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Brachiocephalic Artery Cannulation In Proximal Aortic Surgery That Requires Circulatory Arrest, Mehmet Unal, Oguz Yilmaz, Ilker Akar, Ilker Ince, Cemal Aslan, Fatih Koc, Haluk Kafali

The Texas Heart Institute Journal

The brachiocephalic artery is an alternative cannulation site in the repair of ascending aortic lesions that require circulatory arrest. We evaluate the effectiveness and safety of this technique.

Proximal aortic surgery was performed in 32 patients from 2006 through 2012 via brachiocephalic artery cannulation and circulatory arrest. Twenty-four (75%) of the patients were men. The mean age was 48.69 ± 9.43 years (range, 30–68 yr). Twelve had type I dissection, 2 had type II dissection, and 18 had true aneurysms of the ascending aorta. All operations were performed through a median sternotomy. The arterial cannula was inserted through an 8-mm …

Anticoagulation With Bivalirudin During Deep Hypothermic Circulatory Arrest In A Patient With Heparin-Induced Thrombocytopenia, Agamemnon Pericleous, Mostafa Sadek, Mary Fitzmaurice, Constance Caldwell, Kris Natividad, Konstadinos A Plestis

The Texas Heart Institute Journal

Heparin-induced thrombocytopenia is a well-recognized complication of anticoagulation with heparin. We present the case of a patient with recent heparin-induced thrombocytopenia who subsequently needed surgery on an emergency basis for acute type A aortic dissection. This article reports the successful use of bivalirudin, a direct thrombin inhibitor, as an alternative to heparin throughout cardiopulmonary bypass and deep hypothermic circulatory arrest. We contend that bivalirudin is a safe alternative to heparin when performing surgery for aortic dissection and should be considered as an option for use in patients who present with heparin-induced thrombocytopenia.

Lkb1 Deficient Non-Small Cell Lung Cancer Cells Are Vulnerable To Energy Stress Induced By Atp Depletion, Chao Yang

Dissertations and Theses (Open Access)

Lung cancer is the second most frequent cancer in United States, which represents about 13.5% of new cancer cases every year. It accounts for about 27.2% of all cancer related deaths, which is more than the sum of deaths caused by prancretic, breast and colorectal. On average, only about 16% of lung cancer patients survive beyond 5 years. LKB1 is the third most mutated gene in lung cancer. It has been shown that LKB1 is mutated in at least 15% to 30% of NSCLC. Tumor with LKB1 mutation is associated with poor differentiation, high metastasis and worse response to chemotherapy. …

Swarna Ramaswamy_Thesis, Swarna S. Ramaswamy

Dissertations and Theses (Open Access)

STRUCTURAL INVESTIGATIONS OF LIGAND GATED ION CHANNELS

Swarna Ramaswamy, B.S

Advisor: Vasanthi Jayaraman, Ph.D.

Ion channels form an integral part of membrane proteins. In the nervous system including the central and the peripheral nervous system, ligand gated ion channels form a very important part of intercellular communications. They receive chemical signals and convert them to electrical signal, mainly by allowing ion passage across the cell membrane. Ion passage also translates into downstream signaling events. Faithful translation of these signals and transmittance is crucial for several physiological functions, implying that irregular ion channel function could lead to serious consequences.

This thesis …

The Role Of Mir-34a In Inhibition Of Prostate Tumor Growth In The Bone And Induction Of Autophagy, Sanchaika Gaur

Dissertations and Theses (Open Access)

Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men in the United States, with most deaths occurring from bone metastasis. Several new therapies have been FDA approved for bone-metastatic PCa, but patient survival has only marginally improved due to therapy resistance, which often arises from constitutive activation of compensatory signaling pathways. This dissertation work focused on a mechanistic understanding of how cross talk between tyrosine kinase receptors contributes to therapy resistance, and how this may be overcome by downregulating expression of these receptors. In PCa cell lines and xenograft models, I demonstrated that activation of IGF-1R …

Sox2-Dependent Transcriptional Control Of Airway Differentiation In The Mouse Lung, Belinda J. Hernandez

Dissertations and Theses (Open Access)

The lung is a highly branched tree-like tubular system that results from more than 20 generations of the conducting airways and consists of 300 million alveoli for gas exchange. Airway branches form via branching morphogenesis and then mature into conducting airways, in which the number and distribution of different cell types need to be precisely controlled. The conducting airways contain four lung cell types: club cells, ciliated cells, basal cells, and neuroendocrine cells.SOX2 is a well-known conducting airway marker. SOX2 is a transcription factor that is known to be important in embryonic development and induction of pluripotent stem cells. We …

Hypoxia Mediated Downregulation Of Mirna Biogenesis Leads To Increased Tumor Progression, Rajesha Rupaimoole

