Preferred Health Information Sources: An Examination Of Vulnerable Middle-Aged And Older Women, Caroline D. Bergeron, Marcia Ory, Heather H. Goltz, Samuel D. Towne Jr, Sangnam Ahn, Nelda Mier, Matthew Lee Smith

Journal of Family Strengths

Background. Women are the greatest consumers of health information. Despite this fact, little is known about middle-aged and older women’s preferred sources for health information.

Objectives. This study aims to: (1) identify preferred sources of health-related information among middle-aged and older women; and (2) examine sociodemographics, family/household characteristics, health status, and health-related behaviors associated with their preferred sources for health information.

Methods. Data were collected from 3,946 middle-age and older women using a randomized multimodal survey of households in an eight-county region of Texas. Frequencies, Pearson’s chi-squares and one-way ANOVA were used to examine relationships to the respondent’s preferred sources …

Associations Among Meaning Of Illness, Quality Of Life, Symptom Burden And Depression In Patients With Leptomeningeal Metastasis, Julie Walker

Dissertations and Theses (Open Access)

Background Patients with leptomeningeal metastasis (LM) have symptoms related to disease within the neuroaxis, cancer sites outside the neuroaxis and treatment toxicities. Furthermore, the meaning ascribed to advanced cancer, such as LM, may impact the perceived severity, frequency and distress of symptoms as well as quality of life (QoL) and depression. Our aim was to explore and describe relationships among meaning of illness (MoI), depression, QoL and symptom burden in LM patients and to explore whether adding spine-related items from the MD Anderson Symptom Inventory-Spine (MDASI-SP) to the MDASI-Brain Tumor (BT) enhanced understanding of symptom burden in this population.

Methods …

Cyclin B1 Mediates The Effect Of Uchl1 In Promoting Cell Cycle Progression In Uterine Papillary Serous Carcinoma, Suet Ying Kwan

Dissertations and Theses (Open Access)

Uterine papillary serous carcinoma (UPSC) is an aggressive form of endometrial cancer with poor survival rates and a high risk of recurrence. The rarity of UPSC poses challenges to the discovery of novel targeted therapies. Therefore, the purpose of this dissertation was to identify novel therapeutic targets that could aid in the management of UPSC. To do so, we began with the relatively large cohort of UPSC cases in the TCGA data set, which was used to identify differentially expressed genes between UPSC and low-grade endometrioid endometrial carcinoma (EEC) and normal tissue.

We identified Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCHL1 …

Barriers To Expansion Of Supervision Networks At Genetic Counseling Training Programs, Jordan E. Berg

Dissertations and Theses (Open Access)

Job openings outpace new graduates due to exponential growth in genetic counseling, leading to a workforce shortage. Expanding training slots to meet this demand presumably is linked to the number of supervisors. Thus, there is a need to systematically review barriers to supervision. This study aimed to determine and compare barriers to expansion of supervision networks at genetic counseling training programs as perceived by current supervisors, non-supervisors, and Program Directors. Certified genetic counselors were recruited via National Society of Genetic Counselors e-blast with an invitation to complete an online survey; Program Directors were emailed personal letters of invitation. Twenty-three Program …

Clinical Applicability Of Proposed Algorithm For Identifying Individuals At Risk For Hereditary Hematologic Malignancies, Maggie Clifford

Dissertations and Theses (Open Access)

Over the past decade, more than 12 genes have been identified to cause hereditary predispositions to hematologic malignancies. These syndromes are characterized by an increased risk to develop myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), or aplastic anemia (AA) at young ages, with various phenotypic features including peripheral cytopenias, immune dysfunction and skeletal defects. In 2013, Churpek et al. proposed a referral algorithm which consists of certain criteria for identifying leukemia patients who may benefit from genetic assessment for these hereditary syndromes. These criteria assess personal history of cytopenias, skin or nail abnormalities, immune deficiencies/atypical infections, and other associated clinical …

