Medicine and Health Sciences Commons^™

Developmental Origins Of Renal Connecting Tubule And Collecting Duct: Role Of Aqp2+ Progenitor Cells, Lihe Chen

Dissertations and Theses (Open Access)

The connecting tubule interconnects the nephron and collecting duct, which arise from kidney mesenchyme and the ureteric bud, respectively, to generate the functional tubular networks. The collecting duct is comprised of principal cells and intercalated cells, which bear different molecular signatures and regulate sodium/water and acid/base balance, respectively. The progenitor cells of the connecting tubule and the collecting duct remain virtually unknown.

We generated two Aqp2 lineage tracing mouse models. In these models, Aqp2Cre transgene drives Cre expression by the Aqp2 promoter to exclusively either inactivate histone H3 K79 methyltransferase Dot1l (Dot1l^f/f Aqp2Cre) or activate RFP in …

Targeted Inhibition Of Pi3k, Mtor, And Igf1r For The Treatment Of Undifferentiated Pleomorphic Sarcoma, Caitlin Denise May

Dissertations and Theses (Open Access)

Undifferentiated pleomorphic sarcoma (UPS) is an aggressive mesenchymal malignancy largely devoid of indicators for its originating tissue. Surgery remains the standard of care, as radiation therapy and systemic chemotherapy have limited efficacy in UPS patients with localized and metastatic disease, respectively. Therefore, it is imperative to identify and evaluate novel therapeutic targets in UPS in order to provide more efficacious treatment options for patients. Previous studies have revealed that members of the phosphatidylinositol-3-kinase/mammalian target of rapamycin (PI3K/mTOR) signaling pathway can be used to predict patient outcome in cohorts containing patients with various subtypes of soft tissue sarcoma. Furthermore, we have …

Texas Physicians' Awareness And Utilization Of Genetic Services, Callie L. Jenevein

Dissertations and Theses (Open Access)

The number of disorders for which genetic testing is available has increased nearly 500% in the past 15 years. Access to the majority of genetic tests and services hinges on physicians’ ability to identify patients at risk for genetic disease and provide appropriate testing and counseling or refer to genetic specialists. Recent research demonstrates the need for referrals to genetic specialists by showing that many physicians lack skills required to perform appropriate genetic services, such as making proper risk assessments, providing genetic counseling, ordering genetic testing and interpreting results. However, little research exists on physicians’ awareness and utilization of genetic …

Spiritual Exploration In The Prenatal Genetic Counseling Session, Katelynn G. Sagaser

Dissertations and Theses (Open Access)

Religion and spirituality are important components of many individuals’ lives, and spiritual needs may present among persons receiving medical care. Spirituality has been demonstrated to be significant in the coping of women experiencing pregnancy complications (Breen et al. 2006; Price et al. 2007). To characterize the manner in which prenatal genetic counselors might address spiritual issues with their patients, we surveyed 283 patients receiving prenatal genetic counseling using the Brief RCope and a series of questions that examined interest in spiritual exploration. Counselors were concurrently surveyed to identify the spiritual language used within the session and the counselor’s perceived importance …

Selection Methods For Genetically-Modified T Cells: In Support Of Translational Therapy, David Rushworth

Dissertations and Theses (Open Access)

T cells are blood cells which organize the immune system of the host. These cells are necessary for the host to respond appropriately to threats from foreign organisms and cancerous growth. However, in the case of certain infections and cancer, T cells are unable to respond appropriately to a threat and establish immunity. This leads to disease when the infection or cancer is not sufficiently eliminated. On the other hand, T cells can lack tolerance for healthy tissue and perceive healthy tissue as infected. The ensuing over-reactive immune response also leads to disease. A delicate balance must exist between immunity …

Evaluation Of Current Knowledge Of Genetics Among Dental Students, Residents And Dental Hygiene Students, Carla Mcgruder

Dissertations and Theses (Open Access)

