Digital Commons Network^™

Ube4b Levels Determine The Efficacy Of Egfr And Stat5 Inhibitors In Treatment Resistant Neuroblastoma, David James Savage

Dissertations and Theses (Open Access)

Neuroblastoma is the most common malignancy in infants. Overexpression of the epidermal growth factor receptor (EGFR) in neuroblastoma tumors can result in enhanced EGFR signaling, uncontrolled proliferation, and may provide a mechanism for chemotherapy resistance. UBE4B, an E3/E4 ubiquitin ligase, ubiquitinates the EGFR and promotes its lysosomal degradation ultimately attenuating EGFR signaling. Interestingly, the UBE4B gene lies in a chromosomal region (1p36) whose loss is correlated with poor patient outcomes due to inefficient EGFR degradation and enhanced cell proliferation. We examined whether depletion of UBE4B in a chemoresistant neuroblastoma cell line would affect tumor responses to drugs that specifically target …

Auto-Delineation Of Oropharyngeal Clinical Target Volumes Using Deep Learning Techniques, Carlos Eduardo Cardenas

Dissertations and Theses (Open Access)

Head and neck intensity modulate radiation therapy allows for the delivery of high-precision radiotherapy by conforming radiation dose to the defined treatment targets achieving more accurate target dose distribution and better sparing of normal tissues. However, producing very precise treatment plans may be ineffective if the target volumes are not defined accurately. Furthermore, there are several reports of significant inter-observer variability when delineating these target volumes for head and neck cancers making this variability one of the largest sources of uncertainty in head and neck radiation therapy.

The purpose of this study was to develop algorithms to automate target delineation …

Microrna Functions In Uv-Induced Cutaneous Squamous Cell Carcinoma, Tran Nguyen

Dissertations and Theses (Open Access)

Cutaneous squamous cell carcinoma (cuSCC) is the second most common skin cancer, for which long term UV exposure and chronic wounding are the dominant risk factors. Despite these clinically established connections, little is understood about the early molecular response of human skin to UV exposure and its connection to acute wounding and cuSCC. Thus, our goal is to find common and specific signatures driven by UV-exposure and wounding as a means of developing new approaches for treating and preventing cuSCC.

Here, we perform integrated analyses of RNA-seq and miR-seq on 3 datasets: (1) UV-unexposed and acute UV-exposed human skin, (2) …

Genomic And Transcriptomic Landscape Of Colorectal Premalignancy, Kyle Chang

Dissertations and Theses (Open Access)

Colorectal cancer (CRC) is the third most commonly diagnosed cancer among men and women in the United States, with 3 to 5 percent of the cases diagnosed in the background of a hereditary form of the disease. Biologically, CRC is divided into two groups: microsatellite instable (MSI) and chromosomally unstable (CIN). Genomic and transcriptomic characterization of CRC has emerged from large-scale studies in recent years due to the advancement of next-generation sequencing technologies. These studies have identified key genes and pathways altered in CRC and provided insights to the discovery of therapeutic targets. Despite the wealth of knowledge acquired in …

Enhancing Radiation Sensitivity In Non-Small Cell Lung Cancer, Yifan Wang

Dissertations and Theses (Open Access)

Lung cancer is the leading cause of cancer-related death. While radiation therapy is one of the standard treatments for lung cancer, the disease outcome after radiotherapy is still far from satisfactory despite ongoing advances in radiation techniques. Enhancing the radiosensitivity of lung cancer has the potential to improve the disease outcome of radiation treatments. Using a novel high throughput radiation sensitizing screen, previous work in the lab has identified several potent radiation sensitizers. The focus of my dissertation is on two of the identified pathways, HSP90 and MEK, using the potent and clinically relevant inhibitors ganetespib and trametinib. Using both …

Mir-484 Functions As An Onco-Mir In Triple Negative Breast Cancer, Nashwa Kabil

Dissertations and Theses (Open Access)

Triple negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer (BC), with a poor prognosis with currently used therapies, and thus represents an unmet therapeutic challenge. Lack of molecular targets (i.e. ER, PR, HER2) and significant genetic heterogeneity are the major reasons contributing to early relapse and high mortality rates. Numerous studies have indicated that microRNAs (miRs) have an important role in BC progression, invasion, angiogenesis, and metastasis. We analyzed miRNA expression profiles of BC patient data bases and identified that miR-484 is highly upregulated in all subtypes of BC patients, with the highest expression in TNBC …

