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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 …

Piloting A Spanish-Language Web-Based Tool For Hereditary Cancer Genetic Testing, Gretter Manso

USF Tampa Graduate Theses and Dissertations

Cancer genetic services (including genetic counseling and testing) help identify patients and families at increased risk of developing cancer so that steps can be taken to reduce risks or find cancers early. Receipt of genetic services in the Hispanic/Latinx population is low due, in part, to a shortage of Spanish-speaking genetic counselors. To address this concern, a 12-minute online tool designed to inform individuals about cancer genetic services was translated into Spanish. The objectives of this pilot study were to determine if the educational tool improves knowledge and informed decision making and to assess usability and appropriateness of the tool …

Host-Pathogen Coevolution Between Tasmanian Devils (Sarcophilus Harrisii) And Devil Facial Tumor Disease, Dylan Garret Gallinson

USF Tampa Graduate Theses and Dissertations

Coevolution is a driving force of rapid evolution, yet the complexity of coevolutionary interactions has made it difficult to characterize the genomic basis of traits mediating such relationships. Coevolutionary dynamics are especially important in host-pathogen systems where the host and pathogen must constantly adapt to one another. The Tasmanian devil and its species-specific transmissible cancer, devil facial tumor disease (DFTD), provide the rare opportunity to study host-pathogen coevolution in a complex natural system. Extensive spatiotemporal devil sampling, high linkage disequilibrium in devils, and a large selective pressure imposed by DFTD facilitate a system tractable for study. Here, we characterized devil …

Evolution Of Targeted Therapy Resistance In Eml4-Alk Positive Non-Small Cell Lung Cancer, Robert Vander Velde

USF Tampa Graduate Theses and Dissertations

Targeted therapies have emerged as potent treatments that lead to the remission of many tumors. However, they rarely cure cancers in advanced, metastatic settings. This is due to the evolution of resistance, which in turn can be ascribed to the survival of small subpopulations of tolerant and/or resistant cells. Here we investigated the evolution of resistance to EML4-ALK inhibitors in non-small cell lung cancer (NSCLC) and demonstrated that resistance evolves gradually, from unique pre-treatment sub-populations, as multiple resistance mechanisms accumulate in a Darwinian fashion. Despite accumulating multiple changes, cells evolved, in parallel, toward similar inhibitor specific phenotypes. Evolving cells have …

“They Will Think We Are The Cancer Family”: Studying Patterns Of Cancer Disclosure And Communication Among Indian Immigrants In The United States, Kanan Mehta

USF Tampa Graduate Theses and Dissertations

Studies of Indian immigrants in Western countries show that the rates of cancer increase significantly within a generation in the host country. The negative social perceptions associated with health outcomes of cancer often perpetuate limited disclosure regarding the diagnosis of cancer among patients and families. This can result in disrupted communication in clinical settings, while causing increased stress among patients and caregivers. These findings demonstrate the need for studying lived experiences of cancer-related illness and its impacts on social relationships in the domestic and public sphere.

This study explored cancer disclosure and communication among Indian immigrants in the United States …

Contribution Of Sleep Disruption And Physical Inactivity To Fatigue In Survivors Of Allogeneic Hematopoietic Cell Transplant, Ashley M. Nelson

USF Tampa Graduate Theses and Dissertations

Background: Fatigue is a prominent quality of life concern among cancer patients who have undergone allogeneic hematopoietic cell transplantation (HCT). The high percentage of HCT patients reporting fatigue concerns warrants investigation into factors that may contribute to or alleviate fatigue. The present study sought to elucidate relationships among fatigue and behavioral factors including sleep disruption and sedentary activity.

Method: Allogeneic HCT recipients who were one to five years post-transplant were invited to participate in the present study. Participants wore an actigraph assessing sleep efficiency and sedentary behavior for one week, completed daily assessments of fatigue and sleep during the same …

The Moderating Effect Of Religion On Death Distress And Quality Of Life Between Christian Cancer Patients In The United States With Muslim Cancer Patients In Saudi Arabia, Doaa Almostadi

USF Tampa Graduate Theses and Dissertations

Cancer is an illness that knows no international boundaries. There are more than eight million global cancer deaths each year. A life-threatening diagnosis generates significant emotional problems for many patients across cultures. Death distress—consisting of death depression, death anxiety and death obsession—often results in poorer treatment adherence and lower overall health and quality of life. The purpose of this study was to determine whether religiosity has a moderating effect on the relationship between death distress and quality of life among patients facing a life-threatening cancer diagnosis.

