Medicine and Health Sciences Commons^™

Investigating Biological Mechanisms Of Radiation Resistance In Advanced Stage Cervical Cancer, Fiona Ruiz

Arts & Sciences Electronic Theses and Dissertations

The current standard of care treatment for locally advanced cervical cancer is curative intent pelvic radiation with concurrently administered platinum chemotherapy (CRT). This treatment strategy is effective for many patients, but 33-50% of patients treated with CRT develop disease recurrence. Metastatic and recurrent cervical cancer is an incurable condition, and many of the currently available treatments are associated with significant morbidity and mortality. Identifying these patients upfront is a challenge that clinicians face when developing treatment strategies. Previous studies used to catalog the genomic and transcriptomic landscape of cervical cancer lacked high quality corresponding clinical follow up data for patients, …

Reconciling Incongruencies: Examining The Meaning And Influencing Factors Of Oncology Nurses' Professional Quality Of Life, Rebecca Lynne Boni

UNLV Theses, Dissertations, Professional Papers, and Capstones

Nurses often witness suffering and loss. These experiences are intrinsic to the practice of nursing and can exert a strong, cumulative effect on nurses’ professional quality of life (QOL). Stamm (2010b) conceptualizes professional QOL as a composite of compassion fatigue and compassion satisfaction. Inferior professional QOL has been linked to numerous negative healthcare outcomes. Oncology nurses are particularly vulnerable to compassion fatigue. The Professional Quality of Life Scale (ProQOL), created by Stamm (2009), is the current survey used to measure professional QOL, but it may not be specific enough for oncology nurses.

The purpose of this grounded theory study was …

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 …

T Cell Immunity In Pancreatic Cancer Is Undermined By Dendritic Cell Dysfunction, Samarth Hegde

Arts & Sciences Electronic Theses and Dissertations

Pancreatic cancer carries a dismal prognosis, and desperately needs viable therapeutic interventions beyond chemo-radiation. T cell-dependent immunotherapies have shown great promise in several tumor types, but have not been effective for the vast majority of pancreatic cancer patients. This is, in part, due to our limited understanding of how antigenicity of pancreatic lesions is recognized, and how adaptive immunity is overcome in this disease. We sought to study tumor-immune interactions and identify mechanisms for this immune-failure using several spontaneous and unperturbed mouse models of pancreatic adenocarcinoma. We found that early pancreatic lesions fail to elicit tumor-limiting CD4+ TH1 and CD8+ …

Examining Racial & Ethnic Disparities In The Reach Of The Medicare Shared Savings Program, Lindsey Arneson

Capstone Experience

It is important to understand the quality of health care for racial and ethnic minorities covered under the largest U.S. government-run insurance program, Medicare, because the demographics of the U.S. are becoming older and more diverse. A new value-based program under Medicare is the Shared Savings Program (MSSP), which creates incentives to improve care quality and health outcomes for Medicare beneficiaries with a specific focus on increasing the provision of preventive care services. This capstone project aims to understand the representation of racial/ethnic minority Medicare beneficiaries, namely African Americans/Blacks and Hispanics/Latinxs, that receive care from providers or facilities (i.e., Accountable …

Association Between Gastroduodenal Ulcer And Age Of Diagnosis Of Head And Neck, Gastroduodenal And Pancreatic Cancer, Rukevwe Madusor

Capstone Experience

Background: Cancer is the second leading cause of death in the United States and remains a major public health problem worldwide. Epidemiological studies have demonstrated that insulin like growth factor-1 (IGF-1) is linked to ulcers and most cancers. Although studies have investigated the role of IGF1 in ulcer healing and cancer pathogenesis, the link between ulcer and cancer remains unclear. Hence, we assessed the relationship between ulcers and cancers.

Methods: This study consists of a sample of 180 cancer patients obtain by convenience sampling who were seen at Nebraska Medicine and were enrolled in the integrated cancer repository for cancer …

Identification And Molecular Analysis Of Dna In Exosomes, Jena Tavormina

Dissertations & Theses (Open Access)

Exosomes are heterogeneous nanoparticles 50-150nm in diameter. Exosomes contain many functional cargo components, such as protein, DNA, and RNA. While protein and RNA exosome content has been extensively studied, very little work has been done to characterize exosomal DNA. Here, we demonstrate that exosomal DNA is heterogeneous and its packaging into exosomes is dependent on the cell of origin. Furthermore, through a rigorous assessment of various isolation methods, we identify Size Exclusion Chromatography (SEC) as the best method for the isolation of exosomal DNA for downstream applications. Additionally, we evaluate the methylation status of exosomal DNA and demonstrate that exosomal …