Design, Fabrication, And Validation Of 3d Printed, Patient-Specific Compensators For Postmastectomy Radiation Therapy, Daniel Craft

Dissertations and Theses (Open Access)

The purpose of this study was to use 3D printed, patient-specific tissue compensators to overcome the 3D planning limitations for postmastectomy radiation therapy (PMRT). Tissue compensators can be used to reduce dose heterogeneity, hot and cold spots at field junctions, and treatment complexity, but are currently seldom used due to the difficulty in designing, fabricating, and validating them.

To produce compensators using 3D printing technology, suitable materials had to be found and characterized. Several materials were found to be promising, but previously unreported material uncertainties were also discovered that must be carefully controlled for in 3D printing studies. A new …

Omics Approaches To Uncover Germline And Somatic Variation Underlying Inherited Sarcomagenesis, Justin Wong

Dissertations and Theses (Open Access)

Sarcomas are rare mesenchymal tumors, making up 15% of all childhood and 1% of all adult tumors. They account for a disproportionate share of mortality in young adults, and if left untreated, are highly likely to metastasize. However, sarcoma etiology is poorly understood, and having numerous histological subtypes has complicated elucidation. To better understand factors underlying sarcomagenesis, we leveraged two rare inherited cancer predisposition syndromes, Li-Fraumeni Syndrome (LFS), and LFS-like (LFSL), both with a high incidence of sarcomas. LFS is caused by mutations in the tumor suppressor gene TP53 (p53), but has variable and incomplete penetrance, suggesting additional acquired …

Meta-Analysis Of The Incidence And Patterns Of Second Neoplasms After Photon Craniospinal Irradiation In Children With Medulloblastoma, Abhishek Bavle, Sayani Tewari, Amy Sisson, Murali Chintagumpala, Michael Anderson, Arnold C Paulino

Library Staff Publications

BACKGROUND: Second neoplasms (SNs) are a well-established long-term adverse effect of radiation therapy (RT), but there are limited data regarding their incidence and location relative to the radiation field, specific to medulloblastoma (MB) survivors after craniospinal irradiation (CSI).

METHODS: A systematic literature review, per Preferred Reporting Items for Systematic Reviews and Meta-Analyses, identified six studies reporting the incidence and locations of SNs for 1,114 patients with MB, after CSI, with a median follow-up of ∼9 years (7.6-15.4 years). The study-specific cumulative incidence (CI) of SNs, second benign neoplasms (SBNs), and second malignant neoplasms (SMNs) were standardized to a 10-year time …

High-Risk Cardiovascular Conditions In Sports-Related Sudden Death: Prevalence In 5,169 Schoolchildren Screened Via Cardiac Magnetic Resonance, Paolo Angelini, Benjamin Y Cheong, Veronica V Lenge De Rosen, Alberto Lopez, Carlo Uribe, Anthony H Masso, Syed W Ali, Barry R Davis, Raja Muthupillai, James T Willerson

The Texas Heart Institute Journal

Improving preparticipation screening of candidates for sports necessitates establishing the prevalence of high-risk cardiovascular conditions (hr-CVC) that predispose young people to sudden cardiac death (SCD). Our accurate, novel protocol chiefly involved the use of cardiac magnetic resonance (CMR) to estimate this prevalence.

Middle and high school students from a general United States population were screened by means of questionnaires, resting electrocardiograms, and CMR to determine the prevalence of 3 types of hr-CVC: electrocardiographic abnormalities, cardiomyopathies, and anomalous coronary artery origin from the opposite sinus with intramural coronary course (ACAOS-IM). We examined the range of normal left ventricular size and function …

Genetic Testing In Cardiovascular Medicine, Ali J Marian

The Texas Heart Institute Journal

No abstract provided.

Characterization Of Metronidazole- And Vancomycin-Resistant Clinical Isolates Of Clostridium Difficile, Chioma Odo

Dissertations and Theses (Open Access)

Characterization of Metronidazole- and Vancomycin-Resistant Clinical Isolates of Clostridium difficile

Chioma Odo, MS.

