Digital Commons Network^™

Attributing Meaning To Online Social Network Analysis For Tailored Socio-Behavioral Support Systems, Sahiti Myneni

Dissertations & Theses (Open Access)

Ubiquitous online social networks provide us with a unique opportunity to deliver scalable interventions for the support of lifestyle modifications in order to change behaviors that predispose toward cancer and other diseases. At the same time these networks act as rich data sources to inform our understanding of end-user needs. Traditionally, social network analysis is based on communication frequency among members. In this work, I introduce communication content as a complementary frame for studying these networks.

QuitNet, an online social network developed to provide smoking cessation support is considered for analysis. Qualitative coding, automated content analysis, and network analysis were …

Radiogenic Second Cancer Risk Differences In Female Hodgkin Lymphoma Patients Treated With Proton Versus Photon Radiotherapies, Kenneth L. Homann

Dissertations & Theses (Open Access)

Hodgkin Lymphoma (HL) is the most common cancer diagnosis of young adults in the United States. Advances in curative treatments for HL, including the use of photon radiation therapy (RT) techniques, have increased 10 year survival rates to approximately 90% among young patients. These RT treatments, however, contribute to an increased incidence of radiogenic second cancer (RSC) formation to the healthy tissue surrounding the tumor volume relative to the general population. These RSCs are the leading cause of death among long-term HL survivors. Proton therapy has been shown to reduce the therapeutic dose, and therefore, the risk of developing a …

The Role And Mechanism Of The Homeobox Gene Hoxa9 In The Growth Of Epithelial Ovarian Cancer, Song Yi Ko

Dissertations & Theses (Open Access)

Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer death among women in the United States. The high lethality of EOCs stems from rapid peritoneal involvement. EOCs frequently colonize peritoneal surfaces that overlie connective and adipose tissues. However, the mechanisms that enable ovarian cancer cells to readily adapt to the peritoneal environment are poorly understood. HOXA9, a homeobox gene that is normally expressed in the developing female reproductive tract, is aberrantly expressed in EOCs and controls the morphologic features of these tumors. The differentiation pattern of a tumor is an important determinant of its clinical behavior and …

Characterization Of Oslds For Use In Small Field Photon Beam Dosimetry, Christopher Pham

Dissertations & Theses (Open Access)

The goal of this study was to redesign a Radiological Physics Center (RPC) mailable remote audit tool used for stereotactic radiosurgery (SRS) single beam dosimetry. A prototype phantom was designed and built housing nanoDot (Landauer Inc., Glenwood, IL) Al₂O₃:C optically stimulated luminescence dosimeters (OSLDs) whose visible active luminescent area has been masked. The phantom has two measurement points with two OSLDs at each location and a film insert for localization purposes only. The masked OSLDs were characterized accounting for various correction factors associated with OSLD dose calculations. The uncertainties for each correction factor were also investigated. …

Ezh2 T416 Phosphorylation Enhances Breast Cancer Tumorigenesis, Adam M. Labaff, Adam M. Labaff

Dissertations & Theses (Open Access)

Enhancer of zeste homologue 2 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and catalyzes the trimethylation of histone H3 on lysine 27 (H3K27Me3), to repress gene transcription. Many types of cancer stem and progenitor cells, including breast, have demonstrated EZH2 to be fundamental in the biology and promoting the expansion of their cellular populations. How EZH2 regulates each of these respective tumor initiating cells (TICs) populations has been studied, but the signaling transduction mechanisms that regulate EZH2 in these TIC populations is yet to be elucidated. Phosphorylation of EZH2 by cyclin dependent kinases (CDK) has been …

Scanned Ion Beam Therapy For Thoracic Tumors, John Gordon Eley

Dissertations & Theses (Open Access)

