Medicine and Health Sciences Commons^™

Pharmacogenomic Precision Medicine: Best Practice Toolkit For Improving Patient Screening For Adult Metastatic Cancer Patients, Rena L. Stewart

Student Scholarly Projects

Precision medicine utilizes pharmacogenomic testing as a therapeutic approach. Genomic testing can assess the impact of an individual's genome on their reaction to specific medications. The main objective is to find variants that may affect an individual's response to a given medication. The implementation of pharmacogenomics in oncology facilitates informed decision-making by clinicians in drug selection and dosage determination.

Analyzing Prominent Genes In Acute Lymphocytic Leukemia (All), Shima Z. Omar

Honors College Theses

Acute lymphocytic leukemia (ALL) is the most common type of childhood cancer. Leukemia is a type of cancer that involves the bone marrow and blood. This research study examined prominent genes in the disease. Two groups of genes, tumor suppressor and cell differentiation, were compared using statistical analysis to compare their binding potential and epigenetic potential. It is most likely that I failed to detect significant differences either because these genes’ function in the disease etiology is not strongly contexed to changes in expression, or that the magnitude of the differences were too slight to be detected with these methods. …

Distinct Nrf2 Signaling Thresholds Mediate Lung Tumor Initiation And Progression, Janine M. Deblasi

USF Tampa Graduate Theses and Dissertations

NRF2 is a redox-responsive transcription factor the directs the antioxidant program and several critical metabolic processes. Mutations in NRF2 or its negative regulator KEAP1 occur in up to one third of non-small cell lung cancers (NSCLCs) and are often associated with resistance to therapy and poor outcomes. In the present studies, murine alleles of the Keap1 and Nrf2 mutations found in human NSCLC were developed and I comprehensively investigated their impact on tumor initiation and progression. I observed that chronic Nrf2 stabilization by Keap1 loss-of-function or Nrf2 activating mutation was not sufficient to cause lung tumor initiation, even when p53 …

Investigation Of Nanosecond Pulsed Electric Fields (Nspef) Induced Anti-Cancer Mechanism And Enhanced B16f10 Melanoma Cancer Treatment, Kamal Asadipour

Biomedical Engineering Theses & Dissertations

The use of nanosecond pulsed electric fields (nsPEF) has emerged as a promising area of research with vast implications across various scientific disciplines. The ability to generate ultra-short, high-voltage electric pulses has paved the way for numerous applications, ranging from fundamental investigations of biological phenomena to the development of innovative medical therapies. The aim of this thesis is to highlight the importance of nsPEF in two critical areas: 1) Understanding the impact of subtle postpulse waveforms through a comprehensive analysis of two common pulse generators and 2) using this knowledge to advance melanoma treatment by enhancing the therapeutic effect of …

Structural Insights Into The Cl-Par-4 Protein: Ionic Requirements, Conformational Transitions, And Interaction With Cisplatin, Krishna Kumar Raut

Chemistry & Biochemistry Theses & Dissertations

Cancer continues to be the leading global cause of death, with challenges in early diagnosis, drug resistance, non-specific drug targeting, and cancer recurrence and metastasis posing formidable obstacles in cancer therapy. In this context, Prostate Apoptosis Response-4 (Par-4), a pro-apoptotic tumor suppressor protein, emerged as a promising therapeutic target due to its ability to selectively induce apoptosis in cancer cells, thereby minimizing the drug-associated adverse effects. However, a comprehensive understanding of the structural features of Par-4, specifically the caspase-cleaved fragment (cl-Par-4), is crucial for therapeutic advancements.