The Role Of Atypical Protein Kinase C In Colorectal Cancer Cells Carcinogenesis, S M Anisul Islam

USF Tampa Graduate Theses and Dissertations

Colorectal cancer (CRC) is the third most common malignancy and the fourth most common cause of cancer-related death worldwide. CRC is a life-threatening disease due to therapy-resistant cancerous cells. The exact mechanisms of cell growth, survival, metastasis and inter & intracellular signaling pathways involved in CRC are still a significant challenge. Moreover, the treatment of metastatic CRC considered palliative for many years aimed for an improved life, with little hope of a cure, highlighting the need for developing novel targeted therapy for CRC. Hence, investigating new molecular mechanism(s) that lead to colorectal carcinogenesis may give insight into the therapeutic target. …

Multimodal Treatment And Neoadjuvant Chemotherapy Trends, Utilization And Survival Effects In Intrahepatic Cholangiocarcinoma – A Propensity Score Analysis, Ovie Utuama

USF Tampa Graduate Theses and Dissertations

Intrahepatic Cholangiocarcinomas (ICC) are fatal malignancies common among the elderly. Patients are diagnosed late and often relapse, even after curative-intent surgery (CIS). In this context, additional systemic chemotherapy (multimodal treatment) is recommended for most patients but reported survival benefits are minimal and are limited to small single institutional studies. For this reason, using a national cancer registry, we sought to characterize multimodal treatment trends and utilization in general and neoadjuvant chemotherapy, specifically, as well as evaluate their survival effects among the larger population. We hypothesized that, 1). Elderly ICC patients would have survival benefits equivalent to younger patients, 2). Neoadjuvant …

Understanding The Influence Of The Cancer Microenvironment On Metabolism And Metastasis, Shonagh Russell

USF Tampa Graduate Theses and Dissertations

Cancer is a complex and heterogeneous disease. Not only is there considerable variability between different cancer types, but there is enormous variability between and within patients who have the same type of cancer. Within tumors, there are multiple cell types, including cancer cells, stromal cells, and immune cells. The tumor microenvironment often induces the healthy cells to become pro-tumorigenic. Cell metabolism is exquisitely sensitive to changes in the tumor microenvironment and can be measured to infer the aggressiveness of cancer and predict response to therapy. In this dissertation, we aim to understand how the microenvironment, specifically low pH, affects the …

Understanding Young Adult Survivors Of Childhood Cancers’ Participation In Late Effects Screening: A Mixed Methods Approach, Kristen Trost Mantlo

Health Services Research Dissertations

Significant advancements in the treatment of childhood cancers have helped to increase the 5-year survival rate from 56% in the early 1970s to approximately 80-85% in the early 2000s (Greenlee, Murray, Bolden, & Wingo, 2000; Hampton, 2005). Treatment modalities such as chemotherapy and radiation have led to many serious long-term side effects, known as late effects. Between 60% and 90% of survivors develop some form of long-term chronic condition due to their treatment and up to 40% of those conditions will be life-threatening (Howlader, N. et al., 2013). While the majority of young adult survivors of childhood cancer are at …

Generation Of An Oncolytic Adenovirus Targeting The Cxcr4 And Cxcr7 Chemokine Receptors In Breast Cancer, Samia Melissa O'Bryan

LSU Doctoral Dissertations

Breast cancer is the most diagnosed cancer in women under 60 and the second most diagnosed cancer in women over 60. While treatments for localized breast cancer are quite successful with high survival rates at 99%, advanced breast cancer remains hard to treat with a nearly 75% decrease in survival. Current treatments are inefficient at treating advanced stages of breast cancer, and thus, new therapies are sorely needed to address the complexity of advanced stage breast cancer. The ideal therapy would be capable of systemic administration, targets cancer cells and spares normal tissue. Oncolytic adenovirus is an ideal therapeutic vector …

Oxidative Phosphorylation: A Critical Feature And Novel Therapeutic Target In Melanoma Brain Metastases, Grant Fischer

Dissertations & Theses (Open Access)

We recently showed via RNA-sequencing (RNA-seq) analysis of clinical samples that melanoma brain metastases (MBMs) have higher expression of oxidative phosphorylation (OXPHOS) genes (including PPARGC1A or PGC1α) than patient-matched extracranial metastases (ECMs). Thus, the central hypothesis of this dissertation is that OXPHOS plays a critical role in the pathogenesis of MBMs.