Although frequently cured of Hodgkin lymphoma, adolescents and young adults can develop radiation induced second cancers. These patients could potentially benefit from scanned ion radiotherapy yet likely would require motion mitigation strategies. In theory, four-dimensional (4D) optimization of ion beam fields for individual motion states of respiration can enable superior sparing of healthy tissue near moving targets, compared to other motion mitigation strategies. Furthermore, carbon-ion therapy can sometimes provide greater relative biological effectiveness (RBE) for cell sterilization in a target but nearly equivalent RBE in tissue upstream of the target, compared to proton therapy. Thus, we expected that for some …

Cxcr2 Expression In Tumor Cells Is A Poor Prognostic Factor And Promotes Invasion And Metastasis In Lung Adenocarcinoma, Erminia Massarelli

Dissertations & Theses (Open Access)

CXC chemokine receptor 2 (CXCR2) is a G-protein coupled receptor which mediates signaling by binding to CXC chemokines CXCL1-3 and 5-8. In non-small cell lung cancer CXCR2 has been studied mainly in stromal cells and is known to increase tumor inflammation and angiogenesis. However, there is controversial data in the literature about CXCR2 expression in tumor cells and its role in the tumor microenvironment. We hypothesized that tumoral expression of CXCR2 and its ligands promote tumor invasion and metastasis in non-small cell lung cancer. The effect of CXCR2 expression on tumor cells was studied using stable knockdown clones derived from …

The Staphylococcus Pseudintermedius Adhesin Spsd Contains A Central Fibronectin-Binding Domain, Andrea S. Bordt

Dissertations & Theses (Open Access)

Staphylococcus pseudintermedius is a Gram-positive bacterium significant because of its ability to cause costly and difficult to treat veterinary infections worldwide. It exhibits several similarities to Staphylococcus aureus, however, very little is known about its surface adhesins. Surface adhesins in S. aureus are significant contributors to pathogenesis. S. pseudintermedius encodes the surface protein SpsD, which contains characteristics of the microbial surface components recognizing adhesive matrix molecules family and confers attachment of the heterologous host Lactococcus lactis to fibronectin. This work has identified a centrally-located fibronectin binding domain in SpsD which binds the 30 kDa N-terminal domain of fibronectin with …

Characterizing The Effect Of Dasatinib On Anti-Tumor Immune Response And Exploring The Potential Of Combining Targeted Therapy And Immunotherapy In A C-Kit Mutant Mastocytoma Model, Yan Yang

Dissertations & Theses (Open Access)

Targeted therapy and immunotherapy eradicate malignant cells through different mechanisms, and the strengths and weaknesses of these two approaches are potentially complementary. Therefore, the combination of molecular targeted drugs with immune- based therapies is considered an attractive approach for improving the therapeutic efficacy of cancer treatment. The mutation and amplification of the c-KIT proto- oncogene are associated with multiple different cancer types, and multiple c-KIT inhibitors have been tested clinically. In spite of some encouraging results using these agents, most patients with c-KIT mutant cancers still relapse due to drug resistance. This also demonstrates the inherent limitation of molecular targeted …

Ventral Tegmental Area Neuronal Responses To Methylphenidate Correlated To Behavioral Responses Of Adolescent And Adult Rats, Zachary Jones

Dissertations & Theses (Open Access)

Methylphenidate (MPD) is a psychostimulant used in the treat treatment of attention deficit hyperactivity disorder and more recently is being used as a cognitive enhancement and recreational drug. Its therapeutic effects are not fully understood, nor are the long term effects of the drug on brain development. The ventral tegmental area (VTA) is a site of psychostimulant action thought to be involved in behavioral sensitization. The aim of the this study was to first determine if there are differences in neuronal responses between individuals, with respect to neuronal firing patterns in the ventral tegmental area (VTA), and whether these differences …

C-Jun N-Terminal Kinases Regulate Adenovirus-Mediated Autophagy And Antigen Presentation, Sarah R. Klein

Dissertations & Theses (Open Access)