This dissertation investigated the effects of various ions, both monovalent and divalent, on the …

Comparative Retrospective Study Of Proton Arc Planning With Elsa Algorithm And Impt With Monte Carlo Algorithm With Raystation Treatment Planning System, Matthew L. Carpenter Ms, Msha, Bsrt(R)(T)

Culminating Experience Projects

Proton arc therapy (PAT) will become widely available soon. It is crucial to determine if this technique and the associated calculation algorithms provided by treatment planning system vendors compete favorably with established proton therapy techniques like intensity modulated proton therapy (IMPT) and the Monte Carlo dose calculation algorithm used to compute IMPT doses in today’s clinic. RaySearch Laboratories have produced a modified Monte Carlo algorithm called ELSA.

ELSA stands for early layer spot assignment and is RaySearch Laboratories proposed solution to reduce optimization time during treatment planning for PAT. This research study will look at proton plan robustness to determine …

About Dying And Death: Thanatology's Place In Medical Curriculum, Jill Dombroski

Electronic Thesis and Dissertation Repository

This study explored how healthcare providers engage in advance care planning and end-of-life care conversations. The research explored what shapes their understanding and the extent to which concepts from thanatology they intuitively bring in, explicitly bring in, and maybe fail to recognize. To achieve this, constructivist grounded theory (CGT) methodology guided the design, data collection, analysis, and interpretation of the findings, which allowed for iteration across interviews and analysis with existing theories and data in the literature. The CGT design encouraged further engagement with the literature in an ongoing iterative fashion as well as with the analysis of the data. …

Role Of Ripk3 In The Pathogenesis Of Tet2 Mutant Hematopoietic Malignancies, Kanak Joshi

Dissertations

Hematopoiesis is dynamically controlled by an epigenetic landscape that regulates gene transcription. Ten-eleven translocation 2 (TET2) is a Fe2+ and α-ketoglutarate (α-KG)-dependent dioxygenase that regulates the transcriptional status of genes associated with hematopoietic stem cell self-renewal and multiple stages of lineage commitment and differentiation. TET2 mutations are commonly detected in almost all types of hematopoietic malignancies, including myeloproliferative disorder, acute myeloid leukemia, and peripheral T-cell lymphomas. In most cases, TET2 is a founder mutation that occurred in hematopoietic stem/progenitor cells (HSPCs). The mutant HSCs undergo clonal expansion and evolution with the accumulation of additional mutations for malignant transformation. Microbial-stimulated inflammatory …

A Quantitative Visualization Tool For The Assessment Of Mammographic Risky Dense Tissue Types, Margaret R. Mccarthy

Electronic Theses and Dissertations

Breast cancer is the second most occurring cancer type and is ranked fifth in terms of mortality. X-ray mammography is the most common methodology of breast imaging and can show radiographic signs of cancer, such as masses and calcifcations. From these mammograms, radiologists can also assess breast density, which is a known cancer risk factor. However, since not all dense tissue is cancer-prone, we hypothesize that dense tissue can be segregated into healthy vs. risky subtypes. We propose that risky dense tissue is associated with tissue microenvironment disorganization, which can be quantified via a computational characterization of the whole breast …

Dosimetric Evaluation Of Left-Sided Chest Wall Vmat Treatment With And Without Jaw Tracking; Dose Comparison Of Left Anterior Descending Artery Versus Heart Mean Dose, Jacqueline J. Emus

Culminating Experience Projects

Radiation therapy has significantly improved breast cancer survival rates; however, it can still lead to long-term side effects, particularly affecting the heart. Left-side breast cancer patients face higher risks due to the proximity of the heart to the treatment area. To mitigate cardiac toxicity, various strategies, including jaw tracking and Volumetric Modulated Arc Therapy (VMAT), have been proposed. This study investigates the dosimetric impact of VMAT plans with and without jaw tracking on the left anterior descending artery (LAD) dose and heart mean dose in post-mastectomy breast cancer patients. Ten patients previously treated with VMAT were evaluated, and the results …

A Retrospective Comparison Of Dose Distribution Within Density Override And Avoidance Structures In Volumetric Arc Therapy Prostate Plans With Hip Prosthetics: A Dosimetric Evaluation, Jared Richard Brinkman

Culminating Experience Projects

Introduction

Prostate cancer is one of the most common cancers among men, and its incidence is a significant health concern. The optimal radiation treatment for prostate cancer patients needs to be tailored to reduce toxicities to organs at risk within the treated area. This study aims to retrospectively evaluate the dose distribution to organs at risk (OARs) in patients with hip prosthetics for volumetric modulated arc therapy (VMAT) prostate cancer plans.

