Digital Commons Network^™

Diabetes And Obesity Induce Transcriptomic And Metabolomic Changes Enhancing Pancreatic Cancer Aggressiveness, Guermarie Velázquez Torres

Dissertations and Theses (Open Access)

Pancreatic cancer is one of the most aggressive types of cancer, with poor prognosis that lacks effective diagnostic markers and therapies. It is expected that in 2014 the incidence and the mortality of pancreatic cancer in the United States will be 46,420 and 39,590 respectively. Diabetes and obesity are modifiable risk factors associated with accelerated pancreatic carcinogenesis and tumor progression, but the biological mechanisms are not completely understood. The purpose of this study is to demonstrate direct evidence for the mechanisms mediating these epidemiologic phenomena. Our hypothesis is that obesity and diabetes mellitus type 2 (DM2) accelerate pancreatic cancer and …

Evaluation Of Current Clinical Criteria For Li-Fraumeni Syndrome In A Diverse Sample Of Tp53 Mutation Carriers, Emily A. Parham

Dissertations and Theses (Open Access)

Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome caused by heterozyogous germline mutations in the TP53 gene and characterized by an excess of early-onset cancers, high lifetime risk of cancer, and a wide range of tumor types. Recent studies suggesting a benefit in comprehensive screening protocols for both children and adults make the timely identification of individuals with LFS increasingly important.

A number of criteria have been proposed to identify patients with LFS. The National Comprehensive Cancer Network (NCCN) combines several in its Clinical Practice Guidelines for TP53 genetic testing. Prior studies have shown that the cumulative sensitivity of …

Car-Modified T Cells Capable Of Distinguishing Normal Cells From Malignant Cells, Hillary G. Caruso

Dissertations and Theses (Open Access)

T cells can be redirected to target tumor-associated antigen (TAA) by genetic modification to express a chimeric antigen receptor (CAR), which fuses the specificity derived from an antibody to T-cell activation domains to result in lysis of TAA-expressing cells. Due to the potential for on-target, off-tissue toxicity, CAR⁺ T-cell therapy is currently limited to unique or lineage-restricted TAAs. Glioblastoma, a grade IV brain malignancy, overexpresses epidermal growth factor receptor (EGFR) in 40-50% of patients. EGFR also has widespread normal tissue expression. To target EGFR on glioblastoma while reducing the potential for normal tissue toxicity, EGFR-specific CAR generated from cetuximab, …

Cancers Associated With Brca1 And Brca2 Mutations Other Than Breast And Ovarian, Jacqueline Mersch

Dissertations and Theses (Open Access)

Mutations in BRCA1 and BRCA2 cause tumor development in Hereditary Breast and Ovarian Cancer syndrome (HBOC) through accumulation of unrepaired DNA damage. Extensive research of BRCA1 and BRCA2 mutations has led to well-defined breast and ovarian cancer risks in individuals with HBOC. Previous studies have reported additional cancers associated with BRCA mutations; however, the type of cancer, magnitude of risk, and differences between sexes remains to be clarified. Ultimately, a consensus of additional cancer risks can aid in better recommendations for genetic testing and more effective screening and prevention guidelines.

A retrospective chart review of MD Anderson Cancer Center patients …

The Regulation Of Microrna Biogenesis By Ribosome-Interacting Proteins, Brian Pickering

Dissertations and Theses (Open Access)

MicroRNA (miRNA) are small, non-coding RNAs that affect gene expression through degradation of complementary mRNA targets or inhibition of translation. As they affect approximately 50% of all cellular processes, miRNA are tightly regulated by the cell through transcriptional and post-transcriptional mechanisms. Transcribed miRNA are capped and polyadenylated (referred to as pri-miRNA) which are cleaved by Drosha and DGCR8 to generate 60-90 nucleotide precursor miRNA. The precursors are cleaved again by Dicer and loaded into the RNA-induced silencing complex (RISC) of which Argonaute 2 is the functional component. Many of the proteins involved in miRNA biogenesis share a common role in …

Proteasome Inhibition Enhances The Effect Of Bikdd Gene Therapy, Ye Sun

Dissertations and Theses (Open Access)