Molecular Determinants Of Residual Disease In Ovarian Cancer, Kshipra M. Gharpure

Dissertations and Theses (Open Access)

The standard treatment for high grade serous ovarian cancer is primary cytoreductive surgery followed by adjuvant chemotherapy. Residual disease followed by surgery is associated with adverse overall and progression-free survival as well as poor response to adjuvant chemotherapy. Accurate identification of patients at high risk of residual disease will help avoid unnecessary surgeries and help in triaging these patients to neoadjuvant chemotherapy prior to interval surgical debulking. In this study, we address this clinical issue by identifying and validating molecular biomarkers that can predict the likelihood of residual disease in ovarian cancer patients. Using publically available databases and microarray datasets, …

Phopsphorylation And Ubiquitin Modification At Dna Damage Sites In Response To Double-Strand Breaks, Atanu Paul

Dissertations and Theses (Open Access)

Genomes of all organisms are continuously damaged by numerous exogenous and endogenous sources leading to different kinds of DNA lesions, which if not repaired efficiently may trigger wide-scale genomic instability, a hallmark of cancer development. To overcome this, cells have evolved a sophisticated sensory network called the DNA damage response (DDR) comprised of a large number of distinct protein complexes categorized as sensor, mediator, transducer and effector proteins that amplify the DNA damage signal and activate cell cycle checkpoint to initiate DNA repair or trigger apoptosis where the defect is beyond repair. This intricate signaling pathway is tightly regulated by …

The External Globus Pallidus: Bidirectional Control Over Anxiety-Related Behavior Mediated By Crfr1, Albert J. Hunt Jr

Dissertations and Theses (Open Access)

Abstract

THE EXTERNAL GLOBUS PALLIDUS: BIDIRECTIONAL CONTROL OVER ANXIETY-RELATED BEHAVIOR MEDIATED BY CRFR1

Albert Lee Joseph Hunt, Jr., B.S.

Advisory Professor: Shane Cunha, Ph.D.

Corticotropin-releasing factor receptor 1 (CRFR1), the principle receptor responsible for the anxiogenic activity of the stress peptide CRF, is abundantly expressed in the external globus pallidus (GPe) raising the question whether activity in the GPe is altered in response to stress. I show that CRFR1 expressing neurons are of the “prototypic” subtype of GPe neurons. I provide evidence of novel circuits from CRF neurons in stress-responsive nuclei, including the paraventricular nucleus of the hypothalamus (PVN) and …

Visualizing The Dynamics Of Immune Surveillance In Brain Tumors By Intravital Multiphoton Microscopy, Felix Nwajei

Dissertations and Theses (Open Access)

Visualizing the dynamics of immune surveillance in brain tumors by intravital multiphoton microscopy

By

Felix I. Nwajei, MD

Supervisory Professor: Tomasz Zal, Ph.D.

Brain tumors (BTs) generally have a bad prognosis despite conventional treatment strategies. Immunotherapy is a relatively novel treatment approach that has shown benefit for durable treatment of melanoma, and is a promising candidate for different tumor types including BTs. Immunotherapeutic strategies work by exploiting and/or enhancing natural anti-tumor immune response, a process that is critically dependent on adaptive immunity, T cell infiltration and surveillance of tumor. However, little is known about the dynamics and regulation of T …

Parp Inhibitor Upregulates Pd-L1 Expression And Enhances Cancer-Associated Immunosuppression, Shiping Jiao

Dissertations and Theses (Open Access)

With recent approvals for therapeutic antibodies that block CTLA4, PD-1 and PD-L1, immune checkpoints have emerged as new targets in cancer therapy. In addition, there is accumulating evidence highlighting the role of cancer-associated immunity in patient response to cytotoxic anticancer agents. Inhibitors of poly (ADP-ribose) polymerase (PARP) have shown substantial cytotoxic effects against tumors with defects in DNA damage responses. However, whether a crosstalk between PARP inhibition and immune checkpoints exists remains unclear. Here, it has been shown that PARP inhibitors (PARPis) upregulate PD-L1 expression in multiple cancer cell lines, human xenograft tumors, and syngeneic mouse tumors. Mechanistically, PARPi inactivates …