Methods

The study included ten prostate cancer patients with at least one prosthetic hip who received VMAT plans at a Midwest Radiation Oncology Center. Various data points, including target …

What Effect Does Flexible Work Arrangements Have On Efficiency And Job Satisfaction In Medical Dosimetry?, Michelle Walters

Culminating Experience Projects

Abstract

The purpose of this research study is to determine new trends in the medical dosimetry profession that relate to when and where work is being completed. It is also of interest to understand efficiencies within radiation oncology departments as well as how medical dosimetrists work arrangements impact job satisfaction. A voluntary survey of current medical dosimetrists was conducted which asked close-ended questions about simulation to treatment time frames, employment type, hours worked, departmental efficiency and perceived job satisfaction. It was established that the resulting 185 responses provided statistically significant results. Greater than half of participants answered yes to either …

Dosimetric Comparison Of Glioblastoma Radiotherapy Treatment Plans On A Low-Field Mri-Guided Linear Accelerator Compared To Conventional C-Arm Linear Accelerator, Emily J. Moats

Culminating Experience Projects

Introduction

MRI-guided radiation therapy has proven to provide many benefits such as real-time tracking, dose escalation, and the ability to perform online adaptive therapy. The objective of this study is to compare curative treatment plans for glioblastoma tumors on a low-field MR-guided linac vs a C-Arm linac and evaluate if they are comparable in terms of coverage, organ at risk sparing, delivery time, and deliverability.

Methods

This is a retrospective study that consisted of 15 previously treated patients who received radiation therapy for glioblastoma on a C-Arm linac. The CT simulation data that was used for the original treated plans …

Auto-Segmentation In Pancreatic And Liver Radiation Therapy, Cenji Yu

Dissertations & Theses (Open Access)

Background

Gastrointestinal cancers exhibit a high mortality rate compared to other cancer types. Among these, pancreatic cancer ranks as the fourth leading cause of cancer-related deaths worldwide. The five-year survival rate remains alarmingly low at a mere 9%. Hepatocellular carcinoma (HCC), another aggressive form of cancer, is rapidly becoming the primary cause of cancer-related deaths in the United States. The treatment of both liver cancer and pancreatic cancer heavily relies on a multidisciplinary approach. Innovative treatment strategies involving dose-escalated regimens, such as stereotactic body radiation therapy (SBRT), are emerging as an important pillar of the management of liver and pancreatic …

An Existential Punchline: How Humor Functions In A Young Adult Friendship Facing Advanced Cancer, Megan E. Solberg

Electronic Theses and Dissertations

Young adults (i.e., age 18-39) only comprise 4% of the total cancer population, yet cancers in this group are commonly found at more advanced stages due to situational factors influencing delayed diagnosis including access to healthcare, quality health insurance and competing life demands that may hinder prioritization of healthcare. Young adults with cancer also face unique challenges including higher rates of psychological distress, which may contribute to increased risk of social disconnection in response to cancer. Research suggests that humor may be a helpful coping approach and communication mechanism for mitigating distress and discussing difficult topics. Grounded within the frameworks …

The Development Of Artificial Intelligence-Based Tools For Expert Peer Review Of Radiotherapy Treatment Plans, Mary Gronberg

Dissertations & Theses (Open Access)