BikDD is a phosphorylation mimic mutant form of pro-apoptotic protein Bik, and possesses a stronger apoptosis induction capability. By constructing into a highly amplified “VISA” (VP16-GAL4-WPRE integrated systemic amplifier) system under the control of a cancer specific promoter, previous studies have verified the specific killing effect of BikDD in cancer cells both in in vitro and in vivo models. C-VISA-BikDD delivered by liposome has been approved by FDA for clinical trial in advanced pancreatic cancer. In this study, we proposed proteasome inhibition as a combinational therapy strategy with BikDD gene therapy to enhance the clinical benefits. Proteasome inhibition stabilized exogenously …

No-Independent Modulation Of Soluble Guanylyl Cyclase (Sgc) Activity And Function, George L. Britton Jr

Dissertations and Theses (Open Access)

Soluble guanylyl cyclase (sGC) plays a key role in the nitric oxide (NO) signaling pathway, where it functions as an NO receptor and generator of a secondary intracellular messenger, cGMP. In addition to NO, investigators have identified a number of proteins that interact with sGC and modulate its function. For example, the interaction of sGC with ADP-ribosylation factor GTPase activating protein 1 (AGAP1) governs sGC’s intracellular distribution and therefore mediates localized production of cGMP. Interactions of sGC with heat-shock protein 90 (HSP90) or HSP70 promote the extent of sGC activation upon NO stimulation, while interaction of sGC with the η …

Latinas And The Traditional Genetic Counseling Model: A Qualitative Study, Stephanie Thompson

Dissertations and Theses (Open Access)

The traditional genetic counseling model reflects an individualized counseling session that includes the presentation of information about genes, chromosomes, personalized risk assessment, and genetic testing and screening options. Counselors are challenged to balance providing educational information with discussion of implications of this information in an allotted amount of time. The aim of this study was to explore the perceptions of pregnant Latinas on the benefits and limitations of the traditional prenatal genetic counseling model and to determine the specific preferences for receiving prenatal genetic counseling. Data were collected through focus groups and one-on-one, semi-structured interviews of twenty-five Spanish speaking Latinas …

P53 Maintains Hepatic Cell Identity During Liver Regeneration, Zeynep Hande Coban Akdemir

Dissertations and Theses (Open Access)

p53 MAINTAINS HEPATIC CELL IDENTITY DURING LIVER REGENERATION

Zeynep Hande Coban Akdemir, B.S.,M.A.

Advisory Professor: Michelle Craig Barton, Ph.D.

p53 is a tumor suppressor that has been well studied in tumor-derived, cultured cells. However, its functions in normal proliferating cells and tissues are generally overlooked. We propose that p53 functions during the G1-S transition can be studied in normal, differentiated cells during surgery-induced liver regeneration. Two-thirds partial hepatectomy (PH) of mouse liver offers a unique model to compare p53 functions in regenerating versus sham (control) cells. My hypothesis is that intersection of global expression analyses (microarray and RNA sequencing) and …

The Epigenetics Of Small Cell Prostate Cancer, Brittany N. Kleb

Dissertations and Theses (Open Access)

Small cell prostate cancer (SCPC) is an androgen receptor (AR) negative variant that can develop during the progression of castration-resistant AR-positive (AR⁺) prostate adenocarcinomas. While rare at initial diagnosis, SCPC is present in 10-20% of patients resulting in an aggressive clinical course with poor response to hormonal therapies and a short median survival. Our studies in patient-tumor derived xenografts revealed that the AR-negative small cell prostate carcinomas (AR^-SCPC) express genes involved in neural development instead of the prostate luminal epithelial gene expression that characterizes AR-positive castration-resistant adenocarcinomas (AR⁺ADENO). We hypothesized that the differences in …

Regulation Of Mammary Gland Development And Tumorigenesis By 14-3-3 Zeta, Sumaiyah Rehman

Dissertations and Theses (Open Access)

