden will only rise. There are a multitude of reasons for lack of access but two themes among them are the lack of access to affordable and reliable teletherapy units and insufficient properly trained staff to deliver high quality care. The purpose of this work was to investigate to two proposed efforts to improve access to radiotherapy in low-resource areas; an upright radiotherapy …

A Cancer-Targeted Gold Nanoparticle-Based Mri Contrast Agent., Nagwa El-Baz

Electronic Theses and Dissertations

In oncology, imaging plays a major role in terms of early detection and treatment of most types of cancer. Magnetic resonance imaging (MRI) is mostly used for cancer diagnosis due to its excellent contrast resolution. However, MRI for cancer diagnosis is somewhat limited by its sensitivity. In this thesis, we assessed the ability of theranostic platform consisting of gold nanoparticles functionalized with a cancer targeting aptamer; AS1411 and gadolinium chelate (Dotarem thiol derivative; Gd (III)-DO3A) as a MRI contrast agent to target malignant tumors by enhancing the MRI contrast of the detected tumor. The proposed technology is a novel injectable …

Evaluation Of Drug-Loaded Gold Nanoparticle Cytotoxicity As A Function Of Tumor Tissue Heterogeneity., Hunter Allan Miller

Electronic Theses and Dissertations

The inherent heterogeneity of tumor tissue presents a major challenge to nanoparticle-medicated drug delivery. This heterogeneity spans from the molecular to the cellular (cell types) and to the tissue (vasculature, extra-cellular matrix) scales. Here we employ computational modeling to evaluate therapeutic response as a function of vascular-induced tumor tissue heterogeneity. Using data with three-layered gold nanoparticles loaded with cisplatin, nanotherapy is simulated with different levels of tissue heterogeneity, and the treatment response is measured in terms of tumor regression. The results show that tumor vascular density non-trivially influences the nanoparticle uptake and washout, and the associated tissue response. The drug …

Febrile Neutropenia, Tonja Plew

Nursing Student Class Projects (Formerly MSN)

Febrile Neutropenia (FN) is a common, yet potentially life-threatening, complication in cancer patients receiving myelosuppressive chemotherapy. FN occurs when a patient has a temperature of greater than 100.4℉ with an absolute neutrophil count of less than 500cells/mm³, which places the patient at a high risk for infection. Fever may be the only sign of FN. FN is an oncologic emergency, requiring immediate, aggressive treatment with broad-spectrum antibiotics. FN is associated with high morbidity and mortality in cancer patients.

Implementation Of National Pediatric Guidelines To Prevent Chemotherapy Induced Nausea And Vomiting In Children With Cancer, Taryn Sandheinrich

Dissertations

Purpose: The purpose of this study was to assess the use of supplemental, as needed (prn) pharmacologic interventions for uncontrolled acute chemotherapy induced nausea and vomiting (CINV) in children with cancer after implementation of new pediatric CINV prophylaxis guidelines. Description of Project: A retrospective chart review was completed on forty-three children admitted to the hospital for chemotherapy during a 3 month period in 2017 to document the use of medications given for acute breakthrough CINV. The pre-implementation group received anti-emetics based on the institutional standard of care. A second retrospective chart review was completed on thirty-three children admitted to …

Study Of Alpha Mangostin As A Chemoprotective Agent For Breast Cancer Via Activation Of The P53 Pathway, Vanessa Van Oost

Pence-Boyce STEM Student Scholarship

Breast carcinoma is the most frequently diagnosed cancer among women and causes over 400,000 deaths yearly worldwide. Current treatments such as chemotherapy are not selective for cancerous tissues but are destructive to normal tissues as well. This causes a range of side effects including pain, nausea, hair loss, weakness, and more. Inactivation of p53 is an almost universal mutation within human cancer cells. The ability to activate the p53 pathway which protects cells from tumor formation is lost in 50% of cancers. Due to the prevalence of this mutation, p53 is a uniquely valuable target for applied research. Alpha mangostin …

Molecular Interplay Of Chromatin Remodeling Factor Brg1 And Transcription Factor Stat3 Regulates Stemness, Chemosensitivity And Tumorigenicity Of Glioma Tumor Initiating Cells, Debolina Ganguly

Theses and Dissertations (ETD)

Glioblastoma Multiforme (GBM) is an aggressive brain tumor, characterized by high cellular heterogeneity, is refractory to treatment and has dismal prognosis. These characteristics of GBM have suggested the presence of stem-like cells that have the ability to initiate and maintain tumors of a heterogeneous nature, and bestow resistance to current therapeutic regimens. It is therefore imperative to identify the dysregulated molecular pathways which enable the maintenance of these cells in a stem-like state in order to inform strategies to therapeutically target them.

