Digital Commons Network^™

Targeting Breast Cancer With Bacteriophage Associated Silicon Particles, Srimeenakshi Srinivasan

Dissertations and Theses (Open Access)

Nanoparticle based therapeutics have been successfully used in the treatment of breast cancer. Development of nanovectors targeted to cancer cells or elements in the tumor microenvironment has been pursued to improve their site specific accumulation while reducing the non-specific delivery to normal tissues. However, addition of targeting ligands to the surface of nanovectors while maintaining their payload carrying potential is generally challenging. Therefore, there is a critical need to develop surface decoration strategies that allow for effective combination of targeting and payload delivery to the tumor.

In this study, we propose a novel strategy for covering the surface of mesoporous …

Availability Of Dental Anomaly Phenotype In Individuals With Familial Adenomatous Polyposis, Andrea M. Lewis

Dissertations and Theses (Open Access)

Background: Mutations in the APC gene cause familial adenomatous polyposis (FAP), an autosomal dominant colorectal cancer predisposition associated with the development of hundreds to thousands of adenomatous colorectal polyps beginning in childhood or adolescence. Both malignant and non-malignant extracolonic manifestations are associated with APC gene mutations, including approximately 17% of individuals with various dental anomalies. The availability of dental anomaly information in the medical record remains to be evaluated.

Methods: Medical records were reviewed for documentation of dental anomalies. Dental questionnaires were mailed to 271 individuals with FAP at The University of Texas M. D. Anderson Cancer Center (UTMDACC) to …

Functional Analysis Of Cytosolic Hsp70 Nucleotide Exchange Factor Networks In Yeast, Jennifer Lynn Abrams

Dissertations and Theses (Open Access)

The Hsp70 class of molecular chaperones play critical roles in protein homeostasis via an ATP-dependent folding cycle. Cytosolic Hsp70s in the budding yeast Saccharomyces cerevisiae, Ssa and Ssb, interact with up to three distinct nucleotide exchange factors (NEFs) homologous to human counterparts; Sse1/Sse2/HSP110, Fes1/HspBP1, and Snl1/Bag1. In an effort to understand the differential functional contributions of the cytosolic NEFs to protein homeostasis (“proteostasis”), I carried out comparative genetic, biochemical and cell biological analyses. For these studies, I developed protocols to monitor protein disaggregation and reactivation in a near real-time coupled assay that revealed the importance of aggregate dynamics in the …

Gain-Of-Function Mouse Models To Investigate Biological Roles Of Prmt6, Alessandra Di Lorenzo

Dissertations and Theses (Open Access)

Gain-of-function Mouse Models to Investigate Biological Roles of PRMT6

Alessandra Di Lorenzo, Ph.D. Candidate

Mentor: Dr. Mark T. Bedford

Protein Arginine Methyltransferase 6 (PRMT6) is the histone tail writer that methylates the H3R2 (arginine 2 of histone H3) residue, which counteracts the activating H3K4me3 mark. PRMT6 has been shown to behave both as transcriptional co-repressor (i.e. trhrombospondin-1, p21, p53), and co-activator (nuclear receptors). The co-repressor function of PRMT6 is likely the result of H3K4me3 antagonism, while the mechanism by which PRMT6 exerts its co-activator function has yet to be elucidated. PRMT6 is over-expressed in several types of tumors including small …

Systematic Methodology For The Identification Of A Novel Autosomal Dominant Retinitis Pigmentosa Disease-Causing Gene, Jennifer D. Churchill

Dissertations and Theses (Open Access)

Retinitis pigmentosa (RP) is an inherited retinal disease that leads to degeneration of the retina through loss of rod and cone photoreceptor cells and subsequent loss of vision. RP affects approximately 1.5 million people world-wide. Mutations causing autosomal dominant retinitis pigmentosa (adRP) have been identified in 23 different genes. However, these mutations only account for approximately 70% of known adRP cases in Caucasians of Western-European origin and for an even smaller percentage of cases in other ethnicities. My research aims to increase the number of known genes associated with adRP by using an array of advanced genetic techniques to search …