Effect Of Entinostat On Nk Cell-Mediated Cytotoxicity Against Os Cells And Os Lung Metastsis, Simin Kiany

Dissertations and Theses (Open Access)

The purpose of this study was to investigate the effect of the HDAC inhibitor entinostat on the efficacy of NK cell therapy for OS lung metastasis. The Lung is the most common site of OS metastatic spread in OS and pulmonary metastasis is the main cause of mortality. We have previously demonstrated that NK cell therapy has minimal efficacy against OS metastasis. We wished to determine whether we could augment the killing of OS cells in vitro and improve the efficacy of NK cell therapy in vivo by adding oral administration of entinostat. We elected to use our nude mouse …

The Hypoxic Adenosine Response Modulates Macrophage Differentiation And Contributes To Lung Disease, Kemly Mary Philip

Dissertations and Theses (Open Access)

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease which affects 5 - 8 million individuals worldwide and 200,000 individuals in the United States alone. Although prevalent, we do not know what causes IPF and no effective curative treatment exists for this disease. Our laboratory has shown that extracellular accumulation of adenosine and subsequent activation of the adenosine 2B (ADORA2B) receptor promotes immune cell invasion, airspace destruction, and fibrosis in chronic lung disease. Additionally, alternatively activated alveolar macrophages (AAMs) expressing ADORA2B, have been implicated in mediating adenosine’s pro-fibrotic effects in IPF. However, the exact role of AAMs in the hypoxic …

Role And Regulation Of Sphingosine 1-Phosphate In Erythrocyte, Kaiqi Sun

Dissertations and Theses (Open Access)

Sphingosine 1-phosphate (S1P) is a bioactive signaling sphingolipid produced in every mammalian cell. It plays a variety of important roles both in and outside of cells. S1P is highly enriched in mature erythrocytes because of the high enzymatic activity of the S1P-generating enzyme Sphingosine Kinase 1 (Sphk1) and the absence of S1P degrading enzymes. Erythrocytes are considered only a major reservoir for S1P because they supply S1P to the circulation for the regulation of various physiological processes which include but are not limited to immune cell trafficking, endothelial integrity and hematopoietic stem cell mobilization. However, if S1P plays a role …

Integrative Analysis Of Omics Data In Adult Glioma And Other Tcga Cancers To Guide Precision Medicine, Xin Hu, Xin Hu

Dissertations and Theses (Open Access)

Transcriptomic profiling and gene expression signatures have been widely applied as effective approaches for enhancing the molecular classification, diagnosis, prognosis or prediction of therapeutic response towards personalized therapy for cancer patients. Thanks to modern genome-wide profiling technology, scientists are able to build engines leveraging massive genomic variations and integrating with clinical data to identify “at risk” individuals for the sake of prevention, diagnosis and therapeutic interventions. In my graduate work for my Ph.D. thesis, I have investigated genomic sequencing data mining to comprehensively characterise molecular classifications and aberrant genomic events associated with clinical prognosis and treatment response, through applying high-dimensional …

Tumor-Cell Derived Inhibin, Beta A Is Essential For Adrenergic Effects On Fibroblast Activation, Archana Sidalaghatta Nagaraja

Dissertations and Theses (Open Access)

Objectives: Catecholamine-mediated effects driven by elevated adrenergic signaling are known to increase tumor growth and metastasis by direct effects on tumor cells. However, knowledge of effects of adrenergic signaling on other cells such as cancer-associated fibroblasts (CAFs) within the tumor microenvironment is limited. We hypothesize that adrenergic signaling and norepinephrine can accelerate the induction of CAF-phenotype to promote inflammation and metastasis.