RNA-seq analysis identified increased expression of OXPHOS genes in intracranial (ICr) vs. subcutaneous (SQ) xenografts of 4 different human melanoma cell lines. Increased OXPHOS in the ICr xenografts was confirmed by direct metabolite analysis and [U-¹³C]-glucose tracing analysis. Together, these studies indicate that the brain TME …

Evaluating The Therapeutic Efficacy Of Grb2 Inhibition In Ovarian Malignancies, Olivia Lara

Dissertations & Theses (Open Access)

Purpose: Adaptor proteins such as growth factor receptor-bound protein-2 (Grb2) play important roles in cancer cell signaling. In the present study, we examined the biological effects of liposomal antisense oligodeoxynucleotide that blocks Grb2 expression (L-Grb2) in ovarian cancer models.

Experimental Design: Murine orthotopic models of ovarian cancer (OVCAR5 and SKOV3ip1) were used to study the biological effects of L-Grb2 on tumor growth. In vitro experiments (cell viability assay, Western blot analysis, siRNA transfection, and reverse phase protein array) were carried out to elucidate the mechanism and potential predictors of tumor response to L-Grb2.

Results: Treatment with L-Grb2 decreased tumor growth …

Tracking Treatment Response And Resistance To Parp Inhibition (Talazoparib) In Hereditary Pancreatic Cancer., Jennifer Goldstein

Dissertations & Theses (Open Access)

polyADP ribose polymerase (PARP) inhibitors are a class of drugs that block the PARP enzymes, involved in the repair of singe-stranded DNA breaks through the base excision repair pathway. PARP inhibition leads to replication-associated double stranded DNA breaks, which are repaired by homologous recombination (HR). In tumors with HR defects (i.e. BRCA mutants), there is a shift to error-prone DNA repair and subsequent genomic instability and cell death.

In 2014, Olaparib became the first FDA-approved PARP inhibitor for the treatment of BRCA-mutant ovarian cancer. In the phase III POLO (Pancreas cancer OLaparib Ongoing) trial presented at the American Society …

Characterizing The Role Of Extracellular Matrix In Non-Small Cell Lung Carcinoma Metastasis Using A 3d Microenvironment Mimetic In-Vitro Culture System., Douglas John Owulaku Saforo

Electronic Theses and Dissertations

Lung cancer is the leading cause of cancer related death in the United States and worldwide. Five-year survival rates for non-small cell lung carcinoma patients have not improved in decades, and a majority of patients succumb to metastasis. Identification of therapeutic targets for metastatic disease is essential for the development of novel therapies. However, current 2-dimensional (2D) in vitro models are not reflective of the tumor microenvironment (TME) and are inadequate in identifying therapeutic targets. We adapted a 3-dimensional (3D) extracellular matrix (ECM) in vitro model to a hypoxic incubator to approximate physiological hypoxia of the TME in a microenvironment …

Obesity Suppresses Pigment Epithelium-Derived Factor And Alters Pro-Tumorigenic Signaling Pathways In Prostate Cancer, Nizar Ahmed Khamjan

Theses and Dissertations

Background: Pigment epithelium-derived factor (PEDF), a multifunctional protein, is a potent tumor suppressor and anti-angiogenic factor. PEDF has been identified as a novel regulator of lipid metabolism via binding and activating adipose triglyceride lipase, which stimulates lipolytic pathways. PEDF-deficient mice develop prostatic hyperplasia that progresses to cancer when these mice are fed a high fat diet (HFD). PEDF expression is decreased in prostate cancer (PCa) patient tissues. Conversely, PEDF treatment inhibits PCa growth in mouse models. Recently, our lab has demonstrated that excess oleic acid (OA) treatment, an in vitro obesity model, suppresses secreted PEDF expression in PCa cell lines …

Modeling Proton Relative Biological Effectiveness Using Monte Carlo Simulations Of Microdosimetry, Mark A. Newpower

Dissertations & Theses (Open Access)

Proton therapy is a radiotherapy modality that can offer a better physical dose distribution when compared to photon radiotherapy by taking advantage of the Bragg peak, a narrow region of rapid energy loss. Proton therapy is also known to offer an enhanced relative biological effectiveness (RBE) compared to photons. In the current clinical standard, RBE is fixed at 1.1 at all points along the proton beam, meaning protons are assumed to require 10% less dose than photons to achieve target coverage and organ at risk (OAR) sparing. However, there is mounting clinical evidence, and a significant number of in vitro …

