Neoplasms Commons^™

Zebrafish Models To Uncover Targetable Mechanisms Of Self-Renewal In T-Cell Acute Lymphoblastic Leukemia, Majd Al-Hamaly

Theses and Dissertations--Pharmacology and Nutritional Sciences

Relapsed T-cell Acute Lymphoblastic Leukemia (T-ALL) patients have dismal prognosis, with 5-year overall survival rates of 10% for adults and 36% for children. Relapse is attributed to the inability of chemotherapy agents to eliminate Leukemia Stem Cells (LSCs) that can repopulate the leukemia. Those cells exist with a unique genetic, transcriptomic, and metabolic profile compared to the rest of the leukemia and thus, finding targeted therapies toward this population of cells can result in disease eradication and elimination of relapse. However, investigating LSCs is challenging-particularly in T-ALL- for two reasons: 1) the lack of robust surface markers that define LSCs …

Inhibiting Pi3k/Akt To Enhance Brain Uptake Of Anticancer Agents In Glioblastoma, Louis Rodgers

Theses and Dissertations--Pharmacy

Glioblastoma (GBM) is the deadliest and most common malignant CNS tumor. Despite advances in understanding its biology and the development of targeted therapies, effective treatment options remain limited. As a result, patient survival rates are dismal, with a 5-year survival rate of only 6.8% and an overall survival of less than two years. This poor outcome is partly due to our inability to treat GBM cells that infiltrate the whole brain. Focal treatments like surgery and radiotherapy alone are insufficient due to these invasive tumor cells. Therefore, chemotherapy following resection and irradiation of the primary tumor is essential to eliminate …

Developing Radiosensitizers To Enhance Radiotherapy In Treating Gastroenteropancreatic Neuroendocrine Tumor, Zeta Chow

Theses and Dissertations--Clinical and Translational Science

Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET) is a heterogeneous group of malignancies arising from multipotent neuroendocrine stem cells in the gastrointestinal tract. The incidence of GEP-NET continues to rise, possibly due to the advancement of imaging and biomarkers available for diagnosis. However, even though the majority of patients are diagnosed with low-grade and localized disease, a significant percentage of patients present with advanced-stage metastatic disease with poor prognosis in months to a few years. These advanced-stage GEP-NET patients can also present with a variety of debilitating symptoms that significantly impact their quality of life. The role of palliative-intent surgery is limited, and …

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 …

Understanding And Targeting The Tph1-Serotonin-Htr3a Axis In Small Cell Lung Cancer, Yanning Hao

Theses and Dissertations--Toxicology and Cancer Biology

Small cell lung cancer (SCLC), which accounts for 10-15% of all lung cancer, is the most malignant type that tends to grow fast and spread in its early stages. The 5-year survival rate remains low at 6% overall. Thus, new therapeutic methods and pharmacological targets for SCLC patients are urgently needed. We present novel data indicating that the synthesis of serotonin is upregulated in SCLC compared to normal bronchial epithelial cells and non-small cell lung cancer. Serotonin signaling plays a critical role in various physiological and pathological processes. However, its contribution to SCLC development has not been well understood. The …

The Development And Characterization Of Nanobodies Specific To Protein Tyrosine Phosphatase 4a3 (Ptp4a3/Prl-3) To Dissect And Target Its Role In Cancer., Caroline Smith

Theses and Dissertations--Molecular and Cellular Biochemistry

Protein Tyrosine Phosphatase 4A3 (PTP4A3 or PRL-3) is an oncogenic dual-specificity phosphatase that drives tumor metastasis, promotes cancer cell survival, and is correlated with poor patient prognosis in a variety of solid tumors and leukemias. The mechanisms that drive PRL-3’s oncogenic functions are not well understood, in part due to a lack of research tools available to study this protein. The development of such tools has proven difficult, as the PRL family is ~80% homologous and the PRL catalytic binding pocket is shallow and hydrophobic. Currently available small molecules do not exhibit binding specificity for PRL-3 over PRL family members, …

Understanding Cancer Patients' Desire To Quit Tobacco Without Assistance: A Mixed-Methods, Longitudinal Study, Tia Borger

Theses and Dissertations--Psychology

Introduction: Unassisted attempts to quit tobacco are a well-established reason for quit failure. Nonetheless, many cancer patients prefer to make a quit attempt without using evidence-based tobacco treatment. This study aimed to understand the rationale that underlies cancer patients’ desire to quit tobacco without assistance and to track longitudinally the smoking cessation outcomes of patients with this preference. Method: In a mixed-methods, longitudinal study, 35 cancer patients who were current tobacco users and declined tobacco treatment because of the desire to quit on their own provided data via three questionnaires and 1-2 semi-structured interviews across 60 days. Participants were recruited …

An Ecological Study Of Glyphosate Use And Non-Hodgkin’S Lymphoma, Dexter Corlett, Steven R. Browning

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

Glyphosate is currently the most widely used herbicide in the world. Initially thought to be non-carcinogenic in humans, in 2015 glyphosate was classified as a “probable carcinogen” by the International Agency for Research on Cancer due to several small epidemiological studies indicating a link between the pesticide and hematologic cancers, especially non-Hodgkin’s lymphoma (NHL). The current work is an ecological study using counties in Kentucky, Arkansas, and Iowa to compare glyphosate usage to NHL incidence using a multivariate Poisson regression. We found no significant correlation between glyphosate use and NHL incidence, though caution should be taken to draw significance from …

Abc Transporters In Glioblastoma: Anticancer Drug Transport And Transporter Regulation At The Blood-Brain Barrier, Julia A. Schulz