The study sample consisted of 118 cancer patients: 82 cancer patients from a National …

Sleep Disruption Among Cancer Patients Following Autologous Hematopoietic Stem Cell Transplantation, Ashley M. Nelson

USF Tampa Graduate Theses and Dissertations

Background: Sleep disruption is one of the most commonly reported quality of life concerns among cancer patients who have undergone hematopoietic stem cell transplantation (HSCT). Despite the high percentage of patients reporting sleep concerns, relatively little research has characterized sleep problems or explored relationships with psychological factors. In addition, no studies have used actigraph technology to characterize sleep issues among transplant recipients.

Method: Autologous HSCT recipients who were 6 to 18 months post-transplant were invited to participate. Patients completed self-report measures of cancer-related distress, fear of cancer recurrence, dysfunctional cognitions about sleep, and maladaptive sleep behaviors upon enrollment, wore an …

Cell Cycle Arrest By Tgfß1 Is Dependent On The Inhibition Of Cmg Helicase Assembly And Activation, Brook Samuel Nepon-Sixt

USF Tampa Graduate Theses and Dissertations

Tumorigenesis is a multifaceted set of events consisting of the deregulation of several cell-autonomous and tissue microenvironmental processes that ultimately leads to the acquisition of malignant disease. Transforming growth factor beta (TGFß) and its family members are regulatory cytokines that function to ensure proper organismal development and the maintenance of homeostasis by controlling cellular differentiation, proliferation, adhesion, and survival, as well as by modulating components of the cellular microenvironment and immune system. The pleiotropic control by TGFß of these cell intrinsic and extrinsic factors is intimately linked to the prevention of tumor formation, the specifics of which are dependent on …

A Trans-Dimensional View Of Drug Resistance Evolution In Multiple Myeloma Patients, Timothy Jacobson

USF Tampa Graduate Theses and Dissertations

Multiple Myeloma (MM) is a treatable, yet incurable, malignancy of bone marrowplasma cells. This cancer affects many patients and many succumb to relapse of tumor burden despite a large number of available chemotherapeutic agents developed for therapy. This is because MM tumors are heterogeneous and receive protection from therapeutic agents by the microenvironment and other mechanisms including homologous MM-MM aggregation. Therefore, therapy failure and frequent patient relapse is due to the evolution of drug resistance, not a lack of available drugs. To analyze and understand this problem, the evolution of drug resistance has been explored and presented herein. We seek …

Genomic Aberrations At The 3q And 14q Loci: Investigation Of Key Players In Ovarian And Renal Cancer Biology, Punashi Dutta

USF Tampa Graduate Theses and Dissertations

Genomic aberrations are primary contributors to the pathophysiology of cancer [11]. Dysregulated expression of genes located within these aberrations are important predictors of chemoresistance, disease prognosis, and patient outcome [12]. This dissertation is focused on understanding the regulation and/or functions of specific genes located at dysregulated genomic regions such as 3q26 and 14q32 in the biology of ovarian and renal cancer, respectively.

Serous epithelial ovarian cancer (EOC) manifest amplification at the 3q26.2 locus [2], an observation consistent with the cancer genome atlas (TCGA) [13]. The most amplified gene in this region is EVI1 which has been extensively studied in hematological …

Framing Colombian Women's Beliefs, Values And Attitude Towards Sex And Sexual High-Risk Behaviors, Rosa Ore

USF Tampa Graduate Theses and Dissertations

Hispanic immigrants constitute the largest and fastest growing groups of minorities in the United States. According to the 2010 Census, there are 50.5 million Hispanics in the United States, making up 16.3% of the total population (Passel, Cohn & Lopez, 2011). Furthermore, the state of Florida is home to 4,223,806 Hispanics (U.S. Census Bureau, 2010). Because the Hispanic population continues to grow, it is important to study their sexual health behaviors because diseases linked to risky sexual behaviors account for approximately 20,000 U.S. deaths each year, and are linked to a number of adverse reproductive outcomes (Abraido-Lanza, Chao, & Florez, …

Computational Approaches For Structure Based Drug Design And Protein Structure-Function Prediction, Sai Lakshmana Kumar Vankayala