Use Of Positron Emission To Mography For Proton Therapy Verification, Jongmin Cho

Dissertations and Theses (Open Access)

Positron emission tomography (PET), a tool commonly used for cancer staging and response monitoring, has recently been used for proton therapy verification. By imaging tissue activation following proton treatment, attempts have been made to verify proton dose and range. In this dissertation, two novel approaches were developed and tested for the purpose of help improve the proton dose and range estimation as well as verification.

Although there are still some challenges, attempts for proton dose verification using PET has been made by comparing Monte Carlo dose and PET simulations with treatment planned dose and measured PET. In this approach, …

Image-Guided Proton Therapy For Online Dose-Evaluation And Adaptive Planning, Joey P. Cheung

Dissertations and Theses (Open Access)

The main advantage for using protons in radiotherapy is their finite range in patients, allowing for potential improved sparing of normal tissues. However, this comes at a cost of increased sensitivity to range uncertainties. Density changes along the beam path will affect the proton range and the resultant dose distribution, making it difficult to estimate the impact of visible anatomic changes to the patient dose distribution. In order to better understand the effect of anatomy change on proton dose, some form of treatment-time verification is required and methods to correct for observed changes would be beneficial. Therefore, this project aims …

Role Of Talin1 Phosphorylation In Beta1 Integrin Activation And Prostate Cancer Metastasis, Jung-Kang Jin

Dissertations and Theses (Open Access)

Talins are adaptor proteins that regulate focal adhesion signaling by conjugating integrins to the cytoskeleton. Talins directly bind and activate integrins but the mechanism by which this occurs is unknown. As integrin activation and overexpression of talins promote prostate cancer metastasis, understanding the mechanism by which talins activate integrins will better elucidate their roles in Prostate cancer metastasis. Phosphorylation of talins on serine 425 has been associated with β1 integrin functions. Work in this dissertation tested the hypothesis that increased talin1 S425 phosphorylation was required for β1 integrin activation and promotion of prostate cancer metastasis.

I first used shRNA to …

Anti-Insulin Resistance Treatments Suppress Her2+ Breast Cancer Growth Via Altering Metabolism, Ping-Chieh Chou

Dissertations and Theses (Open Access)

Epidemiological studies have identified that type 2 diabetes mellitus (DM2) is a significant risk factor for carcinogenesis and cancer death, including breast cancer. Our previous finding in patients showed that anti-insulin resistance treatments are associated with improved HER2⁺ breast cancer survival of diabetic women. However, there were no transgenic mouse models to study the correlation and explain the detailed mechanism. We generated a mouse model of HER2⁺ breast cancer with DM2 by crossing leptin receptor point mutation (Lepr ^db/+) and MMTV-ErbB2 (neu) mice. The MMTV-ErbB2/Lepr ^db/db mice had a poor survival rate compared …

Characterization Of Ftsa-Ftsn Interaction During Escherichia Coli Cell Division, [email protected] K. Busiek

Dissertations and Theses (Open Access)

Division of a bacterial cell into two equal daughter cells requires precise assembly and constriction of the division machinery, or divisome. The Escherichia coli divisome includes nearly a dozen essential cell division proteins that assemble at midcell between segregating sister chromosomes. FtsZ, a homolog of eukaryotic tubulin, is the first essential cell division protein to localize at midcell where it polymerizes into a ring-shaped scaffold (Z ring). Establishment of the Z ring is required for recruitment of downstream cell division proteins including FtsA, a cytoplasmic protein that tethers the Z ring to the inner membrane. Following localization of FtsA and …

Support Desired By Women Following Termination Of Pregnancy For A Fetal Anomaly, Aarti Ramdaney

Dissertations and Theses (Open Access)