Supervisory Professor: Charles Darkoh, Ph.D.

ABSTRACT

The incidence of C. difficile infections (CDI) has been increasing at an alarming rate. This was precipitated by the emergence of strains with increased virulence, disease severity, and high recurrence rates. These strains also exhibit high propensity for resistance to antibiotics such as fluoroquinolones and beta lactams, which has made the treatment of CDI very challenging. Currently, metronidazole and vancomycin are the most commonly used drugs for the treatment of primary CDI. Metronidazole is used for the treatment of mild to …

Critical Issues: Defining And Debunking Misconceptions In Health, Education, Criminal Justice, And Social Work/Social Services, Leigh G. Van Horn Dr., Nina Barbieri, Ronald Beebe, Heather H. Goltz, Bernardo E. Pohl Jr, Rebecca Pfeffer Ph.D., Jace Valcore

Journal of Family Strengths

The University of Houston Downtown Committee for the Journal of Family Strengths introduces Volume 18, Issue 1: Critical Issues: Defining and Debunking Misconceptions in Health, Education, Criminal Justice, and Social Work/Social Services.

Stranger Danger: A Mother's Perspective, Priscilla Salas

Journal of Family Strengths

Priscilla Salas gives a mother's perspective on the stranger danger misconception.

Book Review: The Importance Of Being Little: What Young Children Really Need From Grownups, Caroloyn Wade

Journal of Family Strengths

The Importance of Being Little: What Young Children Really Need from Grownups, by Erika Christakis. New York, NY: Penguin, 2016. 376 pp., $15.59 (hardcover).

Precision Oncology Decision Support: Current Approaches And Strategies For The Future, Katherine C Kurnit, Ecaterina E Ileana Dumbrava, Beate Litzenburger, Yekaterina B Khotskaya, Amber M Johnson, Timothy A Yap, Jordi Rodon, Jia Zeng, Md Abu Shufean, Ann M Bailey, Nora S Sánchez, Vijaykumar Holla, John Mendelsohn, Kenna Mills Shaw, Elmer V Bernstam, Gordon B Mills, Funda Meric-Bernstam

Faculty, Staff and Student Publications

With the increasing availability of genomics, routine analysis of advanced cancers is now feasible. Treatment selection is frequently guided by the molecular characteristics of a patient's tumor, and an increasing number of trials are genomically selected. Furthermore, multiple studies have demonstrated the benefit of therapies that are chosen based upon the molecular profile of a tumor. However, the rapid evolution of genomic testing platforms and emergence of new technologies make interpreting molecular testing reports more challenging. More sophisticated precision oncology decision support services are essential. This review outlines existing tools available for health care providers and precision oncology teams and …

Ms 098 Guide To John T. Armstrong, Md Papers (1914-1987), John T. Armstrong (1912-1999)

Manuscript Finding Aids

The John T. Armstrong, MD papers contains professional correspondence, personal correspondence, family papers, institutional documents, institutional publications, research, medical data, memos, minutes, newspaper clippings, legal documents, insurance documentation, and professional diaries that document the career and life of Dr. John T. Armstrong. See more at MS 098.

Obstructive Sleep Apnea In Heart Failure: Review Of Prevalence, Treatment With Continuous Positive Airway Pressure, And Prognosis, Himad K Khattak, Faisal Hayat, Salpy V Pamboukian, Harvey S Hahn, Brian P Schwartz, Phyllis K Stein

The Texas Heart Institute Journal

Obstructive sleep apnea is a sleep-related breathing disorder that has a major impact on cardiovascular function. It has been associated with hypertension, coronary artery disease, cardiac arrhythmias, sudden cardiac death, and heart failure. This review focuses on the relationship between obstructive sleep apnea and heart failure with either reduced or preserved ejection fraction. We discuss the pathophysiology of obstructive sleep apnea, as well as its prevalence, treatment outcomes with continuous positive airway pressure, and prognosis in these 2 distinct types of heart failure. We also identify areas in which further work is needed to improve our understanding of this association …

Reframing Medical Education, Herbert L Fred, Jed D Gonzalo

The Texas Heart Institute Journal

No abstract provided.