Signaling pathways that play critical roles in organ development are often aberrantly regulated during cancer initiation and progression. 14-3-3z is overexpressed in more than 40% of breast cancers and is associated with poor patient prognosis. Therefore, the function of 14-3-3z in cancer and normal mammary gland development was investigated utilizing multiple in vivo and in vitro approaches. 14-3-3z is a chaperone protein that interacts with a multitude of oncogenes and tumor suppressor genes, thereby functioning as a critical node in multiple oncogenic signaling networks. Mammary gland-specific 14-3-3z transgenic mouse models showed that 14-3-3z overexpression was sufficient to induce mammary tumorigenesis. …

Contribution Of Interleukin 6 Trans Signaling In Pulmonary Fibrosis, Thuy T. Le

Dissertations and Theses (Open Access)

Idiopathic Pulmonary Fibrosis (IPF) is a lethal lung disease with progressive fibrosis and death within 2-3 years of diagnosis. IPF incidence and prevalence rates are increasing annually, and because the pathogenesis is unknown, there are no effective treatments available. Inhibition of interleukin 6 (IL-6) results in the attenuation of pulmonary fibrosis in mice. It is unclear whether this is due to blockade of classical signaling, mediated by membrane-bound IL-6 receptor alpha (mIL-6Rα), or trans signaling, mediated by soluble IL-6Rα (sIL-6Rα). Our study assessed the role of sL-6Rα in IPF. We demonstrated elevations of sIL-6Rα in IPF patients and in mice …

Regulation Of The Candida Albicans Arginine Biosynthetic Pathway, Claudia Jimenez Lopez

Dissertations and Theses (Open Access)

Candida albicans is the most importan thuman-associatedfungus.It is a commensal microorganism but also an opportunistic pathogen able to cause superficial infections aswellaslife-threateninginfectionswhich are associated with a highmortalityrateof 50%. The interactions between C. albicans and the cells of the mammalian innate immune system, which confer the most important protecting mechanisms against disseminated infections, are very dynamic and determine the success of C. albicans as a pathogen. Transcriptional profiling has shown that phagocytosis of C. albicans by macrophages results primarily in the activation of alternative carbon metabolism pathways suggesting that the pathogen is exposed to a glucose poor environment. Changes in …

Gsbs News, Spring 2014, Graduate School Of Biomedical Sciences, University Of Texas Health Science Center At Houston/M.D. Anderson Cancer Center

GSBS News

Cover image by artist Syd Moen; Benefactor News: Smithville fundraiser supports GSBS fellow; New endowment to support MD/PhD Program; Coming full circle: developing and promoting a Core Curriculum; Celebrating 50 Years of Excellence: GSBS Alumni All-Stars shine at Super Panel and 2013 Reunion; Faculty Membership Report; Faculty News: Dr. Vicki Knutson retires; GSBS Outreach Council hosts community Science Night; Student News; 2013-2014 Student Awards; Alumni News; Message to Alumni

Serum Levels Of Soluble Icam-1 In Children With Pulmonary Artery Hypertension, Melahat Melek Oguz, Ayse Deniz Oguz, Cihat Sanli, Ayhan Cevik

The Texas Heart Institute Journal

This prospective cross-sectional study attempted to determine both the usefulness of the serum intercellular adhesion molecule-1 (ICAM-1) as a biomarker for pulmonary artery hypertension secondary to congenital heart disease and the nature of this marker's association with catheter angiographic findings.

Our study included a total of 70 male and female children, comprising 30 patients with both pulmonary artery hypertension and congenital heart disease, 20 patients with congenital heart disease alone, and 20 healthy control subjects. Levels of ICAM-1 in plasma samples from all groups were measured by the enzyme-linked immunosorbent assay method. Cardiac catheterization was also performed in all patients. …

Ms 103 Guide To Don Chapman, Md Papers, Don Chapman (1916-2007)