USF Tampa Graduate Theses and Dissertations

This dissertation thesis consists of a series of chapters that are interwoven by solving interesting biological problems, employing various computational methodologies. These techniques provide meaningful physical insights to promote the scientific fields of interest. Focus of chapter 1 concerns, the importance of computational tools like docking studies in advancing structure based drug design processes. This chapter also addresses the prime concerns like scoring functions, sampling algorithms and flexible docking studies that hamper the docking successes. Information about the different kinds of flexible dockings in terms of accuracy, time limitations and success studies are presented. Later the importance of Induced fit …

Virtual Screening For Inhibitors Of Anti-Apoptotic Proteins: Dck, Bcl-Xl, Mcl-1, Mdmx, And Mdm2, Courtney Jerome Du Boulay

USF Tampa Graduate Theses and Dissertations

←Within this dissertation the topic of virtual screening is discussed with regard to three different cancer targets and also a brief introduction of the tools used in virtual screening. In Chapter 1, the reader will be introduced to virtual screening and the programs that are used in virtual screening. In Chapter 2, the first of three projects are discussed. This project consists of the work that was done to find inhibitors of the P53 binding domain of MDMX. In this project the mobility of residues within the binding site of MDMX are discussed and the ways in which we attempted …

Factors Associated With Fear Of Breast Cancer Recurrence Among Survivors, Jean Marie Lucas

USF Tampa Graduate Theses and Dissertations

The purpose of this cross-sectional, secondary data analysis was to explore, non-modifiable (stable) trait factors and modifiable (transient) state factors associated with fear of recurrence (FOR) in breast cancer survivors. Antecedent trait factors included demographic, clinical, social/behavioral factors, postulated mediator state factors included pain, fatigue, sleep disturbances, depression, state anxiety and perceived stress, and FOR was the outcome variable. The study used baseline data from an R-21 NCI funded (grant #R21CA109168) randomized control trial that examined the effects of mindfulness based stress reduction in early stage breast cancer recovery. Instruments from this study for antecedent variables (trait factors) included a …

The Relationship Between Death Depression And Death Anxiety Among Cancer Patients In Saudi Arabia, Doaa A. Almostadi

USF Tampa Graduate Theses and Dissertations

Abstract

Cancer is one of the main public health problems in the world. People diagnosed with cancer may become depressed and fearful of dying. This causes them to question treatments and sometimes avoid treatment altogether. Cancer may change the person's life and the lives of others around them. The current study focused on the psychosocial impact of impending death for cancer patients in Saudi Arabia. Currently, the relationship between the death anxiety and death depression in persons with cancer in Saudi Arabia is not yet clear. Added to that, little research has been conducted with Muslim cancer patients and their …

Matrix Metalloproteinase Genes Are Transcriptionally Regulated By E2f Transcription Factors: A Link Between Cell Cycle Control And Metastatic Progression, Jacqueline Lea Johnson

USF Tampa Graduate Theses and Dissertations

The RbµE2F transcriptional regulatory pathway plays a critical role in the cell cycle. Rb is inactivated through multiple waves of phosphorylation, mediated mainly by cyclin D and cyclin E associated kinases. Once Rb is inactivated, cells can enter Sµphase. Collectively, three Rb family members and ten E2F proteins coordinate every additional stage of the cell cycle, from quiescence to mitosis. However the RbµE2F pathway is frequently altered in cancer. Aside from cell proliferation, the RbµE2F pathway regulates other essential cellular processes including apoptosis, cell differentiation, angiogenesis and DNA damage repair pathways, but its role in invasion and cancer progression is …

The Role Of Tumor Suppressors, Ship And Rb, In Immune Suppressive Cells, Michelle Marie Collazo Ruiz

USF Tampa Graduate Theses and Dissertations

Regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC) have been extensively studied in the past 30-40 years. Their potent suppressive capacity shown in several pathological and clinical settings, such as cancer and transplantation, has made it evident that better understanding their development and function is critical.

Specifically, Tregs play a pivotal role in preventing autoimmunity, graft-versus-host disease (GvHD), and organ graft rejection. We previously demonstrated that germline or induced SH2 domain-containing inositol 5-phosphatase (SHIP) deficiency in the host abrogates GvHD. Here we show that SHIP-deficiency promotes an increase of FoxP3+ cells in both the CD4+CD25+ and the CD4+CD25- T …

Identification Of Novel Stat3 Target Genes Associated With Oncogenesis, Rachel Haviland

USF Tampa Graduate Theses and Dissertations

Cytokine and growth factor signaling pathways involving STAT3 are frequently constitutively activated in many human primary tumors, and are known for the transcriptional role they play in controlling cell growth and cell cycle progression. However, the extent of STAT3's reach on transcriptional control of the genome as a whole remains an important question. We predicted that this persistent STAT3 signaling affects a wide variety of cellular functions, many of which still remain to be characterized.