In this study, we investigated the role of the Y705 and S727 phosphorylation domains of STAT3, a multifunctional …

Increasing Ph In Cancer: Enabling A New Therapeutic Paradigm Using Novel Carbonate Nanoparticles, Avik Som

McKelvey School of Engineering Theses & Dissertations

Enormous progress has been made to treat cancer, and yet the mortality rate of cancer remains unacceptably high. High clinical resistance to molecularly targeted therapeutics has pushed interest again towards inhibiting universal biochemical hallmarks of cancer. Recent evidence suggests that malignant tumors acidify the local extracellular environment to activate proteases for degrading the tumor matrix, which facilitates metastasis, and explains why more aggressive tumors are more acidic. Current therapies have only focused on using the low pH for enhancing drug release in tumors, thereby still relying on the traditional paradigm of intracellular inhibition of pathways, a method that continues to …

Tumors Interrupt Irf8-Mediated Dendritic Cell Development To Overcome Immune Surveillance, Melissa Ann Meyer

Arts & Sciences Electronic Theses and Dissertations

Tumors employ multiple mechanisms to evade immune surveillance. One mechanism is tumor-induced myelopoiesis, which expands immune suppressive granulocytes and monocytes to create a protective tumor niche shielding even antigenic tumors. As myeloid cells and immune-stimulatory conventional dendritic cells (cDCs) are derived from the same progenitors, it is logical that tumor-induced myelopoiesis might also impact cDC development. The cDC subset cDC1 is marked by CD141 in humans and CD103 or CD8α in mice. cDC1s act by cross presenting antigen and activating CD8+ T cells. Given these functions, CD103+ cDC1s can support anti-tumor CD8+ T cell responses. However, CD103+ cDC1 numbers are …

Sun Prevention Fun (Spf): A Multicomponent Sun Prevention Program For Children In Kindergarten And First Grade, Sarah Gouker

Evidence-Based Practice Project Reports

Skin cancer is an important topic in the United States due to the recent increase in cost and mortality. The purpose of this evidence-based practice (EBP) project was to determine if the early implementation of a multicomponent sun prevention program positively impacted kindergarten and first grade students’ knowledge and behavioral intentions to practice safe sun techniques after a one week period. Kotter’s Model of Change and the ACE Star model were utilized to guide this EBP project. An exhaustive review of the literature yielded 12 articles which were used to develop best practices for education on sun safety. The quality …

Electrophysiological Biomarkers Of Chemotherapy-Related Cognitive Impairment In Hematological Malignancy Patients, David E. Anderson

Theses & Dissertations

Multiple cancer populations frequently report cognitive impairment following treatment with chemotherapy agents (“chemo-brain”). Impaired neuropsychological performance is commonly reported in cognitive domains of attention and executive function. Understanding neural mechanisms underlying cognitive impairments is essential to developing prevention and rehabilitation strategies. Brain imaging studies frequently show chemotherapy-related impairments within the attentional control network, which is comprised of a constellation of cortical regions that govern reportedly impaired cognitive functions. In the current dissertation research, I developed a novel electrophysiology battery aimed at recording near-instantaneous neural activity within the attentional control network during cognitive task performance. Cancer patients diagnosed with hematological malignancy …

The Survival And Treatment Refusal Of Lung Cancer Patients: Analyses Of National Cancer Registries, Poppy Deviany

Theses & Dissertations

Lung cancer is the second most commonly diagnosed cancer and the leading cause of cancer mortality of both genders in the United States. A recent report suggests that the relative five-year survival rate of lung cancer is only 18%. Studies indicate many factors are associated with the survival of lung cancer patients, including age at diagnosis. It is widely known as a disease of older people, but the literature shows a substantial number of young people have been diagnosed with lung cancer. The literature also indicates that the refusal of recommended treatment contributes to cancer-related death and poorer survival. The …

An Analysis Of Socio-Economic Consequences Of Cancer In Nepal, Soumi Roy Chowdhury