Investigating Invasion In Ductal Carcinoma In Situ With To Pographical Single Cell Genome Sequencing, Anna Casasent, Anna Casasent

Dissertations and Theses (Open Access)

Synchronous Ductal Carcinoma in situ (DCIS-IDC) is an early stage breast cancer invasion in which it is possible to delineate genomic evolution during invasion because of the presence of both in situ and invasive regions within the same sample. While laser capture microdissection studies of DCIS-IDC examined the relationship between the paired in situ (DCIS) and invasive (IDC) regions, these studies were either confounded by bulk tissue or limited to a small set of genes or markers. To overcome these challenges, we developed Topographic Single Cell Sequencing (TSCS), which combines laser-catapulting with single cell DNA sequencing to measure genomic copy …

Associations Between Physical Activity, Health-Related Quality Of Life, Regimen Adherence, And Glycemic Control In Jordanian Adolescents With Type 1 Diabetes, Yousef Aljawarneh

Dissertations and Theses (Open Access)

Background: Adolescents with Type 1 Diabetes (T1D) display a greater than two-fold higher risk of developing microvascular and macrovascular complications compared with the non-diabetic population and the risk increases markedly as glycated hemoglobin (HbA1c) increases. The majority of the findings on the associated factors with improved glycemic control are geared toward Western population with a clear lack of studies on Middle Eastern populations.

Purpose: This study aimed to examine the effect of Physical Activity (PA), Health-Related Quality of Life (HRQoL), and regimen adherence on glycemic control in Jordanian adolescents with T1D.

Methods: The study utilized a cross-sectional design. Jordanian adolescents …

Factors Influencing Physical Activity Among Immigrants From South India: A Qualitative Descriptive Study, Jaya Abraham

Dissertations and Theses (Open Access)

Background: In the United States (U.S), the percentage of diabetes and coronary artery diseases is higher among Asian Indian immigrants compared to other ethnic groups. Although research has been useful in describing patterns of physical activity among South Asian groups, very little is known about the factors influencing physical activity among Asian South Indian (ASI) immigrants. There is very limited research performed on the individual, social, cultural and environmental factors influencing physical activity among ASI immigrants.

Purpose: The study purpose was to explore the factors influencing physical activity with the following primary and secondary aims: The primary aim …

Relationships Of Moral Distress Among Interprofessional Icu Teams, Heather Vincent

Dissertations and Theses (Open Access)

Background: Moral distress is the psychological response to knowing the right action required by a healthcare professional but being unable to act upon the right course of action due to internal, external, and institutional constraints.

Purpose: The study investigated: 1. the level of moral distress among interprofessional healthcare providers working in four ICUs of a single academic hospital as measured by the 21-item Moral Distress Scale-Revised (MDS-R), 2. the differences in moral distress among interprofessional healthcare providers based on demographic characteristics and rankings of clinical scenario on the MDS-R.

Method: Descriptive, cross-sectional design using survey methodology.

Outcomes: Significant differences in …

Bridging The Gap Between Food Insecurity And Subsequent Child Body Mass: Mediating Effects Of Dietary Quality And Feeding Styles In Low-Income Hispanic Preschoolers, Nipa Kamdar

Dissertations and Theses (Open Access)

Background: Low-income Hispanic preschoolers face disproportionately high prevalence of food insecurity (FI) and obesity. Consumption of low-cost, energy-dense foods to compensate for FI leads to excess body-mass. FI parents may adopt feeding styles that contribute to decline in children’s dietary quality. Feeding style describes the amount of demandingness (i.e., control of children’s eating) and responsiveness (i.e., warmth used to express demandingness). FI may indirectly contribute to obesity through dietary quality and feeding style.