Targeted immunotherapy with recombinant, oncolytic adenoviruses is under investigation for the treatment of cancer. Evidence indicates adenoviruses induce autophagy that is required for oncolysis, but the molecular regulation of autophagy in infected cells remains under investigation. Our data suggested the canonical pathway regulating starvation-induced autophagy was not implemented in adenovirus-induced autophagy; however, adenovirus infection triggered phosphorylation of c-Jun N-terminal kinases (JNK) that was essential for autophagy. Adenoviral replication within the host cell elicited JNK pathway activation leading to B cell lymphoma-2 (Bcl-2) phosphorylation. JNK-dependent Bcl-2 phosphorylation stimulated the dissociation of Bcl-2/beclin 1 heterodimers, enabling beclin 1 to initiate autophagy. Moreover, …

Symptoms In Early And Long-Term Breast Cancer Survivors Who Have Completed Primary Therapy, Faith Strunk

Dissertations & Theses (Open Access)

Background

Many breast cancer survivors continue to have single or multiple symptoms after they have completed primary cancer therapy. The quantifiable, subjective experience of multiple symptoms and their impact is defined as symptom burden. Previous research has focused on symptoms during primary therapy or shortly after completion of treatment.

Objectives

Our study objectives were to determine whether symptom burden differed according to survivor status (early as opposed to long-term survival) and/or use of endocrine or hormonal adjuvant therapy. We hypothesized that there would be no difference in the symptoms expressed among early- and long-term survivors.

Methods

In this cross-sectional study, …

Therapeutic Efficacy Of P53 Restoration In Mdm2-Overexpressing Tumors, Qin Li

Dissertations & Theses (Open Access)

The TP53 tumor suppressor is the most mutated gene in human cancers. Recent studies using genetically modified mouse models have shown that restoring the expression of wild-type p53 has led to tumor growth suppression in various types of tumors lacking p53. Other mechanisms, e.g. upregulation of Mdm2 levels, exist in tumors to inactivate the p53 pathway. Mdm2, an E3 ubiquitin-ligase that targets p53 for proteasomal degradation, is present at high levels in many tumors with wild-type p53. In this study, we probed the effects of restoring p53 activity in Mdm2-overexpressing tumors genetically using animal models. Here we demonstrated high levels …

Novel Functions Of Cetuximab In Egfr-Targeted Therapy: Radiosensitization, Glycolysis Inhibition, And Cellular Redox Status Regulation, Haiquan Lu

Dissertations & Theses (Open Access)

Epidermal growth factor receptor (EGFR) is overexpressed in the majority of head and neck cancers. The anti-EGFR antibody cetuximab has been approved by the FDA for the treatment of head and neck cancers, however, only a small fraction of patients respond to cetuximab treatment. Further investigation to understand the mechanisms underlying cetuximab-mediated EGFR-targeted therapy and to develop novel therapeutic strategies to improve the efficacy of cetuximab is urgently needed. In the present study, we elucidated the mechanism of cetuximab in radiosensitization, and discovered novel functions of cetuximab in glycolysis inhibition and cellular redox status regulation. We found that cetuximab inhibits …

An Evaluation Of The Consistency Of Imrt Patient-Specific Qa Techniques, Elizabeth M. Mckenzie

Dissertations & Theses (Open Access)

To ensure the integrity of an intensity modulated radiation therapy (IMRT) treatment, each plan must be validated through a measurement-based quality assurance (QA) procedure, known as patient specific IMRT QA. Many methods of measurement and analysis have evolved for this QA. There is not a standard among clinical institutions, and many devices and action levels are used. Since the acceptance criteria determines if the dosimetric tools’ output passes the patient plan, it is important to see how these parameters influence the performance of the QA device. While analyzing the results of IMRT QA, it is important to understand the variability …

Developmental And Molecular Functions Of Plakophilin-3, William A. Munoz

Dissertations & Theses (Open Access)

Plakophilin-3, the less studied member of the plakophilin-catenin subfamily, and the larger catenin family, binds directly to desmosomal cadherin cytoplasmic domains and enhances desmosome formation and stability. In mammals, plakophilin-3 is expressed at the highest levels in desmosome-enriched tissues such as epithelia, with the knock-out in mice producing corresponding reductions in ectodermal integrity. In tissue, cellular and intracellular contexts where plakophilin-3 is not at the desmosomal plaque, little is known about its functions in the cytoplasm or nucleus, where it also localizes.

