Medicine and Health Sciences Commons^™

The Impact Of Lung Cancer Screening Education On Knowledge And Screening Rates In A Kentucky Cancer Survivorship Clinic, Alexandra Isler

DNP Projects

Background: Lung cancer is a significant problem in Kentucky, which ranks fourth in the nation in adults who currently smoke. Early detection, through lung cancer screening, can prevent untimely deaths. Several barriers to screening exist including lack of knowledge and awareness among patients regarding lung cancer screening. By increasing knowledge, at risk patients can take the necessary steps to decrease incidence of late stage diagnoses.

Purpose: The purpose of this project was to evaluate patients’ knowledge of lung cancer screening and referral and screening rates before and after one-on-one patient education.

Methods: This was a quality improvement project that used …

The Effect Of An Educational Intervention On Early Mobility Compliance In Oncology Nurses, Jonathan A. Hacker

DNP Projects

Background: Geriatric adult patients admitted into acute care hospital settings are at risk of functional decline in their capacity for activities of daily living and independent ambulation. Many of these patients fail to achieve pre-hospitalization levels of function and continue to decline, requiring additional support and care after discharge. Current literature supports early mobilization and ambulation during hospitalization. However, ambulation and patient mobilization has been shown to be the most missed item of nursing care. There is a gap in literature and patient outcome data regarding the impact of early mobilization on medical-surgical patient populations.

Purpose: The purpose of this …

Empirical Insights Into Survivorship Care: A Cross-Sectional Study Of Coc Accredited Hospitals In Kentucky, Amanda M. Beckett

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

ABSTRACT

Background:

Cancer survivorship care programs play a vital role in supporting cancer survivors and improving their quality of life. Understanding the landscape of survivorship and the potential barriers is key to optimizing care delivery.

Methods:

The primary purpose of this cross-sectional study was to explore existing cancer survivorship care programs offered by Commission on Cancer (CoC) accredited hospitals in Kentucky. Data from the Markey Cancer Affiliate Network (MCCAN) from 2022 through 2023 was analyzed. Variables included hospital characteristics such as rural code, types of survivorship services offered, and reported barriers to these services.

Results:

Analysis of n=19 CoC facilities …

Enhancing Dna-Damaging Therapy Through The Inhibition Of Dntp Synthesis Using A Synergistic Drug Combination To Treat Pancreatic Neuroendocrine Neoplasms, Jennifer Castle Md

Theses and Dissertations--Clinical and Translational Science

Despite clinical advances, pancreatic neuroendocrine neoplasms (pNEN) remain a difficult clinical entity to treat and can carry a poor prognosis. Systemic therapy is used to treat pNENs which are not amenable to surgical resection. Peptide receptor radionuclide therapy, a form of radiation therapy (RT) and cisplatin are two different forms of DNA-damaging therapy in current use to treat pNENs. However, their efficacy remains poor as single agents. This study aimed to increase the sensitivity of pNENs to the DNA-damaging agents, RT and cisplatin, by inhibiting deoxynucleotide triphosphate (dNTP) synthesis. Triapine, a ribonucleotide reductase inhibitor (RNRi), and ataxia telangiectasia and Rad3-related …

Optimization Of Orally Bioavailable Inhibitors Of Defective In Cullin Neddylation 1 (Dcn-1), Leah Kovalic

Theses and Dissertations--Pharmacy

Ubiquitin (UB) and ubiquitin-like protein (UBL) pathways have emerged as important targets for oncology drug discovery based on the success of proteasome inhibitors (bortezomib or carfilzomib), E3 inhibitors, and the NEDD8 E1 inhibitor pevonedistat (MLN42924). Chemical inhibitors have also proven to be useful probes for identifying and dissecting multifactor UB and UBL regulatory networks. Toward this end, we have pursued approaches to target NEDD8 ligation to Cullins, through developing small molecule inhibitors of DCN1 (defective in Cullin Neddylation 1). DCN1 was discovered as a potentiating RBX1-dependent NEDD8-ligation, through recognizing the acetylated N-terminal methionine of the NEDD8 E2s UBE2M and UBE2F. …

Novel Mechanism Of Endogenous Pancreatic Cancer Cell Expression Of Immune Checkpoint Programmed Cell-Death 1 Protein (Pd-1) Inducing Epithelial-To-Mesenchymal Transition (Emt) Through The Met Pathway And Promoting Cancer Progression In An Immune-Independent Process, Megan M. Harper