Dissertations and Theses (Open Access)

In recent years, there has been a growing recognition of the importance of tumor associated microenvironment in the initiation and progression of tumors. However, a mechanistic understanding of the complicated biological interplay between the stromal framework and malignant regions of the tumor remains incompletely understood. In this study, we address mechanisms by which hypoxia in the tumor microenvironment leads to attenuation of miRNA biogenesis by downregulation of two key enzymes, Drosha and Dicer in cancer cells. Previous data from our laboratory had shown the clinical relevance of downregulated Dicer and Drosha in ovarian and other cancer types, but a clear …

Sustained Adrenergic Signaling Promotes Cervical Cancer Progression, Nouara C. Sadaoui

Dissertations and Theses (Open Access)

Background: Chronic stress and sustained adrenergic signaling are known to promote tumor progression. The underlying mechanisms behind this process are not well understood. We examined the effects of sustained adrenergic signaling on cervical cancer progression through increased expression of HPV oncogenes, E6 and E7.

Materials and Methods: ADRβ expression levels were examined in patient-derived cervical cancer samples. We used an orthotopic model of cervical cancer to investigate the effects of restraint stress on tumor growth and metastasis. We evaluated the in vivo effects of a β-blocker, propranolol, and HPV E6/E7 siRNA. In vitro, ADRβ positive cervical cancer cells were …

Quantitative Analysis And Imaging-Based Insights Into The Characteristics And Mechanisms Of Yeast Pattern Formation, Lin Chen

Dissertations and Theses (Open Access)

Biofilm formation is a common lifestyle adapted by bacteria and fungi in response to various environmental stresses. Bacterial and fungal biofilms adhering to medical devices convey resistance to antibiotics or biocides, causing high rates of clinical infections. Microorganisms are protected from harsh environmental conditions by reduced stress penetration through the complex biofilm architecture with distinct patterns. Although the molecular regulations of surface patterning have been well characterized in bacteria, the mechanisms underlying the complex pattern formation in eukaryotic biofilms remain unclear.

This dissertation aims to investigate the salient features of robust colony expansion in yeast biofilms and the processes driving …

Dual Assembly Nanoparticles Achieve Sustained Silencing Of Znf304: A Novel Transcription Factor For Β1 Integrin, Burcu Aslan

Dissertations and Theses (Open Access)

Ovarian cancer (OC) is a highly metastatic disease, but no effective strategies to this process currently are known. Here, an integrated computational analysis of The Cancer Genome Atlas ovarian cancer dataset coupled with experimental validation identified a novel zinc finger transcriptional factor 304 (ZNF304) as one of the key factors for ovarian cancer metastasis. High tumoral ZNF304 expression was associated with poor overall survival in ovarian cancer patients. Through reverse phase protein array analysis, we demonstrated that ZNF304 promotes multiple proto-oncogenic pathways important for cell survival, migration, and invasion. ZNF304 transcriptionally regulates β1 integrin, which subsequently regulates Src/focal adhesion kinase …

Percutaneous Repair Of Post-Myocardial Infarction Ventricular Septal Defect: Current Approaches And Future Perspectives, Maria D Baldasare, Mark Polyakov, Glenn W Laub, Joseph T Costic, Daniel J Mccormick, Sheldon Goldberg

The Texas Heart Institute Journal

Post-myocardial infarction ventricular septal defect is a devastating complication of ST-elevation myocardial infarction. Although surgical intervention is considered the gold standard for treatment, it carries high morbidity and mortality rates. We present 2 cases that illustrate the application of percutaneous closure of a post-myocardial infarction ventricular septal defect: the first in a patient who had undergone prior surgical closure and then developed a new shunt, and the second as a bridge to definitive surgery in a critically ill patient.

Aortic Valve Reconstruction With Use Of Pericardial Leaflets In Adults With Bicuspid Aortic Valve Disease: Early And Midterm Outcomes, Meong Gun Song, Hyun Suk Yang, Jong Bum Choi, Je Kyoun Shin, Hyun Keun Chee, Jun Seok Kim

The Texas Heart Institute Journal

In this study, we retrospectively analyzed the outcomes of adults with bicuspid aortic valve (BAV) disease who underwent aortic valve reconstructive surgery (AVRS), consisting of replacement of the diseased BAV with 2 or 3 pericardial leaflets plus fixation of the sinotubular junction for accurate and constant leaflet coaptation. From December 2007 through April 2013, 135 consecutive patients (mean age, 49.2 ± 13.1 yr; 73.3% men) with symptomatic BAV disease underwent AVRS. Raphe was observed in 84 patients (62.2%), and the remaining 51 patients had pure BAV without raphe. A total of 122 patients (90.4%) underwent 3-leaflet reconstruction, and 13 (9.6%) …

Repeated Transradial Catheterization: Feasibility, Efficacy, And Safety, Marinos A Charalambous, Savvas S Constantinides, Michael A Talias, Elpidoforos S Soteriades, Christos P Christou

The Texas Heart Institute Journal

Transradial access is an alternative to the transfemoral approach in coronary interventions. It results in less access-site bleeding, shorter hospital stays, lower costs, and less pain for the patient. However, some authors have suggested that the transradial approach might lead to radial artery occlusion, which precludes repeated same-artery catheterizations. Using data from our center, we evaluated the feasibility, safety, and efficacy of repeated transradial catheterization.