Genetic testing is increasingly available in clinical settings. To provide personalized patient care, dental health professionals must have a greater understanding of genetics. The Commission on Dental Accreditation (CODA) credentials all dental schools in the United States and currently does not mandate genetics training for official approval of programs. There is little information about dental genetics education and no known studies that have evaluated dental students, residents and dental hygiene students’ knowledge of human genetics. It is crucial to assess genetics knowledge of this population to ascertain if dental schools are preparing students for the future of personalized dentistry. This …

Social-Demographics, Health Behaviors, Telomere Length In Mexican-American Cohort And Circulating Dna Methylation In Bladder Cancer, Lixia Han

Dissertations and Theses (Open Access)

I. SOCIAL-DEMOGRAPHICS, HEALTH BEHAVIORS, AND TELOMERE LENGTH IN MEXICAN AMERICANS: A COHORT STUDY

Recent studies using a prospective cohort design have suggested that telomere length in peripheral blood leukocytes is not only a potential indicator of cellular aging that has been linked to stressful life experience and health behaviors, but also a prognostic marker for major chronic diseases; however, such study has never been done among adult Mexican Americans. In this current study, we examined cross-sectional associations among social-demographics, lifestyle behaviors, and relative telomere length (RTL) in peripheral blood leukocytes, as well as longitudinal relationships among major chronic diseases, weight …

Rest Regulatory Circuit Controls Distinct Oncogenic Properties Of Glioblastoma Stem Cells Through Specific Micrornas, Anantha L Marisetty

Dissertations and Theses (Open Access)

Glioblastoma Multiforme (GBM) is the most common and aggressive primary malignant brain tumor in adults. With an average survival of only 12-16 months the prognosis for GBM patients remains dismal, with less than 5% of patients surviving 5 years. New mechanism-based approaches are necessary for the management of patients with GBM. Many GBM tumors are believed to be caused by self-renewing, glioblastoma-derived stem-like cells (GSCs). These GSCs are resistant to chemo- and radiation therapies, and are believed to be responsible for tumor recurrence. In a recent paper from our lab we have shown that REST, RE1-silencing transcription factor, regulates oncogenic …

Actions Of Pi3k-Delta Inhibitor, Idelalisib, And Its Combination With Bendamustine In Chronic Lymphocytic Leukemia, Prexy Modi

Dissertations and Theses (Open Access)

Class I phosphatidylinositol 3-kinase isoforms (α, β, δ, and γ) play a major role in cancer cell growth and survival. PI3K α and β are most studied. PI3K pathway is highly dysregulated in many cancers and aberrant PI3K signaling is associated with oncogene mutations and disease progression in solid tumors and in hematologic malignancies.

Chronic lymphocytic leukemia (CLL) is driven by B-cell receptor (BCR) signaling that promotes B-cell proliferation and survival. PI3K is a critical node in BCR pathway and PI3Kδ has a pivotal role in B-cell development and maintenance and this isoform is over-expressed in many B-cell malignancies, including …

Functional In Vivo Screen Identifies Pygo2 As A Putative Gene To Promote Prostate Cancer, Xiaolu Pan

Dissertations and Theses (Open Access)

Poor prognosis of prostate cancer is correlated with rampant chromosomal copy number alterations, highlighting the potential function of genes with copy number gains and losses in driving prostate cancer progression. To identify putative genes promoting prostate cancer, an in vivo tumorigenesis screen was performed for 286 genes that are recurrently amplified and overexpressed in human prostate cancer. The transcription co-activator protein PYGO2 was identified as a major hit for further in vivo functional and clinical validation. Overexpression of PYGO2 could enhance primary tumor growth as well as local invasion to lymph nodes using AR-positive prostate cancer cell line LNCaP. PYGO2 …

Investigating The Roles Of P63 And P73 Isoforms To Therapeutically Treat P53-Altered Cancers, Avinashnarayan Venkatanarayan

Dissertations and Theses (Open Access)

Investigating the roles of p63 & p73 isoforms to therapeutically treat

p53-altered cancers

Avinashnarayan Venkatanarayan, M.S.

Supervisory Professor: Elsa R. Flores, Ph.D.

