Medicine and Health Sciences Commons^™

Structural Characterization And Therapeutic Utility Of The Proton-Coupled Folate Transporter, Michael Roy Wilson

Wayne State University Dissertations

Folate is a B9 vitamin essential to DNA synthesis. The proton-coupled folate transporter (PCFT) is a newly discovered proton/folate symporter with an acidic pH optimum and broad expression across a variety of solid tumor types, with limited expression in normal tissues. Several antifolate molecules have been developed as cancer therapeutics, although these classical antifolates display numerous off-target effects due to transport by the ubiquitous reduced folate carrier (RFC). In this dissertation, we determine the roles of multiple PCFT structure/function domains, and develop PCFT-specific antifolates to target solid tumors. We utilize substituted cysteine accessibility methods (SCAM) to identify a novel reentrant …

Surface-Initiated Polymerizations For The Rapid Sorting Of Rare Cancer Cells, Jacob L. Lilly

Theses and Dissertations--Chemical and Materials Engineering

Cancer metastasis directly accounts for an estimated 90% of all cancer related deaths and is correlated with the presence of malignant cells in systemic circulation. This observed relationship has prompted efforts to develop a fluid biopsy, with the goal of detecting these rare cells in patient peripheral blood as surrogate markers for metastatic disease as a partial replacement or supplement to tissue biopsies. Numerous platforms have been designed, yet these have generally failed to support a reliable fluid biopsy due to poor performance parameters such as low throughput, low purity of enriched antigen positive cells, and insufficiently low detection thresholds …

A Requirement For Y841 In Jak3 Enzymatic Activity And Hematopoietic Cancers, George Steven Martinez

Open Access Theses & Dissertations

A medical need exists for successfully treating people afflicted with leukemia, especially those who develop drug resistant forms. Relapse leukemia cases are particularly high within Hispanic populations where this disease is among the most frequently occurring cancer. Fourteen somatic mutations have been reported in Janus tyrosine kinase 3 (Jak3), including M511I and A573V, from patients with various forms of leukemia. To monitor drug sensitivity, a model system was developed. Indeed, many of these mutations have been shown to possess transforming ability in cell lines such as the IL-3 dependent pro-B cell line Ba/F3. As such, Ba/F3 cells were transformed to …

Self-Efficacy And Coping In Transition Of Care After Remission Of Cancer In Adolescents, Leah M. Mcdonnell

Honors Undergraduate Theses

The improvement in cancer remission rates in children and adolescents due to advances in cancer treatment and therapy has led to the development of guidelines that address long-term follow up for survivors of childhood cancers. Adolescents often experience negative emotions related to the fear of uncertainty about long-term survival after cancer remission, yet often report feelings of hope and optimism for the future more than adult cancer survivors. The purpose of this study was to understand the role of self-efficacy and coping in adolescents after remission of cancer. A secondary purpose was to analyze which coping strategies supported long-term survival …

The Synchronicity Of Hope And Enhanced Quality Of Life In Terminal Cancer, Brianna M. Terry

Honors Undergraduate Theses

Cancer is the second leading cause of death in the United States and a leading cause of death worldwide. The rate of mortality is currently approximately 171.2 out of every 100,000 individuals with a terminal cancer diagnosis annually. Individuals with terminal cancer diagnoses facing probable mortality utilize various coping mechanisms or internal resources in an attempt to maintain an internal sense of well-being, commonly referred to as quality of life (QOL). The purpose of this literature review was to investigate themes prevalent in the literature pertaining to internal coping mechanisms and analyze any correlation or causation linking these resources to …

Improving Communication Between Cancer Patients And Providers During A 15-Minute Office Visit: A Systematic Review Of The Literature, Dr. Tammy Elizabeth Manganelli

Walden Dissertations and Doctoral Studies

Patients undergoing chemotherapy treatments for cancer often experience adverse side effects, including cognitive deficits. These deficits impact the patient's ability to communicate effectively with their oncology provider. Ineffective communication can adversely affect patient outcomes and decrease patient-provider satisfaction. The resulting poor communication can contribute to poor patient outcomes. This systematic literature review focused on assistive communication tools that could be used in an outpatient oncology setting to improve patient-provider communication. The literature review findings led to the development of a resource for providers that includes 15 communication tools that can be used to assess and improve communication in cancer care. …

Intensive Care In Oncology: Admission And Outcomes In Adult Patients With Cancer, Surya John

Honors Undergraduate Theses

Background: Historically, patients with cancer have been perceived as poor candidates for ICU admission. General ICU admission criteria lists cancer patients as low priority in ICU admission depriving them of the care they rightfully deserve. The purpose of this literary synthesis was to examine ICU admission criteria, risk factors, and outcomes of ICU admission in relation to hematological and solid tumor cancers and discuss ways that practitioners and nurses can educate patients with cancer and their families on appropriateness of ICU care.