With the rapidly evolving field of prenatal testing, there is a growing need to provide support for women pursuing a termination of pregnancy following the discovery of a fetal anomaly. Previous studies have documented that women in this situation often feel unsupported after the procedure, but the type of resources desired by this population remains undetermined. A longitudinal study was performed in 51 women terminating for a fetal anomaly at a private clinic at the time of the procedure, at 6 weeks, and at 3 months following the event. Surveys were kept anonymous and investigated the awareness and utilization of …

Cancer Diagnosis During Pregnancy: Evaluating The Challenges Faced By Oncologists, Shannon Kaye Mulligan

Dissertations and Theses (Open Access)

Cancer during pregnancy is occurring more often than in the past, and it is estimated that cancer is diagnosed in approximately 1/1000 pregnancies. A consensus exists that management of these patients should prioritize survival of the mother and minimize teratogenic effects to the fetus, and utilize a multidisciplinary approach, involving medical oncology, surgical oncology, radiation oncology, radiology, and a maternal fetal medicine specialist. In spite of this consensus, there is not a standardized approach for treating cancer in women diagnosed during pregnancy. Due to the relative infrequency of this situation in the oncologic setting, the aims of this study were …

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 …

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 …

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 …

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. …

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. …

Emergent Surgical Pulmonary Embolectomy In A Pregnant Woman: Case Report And Literature Review, Giovanni Saeed, Michael Möller, Jörg Neuzner, Rainer Gradaus, Werner Stein, Uwe Langebrake, Thomas Dimpfl, Meradjoddin Matin, Ali Peivandi

The Texas Heart Institute Journal

Acute pulmonary embolism is a leading cause of death during pregnancy and delivery in the United States. We describe the case of a 25-year-old woman who presented in cardiogenic shock in week 38 of her first pregnancy. After the emergent cesarean delivery of a healthy male neonate, the mother underwent immediate surgical pulmonary embolectomy. We confirmed the diagnosis of pulmonary embolism intraoperatively by means of transesophageal echocardiography and removed large clots from the patient's pulmonary arteries. Mother and child were doing well, 27 months later. In addition to presenting our patient's case, we discuss the other relevant reports and the …

Cardiac Magnetic Resonance Imaging For The Investigation Of Cardiovascular Disorders Part 2: Emerging Applications, Ajit H Goenka, Hui Wang, Scott D Flamm

The Texas Heart Institute Journal

Cardiac magnetic resonance imaging has emerged as a robust noninvasive technique for the investigation of cardiovascular disorders. The coming-of-age of cardiac magnetic resonance—and especially its widening span of applications—has generated both excitement and uncertainty in regard to its potential clinical use and its role vis-à-vis conventional imaging techniques. The purpose of this evidence-based review is to discuss some of these issues by highlighting the current (Part 1, previously published) and emerging (Part 2) applications of cardiac magnetic resonance. Familiarity with the versatile uses of cardiac magnetic resonance will facilitate its wider clinical acceptance for improving the management of patients with …

The Odyssey Of Tavr From Concept To Clinical Reality, Alain G Cribier

The Texas Heart Institute Journal

No abstract provided.

The 1,000th Vad, The Great Rivalry, And The Grand Experiment Of The Texas Medical Center, Todd K Rosengart

The Texas Heart Institute Journal

No abstract provided.

Papillary Muscle Repositioning As A Subvalvular Apparatus Preservation Technique In Mitral Stenosis Patients With Normal Left Ventricular Systolic Function, Gokhan Lafci, Kerim Cagli, Omer Faruk Cicek, Kemal Korkmaz, Osman Turak, Alper Uzun, Adnan Yalcinkaya, Adem Diken, Eren Gunertem, Kumral Cagli

The Texas Heart Institute Journal

Subvalvular apparatus preservation is an important concept in mitral valve replacement (MVR) surgery that is performed to remedy mitral regurgitation. In this study, we sought to determine the effects of papillary muscle repositioning (PMR) on clinical outcomes and echocardiographic left ventricular function in rheumatic mitral stenosis patients who had normal left ventricular systolic function.

