Medicine and Health Sciences Commons^™

Imaging The Tumor Microenvironment Using 1,2-Dioxetane Chemiluminescence Agents, Lucas Ryan

Chemistry Theses and Dissertations

As complex organisms, animals and humans rely on a delicate interplay between many connected systems to maintain proper cellular and whole-body function. Oxygen regulation and homeostasis are vital for proper function in healthy cells, as are core components of aerobic metabolism and efficient ATP generation to supply our energy needs. Maintaining pH homeostasis is also of primary importance; cells maintain pH homeostasis through a host of active and passive transporters to maintain pH balance both inside and outside of the cell.

Events of uncontrolled cellular proliferation, also known as cancer, survive and thrive under conditions that perturb the delicate balance …

Glycemic Variability In Patients With Stage Ii-Iii Colon Cancer, Natalie Mandolfo

Theses & Dissertations

Patients with cancer experience metabolic changes such as hypoglycemia, hyperglycemia, and glycemic variability; collectively termed malglycemia. Glycemic variability, defined as fluctuations in glucose, is a marker of metabolic instability. Higher glycemic variability is associated with adverse health outcomes in the general population and in those with diabetes. Little is known about glycemic variability in patients with cancer, especially those with solid tumor malignancies. Glycemic variability is associated with increased infection, shorter periods of remission, and higher mortality in patients with hematological cancer. This body of work describes the concept and measurement of glycemic variability to assess glycemic control in patients …

Bystanders’ Perspectives On The Provision Of Informal, Hospital-Based Care To Bedridden Patients With Cancer In Sri Lanka, B. Sunil S. De Silva

Nursing ETDs

Due to the nursing shortage in Sri Lanka, patients need informal caregivers, known as bystanders, to help provide patient care. This study described bystanders’ perspectives on informal, hospital-based care to bedridden patients with cancer in Sri Lanka. In this qualitative descriptive study, 17 bystanders at Apeksa/Cancer Hospital, Sri Lanka, were recruited using snowballing sampling. Data were collected through telephone interviews and analyzed using content and thematic analyses. Findings showed that paid and unpaid bystanders cover all caregiving tasks with minimum interaction with nurses. Unpaid bystanders described the need for same-sex bystanders and additional help with patients’ mobilization and specialized care. …

Understanding Radiation Resistance In Head And Neck Tumor Xenografts Using Diffuse Reflectance And Raman Spectroscopy, Sina Dadgar

Graduate Theses and Dissertations

Each year, 800,000 new patients are diagnosed with head and neck squamous cell carcinoma (HNSCC), a majority of whom are treated with a combination of daily fractions of radiation and weekly chemotherapy sessions for up to seven weeks. Current methods to evaluate treatment response of individual patients are limited to anatomical measurements of tumor burden using CT scan or MRI 4-8 weeks after completion of treatment. However, earlier knowledge of radiation-response prior to or at early days after commencement of therapy can aid oncologist with escalating and de-escalating treatment plans for exceptionally non-responding and responding patients. Such a knowledge can …

Investigation Of The Functional Impact Of Anti-Pd-1 On Tumor-Infiltrating Lymphocytes (Til) And Mapping Of Tumor Genomic Features Relevant For Response To Til Therapy, Caitlin Creasy

Dissertations & Theses (Open Access)

With the growing use of both cellular and antibody-based immunotherapies, it has become more important to uncover biomarkers to predict patient response to therapy and ideally aid in patient selection for specific therapeutics, thereby enhancing treatment outcome. At MD Anderson, we have a 43% response rate to therapy when treating metastatic melanoma patients with adoptive cell therapy (ACT) of tumor-infiltrating lymphocytes (TIL), but it is unknown what makes the other 57% of patients not respond to therapy. It is further unknown how particularly early doses of checkpoint inhibitors, like anti-PD-1, attribute to TIL functionality, adding another confounding factor in determining …

An Exploration Of Facial Skin Scarring, Its Impact And Contemporary Evaluation, Michael G. Brandt

Electronic Thesis and Dissertation Repository

Facial skin cancer secondary to surgical treatment may be distressing due to the malignancy itself and from the consequences of its treatment. A visible postsurgical scar is an obvious reminder of the condition. This investigation sought to broaden our understanding of facial scarring and develop a novel tool for its objective evaluation. To this end, skin cancer as the most common etiology of facial scarring was reviewed. The scar scale literature was evaluated in the context of assessing scars through a biopsychosocial lens. Finally, the development of a novel scar scale was presented. Thirty-four individuals completed 13,056 ratings using a …