Purpose: This study investigated: 1. if dietary quality mediated the relationship between food security status (FSS) at Time 1 (T1) and child body-mass at Time 2 (T2), …

Structure Based Drug Design Of High Affinity Kras Inhibitors, Michael Mccarthy

Dissertations and Theses (Open Access)

RAS, one of the most well characterized membrane-associated small GTPases, is a notorious oncogene with >15% of all tumors harboring RAS mutations. When RAS is mutated it becomes constitutively active sending cell growth, survival and proliferation into overdrive, which subsequently leads to cancer. Although, RAS has been aggressively targeted with drug design efforts for more than 30 years an FDA approved direct inhibitor has not yet been developed. There are three isoforms of RAS in cells; HRAS, NRAS and KRAS. We focused on KRAS since it is the most frequently mutated isoform in cancer. To identify novel non-covalent small molecules …

Psychiatric Impact Of Tuberous Sclerosis Complex And Utilization Of Mental Health Treatment, Kate Mowrey

Dissertations and Theses (Open Access)

Tuberous sclerosis complex (TSC) is a multi-system, neurocutaneous disorder with neuropsychiatric features known as TSC-associated neuropsychiatric disorders (TAND). While 90% of individuals with TSC have some TAND features, only 20% receive treatment, leading to a 70% treatment gap. This study evaluated perception of disease severity, presence of anxiety and depression, as well as the utilization and barriers towards mental health services among adults with TSC. Disease severity had a moderate and low-moderate association with anxiety and depression, respectively. Regardless of past utilization, respondents had a positive outlook towards the use of mental health services with the major barrier being cost.

Vascular Injury In Col3a1+/- Mice Model Of Vascular Ehler-Danlos Syndrome, Ping Zhou Ms

Dissertations and Theses (Open Access)

Vascular type of Ehlers-Danlos Syndrome (vEDS) is an inherited cardiovascular disease affecting the middle to large sized arteries, with an incidence rate of 1/5000. vEDS patients also show a significant phenotype of easily bruised skin, indicating aberrant wound healing and injury repair ability. Over 70% of the patients carry a glycine mutation located in their COL3A1 gene, which encodes the propeptide of type III collagen. Mutations in glycine residues lead to a disruption in the assembly and maturation of type III collagen. The goal and significance of the current study was to investigate the potential role of COL3A1 haploinsufficiency …

Evolution Via Gene Duplication And Alternative Splicing In The Eukaryotic Ski7 And Hbs1 Genes, Alexandra Marshall

Dissertations and Theses (Open Access)

Gene duplication and alternative splicing are both recognized as important drivers of proteomic diversity and innovation during evolution, but the evolutionary changes over long periods of time or the interrelations of the two processes has not been extensively studied. Here I study these phenomena for the SKI7 and HBS1 gene pair. These Saccharomyces cerevisiae genes were created as part of a whole genome duplication (WGD) event and have since functionally diverged. Although both genes function in mRNA surveillance pathways, the two genes act on different RNAs and have different effects on the target mRNAs. Ski7 brings the Ski complex and …

Current Genetic Counseling Practice Following Positive Non-Invasive Prenatal Testing For Sex Chromosome Abnormalities, Lauren Fleddermann

Dissertations and Theses (Open Access)

The purpose of this study was to describe current prenatal and pediatric genetic counseling practice following a non-invasive prenatal testing (NIPT) result positive for a sex chromosome abnormality (SCA). The positive predictive value for SCA with NIPT is lower than seen for Trisomy 21 due to natural loss of the X chromosome from maternal cells during aging, confined placental mosaicism, and undiagnosed maternal sex chromosome abnormality. Except for 45,X, individuals with SCA usually have no ultrasound or postnatal findings. This makes follow-up for unresolved positive NIPT necessary; however, there are currently no clinical guidelines. This study used a prospective anonymous …

Attitudes To Ward Updated Genetic Testing Among Patients With Unexplained Mismatch Repair Deficiency, Jessica Omark

Dissertations and Theses (Open Access)

Individuals who have colorectal cancer (CRC) or endometrial cancer (EC) displaying loss of immunohistochemical (IHC) staining of one or more mismatch repair (MMR) proteins without a causative germline mutation are said to have unexplained mismatch repair deficiency (UMMRD, also known as mutation-negative Lynch syndrome). Comprehensive genetic testing that could potentially further clarify Lynch syndrome (LS) carrier status is essential to provide tailored screening guidelines to affected individuals and their family members; however, patient understanding of the potential impact of updated genetic testing for LS is unclear. This study aimed to evaluate the interest in and perceived impact of updated genetic …