We took a broad approach to identify novel STAT3 regulated genes by examining changes in the genome-wide gene expression profile by microarray, using cells expressing …

A Study Of Complex Systems: From Magnetic To Biological, Douglas Carroll Lovelady

USF Tampa Graduate Theses and Dissertations

This work is a study of complex many-body systems with non-trivial interactions. Many such systems can be described with models that are much simpler than the real thing but which can still give good insight into the behavior of realistic systems. We take a look at two such systems. The first part looks at a model that elucidates the variety of magnetic phases observed in rare-earth heterostructures at low temperatures: the six-state clock model. We use an ANNNI-like model Hamiltonian that has a three dimensional parameter space and yields two-dimensional multiphase regions in this space. A low-temperature expansion of the …

A Comparative Study Of Knowledge Of Pain Management In Certified And Non-Certified Oncology Nurses, Sherrie A. Lalande

USF Tampa Graduate Theses and Dissertations

Over 1.4 million people are diagnosed with cancer annually. Of those people, 70-90% experience some form of pain. Numerous efforts have been made to educate nurses in the management of pain, yet 30-50% of cancer patients report that their pain is poorly managed. It is not clear whether nurses who obtain certification in Oncology are better equipped to manage this patient population regarding their pain issues. This study compared the knowledge of Oncology Certified Nurses (OCN) and Non-Certified Oncology Nurses (NCON) regarding pain management.

The sample of 41 oncology nurses included 19 who were certified in oncology and 22 who …

Fatigue Symptom Distress And Its Relationship With Quality Of Life In Adult Stem Cell Transplant Survivors, Suzan Fouad Abduljawad R.N., B.S.N.

USF Tampa Graduate Theses and Dissertations

Fatigue is a common problem among cancer patients, especially those who have received chemotherapy and radiation therapy. Stem cell transplant (SCT) patients are at a particular risk of persistent fatigue as they receive more aggressive therapies. This study examined the prevalence of fatigue after completion of SCT. Further, the level of fatigue symptom distress and its relationship with quality of life (QOL) among long term SCT survivors was examined.

The study involved thirty-three patients, 21 males and 12 females, treated with autologous or allogeneic SCT in a comprehensive cancer center in Southwest Florida. Participants' ages ranged from 36 to 70 …

Development And Psychometric Evaluation Of The Chemotherapy Induced Peripheral Neuropathy Assessment Tool, Cindy S. Tofthagen

USF Tampa Graduate Theses and Dissertations

Chemotherapy induced peripheral neuropathy (CIPN) is a common side effect of several chemotherapy drugs used for the treatment of many common malignancies. CIPN is both under-assessed and underreported and few self-report tools exist that measure CIPN. Existing instruments do not evaluate all of the multi-dimensional characteristics of neuropathic symptoms; intensity, distress, timing, and characteristics. The purpose of this descriptive, cross-sectional study was to develop and psychometrically evaluate a new self - report tool for CIPN, the Chemotherapy Induced Peripheral Neuropathy Assessment Tool (CIPNAT). Interviews with 15 patients with known CIPN guided development of the CIPNAT.

The CIPNAT is a 69 …

Evaluation Of The Public Health Risks Associated With Former Manufactured Gas Plants, Robin Brewer Dehate

USF Tampa Graduate Theses and Dissertations

Regulatory agencies have recently focused on assessing the potential for soil vapor intrusion (SVI) and risk posed to occupants of residential and commercial properties overlying and surrounding former Manufactured Gas Plants (MGPs). This study evaluated the potential for SVI at 10 commercial buildings and 26 single family and multi-family residential properties overlying and/or adjacent to three former MGPs. The potential for SVI exposure was categorized into three groupings according to thickness of the vadose zones: no vadose zone; 0 - 6 feet thick, and 6 to 25 feet thick. Indoor and outdoor air and soil vapor samples were collected and …