Vitamin D Levels Affect Survival In A Bcr-Abl Acute Lymphoblastic Leukemia Mouse Model But Do Not Cause Vitamin-Drug Interactions, Kavya Annu

Theses and Dissertations (ETD)

It is a well-established phenomenon that dietary components containing CYP3A inducers or inhibitors if co-administered with drugs that are CYP3A4 substrates lead to marked drug-drug interactions. Because vitamin D is known to regulate intestinal CYP3A expression and gut CYP3A expression plays an important role in pre-systemic metabolism of CYP3A drugs, we determined the impact of vitamin D (VD3) status on systemic exposure and efficacy of chemotherapeutic agents that are CYP3A substrates. We employed VD3 sufficient and deficient mice to perform pharmacokinetics (PK) and anti-leukemic efficacy studies.

First, using hCYP3A4 transgenic mouse model we evaluated the intestinal, hepatic and renal expression …

Pan-Cancer Analysis Of Telomerase Reverse Transcriptase (Tert) Isoforms, Mathushan Subasri

Electronic Thesis and Dissertation Repository

Reactivation of the multi-subunit ribonucleoprotein telomerase is the primary telomere maintenance mechanism in cancer, but it is rate-limited by the enzymatic component, telomerase reverse transcriptase (TERT). While regulatory in nature, TERT alternative splice variant/isoform regulation and functions are not fully elucidated and are further complicated by their highly diverse expression. In this thesis, I characterized TERT expression across normal and neoplastic tissues using TCGA and GTEx RNA-sequencing data. In doing so, I demonstrated the global overexpression and splicing shift towards full-length TERT in neoplastic tissue. Furthermore, my studies identified tumour subtype expression differences possibly regulated by subtype-specific characteristics, detailed heterogeneity …

The Impact Of Myeloid-Mediated Co-Stimulation And Immunosuppression On The Anti-Tumor Efficacy Of Adoptive T Cell Therapy, Pasquale Patrick Innamarato

USF Tampa Graduate Theses and Dissertations

Adoptive T cell therapy (ACT) in combination with lymphodepleting chemotherapy is an effective strategy to induce the eradication of tumors, providing long-term regression in cancer patients. However, only a minority of patients that receive ACT with tumor infiltrating lymphocytes (TILs) exhibit durable benefit. Thus, there is an urgent need to define strategies that potentiate anti-tumor activity conducted by adoptively transferred T cells. In these studies, we aimed to identify novel strategies to enhance the therapeutic efficacy of ACT. Accordingly, we describe the disparate roles of myeloid cells in the context of ACT characterized by the augmentation of TIL proliferation in …

Impact Of Immunotherapy On The Survival Of Pancreatic Adenocarcinoma Patients: An Analysis Of The National Cancer Database, Saber A. Amin

Theses & Dissertations

Pancreatic adenocarcinoma (PDAC) represents 7.2% of all cancer deaths, and by 2030, it will become the second leading cause of death due to cancer. The median overall survival (OS) is 17-23 months in resectable and 4-6 months in metastatic PC [8-9]. The 5-year survival of resectable PC is 22%, and unresectable PC is 8%. A majority of patients treated with standard treatments such as surgery, chemotherapy, and radiation therapy eventually succumb to the disease due to widespread micrometastases at the time of diagnosis. Due to the minimal effect of the current treatments, novel treatment strategies such as immunotherapeutics have been …

Development Of A Ct Metal Artifact Management Algorithm For Proton Therapy Planning (Ampp) For Head And Neck Cancer Patients, Daniela Branco

Dissertations & Theses (Open Access)

Purpose: Dental amalgams (high Z materials) are common sources of artifacts in Head and Neck (HN) images. Commercial artifact reduction techniques have been offered, but many are impractical, produce inaccurate CT images or are not clinically available, thus not widely implemented. The goal of this work is to use CT gantry tilts to develop and evaluate a stereoscopic HN metal artifact management algorithm and investigate its improvement in proton treatment planning.