My work employed embryos of the amphibian, Xenopus laevis, to examine plakophilin-3’s developmental roles. I first evaluated …

Mtorc1 Signaling In Memory Formation And Dysfunction, Natalia S. Rozas De O'Laughlin

Dissertations & Theses (Open Access)

The mechanistic Target of Rapamycin Complex 1 (mTORC1) pathway integrates cellular availability of growth factors, energy and amino acids to regulate protein synthesis and autophagy. The mTORC1 pathway has also been shown to be required for memory consolidation, and its dysregulation is associated with many neurological disorders. MTORC1 is negatively regulated by the tuberous sclerosis complex (TSC1/2). When ATP and growth factors are available, TSC1/2 is inhibited and mTORC1 activity can be restored. In a complementary regulatory pathway, amino acids signal to mTORC1 through the Rag GTPases and Ragulator complex, which modulate the translocation of mTORC1 from the cytoplasm to …

Basis For Targeting Met Activation Mediated Resistance To Pi3k Inhibition In Breast Cancer, Ana M. Gonzalez-Angulo

Dissertations & Theses (Open Access)

The identification of resistance mechanisms to emerging therapies, such as those targeting the PI3K pathway and the MET receptor, has the potential to benefit a significant number of patients with breast cancer. In this study we hypothesized that concurrent aberrations in PI3K and MET will render breast cancers resistant to therapies targeting each pathway, and that combination therapy targeting the PI3K and MET pathway will optimize therapy-effect by preventing the acquisition of resistance.

We analyzed cMET and phospho-cMET levels in 257 breast cancer samples and found that high levels of both the proteins were seen in all breast cancer subtypes, …

Neural Correlates Of Audiovisual Speech Perception In Aphasia And Healthy Aging, Sarah H. Baum

Dissertations & Theses (Open Access)

Understanding speech in face-to-face conversation utilizes the integration of multiple pieces of information, most importantly the auditory vocal sounds and visual lip movements. Prior studies of the neural underpinnings of audiovisual integration in the brain have provided converging evidence to suggest that neurons within the left superior temporal sulcus (STS) provide a critical neural hub for the integration of auditory and visual information in speech. While most studies of audiovisual processing focus on neural mechanisms within healthy, young adults, we currently know very little about how changes to the brain can affect audiovisual integration in speech. To examine this further, …

Investigation Of Respiratory Motion Management Techniques For Proton And Photon Radiotherapy Of Lung Cancer, Jason E. Matney

Dissertations & Theses (Open Access)

Protons as a source of therapeutic radiation can provide a substantial improvement over dose distributions that can be achieved with conventional sources of radiation such as high-energy photons. However, respiratory motion can significantly impact the delivered proton and photon dose distributions during lung cancer radiotherapy. The goals of this dissertation research were to evaluate the impact of respiratory motion and to estimate the benefit of respiratory gating for passively scattered proton therapy (PSPT) and intensity modulated photon therapy (IMRT).

The first aim of this project was to determine the impact of respiratory motion in PSPT and IMRT. Four dimensional dose …

C-Rel Is A Transcriptional Target Of Mesoderm Inducer In Xenopus Like 1 (Mixl1), Aaron C. Raymond

Dissertations & Theses (Open Access)

MIXL1, an evolutionarily conserved, paired-type homeobox transcription factor induced by BMP4/TGFb signaling, is a critical regulator of embryonic and adult hematopoiesis. Several lines of evidence implicate MIXL1 in hematopoietic transformation: (i) Aberrant MIXL1 expression is seen in human CML ( Chronic Myelogenous Leukemia) in blast crisis, AML (Acute myelogenous leukemia), B cell lymphomas and pediatric ALL (Acute lymphocytic leukemia). (ii) Retroviral transduction of Mixl1 induces AML in murine models. Nonetheless, mechanisms underlying MIXL1 mediated proliferative, survival advantages are unknown.