Economics ETDs

This dissertation investigates the socio-economic burden of cancer patients using a primary survey in Nepal. Given the low uptake rate of cancer screening facilities in developing countries, my study covers three important issues: the need of information dissemination on cancer prevention among asymptomatic individuals, the emotional stress of cancer patients in relation to a control group of patients, and the severity of economic burden due to premature cancer related deaths measured at the national and individual levels. In developing countries with low level of information and awareness, it is difficult to communicate the importance of cancer preventative measures to the …

Computational Insights Into The Generation Of Chromosomal Copy Number Changes, Yihua Liu

Dissertations & Theses (Open Access)

Deviations from a diploid configuration of the human genome, spanning single genes or entire chromosomes, can have wide-ranging impacts on the variation of human phenotypes, including Mendelian and complex forms of diseases. These chromosomal alterations — such as duplications, deletions or copy-neutral loss-of-heterozygosity — are thus important forms of genetic variation for phenotyping populations of individuals as well as populations of cells. Indeed, copy number variants (CNVs) serve as hallmarks of critical changes in the development of particular diseases such as cancer and thus may be used as biomarkers. These CNVs may be either inherited (transmitted by germ cells, originating …

A Systematic Review Of Language Therapy In Pediatric Brain Tumor Survivors, Ari Watt

All Graduate Plan B and other Reports, Spring 1920 to Spring 2023

Purpose: Brain tumors and associated treatments in children have been shown to cause long term neurological damage. While there is a large body of research focusing on treating associated cognitive deficits, relatively little research has focused on improving linguistic ability in this population. This systematic review identified and summarized the available evidence related to language treatment for pediatric brain tumor survivors.

Methods: A systematic electronic database search resulted in the identification of four relevant treatment studies, two position papers and one online forum. A data extraction manual and form was used to methodically extract study information related to participant demographics, …

Potent And Potentially Non-Cardiotoxic Anthracyclines: Their Synthesis, Biological Evaluation, And Comparison Of Hydrozone-Mediated Reductions, Jerrett Holdaway

Boise State University Theses and Dissertations

After nearly half a century since medical approval, the anthracycline doxorubicin (DOX) remains one of the most potent and clinically useful anticancer agents. In spite of its long history, however, the cytotoxic mechanisms of DOX have been debated and remain controversial. Several well-supported mechanisms will be discussed, such as the potential to intercalate DNA and induce apoptosis through topoisomerase poisoning, free radical formation, and DNA cross-linking. While DOX has substantial medical importance, it is plagued by a life-threatening dose-dependent cardiotoxic side effect associated with several structural groups. A number of modifications to DOX have been accomplished to attempt to remove …

The Regulation Of Dna Methylation In Mammalian Development And Cancer, Nicolas Veland

Dissertations & Theses (Open Access)

DNA methylation is an essential epigenetic modification in mammals, as it plays important regulatory roles in multiple biological processes, such as gene transcription, maintenance of chromosomal structure and genomic stability, genomic imprinting, retrotransposon silencing, and X-chromosome inactivation. Dysregulation of DNA methylation is associated with various human diseases. For example, cancer cells usually show global hypomethylation and regional hypermenthylation, which have been implicated in genomic instability and tumor suppressor silencing, respectively. Although great progress has been made in elucidating the biological functions of DNA methylation over the last several decades, how DNA methylation patterns and levels are regulated and dysregulated is …

Pkm2 Influences The Metabolic Fate Of Butyrate In Colorectal Cancer Cells, Megan Louise Pence

Chancellor’s Honors Program Projects

No abstract provided.

Treating Breast Cancer With Light: The Creation Of Two Photodynamic Therapy Agents, Victoria Lackey

Honors Theses

Photodynamic therapy (PDT) is a treatment for a wide display of diseases, including cancer, that has become gradually widespread. The procedure requires the usage of photosynthesizing agents, which are activated in the presence of light. One quite successful photodynamic therapy agent is an aromatic structure made up of four pyrrole rings called a porphyrin. This research focused on producing the water-soluble porphyrins, H2TPP-3-PEG-OH and H2TPP-PiperMe-OH, through the attachment of the starting porphyrin, H2TPPC, with 3-polyethyleneglycol and 3-piperidinemethanol, respectively. The novel, water-soluble agent was purified and characterized by infrared spectroscopy (IR), nuclear magnetic resonance spectroscopy (NMR), and UV-vis spectroscopy. Purity was …

Matters Of Trust: Examination Of The Patient-Provider Relationship In Cancer Care, Krista A. Brown

Capstone Experience

Background: The intangible concept of trust is critical in the patient-provider relationship. Cancer patients may experience positive and negative impacts of trust in this relationship to a higher degree due to the inherently serious nature of their disease and the level of dependence upon treatment providers.