Methods: A total of 768 articles were found in a literature search including all literature from 2005 to …

Investigating Mechanisms Determining Cancer Cell Sensitivity To Carfilzomib And Novel Strategies To Overcome Resistance, Lin Ao

Theses and Dissertations--Pharmacy

Proteasome inhibitors (PIs) are a class of FDA-approved anti-cancer agents which includes the first-generation PI bortezomib (BTZ) and second-generation carfilzomib (CFZ). Drug resistance is a major challenge in PI therapy with no solution currently available. While a few resistance mechanisms had been proposed for BTZ, little was known about CFZ resistance before the start of our studies. In this dissertation work, we investigated multiple mechanisms contributing to CFZ resistance—alterations in the drug transporter activity, metabolic stability, and proteasome activity profiles—and evaluated potential strategies to overcome CFZ resistance.

We observed marked upregulation of the drug efflux transporter P-glycoprotein (P-gp) in our …

Evaluation Of Diet Composition Of Pediatric Cancer Survivors As A Need For Nutrition Counseling, Sean O'Nan

Theses and Dissertations--Nutrition and Food Systems

Prior research has shown that pediatric cancer survivors face a multitude of longterm effects from treatment of their disease. Many of these conditions can be treated or managed through proper nutrition, however patients of the DanceBlue Kentucky Children's Hospital Hematology/Oncology Clinic do not see a registered dietitian. This study looked at food and drink consumption of the past 30 days by the patient using the NHANES Dietary Screener Questionnaire to see if they met nutrition recommendations as outlined by the 2015‐2020 Dietary Guidelines for Americans. Results from the study found that off‐treatment pediatric cancer survivors (n=21) failed to meet …

Testing A Low-Intensity And Accessible Cognitive Behavioral Therapy For Insomnia (Cbt-I) Intervention In Individuals Newly Diagnosed With Cancer, Amma Agyemang

Theses and Dissertations

Insomnia is defined as difficulty initiating or maintaining sleep, or nonrestorative sleep that lasts for at least one month and is accompanied by significant impairment in daytime functioning including fatigue, irritability, and/or difficulty concentrating. It is one of the most common complaints reported by individuals with cancer, especially around the time of cancer diagnosis and treatment. Yet it is often unrecognized and untreated, leading to adverse health consequences and increased healthcare costs. Cognitive Behavioral Therapy for Insomnia (CBT-I) has been recommended as the gold standard for treating insomnia among individuals with cancer. Multiple studies have tested and proven the efficacy …

The Relation Between Patient Education And Picc Line Occlusion, Patricia Louise Petroulias

Wayne State University Dissertations

The purpose of this study was to test the feasibility of using an electronic tablet to supplement patient and caregiver education about PICC line maintenance and to compare the percentage of PICC line complications in the intervention group with national percentage rates for patients and caregivers. Newly diagnosed cancer patients who had PICC lines inserted participated in this study. They used an electronic tablet to learn the 10 steps for flushing their PICC lines correctly. They also met with the researcher via FaceTime to review the steps.

A total of 11 patients participated in this quasi-experimental pilot study. They completed …

Whsc1l1 Regulates Estrogen Receptor Activity In Sum44 Breast Cancer Cells, Jonathan Curtis Irish

Wayne State University Dissertations

Breast cancer is the most common cancer and the second leading

cause of cancer death in women. While ER-positive breast cancer subtypes are initially

well-managed by targeted therapies targeting estrogen signaling, many women are

suffering from recurrence of a more aggressive, hormone insensitive cancer 5 or more years after initial remission. Late recurrence of hormone resistant breast cancer in patients

who were previously successfully treated with anti-estrogen therapies worsens

overall long-term outcomes, and specific oncogenic mutations may be driving late recurring aggressive disease in these patients. More complete characterization of the oncogenome of

a tumor may allow for the possibility …

Evaluating Adherence To Colorectal Cancer Screening, Jaime Bradley-Miller

DNP Projects

Purpose: The purpose of this project and literature review was to determine provider documentation practices of colorectal cancer (CRC) screening, identify the percent of clinic patients who need to be screened, and develop a set of recommendations and targeted interventions which will increase CRC screening rates.

Methods: A retrospective chart review including males and females of all ethnicities between the ages of 45 and 80 was performed in one primary care practice. A randomized sample of 360 office visits between February and November of 2015 were selected, of which 281 met the inclusion and exclusion criteria. Patient demographics and characteristics …

Identification Of Functional Single Nucleotide Polymorphisms Associated With Breast Cancer Based On Chromatin Modifications, Laura E. Hayward

CMC Senior Theses

Breast cancer affects 1 in 8 women and can be deadly; yet when detected early enough it is often treatable. Thus, early detection of breast cancer is imperative to save lives. The success of early detection depends, in part, on being able to stratify risk. A new approach to determining risk involves identifying genetic variants that alter an individual’s risk for developing breast cancer. This thesis identified key functional candidates involved in breast cancer development, some of which have been verified by other studies. For a few of the functional candidates, further research needs to be done in order to …

Federal Policies And Prescription Drugs, Ali Bonakdar Tehrani

Theses and Dissertations

This dissertation comprises three discrete empirical papers, with an introductory essay that evaluates the impact of different federal policies on prescription drug prices, utilization, and spending. Two main databases are used: (a) Medicaid State Drug Utilization Data and (b) the Medical Expenditure Panel Survey (MEPS) data. These two databases are designed to track Medicaid drug utilization and overall medical use and expenditures, respectively. The variables of interest in this dissertation are prescription drug price, prescription drug use and spending, and overall drug expenditures.