Methods: The in-house CT metal artifact management method for proton planning (AMPP) uses two angled CT scans to generate a single image set with no metal artifacts posterior …

Investigating The Metabolic Progression Of Glioblastoma With Hyperpolarized Magnetic Resonance, Travis Salzillo

Dissertations & Theses (Open Access)

Rapid diagnosis and therapeutic monitoring of aggressive diseases such as glioblastoma (GBM) can improve patient survival by providing physicians the time to optimally deliver treatment. This includes early in development, while the tumor is still manageable, or following initial therapy, when alternative treatments should be considered. The main goal of this project was to determine whether metabolic imaging with hyperpolarized magnetic resonance spectroscopy (MRS) could detect changes in tumor progression more rapidly than conventional anatomic magnetic resonance imaging (MRI) in patient-derived GBM murine models. To comprehensively capture the dynamic nature of cancer metabolism, in vivo pyruvate-to-lactate conversion with hyperpolarized MRI, …

Guided Imagery And Deep Breathing: Minimizing Anxiety Experienced By Pediatric Cancer Patients, Bethany Grace Aney

MSU Graduate Theses

This particular research study examined the impact of guided imagery and deep breathing as coping tools to reduce the anxiety levels experienced by pediatric cancer patients ages 6-12 years of age at a children’s hospital in Central Pennsylvania. This quantitative study utilized a pretest-posttest design, in addition to utilizing the State-Trait Anxiety Inventory for Children (STAIC™) as the baseline and post-test assessment. The STAIC™ is a questionnaire tool that assesses individuals’ state and trait anxiety through a total of 40 questions. This particular study had a total of five patients, two male and three female that consented to undergoing three …

Mechanistic And Translational Studies On Skeletal Malignancies, Jeremy Mcguire

USF Tampa Graduate Theses and Dissertations

New treatment strategies are desperately needed for treating skeletal malignancy. Skeletal malignancies can be either primary cancer that originated in the bone, such as osteosarcoma, or metastatic cancer that spread from another organ to the skeleton, as in the case of breast or prostate cancer. In this thesis, I will detail two projects that focus on the discovery of new treatment strategies for both primary skeletal malignancy and metastatic skeletal malignancy.

The first project focuses on the primary skeletal malignancy, osteosarcoma, a rare cancer that is commonly diagnosed in children and young adults and metastasizes to the lungs. The survival …

Utilization Of Evidence-Based Telehealth For Routine Follow-Up Visits In Outpatient Palliative Care, Nienke Sahelijo Bsn, Rn, Dnp-Fnp Student, Kori Fitzgerald Dnp, Fnp-C, Joseph F. Burkard Dncs, Crna

Doctor of Nursing Practice Final Manuscripts

Objectives: Palliative care services constitute a vital part of the oncology treatment plan. Much of the suffering associated directly with cancer itself or as a result of treatments can be mitigated with the early incorporation of palliative services. Unfortunately, access to palliative care remains elusive due to a lack of qualified providers. This evidence-based project was implemented in an effort to address gaps in care for advanced cancer patients. The goal was to provide telehealth visits for follow-up of stable patients to manage symptoms and psychosocial challenges with equivalent or improved satisfaction as compared to their last in-office visit …

Inhibition Of Cancer Causing Genes Through The Delivery Of Omomyc In Anti-Myc Therapy: A Systematic Review, Angie Mcgraw

University Honors Theses

A systematic review of the available studies on the interference of OmoMyc with Myc's function in cancerous cells is presented. Myc is a transcription factor that regulates cellular processes such as apoptosis, proliferation, and differentiation. However, Myc is often overexpressed in a variety of cancers, resulting in abnormal growth of cancer cells. Although the inhibition of Myc has been highly desired, it remained a challenge due to its undruggable characteristics. Attempts to inhibit Myc have involved the usage of small-molecules, but these attempts have failed, causing adverse effects and incomplete inhibition of Myc. Despite promising preclinical studies of OmoMyc, it …

The Effects Of Alpha-Tocopherol And Ascorbic Acid On Metastatic Breast Cancer Cells, Scout Treadwell

Honors Theses

Breast cancer is a multifaceted, complex disease that affects hundreds of thousands of patients every year. Although there has a been a decline in the mortality rate of this disease, it is still vital to investigate and discover new possible treatments. One area of research involves the generation of reactive oxygen species (ROS) in cancer cells and the possibility of ROS-induced apoptosis. Antioxidants such as Vitamin C and Vitamin E have been shown to serve as pro-oxidants. Instead of detoxifying the cell from damaging ROS, these compounds can stimulate ROS production, triggering an apoptotic cascade in the cell. In this …

Development Of Fluorescent Hyaluronic Acid Nanoparticles For Intraoperative Tumor Detection, Nicholas E. Wojtynek