Methods: Ingenuity Pathway Analysis and NetWalker were used to assess gene expression data from patients with known CESD (Center for Epidemiological Studies-Depression)-score alongside microdissected CAFs from primary ovarian cancer. Tumor samples from mice exposed to daily restraint-stress or non-stressed …

Statistical Methods For Two Problems In Cancer Research: Analysis Of Rna-Seq Data From Archival Samples And Characterization Of Onset Of Multiple Primary Cancers, Jialu Li

Dissertations and Theses (Open Access)

My dissertation is focused on quantitative methodology development and application for two important topics in translational and clinical cancer research.

The first topic was motivated by the challenge of applying transcriptome sequencing (RNA-seq) to formalin-fixation and paraffin-embedding (FFPE) tumor samples for reliable diagnostic development. We designed a biospecimen study to directly compare gene expression results from different protocols to prepare libraries for RNA-seq from human breast cancer tissues, with randomization to fresh-frozen (FF) or FFPE conditions. To comprehensively evaluate the FFPE RNA-seq data quality for expression profiling, we developed multiple computational methods for assessment, such as the uniformity and continuity …

The Role Of The Diras Family Members In Regulating Ras Function, Cancer Growth And Autophagy, Margie Nicole Sutton

Dissertations and Theses (Open Access)

DIRAS3 is a maternally imprinted tumor suppressor gene that is downregulated by multiple mechanisms across several tumor types. When re-expressed, DIRAS3 decreases proliferation, inhibits motility, and induces autophagy and tumor dormancy. DIRAS3 encodes a 26 kDa small GTPase with 60% homology to Ras and Rap, differing from oncogenic Ras family members by a 34-amino acid N-terminal extension that is required for its tumor suppressive function in ovarian cancer. By assessing the structure-function relationship, I found that DIRAS3 inhibits Ras-induced transformation and is a natural antagonist of Ras/MAPK signaling. DIRAS3 binds directly to Ras and disrupts cluster formation inhibiting the activation …

Androgen Receptor And Prostate Cancer Cell Heterogeneity, Qu Deng

Dissertations and Theses (Open Access)

Androgen receptor (AR) plays an important role in prostate cancer (PCa) development and has been the main therapeutic target in advanced PCa. AR expression is heterogeneous in both primary PCa and castration resistant prostate cancer (CRPC). However, the functional significance of AR heterogeneity in regulating PCa biology and response to androgen/AR-targeted therapies remains unclear. The overarching hypothesis for my Ph.D is that AR heterogeneity contributes to PCa development, progression, and therapy resistance. A more specific postulate is that PCa cells expressing AR (i.e, AR⁺) and PCa cells expressing little AR (i.e, AR^-/lo) possess intrinsically distinct …

Proteomic Identification Of Histone Post-Translational Modifications Induced By Dna Double-Strand Breaks And Novel Proteins Involved In The Dna Damage Response, Pingping Wang

Dissertations and Theses (Open Access)

Inaccurate repair of DNA double-strand breaks (DSBs) can lead to DNA mutation and chromosome rearrangements, causing human diseases such as cancer. Although we know the basic mechanisms of DSB repair, the added complexities in the chromatin context are unclear. This is partially due to the lack of unbiased systems for identifying proteins and post-translational modifications (PTMs) involved in DSB repair. In this work, we established a novel method, termed DSB-ChAP-MS (Double Strand Break-Chromatin Affinity Purification with Mass Spectrometry), for the affinity purification of a sequence-specific single copy endogenous chromosomal locus containing a DSB, followed by the proteomic identification of enriched …

Fret-Based Investigations Of The Structure-Function Relationships In The Nmda Receptor, Drew M. Dolino

Dissertations and Theses (Open Access)

The N-methyl-D-aspartate (NMDA) receptor is one member of a class of proteins known as the ionotropic glutamate receptors. Ionotropic glutamate receptors mediate the majority of excitatory neurotransmission in the central nervous system, with the NMDA receptor standing out among these receptors for its requirement of a co-agonist, its magnesium-block-based coincidence detection, its slow kinetics, its calcium permeability, its allosteric modulation, and its especially important functional roles in synaptic plasticity, excitotoxicity, and more. In recent years, a wealth of structural information has come about describing endpoint structures to high resolution, but such structures are unable to fully resolve the movements …