We prospectively assigned 115 patients who were scheduled for MVR surgery with mechanical prosthesis to either PMR or MVR-only groups. Functional class and echocardiographic variables were evaluated at baseline and at early and late postoperative follow-up examinations. All values were compared between the 2 groups.

The …

Cardiac Magnetic Resonance Imaging For The Investigation Of Cardiovascular Disorders Part 1: Current Applications, Ajit H Goenka, Scott D Flamm

The Texas Heart Institute Journal

Cardiac magnetic resonance imaging is a robust noninvasive technique for investigating cardiovascular disorders. The evolution of cardiac magnetic resonance and its widening span of diagnostic and prognostic applications have generated excitement as well as uncertainty regarding its potential clinical use and its role vis-à-vis conventional imaging techniques. The purpose of this evidence-based review is to discuss some of these issues by highlighting the current (Part 1) and emerging (Part 2) applications of cardiac magnetic resonance. Familiarity with the versatility and usefulness of cardiac magnetic resonance will facilitate its wider clinical acceptance for improving the management of cardiovascular disorders.

Systemic Effects Of Intracoronary Nitroglycerin During Coronary Angiography In Children After Heart Transplantation, Diego A Lara, Mary K Olive, James F George, Robert N Brown, Waldemar F Carlo, Edward V Colvin, Brad L Steenwyck, F Bennett Pearce

The Texas Heart Institute Journal

Coronary spasm during coronary angiography for vasculopathy in children can be prevented by the intracoronary administration of nitroglycerin. We reviewed the anesthesia and catheterization reports and charts for pediatric transplant recipients who underwent angiography from 2005 through 2010. Correlation analysis was used to study the relation of post-injection systolic blood pressure (SBP) to nitroglycerin dose. Forty-one angiographic evaluations were performed on 25 patients (13 male and 12 female). Mean age was 9.9 ± 3.2 years (range, 3.3–16.1 yr). The mean total dose of nitroglycerin was 2.93 ± 1.60 µg/kg (range, 1–8 µg/kg).

There was a significant drop between the baseline …

Papillary Muscle Repositioning As A Subvalvular Apparatus Preservation Technique In Mitral Stenosis Patients With Normal Left Ventricular Systolic Function, Imthiaz Manoly, Dimos Karangelis, Nicola Viola, Marcus Haw

The Texas Heart Institute Journal

Surgically repairing Bland-White-Garland syndrome (anomalous origin of the left coronary artery from the pulmonary artery) is a challenge if there are variations in the origin of the anomalous artery. We report the successful repair of this congenital abnormality in a 19-year-old woman who presented with an acute anterior myocardial infarction. The anomalous artery originated from the anterior-facing sinus of the pulmonary artery, which precluded typical repair by direct reimplantation or fashioning an intrapulmonary tunnel. We created an extrapulmonary tunnel, using a strip of pulmonary artery anteriorly and an aortic flap posteriorly. Three years postoperatively, the anastomosis was patent and the …

Repair Of Bicuspid Aortic Valve In The Presence Of Endocarditis And Leaflet Perforation, William D T Kent, Hadi D Toeg, Jehangir J Appoo

The Texas Heart Institute Journal

Aortic valve repair can be a good option in younger patients who have severe aortic regurgitation. A systematic, disease-directed approach can simplify repair. This case report describes how a simplified approach can be successfully applied to complex pathologic conditions of the aortic valve.

A 49-year-old man with a bicuspid aortic valve and a history of endocarditis presented with severe aortic regurgitation and evidence of recurrent infection. Intraoperatively, we found congenital and degenerative aortic anatomy with endocarditis and perforation. We performed aortic valve repair to enable leaflet coaptation and to adjust the coaptation height. After 24 months, the patient remained well, …