Objective: The goal of this study was to compare colorectal cancer patients’ levels of trust in their primary care physician and oncologist, along with examining trust differences associated with demographics and other characteristics.

Methods: Colorectal cancer patients (n=158) treated at Nebraska Medicine and consented into the Integrated Cancer Repository for Cancer Research IRB …

The Moderating Effect Of Religion On Death Distress And Quality Of Life Between Christian Cancer Patients In The United States With Muslim Cancer Patients In Saudi Arabia, Doaa Almostadi

USF Tampa Graduate Theses and Dissertations

Cancer is an illness that knows no international boundaries. There are more than eight million global cancer deaths each year. A life-threatening diagnosis generates significant emotional problems for many patients across cultures. Death distress—consisting of death depression, death anxiety and death obsession—often results in poorer treatment adherence and lower overall health and quality of life. The purpose of this study was to determine whether religiosity has a moderating effect on the relationship between death distress and quality of life among patients facing a life-threatening cancer diagnosis.

The study sample consisted of 118 cancer patients: 82 cancer patients from a National …

Parp Pet Imaging Agents, Brandon Carney

Dissertations, Theses, and Capstone Projects

The poly (adenosine-diphosphate (ADP) ribose) polymerase (PARP) family of enzymes has been of interest to researchers and clinicians for over fifty years, especially the first member of the family, PARP1. This enzyme has become a target for cancer therapeutics due the reliance of highly proliferating cells on PARP1 for genomic maintenance. In the coming age of individualized medicine, however, highly specific therapeutic agents like PARP inhibitors are in need of similarly highly specific companion diagnostic agents. These kind of agents have been made possible with the quickly progressing field of molecular imaging. Specifically, positron emission tomography (PET) has enabled the …

New Dyes For Cancer Theranostics, Waqar Rizvi

Dissertations, Theses, and Capstone Projects

Porphyrinoids are robust heterocyclic dyes studied extensively for applications in medicine and as photonic materials because of their tunable photophysical properties, diverse means of modifying the periphery, and the ability to chelate most transition metals. Commercial applications include phthalocyanine dyes in optical discs, porphyrins in photodynamic therapy, and as oxygen sensors. Most applications of these dyes require exocyclic moieties to improve solubility, target disease, modulate photophysical properties, or direct self-organization into architectures with desired photonic properties. The synthesis of the porphyrinoid depends on the desired application, but the de novo synthesis often involves several steps, is time consuming, and results …

Mathematical Modeling Of Nanoparticle Biodistribution, Prashant Dogra

Biomedical Sciences ETDs

The prospects of nanoparticle-based drug delivery and imaging have been hindered by insufficient understanding of the effects of nanoparticle physicochemical properties on their in vivo disposition. Here, we present an integrative mathematical modeling and in vivo imaging approach to quantify the relationship between nanoparticle physicochemical properties, namely, size, surface charge, and surface chemistry, on their in vivo disposition kinetics in healthy rats. We developed simple master equations in closed-form to accurately represent the time-dependent concentration of nanoparticles in different regions of the body and obtain functional relationships for predictive purpose to support rational design of nanomedicine. We further used …

Comprehensive Occupational Therapy In A Breast Cancer Program, Nicole Renee Scheiman

Occupational Therapy Program Student Theses, Dissertations and Capstones

The purpose of this capstone project is to develop an evidenced-based, innovative, and comprehensive occupational therapy evaluation and intervention protocol for breast cancer care. The contents of this paper will include an introduction into the current care provided to survivors, literature review on best practice in breast cancer care, outline of the procedures completed to discover what best practice care should be, results of these procedures, discussion of the results, and conclusion with proposed program and recommendations for further investigation. The concern investigated is the inconsistencies in care provided to survivors from the time of diagnosis throughout their lifespan or …