Theses and Dissertations--Clinical and Translational Science

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers with few treatment options, necessitating an urgent need for novel therapeutics. Immuno-oncologic (IO) therapies have revolutionized anti-cancer regimens in the past decade but typically involve reactivation of adaptive immune responses. In particular, immune checkpoint PD-1 is traditionally expressed only on immune cells while PD-L1 (PD-1 ligand) is overexpressed on cancer cells. When tumor-endogenous PD-L1 binds the PD-1 receptor on T-cells, the immune cells undergo anergy resulting in self-tolerance and cancer cell immune evasion. However, contrary to standard dogma, we previously demonstrated tumor-endogenous PD-1 expression in PDAC. Our data indicated that …

Promotion Of Early Recognition Of Depression To Improve Health Related Quality Of Life In Pediatric Oncology Patients, Jennifer Blankenship

DNP Projects

Background: Depression and anxiety are serious complications of cancer and deemed a challenging diagnosis due to the symptoms of depression mimicking common side effects of chemotherapy and radiation. Signs/symptoms frequently are underrecognized thus appropriate treatment is delayed, compromising the health-related quality of life (HRQOL) for pediatric oncology patients.

Purpose: Analyze existing physician and Advanced Practice Provider (APP) clinical practice regarding depression, via a pre- and post-survey and educational PowerPoint on the use of the Center for Epidemiological Studies Depression Scale for Children (CES-DC) to promote early recognition of depression.

Methods: A prospective, single-arm, study was completed in the Kentucky Children’s …

Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids To Predict Carboplatin Resistance, Justin W. Gorski

Theses and Dissertations--Clinical and Translational Science

The development of patient-derived tumor organoids (TOs) from epithelial ovarian cancer tumor obtained at the time of primary or interval debulking surgery has the potential to play an important role in precision medicine.

Here, we utilize TOs to test front-line chemotherapy sensitivity and to investigate genomic drivers of carboplatin resistance. We developed six high grade serous epithelial ovarian cancer tumor organoids from tissue obtained during debulking surgery (2 neoadjuvant carboplatin exposed, 4 chemo-naïve). Each organoid line was screened for sensitivity to carboplatin at four different doses (100, 10, 1 and 0.1µM). Cell viability curves and resultant EC50 values were determined …

Therapeutic Targeting Of Leukemia Stem Cells To Prevent T-Cell Acute Lymphoblastic Leukemia Relapse, Meghan G. Haney

Theses and Dissertations--Molecular and Cellular Biochemistry

The survival rate of T-cell Acute Lymphoblastic Leukemia (T-ALL) relapse is a dismal 10% of affected adults and 30% of children, largely due to the relapsed disease being more aggressive and treatment resistant than the initial disease. Relapse is thought to occur because conventional chemotherapies are unable to reliably eliminate a unique cell type known as leukemia stem (or propagating) cells (LSCs). LSCs are the only cells within the leukemia with the ability to self-renew and remake or replenish the ALL from a single cell. Currently, the pathways governing self-renewal in LSCs are largely unknown, precluding our ability to successfully …

Examining The Role Of Metabolic Pathways As Therapeutic Modalities For Triple Negative Breast Cancer, Jeremy Andrew Johnson

Theses and Dissertations--Toxicology and Cancer Biology

Triple negative breast cancer (TNBC) comprises 15-20% of breast cancers, affects a younger patient population than other subtypes, and is very aggressive. TNBC is comprised of a diverse group of tumors that have proven refractory to targeted therapy and can be difficult to treat. Patients generally receive neoadjuvant chemotherapy (NAC), surgery, and radiotherapy. The standard of care for NAC includes a taxane, an anthracycline, and/or cyclophosphamide, and administration of NAC has resulted in pathological complete response (pCR) in 30-40% of patients. However, a majority of TNBC patients will not reach pCR and instead have residual disease (RD), which is associated …

The Effect Of A Sun Damage Simulation Photography App On The Skin-Protective Behavior Intentions Of Women With Children Age 18 Or Younger, James Bowlds

DNP Projects

Abstract

Background: Skin cancer is the most common form of cancer diagnosed in the U.S. annually, despite being a largely preventable disease through the limitation of ultraviolet radiation exposure. Attempts to decrease its incidence have focused on appearance-based interventions. These have been effective at improving sun-protective behaviors among various subpopulations including people of color. Anecdotal observations suggest mothers more frequently utilize sun protection for their children than on themselves.