Regulation Of Bax Activation And Apoptosis By Src And Acetylated Mutant P53, Nicholas Taylor Woods

USF Tampa Graduate Theses and Dissertations

Apoptosis is an inherent suicide mechanism that cells invoke for a variety of reasons including embryo cavitation, tissue homeostasis, excessive DNA damage and aberrant oncogene activation. Apoptosis is regulated by a diverse set of proteins including, but not limited to, the Bcl-2 family. This family set is comprised of both pro-death and pro-survival proteins whose relative expression, localization and/or modifications regulate the balance between life and death for each cell. The keystones to this system are the proapoptotic proteins Bax and Bak, which are regulated by their conformation and localization. However, the exact mechanisms by which Bax and Bak become …

Benzene Related Hematological Disorders: Evidence For A Threshold In Animals And Humans, James Mccluskey

USF Tampa Graduate Theses and Dissertations

Significant benzene exposure has historically been associated with the development of a host of hematological disorders in humans and animals. In particular, benzene is known to cause disturbances of the peripheral blood, aplastic anemia and cancer of the lymphohematopoietic system. In 1928, the first modern report of an association between cancer and benzene exposure was published. This case report was followed by additional reports from around the world. In most instances, ailments resulted from long term, high level exposure to benzene found in glues, and through accidental industrial spills. Throughout the 1960's and 1970's, case reports accumulated linking benzene exposure …

Molecular Mechanism Of Aurora-A Kinase In Human Oncogenesis, Lili He

USF Tampa Graduate Theses and Dissertations

Aurora-A is a mitotic kinase, which regulates cell cycle progression through modulating centrosome function. Aurora-A expression is frequently altered in human malignancies. The discrepancy between overexpression and amplification suggests that elevated Aurora-A level is likely to be regulated also by transcriptional and/or translational modifications. In this study, we have demonstrated: 1) transcriptional regulation of Aurora-A by E2F3; 2) feedback regulation between tumor suppressor CHFR and Aurora-A; 3) CNTD2 as a novel Aurora-A partner and oncogene to activate Aurora-A and induce transformation.

Aurora-A expression and activity are cell cycle regulated. The mechanism of Aurora-A upregulation at onset of mitosis is largely …

Rb-Raf-1 Interaction As A Therapeutic Target For Proliferative Disorders, Rebecca Kinkade

USF Tampa Graduate Theses and Dissertations

The retinoblastoma tumor suppressor protein, Rb, is a key regulator of the mammalian cell cycle and its inactivation facilitates S-phase entry. Rb is inactivated through multiple waves of phosphorylation, mediated mainly by kinases associated with D and E type cyclins in the G1 phase of the cell cycle. Our earlier studies had shown that the signaling kinase Raf-1 (c-Raf) physically interacts with Rb upon growth factor stimulation and initiates the phosphorylation cascade. We had shown that an 8 amino acid peptide derived from Raf-1 could disrupt the Rb-Raf-1 interaction leading to an inhibition of Rb phosphorylation, cell proliferation and tumor …

Risk Reduction Decision Making In Women With Brca1/2 Gene Mutations, Heidi M. King

USF Tampa Graduate Theses and Dissertations

With technological advances in testing for gene mutations, a new population of BRCA1/2 women is becoming aware of their increased risk for developing breast and/or ovarian cancer. A salient issue these women face is which risk-reducing option to choose. Little is known about the decision making factors underlying the choice of prophylactic mastectomy for women with a BRCA1/2 mutation. To address this issue, 137 unaffected, positive BRCA1/2 gene mutation carriers (42 who opted for prophylactic mastectomy, 95 who did not) served as participants. All women completed an on-line battery that assessed the following theory-based decision making variables: advantages and disadvantages …

Relationship Between Nurses' Management Of Pediatric Oncology Patients' Symptoms And Job Satisfaction, Jennifer I. Rheingans

USF Tampa Graduate Theses and Dissertations

A primary function of the pediatric oncology nurse is to provide symptom management to children with cancer. Symptom management strategies have been published, but there is scarce literature examining neither the actual use of these nursing interventions, nor the effects of using these interventions on the nurses' perceived work environment. The purpose of this study was to examine the nursing interventions used in treating pediatric oncology patients' symptoms, as well as the emotional sequelae from providing this care. Phase One of this study examined the content validity of the newly developed Nurses Distress and Interventions for Symptoms Survey (NDISS) utilizing …