Creating a patient-specific radiation treatment plan is a time-consuming and operator-dependent manual process. The treatment planner adjusts the planning parameters in a trial-and-error fashion in an effort to balance the competing clinical objectives of tumor coverage and normal tissue sparing. Often, a plan is selected because it meets basic organ at risk dose thresholds for severe toxicity; however, it is evident that a plan with a decreased risk of normal tissue complication probability could be achieved. This discrepancy between “acceptable” and “best possible” plan is magnified if either the physician or treatment planner lacks focal expertise in the disease site. …

Risk And Risk Factors For Colorectal Subsequent Malignancies In Survivors Of Childhood Cancer: A Report From The Childhood Cancer Survivor Study, Constance A. Owens

Dissertations & Theses (Open Access)

Survivors of childhood cancer are at risk for colorectal subsequent malignant neoplasms (SMNs); notably, these cancers are amenable to screening. To identify at-risk survivors that may benefit from early screening, descriptive and risk factor analyses were performed to ascertain risk factors for colorectal SMN in childhood cancer survivors. In particular, we explored detailed radiation therapy (RT) data – colorectal and substructure dose-volume metrics – as risk factors for colorectal SMN risk; metrics that have yet to be thoroughly investigated. We developed a novel population-based anatomical colorectal model with substructures for RT dosimetry in late effects studies of childhood cancer survivors; …

A Comparison Of Hypofractionated Radiation Therapy Breast Plans For Large Breasted Patients - Hybrid 3d Conformal, And Volumetric Modulated Arc Therapy Vs Standard Hypofractionated 3d Conformal, Kelsie Wentland

Culminating Experience Projects

Abstract

Introduction

Patients with a large breast volume are more at risk of adverse skin effects with radiation therapy. Studies concerning these patients are very limited, especially in regard to comparison of planning techniques. While traditional tangent 3D conformal radiation therapy has been the standard of care, recent literature has shown possible benefits of hybrid planning for average breast volume patients. Little has been studied regarding breast cancer patients with large breast volumes and the possible benefits of hybrid planning of this patient demographic. Creating a hybrid plan could have the benefits of both different treatment modalities to provide a …

Development And Testing Of A Mapcheck3-Based Patient-Specific Qa Method For Prime Intensity Modulators Used With Bolus Electron Conformal Therapy, James T. Crist

LSU Master's Theses

Purpose: Irregular surfaces in bolus electron conformal therapy (BECT) create target volume dose inhomogeneity, which off-axis intensity modulation (IM) can reduce. This research developed and tested a patient-specific clinical quality assurance (QA) procedure for fabricated Passive Radiotherapy Intensity Modulation for Electrons (PRIME) devices used for IM-BECT delivery.

Methods: To evaluate MapCheck3 (MC3) diode array accuracy, electron dose measurements beneath PRIME devices were compared with scanned measurements in a water phantom. Lateral dose profile comparisons were made for 35 combinations of five beam energies (7-20MeV) and seven PRIME devices - converging and diverging island blocks (pins) having 100-68.8% intensities. To evaluate …

Understanding How Cancer Adapts To Stress And Therapy Using Evolutionary Game Theory, Mariyah Pressley

USF Tampa Graduate Theses and Dissertations

Adaptive responses in cancer promote disease initiation, progression, and resistance to treatment. Understanding the underlying evolutionary dynamics behind these adaptive responses is crucial for developing effective therapeutic strategies. Evolutionary game theory (EGT) has proven a useful tool in analyzing how different cellular behaviors and evolutionary forces shape the dynamics of tumor growth, response to therapy, and the emergence of resistance. In this dissertation, we utilize EGT to understand the adaptive responses of cancer through the lens of ecology and evolution. By employing fitness-generating models and exploring various ecological contexts, we aimed to unveil critical factors influencing aggressive cell phenotypes, treatment …

Withaferin A And Immune Checkpoint Blocker Therapy For The Treatment Of Non-Small Cell Lung Cancer, Roukiah Khalil