Neoadjuvant Stereotactic Ablative Radiotherapy To Treat Early Stage Breast Cancer Patients: The Role Of Dce-Mri, Matthew Mouawad

Electronic Thesis and Dissertation Repository

The current standard of breast conserving therapy is lumpectomy followed by whole breast radiotherapy which is prohibitively long for many patients (4-6 weeks). In addition, the need for treating the whole breast has been questioned. The London Regional Cancer Program is enrolling early stage breast cancer patients in a prospective Phase I/II clinical trial (SIGNAL) to assess the safety/efficacy of neoadjuvant stereotactic ablative radiotherapy (SABR) to the tumour alone to reduce treatment times. This provides a unique opportunity to assess tumour response to SABR using non-invasive imaging. Patients received a pre-SABR dynamic contrast-enhanced (DCE)-MRI to guide target volume delineation. A …

Exploring Infant Leukemia Through Exome Sequencing And An In Vitro Model Of Hematopoietic Development, Mark Cannon Valentine

Arts & Sciences Electronic Theses and Dissertations

Cancer is a heterogeneous disease with myriad causes and outcomes. Many of the cancers that occur in adult populations have become increasingly well characterized with the advent of affordable high-throughput sequencing. These studies have revealed that cancer is largely a disease of somatic mutation in the adult population. In strong contrast to this, childhood cancers have an exceedingly low rate of somatic mutation. At the extreme end of this spectrum is Infant Leukemia (IL). Sequencing of IL has revealed that these tumors frequently have one or fewer somatic SNP. In the absence of a somatic explanation for IL, many other …

Discoidin Domain Receptor 2 As A Therapeutic Target In Breast And Ovarian Cancer, Whitney Grither

Arts & Sciences Electronic Theses and Dissertations

Discoidin Domain Receptor 2 (DDR2) is a receptor tyrosine kinase that utilizes the extracellular matrix protein collagen as its ligand. Recently, DDR2 was shown to be critical in facilitating breast cancer metastasis. DDR2 stabilizes protein levels of the epithelial-mesenchymal-transition (EMT) inducing transcription factor, SNAIL1 in basal K14+ epithelial cells that are known to be important for invasive leader cell properties during collective invasion/migration. DDR2 expression is present in a majority of human invasive ductal breast carcinomas, and expression is localized to the tumor-stroma boundary. Additionally, in genetic models of breast cancer, deletion of DDR2 within the stroma (MMTV-PyMT; DDR2 fl/fl; …

The Role Of Tumor Stromal Discoidin Domain Receptor 2 (Ddr2) In Breast Cancer Metastasis., Samantha Van Hove Bayer

Arts & Sciences Electronic Theses and Dissertations

Characteristics of breast tumor stroma, including altered collagen architecture and increased stiffness, are known to contribute to tumor invasion and metastasis. However, the cellular and molecular mechanisms by which these changes occur are not fully understood. To address this question, we used a mouse genetic model to delete Discoidin Domain Receptor 2 (DDR2) from mouse tumor stromal cells and interrogated breast cancer associated fibroblasts (CAFs) to determine the molecular events downstream of DDR2 action that may lead to changes in the tumor extracellular matrix (ECM). Our work revealed that the action of DDR2 in breast stromal cells is required for …

The Role Of Ros In The Progression And Treatment Of Castration-Resistant Prostate Cancer, Dannah R. Miller

Theses & Dissertations

Prostate cancer is the second leading cause of cancer-related deaths in U.S. men, primarily due to the development of castration-resistant (CR) prostate cancer (PCa), of which there are no effective treatment options. Reactive oxygen species (ROS) plays a critical role in prostate carcinogenesis, including the progression of the CR PCa phenotype. ROS regulates both cell proliferation and apoptosis; a moderate increase in ROS can promote proliferation; however, a substantial rise in ROS levels will result in apoptosis. Oxidase p66Shc is elevated in clinical PCa cells and has been associated with a metastatic phenotype of CR PCa cells, promoting PCa cell …

Framework For Algorithmically Optimizing Longitudinal Health Outcomes: Examples In Cancer Radiotherapy And Occupational Radiation Protection, Lydia Joyce Wilson

LSU Doctoral Dissertations

Background: Advancements in the treatment of non-infectious disease have enabled survival rates to steadily increase in recent decades (e.g., diabetes, heart disease, and cancer). Epidemiological studies have revealed that the treatments for these diseases can have life-threatening and/or life–altering effects. Thus, realizing the full beneficial potential of advanced treatments necessitates new tools to algorithmically consider all major components of the health outcome, including benefit and detriment. The goal of this dissertation was to develop a framework for improving projected health outcomes following planned radiation exposures in consideration of all beneficial and detrimental, early and late, and fatal and non-fatal …