We reviewed the 3,006 transradial catheterizations performed at our center from 2006 through 2009. Patients who had undergone at least one repeated transradial catheterization were identified, their cases monitored through 2012, and their baseline characteristics …

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

GSBS News

No abstract provided.

Off-Pump Myocardial Revascularization In A High-Risk Patient With Essential Thrombocythemia, Ahmad K Darwazah, Hamad Madi, Rami Zagha, Yahia Hawash

The Texas Heart Institute Journal

Essential thrombocythemia is a rare type of myeloproliferative disorder. Cerebral, myocardial, and peripheral thrombosis are all frequent complications of the disease.

A 71-year-old man presented with severe coronary artery disease, associated with cerebral vascular ischemic changes and erythromelalgia. His platelet count was 1,486 ×103/μL. The patient underwent successful myocardial revascularization by means of an off-pump technique after his platelet count had been reduced by hydroxycarbamide administration.

We conclude that the use of off-pump cardiopulmonary bypass in high-risk patients with essential thrombocythemia is safe. Reducing platelet count via the administration of hydroxycarbamide and the careful balancing of antiplatelets and anticoagulants is …

Use Of A Melody Pulmonary Valve In Transcatheter Valve-In-Valve Replacement For Tricuspid Valve Bioprosthesis Degeneration, David M Filsoof, David F Snipelisky, Brian P Shapiro

The Texas Heart Institute Journal

Bioprosthetic heart valves can degenerate and fail over time. Repeat surgery as a means of replacement increases morbidity and mortality rates, and some patients are not candidates for reoperation. A newer treatment, percutaneous transcatheter valve-in-valve implantation, might delay or substitute for invasive procedures. We present the case of a 51-year-old woman, a poor candidate for surgery who had prosthetic tricuspid valve degeneration and stenosis. We successfully performed valve-in-valve placement of a Melody® valve, using a procedure originally intended to treat pulmonary valve conduit obstruction or regurgitation. To our knowledge, this is among the first case reports to describe the use …

Contemporary Use Of Balloon Aortic Valvuloplasty In The Era Of Transcatheter Aortic Valve Implantation, Dawn S Hui, David M Shavelle, Mark J Cunningham, Ray V Matthews, Vaughn A Starnes

The Texas Heart Institute Journal

The development of transcatheter aortic valve implantation (TAVI) has increased the use of balloon aortic valvuloplasty (BAV) in treating aortic stenosis. We evaluated our use of BAV in an academic tertiary referral center with a developing TAVI program.

We reviewed 69 consecutive stand-alone BAV procedures that were performed in 62 patients (mean age, 77 ± 10 yr; 62% men; baseline mean New York Heart Association functional class, 3 ± 1) from January 2009 through December 2012. Enrollment for the CoreValve® clinical trial began in January 2011. We divided the study cohort into 2 distinct periods, defined as pre-TAVI (2009–2010) and …

Selective Elimination Of Malignant Melanoma Using The Novel Anti-Tumor Agents, Osw-1 And Peitc, Kausar Begam Riaz Ahmed

Dissertations and Theses (Open Access)

Metastatic melanoma is amongst the most refractory of cancers. Drug resistance and lack of therapeutic selectivity are two main challenges to successful melanoma therapy. Herein, we investigated the mechanims of anticancer activity and therapeutic selectivity of two novel agents, 3β, 16β, 17α-trihydroxycholest-5-en-22-one 16-O-[2-O-4-methoxybenzoyl-β-D-xylopyranosyl]- [1→3]-2-O-acetyl-α-l-arabinopyranoside (OSW-1) and β-Phenylethyl Isothiocyanate (PEITC) in melanoma.