Manuscript Finding Aids

The Don Chapman, MD papers contains digitalis research, Diodrast notes, electrolytes, edema congenital heart failure, echocardiograms, electrocardiograms, Eisenmengers complex and syndrome, EKG’s, pulmonary valvular stenosis, primary pulmonary hypertension, ventricular aneurysms, vector cardiography, heart catheterization, arteriovenous fistula, sulfathiazole clearance test, syphilitic aneurysms, thyroid heart disease, ventricular arrhythmias, pyelonephritis, x-rays, fundus of the eye, subaortic stenosis, heart disease and pregnancy, heart tumors, cholesterol, cerebral insufficiency and carotid stenosis, atrial septal defect, atrial ventricular defect, cardiac resuscitation, anxiety heart disease, hypertension, abdominal aneurysms, anatomy and physiology of the heart, surgical treatment for hypertension and hypotension, renal insufficiency, myocardial infraction shock treatment, and other …

Annual Report 2013-2014, Houston Academy Of Medicine-Texas Medical Center Library

Annual Reports: 1943 - Present

This file contains the Annual Report for the library from 2013-2014.

Family Roots: Sustenance For Samoan And Tongan American Elders, Halaevalu F.O. Vakalahi, Emily S. Ihara, Moana P. Hafoka

Journal of Family Strengths

This article discusses the centrality of the family in supporting cultural responsibilities and in the well-being of Samoan and Tongan-American elders. Informed by the Ho’okele model, this grounded theory study was conducted in the State of Hawaii, the port of entry for most Pacific Islander-Americans migrating to the U.S. and the state in which a majority of Samoans and Tongans reside. Qualitative data was collected from 10 Samoan and 10 Tongan elders, and analysis was conducted by immersion in the data and reading for natural emergence of themes, patterns and categories. Cultural foundation of family relationships, expectations of the keepers …

Using State Wide Child And Family Services Review Data To Analyze Policies To Improve Educational Outcomes Of Children In Foster Care, Corie G. Hebert

Journal of Family Strengths

The poor educational outcomes of foster children is recognized as a national problem. The literature is reviewed to define and illustrate the magnitude of the problem. Steps have been taken to improve the problem with passage of the Fostering Connections to Success and Increasing Adoptions Act of 2008; it requires states to ensure the educational stability of foster youth. A description of utilizing state level Child and Family Service Review data to analyze a state’s ability to comply with the Fostering Connections to Success and Increasing Adoptions Act of 2008 is provided.

Making A Community Ready For Oral Health, Paul Casamassimo, Catherine M. Flaitz

Journal of Applied Research on Children: Informing Policy for Children at Risk

The challenges of resolving the oral health disparities among children and other vulnerable populations requires a well-organized community safety net, along with a sincere commitment to prioritize the elimination of this common, but preventable, dental disease. Adequate funding for basic health needs, while incorporating oral health care into a comprehensive primary care model in our neighborhoods provides the best chance for a successful outcome. In order to build better communities for our children, improvement in the access and delivery of dental care must be part of the equation.

Commentary On "Sexual Violence Against Girls In Schools: Addressing The Gaps Between Policy And Practice In Awaso, Ghana", Christabelle Sethna

Journal of Applied Research on Children: Informing Policy for Children at Risk

Invited Commentary on "Sexual Violence against Girls in Schools: Addressing the Gaps between Policy and Practice in Awaso, Ghana"

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

Dissertations and 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, …

Introducing A Novel Method For Genetic Analysis Of Autism Spectrum Disorder, Sepideh Nouri

Dissertations and Theses (Open Access)

Autism is a spectrum of neurological disorders that is characterized by repetitive and stereotyped behaviors, lack of social skills in verbal and non-verbal communications, and intellectual disability. Recent statistics shows that 1 out of every 88 children in the US is affected by autism.

In this thesis, I first review previous studies on genetic association analyses of autism spectrum disorder. A large number of these studies fall into two categories: Genome Wide Association Studies (GWAS) and sequencing studies. Although GWAS are able to identify multiple common risk variants associated with different diseases, these common variants explain only a small portion …

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

Dissertations and 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 …

Scanned Ion Beam Therapy For Thoracic Tumors, John Gordon Eley

Dissertations and 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 …

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

Dissertations and 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 …

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

Dissertations and 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 …

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

Dissertations and 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 …

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

Dissertations and 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 …

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

Dissertations and 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 …