Purpose: The purpose of this project was to gain an understanding of the sun protection practices and beliefs of Caucasian and African American mothers, to assess the response to an appearance-based …

Residential Radon Exposure, Its Contribution To Lung Cancer, And Social Determinants Of Radon Testing, Stacy Stanifer

Theses and Dissertations--Nursing

Lung cancer is a highly preventable form of cancer. Cigarette smoking is the leading cause of lung cancer followed by radon gas exposure and exposure to secondhand smoke. Kentucky leads the nation in both incidence and mortality from lung cancer. Tobacco use in Kentucky continues to be a major public health concern as nearly one-quarter of adults report current tobacco use and just over one-third of Kentucky homes with children lack rules which prohibit smoking in the home. Radon, a colorless, odorless radioactive gas, occurs naturally from the decay of uranium found in rocks and soil and is harmful when …

Antiresorptive Bone Therapy Use In Advanced Lung Cancer And Associated Outcomes, Noor Naffakh

Theses and Dissertations--Pharmacy

Background/Rationale: Studies have shown antiresorptive agents decrease skeletal related events in metastatic non-small cell lung cancer. However, two prevalence studies have found low utilization rates of antiresorptive therapy in advanced lung cancer. The first study reported a rate of 14.8% during the 1995-2009 time period, while the second study reported a 33% usage rate during the time frame of 2002-2011. We believe these low utilization rates are associated with the poor prognosis of these patients. The prognosis of advanced lung cancer has improved significantly since these trials were conducted, and the utilization of denosumab has not been evaluated. We hypothesize …

Evaluating The Effectiveness Of Norton Cancer Institute’S Prompt Care Clinics, Stephanie L. Fred

DNP Projects

Purpose: The purpose of this project was to evaluate outcomes of implementation of the Norton Cancer Institute (NCI) Prompt Care Clinics (PCCs), to include number of emergency room (ER) visits and number of inpatient admissions. A second purpose of the study was to identify presenting symptoms for patients seen in the NCI PCCs and compare the average charge per case for patients seen in the ER or NCI PCCs with the same diagnosis.

Methods: This study employed a pre-post implementation retrospective review of NCI patient electronic medical records (EPIC) to examine the effectiveness of the NCI PCCs on …

Disparities In Stage-Appropriate Therapy For Resectable Non-Small Cell Lung Cancer In Kentucky, Jeremiah T. Martin

Theses and Dissertations--Clinical Research Design

Lung cancer (NSCLC) is the leading cause of cancer related mortality. Lung cancer screening aims to detect treatable cancers, however survival advantage will only be seen with early and appropriate stage-directed therapy. This study aims to understand recent rates of therapy for early-stage lung cancer in Kentucky, and to explore potential sources of disparities in treatment and outcomes. A Kentucky Cancer Registry query was performed of all NSCLC cases treated in the state from 2005-2014. Of 39,763 lung cancer patients, 10,622 were clinically operable. Of these, overall 40% did not receive surgery, while 16% did not receive any stage-appropriate local …

Factors Influencing Preference For Surgical Choice Among Women With Early Stage Breast Cancer, Susan G. Yackzan

Theses and Dissertations--Nursing

Breast cancer is the most common cancer among women in the United States with over 60% of cases diagnosed as early stage disease. For those women without prohibiting clinical or cosmetic concerns, a choice between breast-conserving surgery and mastectomy can be made. Either choice confers equivalent survival. The decision-making process also involves consideration of recurrence risk as well as management of the unaffected, contralateral breast for both future surveillance and risk reduction. In recent years, increasing rates of mastectomy with contralateral prophylactic mastectomy have been reported among women with unilateral, early stage breast cancer. If eligible for a choice among …

Assessing The Impact Timing Of Chemotherapy Education Has On A Patient's Ability To Self-Manage Common Side Effects, Deanna Anderson

DNP Projects

Purpose

A new diagnosis of cancer will often cause an individual to feel overwhelmed, confused and anxious (Kessels, 2003). Many patients often experience anxiety not only related to their cancer diagnosis but also in regards to the plausible side effects of chemotherapy (Greene, Nail, Fieler, Dudgeon, & Jones, 1994; Williams & Schreier, 2004). The purpose of this paper is to evaluate the association between timing of education provided to newly diagnosed patients undergoing chemotherapy for breast cancer and number of self-manageable triage calls to the oncologist’s office

Methods

A retrospective study design was conducted on newly diagnosed breast cancer patients …

The Role Of Progesterone Receptor Membrane Component 1 In Receptor Trafficking And Disease, Kaia K. Hampton