Benefits Of 3d Breat Tinisynthesis Combined With 2d Digital Mammography In Screening Women For Breast Cancer, Danielle M. Swanson

Physician Assistant Scholarly Project Papers

Breast cancer screening imaging options have progressed greatly over the years in sensitivity, specificity, and image quality. According to DynaMed Plus, in 2012 there were 522,000 deaths by breast cancer and 1,677,000 total cases of breast cancer documented (Dynamed, 2018). For years, traditional screening for breast cancer involved 2D digital mammography which obtains two views of each breast. With advances in technology, the use of 3D breast tomosynthesis has become an advantageous addition to routine breast cancer screening protocols at many health care facilities. My literature review of articles was found in PubMed, DynaMed Plus, Cochrane Library, and Clinical Key …

Increasing Adult's Awareness Of The Importance Of End-Of-Life Care Discussions, Taylor Gardner

Capstone Projects and Master's Theses

For many American families, end-of-life care is often not discussed, until advanced illness or injury has fully disrupted everyday life. There are many benefits to discussing end-of-life care prior to any medical complications. Research has shown that individuals who plan their end-of-life processes with a hospice service provider and family members report a higher quality of death than individuals receiving common health care during their final six months of life. In order to make families and friends more comfortable with end-of-life discussions, I will conduct two one-hour educational sessions to students at California State University, Monterey Bay.

Study Of Natural Killer Cells And Their Therapeutic Role In Pediatric Cancer, Hong Ha Rosa Nguyen

Theses and Dissertations (ETD)

NK cells are known to play an important role in the natural defense against viral infections and tumor immune surveillance. Through complex interactions between NK cell receptors and target cell ligands, transformed or unhealthy cells are identified and rapidly eliminated. NK cells have been used for therapeutic purposes in pediatric oncology, for example by harnessing the mechanisms of NK cell surveillance in acute myeloid leukemia (AML) or intervention-augmented antibody-dependent cell-mediated cytotoxicity (ADCC) in neuroblastoma. However, the underlying cellular mechanisms in these processes are not fully understood. In my thesis research, I sought to gain a deeper understanding of the molecular …

Molecular Mechanisms Of Metabolic Reprogramming In Pancreatic Cancer, Sonam Kumari

Theses and Dissertations (ETD)

Pancreatic cancer ranks as third deadliest cancer worldwide in both men and women. The lack of diagnostic methods, chemo-resistance and invasiveness of the disease diminishes the overall survival rate in patients. Dysregulated glucose metabolism and several molecular determinants including oncogenic signaling pathways play pivotal roles in the development, progression and metastasis of pancreatic cancer. The aberrant glucose metabolism is the most prevalent key factor that influences pancreatic tumorigenesis. The cancer cells of pancreas utilize oxygen for the breakdown of glucose to lactate, which is known as Warburg effect. This phenotype of pancreatic cancer encourages proliferation, growth, migration and invasive phenotypes …

Prevention Of Oral Mucositis In Cancer Patients, Patricia E. Biel

Evidence-Based Practice Project Reports

Oral mucositis [OM] is one of the most severe non-hematological problems related to cancer treatments and can impact quality of life. It is linked to poorer outcomes due to the associated weight loss, pain, dehydration, and risk of developing life-threatening infections. The purpose of this evidence-based practice project was to determine if OM is preventable with the use of an oral care protocol and zinc supplementation when compared to use of oral care protocols alone. The Johns Hopkins Nursing Evidence-Based Practice Model was used to guide project implementation in an outpatient oncology office. Recommendations were developed from an exhaustive review …

Contribution Of Retrotransposons To Breast Cancer Malignancy, Isaac D. Raplee

USF Tampa Graduate Theses and Dissertations

The components contributing to cancer progression, especially the transition from early to invasive are unknown. Consequently, the biological reasons are unclear as to why some patients diagnosed with atypia and ductal carcinoma in situ (DCIS) never progress into invasive breast cancer. The “one gene at a time” approach does not sufficiently predict progression. To elucidate the early stage progression to invasive ductal cancer, expression signature of transcripts and transposable elements in micropunched samples of formalin-fixed, paraffin embedded (FFPE) tissue was conducted. A bioinformatics pipeline to analyze poor quality, short reads (>36 nts) from RNA-Seq data was created to compare …