Characterization And Reversal Of Doxorubicin-Mediated Changes In Sensory Neurons, Brittany L. Coughlin

Dissertations and Theses (Open Access)

Chemotherapeutic agents impair memory in humans as well as in animal models. Such memory impairments can be persistent, lasting years after exposure to chemotherapy. Doxorubicin (DOX), a common chemotherapeutic agent, has been associated with memory impairments in humans and induces memory deficits in rodent models. DOX also impairs serotonin (5-HT)-induced long-term synaptic facilitation (LTF) in Aplysia sensorimotor co-cultures, a cellular analog of long-term memory formation. In addition, DOX leads to dynamic activation of extracellular signal-regulated kinase (ERK), consisting of an immediate and a delayed phase of activation, and to transient activation of p38 mitogen-activated protein kinase (p38 MAPK) in Aplysia …

Managing Variant Discrepancy In Hereditary Cancer: Clinical Practice, Barriers, And Desired Resources, Ellen Zirkelbach

Dissertations and Theses (Open Access)

Variants are changes in the DNA whose phenotypic effects may or may not be definitively understood. Because variant interpretation is a complex process, sources sometimes disagree on the classification of a variant, which is called a variant discrepancy. This study aimed to determine the practice of genetic counselors regarding variant discrepancies and to identify the barriers to counseling a variant discrepancy in hereditary cancer genetic testing. This investigation was unique because it was the first to address variant discrepancies from a clinical point of view. An electronic survey was sent to genetic counselors in the NSGC Cancer Special Interest Group. …

Evaluating The Impact Of Post-Translational Modifications By The Secreted Zinc Metalloprotease, Gele, On The Major Autolysin Of E. Faecalis, Atla, And A Stress-Induced Protein, Salb, Emily K. Stinemetz

Dissertations and Theses (Open Access)

AtlA is the major peptidoglycan hydrolase of E. faecalis involved in cell separation of dividing cells. SalB is a secreted stress-induced protein regulated by the CroRS system. In addition, these two proteins also appear to be affected by the virulence factor, gelatinase (GelE). GelE is a secreted zinc metalloprotease known to impact various cellular functions by post- translational modification of protein substrates. The overall objective of this work was to understand how GelE cleavage of secreted proteins, specifically AtlA and SalB, changes their function. Herein, I discovered that GelE modifies both AtlA and SalB. As visualized by Western blot analysis …

Genesurance Counseling: Patient Perspectives, Chelsea Wagner

Dissertations and Theses (Open Access)

Genetic counselors (GCs) have recently reported an increase in the discussion of insurance-related, or “genesurance,” topics during genetic counseling sessions. Despite increasing frequency, little knowledge exists about genesurance conversations and patient expectations. This study aimed to assess patient expectations of GCs in genesurance discussions and evaluate if health insurance literacy impacted these expectations. A 38-item survey, including a validated tool to assess health insurance literacy (HIL) was administered prior to patients receiving prenatal or cancer genetic counseling at three participating institutions. A total of 360 responses were analyzed. Key variables were compared using chi-square analysis and multivariable logistic regression was …

Mathematical Modeling Reveals That G2/M Checkpoint Override, Hui Ju Hsieh

Dissertations and Theses (Open Access)

Cell cycle checkpoints determine whether cells meet requirements to progress through the next stage. In response to DNA damage, how cells activate checkpoints have been well studied, but little is known about checkpoint deactivation (recovery), which directly impacts on cell fate. In tumor cells, the signaling network has been rewired due to epigenetic and genetic alterations, which result in resistance to the cell cycle control, and thus resistance to chemotherapy or radiation therapy. Therefore, it is critical to identify molecules required for checkpoint recovery or adaptation after DNA damage.