USF Tampa Graduate Theses and Dissertations

Lung cancer is the first cause of cancer-related deaths in both men and women with an overall five-year survival rate of 28%. Although immune checkpoint blockers (ICBs) are currently FDA-approved for the treatment of non-small cell lung cancer (NSCLC), only 17-20% of patients achieve durable responses by the induction of immunologic memory. The lack of response in most patients can be attributed to the tumor-intrinsic or tumor-extrinsic immune resistance mechanisms. A biomarker of importance is the Programmed Death Ligand-1 (PD-L1), as higher PD-L1 expression is usually associated with a better response to ICBs. Although studies have attempted to combine ICBs …

Primary Care Providers’ Practices And Attitudes Towards Brca Genetic Testing For Unaffected 19- To 24-Year-Old Patients., Madison C. Groene, Terri Blase Ms, Cgc, Jessica Maxwell Md, Frcsc

Genetic Counseling Capstones

Prior literature has described unique psychosocial considerations for emerging adults (18- to 25-year-olds) considering predictive BRCA genetic testing. Due to these unique concerns, the Society of Gynecologic Oncology (SGO) recommends waiting until individuals are older than 21 before offering testing. While primary care providers (PCPs) are important stakeholders in increasing access to hereditary cancer genetic testing, their approach for emerging adults has not been previously described. We surveyed PCPs in Nebraska regarding their pre- and post-test clinical practices as well as attitudes towards BRCA genetic testing for unaffected 19- to 24-year-olds. Pre-test clinical practice questions and attitudes questions were asked …

Meditation-Type Exercise For The Management Of Chemotherapy Related Cognitive Impairment In Breast Cancer Patients, Christine Cain

Evidence-Based Practice Project Reports

Chemotherapy-related cognitive impairment (CRCI), or “chemobrain”, is one of the most troublesome side effects of chemotherapy (Dijkshoorn et al., 2020). Ongoing CRCI may negatively affect relationships, confidence, sleep, fatigue, anxiety, and the ability to return to work activities leading to a decreased quality of life (Johns et al., 2016; Gokal et al., 2018). The purpose of this evidence-based practice (EBP) project was to assess the efficiency of a meditation-type exercise intervention, chair yoga, on decreasing perceived cognitive impairment (PCI) in breast cancer patients. The PICOT question for this project was: In breast cancer patients with chemotherapy related cognitive impairment (P), …

Improving Dose-Response Correlations For Locally Advanced Nsclc Patients Treated With Imrt Or Pspt, Yulun He

Dissertations & Theses (Open Access)

The standard of care for locally advanced non-small cell lung cancer (NSCLC) is concurrent chemo-radiotherapy. Despite recent advancements in radiation delivery methods, the median survival time of NSCLC patients remains below 28 months. Higher tumor dose has been found to increase survival but also a higher rate of radiation pneumonitis (RP) that affects breathing capability. In fear of such toxicity, less-aggressive treatment plans are often clinically preferred, leading to metastasis and recurrence. Therefore, accurate RP prediction is crucial to ensure tumor coverage to improve treatment outcome. Current models have associated RP with increased dose but with limited accuracy as they …

Automating The Radiation Therapy Treatment Planning Process For Pediatric Patients With Medulloblastoma, Soleil Hernandez

Dissertations & Theses (Open Access)

Over the past 50 years, pediatric cancer 5-year survival rates increased from 20% to 80% in high-income countries, however, these trends have not been mirrored in low-and-middle-income countries (LMICs). This is due in part to delayed diagnosis, higher rates of advanced disease at presentation and a growing lack of access to high quality medical personnel and technology necessary to deliver complex treatments.