Theses & Dissertations

Surgical resection remains to be the primary treatment for the majority of solid tumors, including breast cancer. The complete removal of the primary tumor, local metastases, and metastatic lymph nodes dramatically improve a patient’s treatment outcome and prognosis. Nevertheless, surgeons are limited to tactile and visual cues in distinguishing malignant and healthy tissue. This can result in a positive surgical margin (PSM), which occurs when tumor goes undetected and is left behind in the surgical cavity. PSMs decreases a patient’s prognosis and necessitate additional treatment in the form of surgery, radiation, and chemotherapy. An emerging imaging modality, known as fluorescence-guided …

Integrating Geriatric Assessment And Genetic Profiling To Personalize Therapy Selection In Older Adults With Acute Myeloid, Vijaya R. Bhatt

Theses & Dissertations

Integrating geriatric assessment for patient profiling and genetic profiling of leukemic cells represents an innovative approach to personalize therapy selection in older adults with acute myeloid leukemia (AML). We report results of a pre-planned interim analysis of a pragmatic phase II trial that utilized this strategy to personalize therapy. Patients ≥60 years with a new diagnosis of AML underwent geriatric assessment prior to initiation of treatment. Geriatric assessment of physical function, cognitive function and comorbidity burden were used to determine fitness for chemotherapy. Patients with good or intermediate-risk AML received intensive chemotherapy such as anthracycline and cytarabine (7+3) if determined …

Investigating The Redox Sensitivity Of Mitf Splice Variants, Rachel Berryman

Senior Theses

Within pigment-producing cells known as melanocytes, the transcription factor MITF is intimately involved in regulating genes associated with cell cycle maintenance and melanocyte differentiation. Research, however, has provided conflicting results on the relationship between the expression levels of MITF and melanocyte cell fate. To complicate matters, two splice variants of MITF exist, differing by only 18 base pairs. These variants have been observed at variable levels of expression in melanocyte and melanoma cells, raising the question as to their functional purpose. Building upon previous research by the Leachman/Cassidy lab that identified the redox sensitivity of MITF while additionally establishing a …

Assessing Patient Attitudes Toward Genetic Testing For Hereditary Hematologic Malignancy, Addison Johnson

Dissertations & Theses (Open Access)

Since 2003, more than 15 genes have been identified to predispose to hereditary hematologic malignancy (HHM). Although the diagnostic yield of germline analysis for leukemia is similar to solid tumors, referral for genetic evaluation in adults with leukemia is underperformed. Identifying HHM is important for prognostication, treatment, and donor selection for hematopoietic stem cell transplant. No studies have examined leukemia patients’ attitudes toward genetic testing for HHM. This study aimed to assess leukemia patients’ attitudes toward genetic testing and elicit current perceived distress due to a leukemia diagnosis. Data were elicited through an electronic survey sent to 5,513 patients diagnosed …

Modulation Of Pi3k-Akt Pathway In Colorectal Cancer, Maliha Nusrat

Dissertations & Theses (Open Access)

The phosphatidylinositol-3-kinase (PI3K) signaling pathway is activated in 20-40% colorectal cancers (CRC) through PTEN loss (PTEN^loss) and PIK3CA mutations (PIK3CA^mut). Allosteric AKT inhibition with MK2206 monotherapy has been ineffective in CRC patients. We investigated the impact of MK2206 on pharmacodynamic (PD) markers and signaling pathways using reverse phase protein array (RPPA) on (1) paired tumor biopsies from a clinical trial of MK2206 in PI3K-altered metastatic CRC, (2) PTEN^lossCRC patient derived xenografts (PDX) treated with MK2206 or carrier, and (3) MK2206-treated cell lines. PD inhibition was deep in cell lines, less but significant in …

Parents' Experiences Of Camp For Siblings Of Pediatric Oncology Patients, Kristen Lauren Krueger

MSU Graduate Theses

The diagnosis and treatment of childhood cancer is oftentimes a stressful experience for individuals other than the patient, such as parents and siblings of pediatric oncology patients. Parents and siblings may be impacted in many ways, but there are interventions to help. The purpose of this qualitative study was to understand parents’ lived experiences of having a child who has attended a camp designed for siblings of pediatric oncology patients. Parents (n=5) of siblings that have attended camp for siblings were interviewed with open-ended questions. Data was analyzed using phenomenology procedures. Results from this study indicated that mothers and fathers …