Theses and Dissertations--Pharmacy

Glioblastoma is one of the deadliest cancers, with a median survival of only one year. Even after aggressive treatment consisting of surgical resection, radiation, and chemotherapy, most glioblastoma patients suffer from tumor recurrence within 6-9 months. One reason for treatment failure of anticancer drugs is the blood-brain barrier that protects the brain by impeding xenobiotic uptake from the blood. To this end, efflux transporters at the human blood-brain barrier, such as P-glycoprotein (ABCB1) and Breast Cancer Resistance Protein (ABCG2), prevent many compounds, including anticancer drugs, from entering the brain. Thus far, approaches to deliver anticancer drugs across the blood-brain barrier …

Epigenetic States Regulate Tumor Aggressiveness And Response To Targeted Therapies In Lung Adenocarcinoma, Fan Chen

Theses and Dissertations--Toxicology and Cancer Biology

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, 85% of which are lung adenocarcinomas (LUAD). Although molecular studies of NSCLC identified targetable mutations of some oncogenes including BRAF, EGFR and ALK, no targeted therapies exist for most cases. Cancer epigenetics is the study of epigenetic modifications, including histone modifications, that control gene expression in cancer. Recent advances have revealed numerous epigenetic abnormalities in human cancers, and targeting epigenetic regulators could be effective at reversing dysregulated epigenetic programs or driving sensitivity to other targeted therapies.

Inhibitors of the histone methyltransferase EZH2 have recently been approved as …

The Nuclear Legacy In Appalachia, Michele Morrone, Harold Perkins

Journal of Appalachian Health

Nestled in the rolling hills of Appalachia Ohio is a reminder of the role that the region played in winning the Cold War. For more than 40 years in rural Pike County, the 3,700-acre Portsmouth Gaseous Diffusion Plant (PORTS), or the “A-Plant” as the locals refer to it, enriched uranium for use in nuclear weapons. While the facility produced nuclear fuel for national security, it simultaneously exposed plant workers to chemicals and radiation and discharged pollution into the surrounding community. The A-Plant is now being demolished and the site repurposed. However, the site continues to affect the community as, for …

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 …

Chemoenzymatic Studies To Enhance The Chemical Space Of Natural Products, Jhong-Min Chen

Theses and Dissertations--Pharmacy

Natural products provide some of the most potent anticancer agents and offer a template for new drug design or improvement with the advantage of an enormous chemical space. The overall goal of this thesis research is to enhance the chemical space of two natural products in order to generate novel drugs with better in vivo bioactivities than the original natural products.

Polycarcin V (PV) is a gilvocarcin-type antitumor agent with similar structure and comparable bioactivity with the principle compound of this group, gilvocarcin V (GV). Modest modifications of the polyketide-derived tetracyclic core of GV had been accomplished, but the most …

Clinical And Pathologic Significance Of Integrin Α6Β4 Expression In Human Malignancies, Rachel L. Stewart

Theses and Dissertations--Clinical and Translational Science

Integrins are cellular adhesion molecules that bind cells to the extracellular matrix. The integrin α6β4, a receptor for laminins, is predominantly expressed on epithelial cells where it is present at the basal surface adjacent to the basement membrane. This integrin plays a critical role in maintaining normal cellular functions, yet has also been implicated in promoting invasion and metastasis in human malignancies. While overexpression of the integrin α6β4 has been detected in select human cancers, the clinical significance of integrin α6β4 expression in a number of malignancies has not been determined. The purpose of this study was to examine integrin …

Stress, Coping, Social Support, And Prostate Cancer Risk Among Older African American And Caucasian Men, Ann L. Coker, Maureen Sanderson, Gary L. Ellison, Mary Kay Fadden

CRVAW Faculty Journal Articles

Objectives: While psychosocial stress and high effort coping have been associated with reduced immune function, no epidemiologic study has addressed psychological stress and risk of prostate cancer. The purpose of this analysis was to investigate the association between stress, coping, social support, and risk of prostate cancer among older men (age 65–79 years). Design: Population-based case-control study in South Carolina.

Participants: Cases were 400 incident, histologically confirmed prostate cancer cases identified through the South Carolina Central Cancer Registry between 1999 and 2001 (70.6% response rate). Controls were 385 men identified through the 1999 Health Care Financing Administration Medicare beneficiary file …

Psychosocial Stress And Prostate Cancer: A Theoretical Model, Gary L. Ellison, Ann L. Coker, James R. Hebert, Maureen Sanderson, Charmaine D. Royal, Sally P. Weinrich

CRVAW Faculty Journal Articles

African-American men are more likely to develop and die from prostate cancer than are European-American men; yet, factors responsible for the racial disparity in incidence and mortality have not been elucidated. Socioeconomic disadvantage can lead to psychosocial stress and may be linked to negative lifestyle behaviors. Regardless of socioeconomic position, African-American men routinely experience racism-induced stress. We propose a theoretical framework for an association between psychosocial stress and prostate cancer. With the context of history and culture, we further propose that psychosocial stress may partially explain the variable incidence of prostate cancer between these diverse groups. Psychosocial stress may negatively …

Patients As Subjects For Research: Ethical Dilemmas For The Primary Care Clinician-Investigator, Susan F. Slatkoff, Peter Curtis, Ann L. Coker

CRVAW Faculty Journal Articles

Background: Past studies suggested an association between human papillomavirus (HPV) and cervical intraepithelial neoplasia (CIN). In 1987, University of North Carolina (UNC) Hospitals Family Practice Center clinicians were approached for a control population to study this association. Methods: One hundred fives patients attending the UNC Hospitals Neoplasia Clinic with biopsy-proven CIN 2 or 3 and 268 control patients attending the UNC Family Practice Center for a routine Papanicolaou smear were enrolled in this case-control study. Case and control patients consented to having an additional cervical specimen taken and to being interviewed. The cervical specimens were classified by the Southern blot …