The long-term goal of this study was to alleviate demanding workflows and increase global access to high-quality pediatric radiation therapy by harnessing the power of artificial intelligence to automate the radiation therapy treatment planning process for pediatric patients …

Application Of Informatics Tools To Facilitate The Practice Of Precision Medicine With Genomic Testing And Clinical Data, Michael Sayer

Pharmaceutical Sciences (PhD) Dissertations

The practice of precision medicine considers a variety of sources of information to optimize patient care. Factors such as patient demographics, clinical history, and lab test values have well understood effects on treatment outcomes and influence decision making. However, effective inclusion of biomolecular data such as protein expression and DNA sequencing data within the practice of precision medicine needs continued study. Informatics tools offer solutions to allow these complex data sources to be effectively embraced. Utilization of informatics tools to visualize data pertaining to the gene selection practices of pharmacogenomic (PGx) tests effectively communicated large amounts of information into concise …

Role Of Mitochondrial Outer Membrane Translocase Subunit, Tomm22, In Pancreatic Cancer Pathobiology, Mary Oluwadamilola Haastrup

<strong> Theses and Dissertations </strong>

Pancreatic cancer (PC) is a highly deadly malignancy with no effective biomarkers for early diagnosis, accurate monitoring and/or surveillance. Due to the late staged diagnosis in the majority of the cases, therapeutic interventions are limited resulting in high mortality. Recent studies continue to discover the diverse roles of mitochondria in pancreatic tumorigenesis, potentiating mitochondria as attractive targets for therapeutics and biomarker development. Although mitochondria have their own genome, most mitochondrial proteins (∼99%) are nuclear-encoded and imported into mitochondria by a specialized protein import system consisting of seven machineries. Among these machineries, translocase of the outer mitochondrial membrane (TOMM) machinery, comprising …

Examining Ndufab1 Expression In Head And Neck Squamous Cell Carcinoma, Addison L. Stevens

Honors Theses

Head and neck squamous cell carcinoma (HNSCC) accounts for around 4% of all cancers in the USA. HNSCC includes cancers of the oral cavity, oropharynx, nasopharynx, hypopharynx, and larynx. Reprogramming of mitochondrial metabolism has been known to promote oncogenesis. NDUFAB1, a nuclear encoded subunit of respiratory complex I (RCI) in the inner mitochondrial membrane, is abundantly expressed at the mRNA level in HNSCC patients. Based on this finding, we hypothesize that NDUFAB1 protein expression is high in HNSCC and that NDUFAB1 expression predicts a poor prognosis in HNSCC patients. We determined NDUFAB1 expression in HNSCC using immunohistochemistry and pathology guided …

Apoptosis Induction In Jurkat T-Lymphocytes By Proton Pump Inhibitors (Ppis), Shreya Murali, Randall Reif

Student Research Submissions

Apoptosis, commonly known as programmed cell death, constantly occurs in humans. As a cancer cell increases in acidity, apoptosis is induced. In healthy cells, proton pump proteins allow for H⁺ ions to permeate cellular membranes, regulating pH. However, proton pump inhibitors (PPIs), such as omeprazole, prevent proton movement. In previous studies, omeprazole induced cell death in Jurkat T lymphocytes; however, there was no confirmation of whether the cells died through apoptosis, or through necrosis, where the cell bursts. By using Annexin-V staining, the effects of omeprazole, dexlansoprazole, and esomeprazole on apoptosis induction can be measured. Cell death was observed …

Increasing Colorectal Cancer Screening Uptake Among Hispanic/Latino Patients: A Quality Improvement Initiative, Erick Hernandez Campos, Elizabeth Morse, David Phillippi

DNP Scholarly Projects

Background: In 2021, cancer (CRC) screening rates for Latino men (42%) and women (47.5%) remain well below the Health People 2020 target (70.5%). Extensive documentation of barriers for screening include language, insurance status, and other sociocultural barriers which contribute to delays in diagnosis and/or diagnosis at advanced stages of the disease, and worse health outcomes. Latinos need culturally and linguistically appropriate health promotion interventions aimed to increase CRC screening rates with any modality (FIT, Cologuard, or Colonoscopy).

Methods: The Donabedian Structure-Process-Outcome (S-P-O) Model for quality improvement was used to develop and target a provider-driven, language-concordant communication interventions for …