Theses and Dissertations--Pharmacology and Nutritional Sciences

The progesterone receptor membrane component 1 (PGRMC1) is a multifunctional protein with a heme-binding domain that promotes cellular signaling via receptor trafficking, and is essential for some elements of tumor growth and metastasis. PGRMC1 is upregulated in breast, colon, lung and thyroid tumors. We expanded the analysis of PGRMC1 in the clinical setting, and report the first analysis of PGRMC1 in human oral cavity and ovarian tumors and found PGRMC1 to correlate with lung and ovarian cancer patient survival. Furthermore, we discovered a specific role for PGRMC1 in cancer stem cell viability. PGRMC1 directly associates with the epidermal growth factor …

Self-Reported Adherence To Physical Activity For Cancer Survivors: An Update From The 2015 Nhis Database, Andrew Jackson Shearer

Theses and Dissertations--Kinesiology and Health Promotion

Cancer is the second leading cause of death in America. It’s been suggested that regular physical activity (PA) can improve health outcomes in cancer survivors. An estimate from BRFSS data (2009) suggested that 47% of all cancer survivors met recommended guidelines and that this estimate was not different from the population at large (48%). Several factors were examined from these BRFSS data to determine whether subgroups of survivors existed who might benefit from interventions aimed at improving their PA status. The purpose of this investigation was to obtain more recent estimates of adherence to established PA guidelines for cancer survivors. …

Overcoming Treatment Resistance In Heterogeneous Tumors, Nikhil Hebbar

Theses and Dissertations--Toxicology and Cancer Biology

Most primary tumors are heterogeneous and are often composed of therapy-sensitive and emerging therapy-resistant cancer cells. Rather unexpectedly, treatment of therapy-sensitive tumor cells in heterogeneous tumor microenvironments resulted in apoptosis of the therapy-resistant cancer cells. We identified a novel Par-4 amino-terminal fragment (PAF, which includes amino acids 1-131 of Par-4) that is produced and released by therapy-sensitive cancer cells following therapy-induced caspase-dependent cleavage of the tumor suppressor Par-4. PAF caused paracrine apoptosis in therapy-resistant cancer cells. Unlike Par-4-inducible apoptosis, which is dependent on the cell surface GRP78 receptor, PAF produced cancer-selective apoptosis independent of cell surface GRP78 function. Par-4 contains …

Regulation Of Uv-Protective Pathways Downstream Of The Melanocortin 1 Receptor In Melanocytes, Erin M. Wolf Horrell

Theses and Dissertations--Physiology

Malignant cutaneous melanoma is the deadliest form of skin cancer, and a majority of melanoma diagnoses are a result of exposure to ultraviolet (UV) radiation. UV radiation causes DNA damage, which if not repaired correctly via nucleotide excision repair (NER) can result in mutations and melanomagenesis. The melanocortin 1 receptor (MC1R) is a G_s protein coupled receptor located on melanocyte plasma membranes and is involved in protecting the skin from UV induced damage. MC1R signaling results in the activation of two protective pathways: 1) induction of eumelanin synthesis downstream of micropthalmia-associated transcription factor (MITF) and 2) acceleration of NER …

Investigating The Efficacy Of Vocal Function Exercises In Improving Vocal Function In Adults Irradiated For Laryngeal Cancers: A Three Part Dissertation, Vrushali Angadi

Theses and Dissertations--Rehabilitation Sciences

Deterioration in voice quality following radiation therapy for the treatment of laryngeal cancers (LC) is well documented in literature. The majority of studies show that these voice problems are long term and in some cases permanent. Deterioration in voice quality, especially over a period of time could lead to significant communication difficulties in daily life or in some cases could even result in loss of profession. Despite the negative effects of radiation therapy on voice quality being well documented, few studies have focused on the efficacy of voice therapy in the irradiated LC population.

The purpose of this study was …

Quantification Of Factors Governing Drug Release Kinetics From Nanoparticles: A Combined Experimental And Mechanistic Modeling Approach, Kyle Daniel Fugit

Theses and Dissertations--Pharmacy

Advancements in nanoparticle drug delivery of anticancer agents require mathematical models capable of predicting in vivo formulation performance from in vitro characterization studies. Such models must identify and incorporate the physicochemical properties of the therapeutic agent and nanoparticle driving in vivo drug release. This work identifies these factors for two nanoparticle formulations of anticancer agents using an approach which develops mechanistic mathematical models in conjunction with experimental studies.