The goal of my studies is to understand if and how aberrant MIXL1 expression contributes to leukemogenesis. As a first step, …

Development And Evaluation Of An Ontology-Based Quality Metrics Extraction System, Sina Madani

Dissertations & Theses (Open Access)

The Institute of Medicine reports a growing demand in recent years for quality improvement within the healthcare industry. In response, numerous organizations have been involved in the development and reporting of quality measurement metrics. However, disparate data models from such organizations shift the burden of accurate and reliable metrics extraction and reporting to healthcare providers. Furthermore, manual abstraction of quality metrics and diverse implementation of Electronic Health Record (EHR) systems deepens the complexity of consistent, valid, explicit, and comparable quality measurement reporting within healthcare provider organizations.

The main objective of this research is to evaluate an ontology-based information extraction framework …

Development And Implementation Of A Dynamic Heterogeneous Proton Equivalent Anthropomorphic Thorax Phantom For The Assessment Of Scanned Proton Beam Therapy, James L. Neihart

Dissertations & Theses (Open Access)

DEVELOPMENT AND IMPLEMENTATION OF A DYNAMIC HETEROGENEOUS PROTON EQUIVALENT ANTHROPOMORPHIC THORAX PHANTOM FOR THE ASSESSMENT OF SCANNED PROTON BEAM THERAPY

by

James Leroy Neihart, B.S.

APPROVED:

______________________________
David Followill, Ph.D.

______________________________
Peter Balter, Ph.D.

______________________________
Narayan Sahoo, Ph.D.

______________________________
Kenneth Hess, Ph.D.

______________________________
Paige Summers, M.S.

APPROVED:

____________________________

Dean, The University of Texas

Graduate School of Biomedical Sciences at Houston

DEVELOPMENT AND IMPLEMENTATION OF A DYNAMIC HETEROGENEOUS PROTON EQUIVALENT ANTHROPOMORPHIC THORAX PHANTOM FOR THE ASSESSMENT OF SCANNED PROTON BEAM THERAPY

A

THESIS

Presented to the Faculty of
The University of Texas
Health Science Center at Houston
and
The University of …

Altered Ovarian Cancer Metabolism Increases Neuronal N-Acetylaspartate To Promote Tumor Growth, Behrouz Zand

Dissertations & Theses (Open Access)

Background: Altered metabolism is a well-established trait in many cancers, and is an emerging hallmark of cancer. Recent resurgence of cancer metabolism studies has identified dysregulated metabolic pathways that produce novel oncometabolites in various cancers. However, large scale studies of dysregualted high grade serous epithelial ovarian cancers (HGSOC) are unknown.

Materials and Methods: Following IRB approval, metabolic profiling of 101 HGSOC patients and 15 normal ovaries were obtained using GC/LC mass spectrometry from 2 U.S. academic centers to identify highly up-regulated metabolites. Samples from a cohort of 135 and 208 patients from a single institution were evaluated for gene expression …

Studying Aggregate Formation By Amyotrophic Lateral Sclerosis-Associated Mutant Sod1 Protein In Drosophila Model, Michael Mccarthy

Dissertations & Theses (Open Access)

A common pathological hallmark of most neurodegenerative disorders is the presence of protein aggregates in the brain. Understanding the regulation of aggregate formation is thus important for elucidating disease pathogenic mechanisms and finding effective preventive avenues and cures. Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a selective neurodegenerative disorder predominantly affecting motor neurons. The majority of ALS cases are sporadic, however, mutations in superoxide dismutase 1 (SOD1) are responsible for about 20% of familial ALS (fALS). Mutated SOD1 proteins are prone to misfold and form protein aggregates, thus representing a good candidate for studying aggregate formation. …

Development Of Hif-1Α/Hif-1Β Heterodimerization Inhibitors Using A Novel Bioluminescence Reporter Assay System For In Vitro High Throughput Screening And In Vivo Imaging, Yun-Chen Chiang