The TP53 tumor suppressor is mutated in approximately 50% of human cancers rendering cancer therapies ineffective. p53 reactivation suppresses tumor formation in mice. However, this strategy has proven difficult to implement therapeutically. An alternate approach to overcome p53 loss is to manipulate the p53-family members, p63 and p73, which interact and share structural similarities to p53. p63 and p73, unlike p53 are less frequently mutated and have two major isoforms with distinct functions …

Evaluating The Nccn Clinical Criteria For Hereditary Breast And Ovarian Cancer Syndrome Genetic Testing, Caiqian Wu

Dissertations and Theses (Open Access)

Hereditary Breast and Ovarian Cancer (HBOC) syndrome predisposes females with a BRCA1 or BRCA2 mutation to an up to 85% lifetime risk for breast cancer and an up to 40% lifetime risk for ovarian cancer. It is crucial for individuals with HBOC to be identified to allow for proper screening, management, and identification of at-risk family members in order to reduce mortality. The National Comprehensive Cancer Network (NCCN) has established clinical guidelines for when to recommend BRCA1/2 testing. A retrospective chart review of 1123 M.D. Anderson Cancer Center breast cancer patients was performed in order to evaluate the positive predictive …

Gene Set Analysis Of Post-Lactational Mammary Gland Involution Gene Signatures In Inflammatory And Triple Negative Breast Cancer, Arvind Bambhroliya

Dissertations and Theses (Open Access)

With each cycle of pregnancy and lactation, the mammary gland undergoes dramatic changes. Clarkson et al. (2004) and Stein et al. (2004) conducted a detailed analysis of these changes in the mouse mammary gland. Their results showed that tissue remodeling during post-lactational involution period mimics wound healing and tumorigenesis like pathological conditions. This indicates that post-lactational involution may create the microenvironment that initiates the development of precancerous mammary cells and promotes the progression of precancerous cells into cancer cells. Moreover, epidemiological studies have found that triple-negative (TN) breast cancer (BC) is associated with lower frequency and duration of breastfeeding compared …

Thermal Ablation Alters The Tumor Microenvironment Activating A Robust Immune Response., Matthew T. Campbell M.D.

Dissertations and Theses (Open Access)

THERMAL ABLATION ALTERS THE TUMOR MICROENVIRONMENT ACTIVATING A ROBUST IMMUNE RESPONSE.

Matthew T Campbell, M.D.

Advisor Professor: Padmanee Sharma, M.D Ph.D

Ablation techniques including radiofrequency ablation (RFA) and cryoablation have been shown to influence the immune system in animal models. Rare abscopal events, a distant metastatic response to a local procedure, have been observed in humans following both RFA and cryoablation. These rare observations have led to interest in further defining the impact of ablation procedures on the immune signature in the tumor microenvironment and in the systemic circulation.

Retrospectively 9 patients with nephrectomy alone (control) were compared to 16 …

Post-Translational Regulation Of Zeb1 Contributes To Tgfβ-Mediated Emt, Roxsan Manshouri

Dissertations and Theses (Open Access)

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the United States due in part to the affinity of tumors to metastasize. Understanding the process which contributes to metastasis provides promise for the discovery of novel therapeutic targets. Epithelial-to-mesenchymal transition (EMT) is a proposed model for the initiation of metastasis. During EMT epithelial cells lose their cell adhesion properties and acquire a mesenchymal-like phenotype, allowing tumor cells to migrate from their epithelial cell community and invade remote locations. EMT is mediated by several signaling pathways, with transforming growth factor-beta (TGF-β) receiving attention for its up-regulation in …

Correlation Matrix Analysis Identifies Gene Signatures Of Immune Cell Subsets And Their Interactions In Follicular Lymphoma, Jason R. Westin

Dissertations and Theses (Open Access)

There are important but ill-defined interactions between benign immune cell subsets and neoplastic B cells within follicular lymphoma (FL). Using the novel technique of correlation matrix analysis (CMA) of publicly available FL whole-tumor gene expression profiling (GEP) data, we have identified signatures of immune cell subsets. Overall survival correlated most highly with a model using signatures of macrophages, T cells, and stroma, which was able to add significantly to existing clinical prognostic tools. From our own data of a cohort of 43 FL tumors sorted into B-cell and non-B cell (NB) fractions for GEP, CMA of the tumor infiltrating NB …