A non-sink ultrafiltration method was developed to monitor liposomal release kinetics of the anticancer agent topotecan. Mathematical modeling allowed simultaneous determination of drug permeability and interfacial binding to the bilayer from release …

Phosphatidylinositol 3-Kinase (Pi3k) As A Therapeutic Target In Nsclc, Christopher W. Stamatkin

Theses and Dissertations--Pharmacy

Deregulated activation of phosphatidylinositol 3-kinase (PI3K) pathway is central to many human malignancies. The functions of this pathway are critical for normal cell metabolism, proliferation, and survival. In lung cancers, the PI3K pathway activity is often aberrantly driven by multiple mutations, including EGFR, KRAS, and PIK3CA. Molecules targeting the PI3K pathway are intensely investigated as potential anti-cancer agents. Although inhibitors of the pathway are currently in clinical trials, rational and targeted use of these compounds, alone or in combination, requires an understanding of isoform-specific activity in context. We sought to identify class IA PI3K enzyme (p110a/PIK3CA, p110b/PIK3CB, p110d/PIK3CD) activities using …

Reevaluation Of The Aapm Tg-43 Brachytherapy Dosimetry Parameters For An 125I Seed, And The Influence Of Eye Plaque Design On Dose Distributions And Dose-Volume Histograms, Prakash Aryal

Theses and Dissertations--Physics and Astronomy

The TG-43 dosimetry parameters of the Advantage^{TM 125}I model IAI-125A brachytherapy seed were studied. An investigation using modern MCNP radiation transport code with updated cross-section libraries was performed. Twelve different simulation conditions were studied for a single seed by varying the coating thickness, mass density, photon energy spectrum and cross-section library. The dose rate was found to be 6.3% lower at 1 cm in comparison to published results. New TG-43 dosimetry parameters are proposed.

The dose distribution for a brachytherapy eye plaque, model EP917, was investigated, including the effects of collimation from high-Z slots. Dose distributions for …

Redox-Regulated Relb-Ar Axis Mediates Prostate Specific Antigen Expression: Insight In Prostate Cancer Response To Radiation Therapy, Lu Miao

Theses and Dissertations--Toxicology and Cancer Biology

Although the prostate specific antigen (PSA) test is widely used in clinical settings for prostate cancer (PCa) diagnosis and post-treatment follow-up monitoring, false positive PSA test results, which contribute to over-diagnosis of PCa, and false negative results, which miss some patients with aggressive PCa, remain problems of clinical importance.

Our study demonstrates that radiation therapy, which is widely used for treatment of localized PCa, generates TNF-α in tumor cells and stromal fibroblasts, redox dependently. Interestingly, TNF-α rapidly and transiently triggers the RelA-mediated NF-κB canonical pathway, but its effect on RelB expression is more robust and long lasting, which leads to …

Doxorubicin-Induced, Tnf-Α-Mediated Brain Oxidative Stress, Neurochemical Alterations, And Cognitive Decline: Insights Into Mechanisms Of Chemotherapy Induced Cognitive Impairment And Its Prevention, Jeriel T. Keeney

Theses and Dissertations--Chemistry

The works presented in this dissertation provide insights into the mechanisms of chemotherapy-induced cognitive impairment (CICI or “ChemoBrain”) and take steps toward outlining a preventive strategy. CICI is now widely recognized as a complication of cancer chemotherapy experienced by a large percentage of cancer survivors. Approximately fifty percent of existing FDA-approved anti-cancer drugs generate reactive oxygen species (ROS). Doxorubicin (Dox), a prototypical ROS-generating chemotherapeutic agent, produces the reactive superoxide radical anion (O₂^-•) in vivo. Dox treatment results in oxidation of plasma proteins, including ApoA-I, leading to TNF-α-mediated oxidative stress in plasma and brain. TNF-α elevation in brain …

Influence Of Oncotype Dx® On Chemotherapy Prescribing In Early Stage Breast Cancer Patients: A Claims-Based Evaluation Of Utilization In The Real World, Kenneth Neil Kennedy

Theses and Dissertations--Pharmacy

The decision for adjuvant therapy in women with early stage breast cancer (ESBC) has historically been guided by the presence or absence of specific biological markers (hormone and HER2 receptors), age, and extent of nodal involvement. Oncotype DX® is a validated assay that quantifies protein expression that can predict the risk of cancer recurrence. This study evaluates if the use of Oncotype DX® impacts chemotherapy prescribing in ESBC. This retrospective, cohort study identified patients with ESBC from a large commercially insured population from January 2007 through June 2009. Patients were identified as having ESBC by utilizing procedure and diagnosis codes …