Genetic Counselors' Approaches To Direct-To-Consumer Genetic Testing For Hereditary Breast Cancer, Sarah Burke

Dissertations & Theses (Open Access)

Given the increasing availability of health-related direct-to-consumer genetic testing (DTC-GT) and third-party interpretation (TPI) services, it is likely that genetic counselors (GCs) will continue to encounter consumers that require follow-up counseling for their results. The National Comprehensive Cancer Network recommends clinical-grade genetic testing to confirm commercial results; however, the type of testing that GCs select remains uncharacterized. Therefore, we aimed to describe the specific recommendations that cancer GCs make for confirmatory genetic testing in probands who have already obtained DTC-GT results or TPI data that reported a BRCA1/2 pathogenic variant. We recruited 80 GCs specializing in hereditary cancer and administered …

Impact Of A Protocol Implementation On Identification And Referral Of Women At-Risk For Hereditary Breast Cancer, Chrysanthemum Davis Lawson

Evidence-Based Practice Project Reports

Breast cancer is the foremost new cancer diagnosis and the second highest cause of cancer death in American women (American Cancer Society, 2019). Hereditary breast cancer is most commonly caused by a mutation within the breast cancer susceptibility genes, BRCA 1 or 2, which increases women’s risk for breast cancer by five to ten-fold the average population (Mayo Clinic, 2019). The U.S. Preventive Services Task Force has assigned a Grade B recommendation advising health care providers to use a risk assessment tool, such as the Breast Cancer Genetics Referral Screening Tool (B-RST™), to recognize and provide medical management recommendations for …

Novel Inference Methods For Generalized Linear Models Using Shrinkage Priors And Data Augmentation., Arinjita Bhattacharyya

Electronic Theses and Dissertations

Generalized linear models have broad applications in biostatistics and sociology. In a regression setup, the main target is to find a relevant set of predictors out of a large collection of covariates. Sparsity is the assumption that only a few of these covariates in a regression setup have a meaningful correlation with an outcome variate of interest. Sparsity is incorporated by regularizing the irrelevant slopes towards zero without changing the relevant predictors and keeping the resulting inferences intact. Frequentist variable selection and sparsity are addressed by popular techniques like Lasso, Elastic Net. Bayesian penalized regression can tackle the curse of …

Analysis Of Gene Expression In Early-Stage Pancreatic Cancer And Investigation Of 1,2,3,4,6-Penta-O-Galloyl-Β-D-Glucopyranoside As A Therapeutic, Zachary R. Heinzman

Honors Program Theses

Pancreatic cancer (PC) is one of the deadliest cancers among both men and women. However, if it is detected early, there is a significant increase in the 5-year survivability of the disease1 . Currently, there are no truly efficient detection mechanisms available to detect earlystage PC when treatment options are more viable. The first objective of this project was to determine the expression levels of AHNAK2, IGHG3, EPPK1, CTHRC1, CEL, PLA2G1B, and GNMT—all known to be aberrantly expressed in PC cell lines—in early-stage PC tissue and assess the feasibility of their use as potential biomarkers for PC. To accomplish this, …

Oncolytic Viruses: Cancer Treatment Going Viral, Rhianna N. Bronson

Chancellor’s Honors Program Projects

No abstract provided.

Hdr Brachytherapy For Skin Cancer Using H.A.M. Applicator, Timothy Richard Thatcher

UNLV Theses, Dissertations, Professional Papers, and Capstones

Skin cancer is the most common type of malignancy affecting both men and women in the United States. A majority of these cases are nonmelanoma skin cancers (NMSC) such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The goal of any skin cancer treatment is to cure the lesion itself while also preserving function and optimizing superficial cosmesis. High dose rate (HDR) brachytherapy provides an alternative to superficial x-ray or electron beam for skin cancer treatment. Utilizing an Iridium 192 source soldered to the end of a wire, surface dose can be administered at predetermined positions with sharper …

Lymphatouch™ As A Preparatory Method For Chemo-Induced Peripheral Neuropathy And Radiation-Induced Fibrosis: A Case Study, Abigail Harris

OTD Capstone Projects

Quality Improvement: Aims to explore the ability to expand the services offered at the Nashville Breast Center and potentially provide improved health-related quality of life for patients in the survivorship stage of breast cancer. Case Study: To assess the LymphaTouch ™ device for use in treating Chemo-Induced Peripheral Neuropathy and Radiation-Induced Fibrosis.