Isoform Selective Regulation Of Adenylyl Cyclase By Small Molecule Inhibitors And Gbetagamma Protein, Cameron S. Brand

Dissertations and Theses (Open Access)

The nine membrane-bound isoforms of adenylyl cyclase (AC), via synthesis of the signaling molecule cyclic AMP (cAMP), are involved in many isoform specific physiological functions. All nine isoforms share a similar structural organization; thus, AC isoform differences in physiological function are due to different regulatory profiles. A physiological example is Gβγ, which can conditionally enhance stimulation of ACs 2, 4, 5, 6, and 7, but inhibit ACs 1, 3, and 8. There is also pharmacological control of AC isoforms through small molecule inhibitors.

Isoform specific AC functions could be explained by regulatory differences as subtle as single amino acid changes. …

Measuring Single Cell Responses To Lapatinib In A Heterogeneous Population, Preety Priya

Dissertations and Theses (Open Access)

Cancer is notonedisease butasaga of diseases and is the outcome of disturbed homeostasis in the normal cells due to the deregulation of its genetic makeup. With advent of technologies thatallowdetailed molecular characterizationoftumors, targeted therapies have emerged as a more promising and specific mode of treatment. However, a major challenge with targeted therapy is the acquired resistance in the cancer cells to these therapies, quite often very rapidly in the course of a few months. One of the major targets in cancer has been the EGFR/ErbB2 network in breast and other cancer types. Prior work from our lab and others have …

Regulation Of Cell Adhesion By The Ferm Proteins, Ptpn14 And Merlin, Patty Dimarco Hewitt

Dissertations and Theses (Open Access)

Cell-cell adhesion is critical for the control of tissue organization and homeostasis. A family of proteins that regulate cell-cell adhesions is the FERM (4.1 protein, Ezrin, Radixin, Moesin) domain-containing proteins.One FERM domain protein, the non-receptor tyrosine phosphatase PTPN14, is mutated or deleted in several human cancers suggesting that it may be involved in tumor development and/or progression. Additionally, the loss of the FERM domain protein Merlin is associated with tumor development and metastasis.Both PTPN14 and Merlin have been shown to localize and possibly regulate adherens junction (AJ) functions. This work sought to determine if …

Gsbs News, Spring 2015, Graduate School Of Biomedical Sciences, University Of Texas Health Science Center At Houston/M.D. Anderson Cancer Center

GSBS News

No abstract provided.

Prenatal Diagnosis Of Left Pulmonary Artery-To-Pulmonary Vein Fistula And Its Successful Surgical Repair In A Neonate, Oleksii Ostras, Andrii Kurkevych, Lyubomyr Bohuta, Tetyana Yalynska, Tammo Raad, Mark Lewin, Illya Yemets

The Texas Heart Institute Journal

Pulmonary arteriovenous fistula is a rare disease. To the best of our knowledge, prenatal diagnosis of a fistula between the left pulmonary artery and the left pulmonary vein has not been described in the medical literature. We report a case of the prenatal diagnosis of a left pulmonary artery-to-pulmonary vein fistula, followed by successful neonatal surgical repair.

Transcatheter Aortic Valve Implantation Despite Challenging Vascular Access, Angelo Nascimbene, Federico Azpurua, James J Livesay, R David Fish, Zvonimir Krajcer

The Texas Heart Institute Journal

We describe transcatheter aortic valve implantation in a patient who had severe peripheral artery disease. The patient's vascular condition required additional preliminary peripheral intervention to enable adequate vascular access.

A 78-year-old man with severe aortic stenosis, substantial comorbidities, and severe heart failure symptoms was referred for aortic valve replacement. The patient's 20-mm aortic annulus necessitated the use of a 23-mm Edwards Sapien valve inserted through a 22F sheath, which itself needed a vessel diameter of at least 7 mm for percutaneous delivery. The left common femoral artery was selected for valve delivery. The left iliac artery and infrarenal aorta underwent …

When The Chief Complaint Tells It All, Herbert L Fred

The Texas Heart Institute Journal

No abstract provided.