The objective of the first paper (Chapter 2) is to examine whether oncology drug prices have significantly …

Factors Associated With Late Stage Diagnosis Of Cervical Cancer In The United States, Marianne S. Pelletier

Walden Dissertations and Doctoral Studies

Cervical cancer represents a significant public health problem in the United States. According to the Centers for Disease Control and Prevention, the prognosis is related to stage at diagnosis, with the 5-year survival rate being 91.2% for early stage disease and only 17.0% for those with late stage disease. There is a gap in the literature examining the association of insurance status with late stage cervical cancer diagnosis across a large segment of the United States population. There is also a gap in the literature examining women residing in the United States with late stage cervical cancer diagnosis and identifying …

Atp6v1c1 Enhances Breast Cancer Growth By Activating V-Atpase Mediated Mtorc1 Signaling And Metastasis By Increasing V-Atpase Activity In Cancer Cells, Matthew J. Mcconnell

All ETDs from UAB

It is known that the vacuolar ATPase has a number of functions related to tumor growth and progression such as involvement in drug resistance, pH regulation, autophagy, and lysosomal acid protease activation, as well as invasion and metastasis. Here we specifically describe the role of ATP6v1c1 in murine and human models of breast cancer. ATP6v1c1 is the dominant isoform of the coordinating subunit (ATP6v1c) involved in the assembly of the vacuolar ATPase complex which plays a key role in cancer growth and progression. We also describe how ATP6v1c1 knockdown impairs tumor nutrient signaling through mTORC1 and tumor cell proliferation, by …

The Use Of An Open-Label Placebo To Treat Cancer-Related Fatigue In Cancer Survivors, Theresa Walker Hoenemeyer

All ETDs from UAB

Background: A placebo is an inert substance (e.g., sugar pill) or procedure (e.g., sham surgery) that should confer no beneficial effects. Nonetheless, typically, 30-50% of those randomized to placebos report significant benefits. New studies indicate that the use of disclosed or open-label placebos reduces self-reported symptoms among patients with irritable bowel syndrome, migraine attacks, and major depression. Methods: The investigator conducted a 7-week pilot study to evaluate the feasibility and effects of an open-labeled administration of placebo pills on patient-reported clinical and psychosocial outcomes among cancer survivors seeking relief from cancer-related fatigue. The specific aims of this study were to: …

Stimuli Responsive Nanoparticle For Cancer Targeted Therapy, Huacheng He

Theses and Dissertations

Nanoparticle is the particle with a size in the range from several nanometers to hundreds of nanometers. It has been extensively used for cancer diagnosis and therapy. However, it is still a great challenge to fabricate nanoparticles with spatiotemporally controllable delivery of anticancer drugs to tumors and with high therapeutic efficacy. This thesis mainly focuses on the development of stimuli responsive nanoparticles for cancer targeted therapy. These nanoparticles either response to internal stimuli such as pH and redox potential or external stimuli like temperature and light could effectively target tumors and control the release of anticancer drugs there to improve …

Factors Influencing Resilience Among Haematological Cancer Survivors, Katherine S. Gallager

Theses: Doctorates and Masters

Haematological cancers in bone marrow (leukaemia) and the immune system (lymphomas or myeloma) represent the sixth most common adult tumour group in Australia. These cancers often develop without warning and require intensive treatment regimes that last on average eight months, but may continue for a lifetime depending on the diagnosis. Encouragingly, advancing cancer treatments, a key accomplishment of cancer research over the past 40 years, have resulted in a growing community of cancer survivors. Approximately two in three adults diagnosed with haematological cancer (HC) can now expect to survive more than five years. However, they must attempt to navigate the …

Multifunctional Nanocarriers For Cancer Therapy, Bei Cheng

Theses and Dissertations

Cancer is one of the leading causes of human mortality and mortality in all diseases. There has been a boost in developing nanocarrier-based therapies for treating cancer or other diseases during the past decade. One of the major advantages about nanocarrier (with the size range from 1-1000 nm) lies in its ability to specifically target tumor and maximize drug accumulation in tumor foci through the enhanced permeability and retention effect. Advancement in nanotechnology has opened a new paradigm in pharmaceutical field. But new challenges have to be overcome in order to fully exploit the technology and improve safety in clinical …