Dissertations & Theses (Open Access)

Tumor growth often outpaces its vascularization, leading to development of a hypoxic tumor microenvironment. In response, an intracellular hypoxia survival pathway is initiated by heterodimerization of hypoxia-inducible factor (HIF)-1α and HIF-1β, which subsequently upregulates the expression of several hypoxia-inducible genes, promotes cell survival and stimulates angiogenesis in the oxygen-deprived environment. Hypoxic tumor regions are often associated with resistance to various classes of radio- or chemotherapeutic agents. Therefore, development of HIF-1α/β heterodimerization inhibitors may provide a novel approach to anti-cancer therapy. To this end, a novel approach for imaging HIF-1α/β heterodimerization in vitro and in vivo was developed in this study …

A Novel Cardiac Function Of Sumo2/3 And Senp5 Dependent Pathway And Its Physiological Impact On Congestive Cardiomyopathy, Eun Young Kim

Dissertations & Theses (Open Access)

A Novel cardiac function of SUMO2/3 and SENP5 dependent pathway and its physiologic impact on congestive cardiomyopathy

Publication No.___________

Eun Young Kim, M.S.

Supervisory professor: Robert J. Schwartz, Ph.D.

SUMOylation regulates diverse cellular processes including transcription, cell cycle, protein stability, and apoptosis. Although SUMO1 has been extensively studied so far, relevance of SUMO2/3 is unclear, especially in heart. Here we show that failing heart induces SUMO2/3 conjugation. Increased SUMO2/3-dependent modification leads to congestive heart disease such as cardiac hypertrophy by promoting cardiac cell death. Calpain2 and Calpastatin as a novel SUMO2 targets have been known to be involved in mitochondrial-independent …

Evaluating The Utility Of Clinical Criteria For The Identification Of Lynch Syndrome Among Endometrial Cancer Patients, Amanda S. Bruegl

Dissertations & Theses (Open Access)

Background: Lynch Syndrome (LS) is a familial cancer syndrome with a high prevalence of colorectal and endometrial carcinomas among affected family members. Clinical criteria, developed from information obtained from familial colorectal cancer registries, have been generated to identify individuals at elevated risk for having LS. In 2007, the Society of Gynecologic Oncology (SGO) codified criteria to assist in identifying women presenting with gynecologic cancers at elevated risk for having LS. These criteria have not been validated in a population-based setting.

Materials and Methods: We retrospectively identified 412, unselected endometrial cancer cases. Clinical and pathologic information were obtained from the electronic …

Conformational Dynamics Of K-Ras And H-Ras Proteins: Is There Functional Specificity At The Catalytic Domain?, Nandini Rambahal

Dissertations & Theses (Open Access)

Ras proteins serve as crucial signaling modulators in cell proliferation through their ability to hydrolyze GTP and exist in a GTP “on” state and GTP “off” state. There are three different human Ras isoforms: H-ras, N-ras and K-ras (4A and 4B). Although their sequence identity is very high at the catalytic domain, these isoforms differ in their ability to activate different effectors and hence different signaling pathways. Much of the previous work on this topic has attributed this difference to the hyper variable region of Ras proteins, which contains most of the sequence variance among the isoforms and encodes specificity …

Rna-Sequencing Applications: Gene Expression Quantification And Methylator Phenotype Identification, Guoshuai Cai

Dissertations & Theses (Open Access)

My dissertation focuses on two aspects of RNA sequencing technology. The first is the methodology for modeling the overdispersion inherent in RNA-seq data for differential expression analysis. This aspect is addressed in three sections. The second aspect is the application of RNA-seq data to identify the CpG island methylator phenotype (CIMP) by integrating datasets of mRNA expression level and DNA methylation status.

Section 1: The cost of DNA sequencing has reduced dramatically in the past decade. Consequently, genomic research increasingly depends on sequencing technology. However it remains elusive how the sequencing capacity influences the accuracy of mRNA expression measurement. We …