Regression Of Left Ventricular Mass After Implantation Of The Sutureless 3f Enable Aortic Bioprosthesis, Giovanni Concistrè, Antonio Miceli, Federica Marchi, Francesca Chiaramonti, Mattia Glauber, Marco Solinas

The Texas Heart Institute Journal

Left ventricular hypertrophy in aortic stenosis is considered a compensatory response for the maintenance of systolic function but a risk factor for cardiac morbidity and death. We investigated the degree of left ventricular mass regression after implantation of the sutureless Medtronic 3f Enable® Aortic Bioprosthesis.

We studied 19 patients who, from May 2010 through July 2011, underwent isolated aortic valve replacement with the 3f Enable bioprosthetic valve, with clinical and echocardiographic follow-up at 6 months. The mean age was 77.1 ± 5.1 years (range, 68–86 yr); 14 patients were women (73.7%); and the mean logistic EuroSCORE was 15.4% ± 11.8%. …

Pathways Involved In Interleukin-1Β-Mediated Murine Cardiomyocyte Apoptosis, Yi Shen, Jie Qin, Peili Bu

The Texas Heart Institute Journal

Accumulating evidence suggests that interleukin-1 (IL-1) signaling plays an essential role in the pathogenesis of heart failure by inducing cardiomyocyte apoptosis, but the mechanisms of this process are poorly defined. We further explored these molecular pathways.

We isolated cardiomyocytes from neonatal mice and then cultured and stimulated them with murine IL-1β in vitro. Cell apoptotic ratios were measured by means of flow cytometry. Expression of effector molecules was analyzed by means of enzyme-linked immunosorbent assay, Western blotting, and real-time quantitative polymerase chain reaction. The results showed that IL-1β induced murine cardiomyocyte apoptosis through a release of cytochrome c into cytoplasm …

Ms171: Interview With Robin Britt, Robin Britt Edd, Rn, Houston Academy Of Medicine-Texas Medical Center Library

Texas Medical Center - Women's History Project

An oral history interview with Robin Britt, EDD, RN of Texas Woman's University College of Nursing. See more at Texas Medical Center-Women's History Project and its finding aid.

Ms171: Interview With Elizabeth Travis, Elizabeth Travis Ph.D., Houston Academy Of Medicine-Texas Medical Center Library

Texas Medical Center - Women's History Project

An oral history interview with Elizabeth Travis, PhD of MD Anderson Cancer Center. See more at Texas Medical Center-Women's History Project and its finding aid.

Ms171: Interview With Asha Kapadia, Asha Kapadia Ph.D., Houston Academy Of Medicine-Texas Medical Center Library

Texas Medical Center - Women's History Project

An oral history interview with Asha Kapadia, PhD of University of Texas School of Public Health. See more at Texas Medical Center-Women's History Project and its finding aid.

Ms171: Interview With Janet Butel, Janet Butel Ph.D., Houston Academy Of Medicine-Texas Medical Center Library

Texas Medical Center - Women's History Project

An Oral history interview with Janet Butel, PhD of Baylor College of Medicine. See more at Texas Medical Center-Women's History Project and its finding aid.

Early Detection Of A Cavopulmonary Tumor Embolus With The Use Of Transesophageal Echocardiography, Magdy M El-Sayed Ahmed, Raed M Al-Najjar, Muhammad Aftab, James M Anton, John S Colen, Ross M Reul

The Texas Heart Institute Journal

Pulmonary tumor embolization from renal cell carcinoma is associated with severe cardiopulmonary morbidity and high perioperative mortality rates. We report the case of a 71-year-old woman who presented with right-sided abdominal pain. Magnetic resonance images revealed a mass originating from the upper pole of the right kidney and extending into the infrahepatic portion of the inferior vena cava. Transesophageal echocardiography was continuously used to monitor the mass during intended radical nephrectomy and tumor resection. When the right kidney was mobilized, intracaval thrombus detached and migrated to the patient's right atrium, causing severe hemodynamic instability. After emergent sternotomy and during the …