To achieve this goal, we performed a multidisciplinary study combining reverse …

On The Origin Of Sensory Errors, Jonathan R. Flynn

Dissertations and Theses (Open Access)

Estimation of perceptual variables is imprecise and prone to errors. Although the properties of these perceptual errors are well characterized, the physiological basis for these errors is unknown. One previously proposed explanation for these errors is the trial-by-trial variability of the responses of sensory neurons that encode the percept. Initially, it would seem that a complicated electrophysiological experiment would need to be performed to test this hypothesis. However, using a strong theoretical framework, I demonstrate that it is possible to determine statistical characteristics of the physiological mechanism responsible for perceptual errors solely from a behavioral experiment. The basis for this …

Attitudes To Ward And Uptake Of Prenatal Genetic Screening And Testing In Twin Pregnancies, Kathryn M. Reese

Dissertations and Theses (Open Access)

The rate of twinning is rising and is associated with delayed age at childbirth and increased infertility treatments. Since the introduction of non-invasive prenatal testing, interest in and uptake of genetic screening and testing in twin pregnancies has not been investigated. Therefore, this study aimed to describe the attitudes toward and uptake of current prenatal genetic screening and testing options in twin pregnancies. Forty-two women with twin gestations were recruited from UTHealth and Baylor College of Medicine sites between August 2016 and January 2017 for participation in a descriptive study consisting of a questionnaire (n=42) and semi-structured phone interview (n=15). …

Investigation Of The Roles Of Asf1 And Caf-1-Mediated Chromatin Assembly In The Human Dna Damage Response, Ting-Hsiang Huang

Dissertations and Theses (Open Access)

The access-repair-restore model for the role of chromatin in DNA repair infers that chromatin is a mere obstacle to DNA repair. However, here we show that blocking chromatin assembly of newly-synthesized histones, via knockdown of the histone chaperones ASF1A, CAF-1 or a mutation that specifically prevents ASF1 binding to histones, hinders loading of Rad51 onto ssDNA during homologous recombination, as a consequence of reduced recruitment of the Rad51 loader MMS22L/TONSL to ssDNA, resulting in persistent RPA foci, extensive DNA end-resection, and persistent activation of the ATR-Chk1 pathway. By contrast, ASF1 and CAF-1 render the rapid inactivation of ATM Chk2 pathway …

Developing Novel Approaches To Improve Response To T Cell Based Cancer Immunotherapy, Rina M. Mbofung

Dissertations and Theses (Open Access)

Recently, T cell based immunotherapies have moved to the forefront of cancer immunotherapy with the success of Adoptive T cell therapy (ACT) and Immune checkpoint blockade.ACT, where patients are treated with tumour infiltrating T cells (TILs), conferred a clinical response rate of ~50%. Treatment with anti-CTLA4 and anti –PD1 therapy, conferred response rates of up to 50%, greatly improving the overall survival of patients with advanced melanoma amongst other cancer types. Despite the encouraging outcomes, there are relatively low response rates coupled with the delay of weeks to months before tumour shrinkage can be appreciated. Thus, understanding what tumour intrinsic …

The Utilization Of Prenatal Microarray: A Survey Of Current Genetic Counseling Practices And Barriers, Leslie N. Durham, Leslie Durham

Dissertations and Theses (Open Access)

Chromosomal microarray (CMA) assesses chromosome copy number variants (CNVs) missed by standard karyotyping. The American College of Obstetricians and Gynecologists (ACOG) recommends CMA for all patients with fetuses with an ultrasound anomaly and suggests that it be made available to all women undergoing invasive testing. In order to assess prenatal genetic counselors’ (GCs) practices regarding the utilization of CMA we conducted a survey of their current practices, attitudes, and perceived barriers. Of the 192 respondents, 183 (95%) have incorporated CMA into clinical practice with the majority (64%) believing that the benefits of CMA outweigh the harms. However, only half (52%) …