OSW-1 inhibited melanoma cell viability at nanomolar concentrations with minimal toxicity to normal melanocytes. Mechanistic studies revealed that OSW-1 suppressed Disialoganglioside 3 Synthase (GD3S) gene expression in melanoma cells, leading to inhibition of gangliosides GD3 and GD2. GD3 is an abundantly expressed melanoma …

Effect Of Electrocautery On Endothelial Integrity Of The Internal Thoracic Artery: Ultrastructural Analysis With Transmission Electron Microscopy, Burak Onan, Mehmet Yeniterzi, Ismihan Selen Onan, Burak Ersoy, Suheyla Gonca, Elif Gelenli, Seyhun Solakoglu, Ihsan Bakir

The Texas Heart Institute Journal

The internal thoracic artery (ITA) is typically harvested from the chest wall by means of conventional electrocautery. We investigated the effects of electrocautery on endothelial-cell and vessel-wall morphology at the ultrastructural level during ITA harvesting. Internal thoracic artery specimens from 20 patients who underwent elective coronary artery bypass grafting were investigated in 2 groups. The ITA grafts were sharply dissected with use of a scalpel and clips in the control group (n=10) and were harvested by means of electrocautery in the study group (n=10). Each sample was evaluated for intimal, elastic-tissue, muscular-layer, and adventitial changes. Free flow was measured intraoperatively. …

Inflammation And C-Reactive Protein In Atrial Fibrillation: Cause Or Effect?, Roberto Galea, Maria Teresa Cardillo, Annalisa Caroli, Maria Giulia Marini, Chiara Sonnino, Maria L Narducci, Luigi M Biasucci

The Texas Heart Institute Journal

Atrial fibrillation is associated with substantial morbidity and mortality rates. The incompletely understood pathogenesis of this cardiac dysrhythmia makes it difficult to improve approaches to primary and secondary prevention. Evidence has accumulated in regard to a relationship between inflammation and atrial fibrillation. Investigators have correlated the dysrhythmia with myocarditis, pericardiotomy, and C-reactive protein levels, suggesting that inflammation causes atrial fibrillation or participates in its onset and continuation. Conversely, other investigators suggest that atrial fibrillation induces an inflammatory response. In this review, we summarize and critically discuss the nature and clinical role of inflammation and C-reactive protein in atrial fibrillation.

Association Of Cardiorespiratory Fitness And Adiposity With Inflammatory Biomarkers In Young Adults, Eunduck Park

Dissertations and Theses (Open Access)

Background: Low grade systemic inflammation plays a key role in atherosclerosis, and C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor- alpha (TNF -a), markers of systemic inflammation, are associated with cardiovascular events and adiposity. Cardiorespiratory fitness has shown health benefits by reducing circulating levels of inflammatory markers. However, it remains uncertain whether the negative association between cardiorespiratory fitness and inflammatory biomarkers is due to cardiorespiratory fitness itself or results from lower levels of adiposity. Moreover, the evidence examining the interaction between cardiorespiratory fitness and adiposity in inflammation in young adults is lacking.

Purpose: The aims of this study were …

Abdominal Fat Suspension Device For Maintaining Normal Cardiorespiratory Function In Patients Undergoing Conscious Sedation During Surgery: A Feasibility Study, Norman F Truong, Joanna C Nathan, Daeun Yoon, Gabriel Ochoa, Marisa Prevost, Sehyun Yun, Z Maria Oden, Mehdi Razavi

The Texas Heart Institute Journal

Obese patients undergoing conscious-sedation surgery have increased perioperative morbidity because their excess abdominal tissue limits diaphragmatic excursion. We describe a simple device that might help attenuate this risk. We created a noninvasive suction device for abdominal suspension. By lifting the burden of excess weight, this device should decrease respiratory effort. To test the feasibility of excess weight removal in relieving cardiac stress, we tested 22 supine, healthy, normal-weight subjects by measuring their heart rates with and without a 13-kg tissue model on their abdomen to simulate excess weight. There was no significant difference in blood oxygen saturation before and after …

Strategies To Sensitize Bladder Cancer Cells To Small Molecule Inhibitors Targeting The Pi3k Pathway, Giovanni Nitti

Dissertations and Theses (Open Access)

After many years of cancer research, it is well accepted by the scientific community that the future cure for this disease lies in a personalized therapeutic approach. Anticipating therapeutic outcome based on the genetic signature of a tumor has become the new paradigm. The PI3K pathway represents an ideal target for bladder cancer, as many of the key proteins of this pathway are altered or mutated in this particular type of cancer. Several small molecule inhibitors have been developed to target this pathway, but their efficacy has been shown to be heterogeneous among different cell lines and mostly cytostatic but …

Mapping The Human Vasculature By In Vivo Phage Display, Julianna Bronk

Dissertations and Theses (Open Access)

In vivo phage display screenings by intravenous injection of a random phage-displayed peptide library allow for the selection of peptides that localize to specific vascular beds. At the University of Texas MD Anderson Cancer Center, we have had the opportunity to perform phage display screenings in cancer patients in order to select for cancer specific targets directly in humans. These targets serve to define biochemical diversity of endothelial cell surfaces and can be validated and explored towards the design of vascular-targeted pharmacology. In the most recent patient screen, samples were recovered from hepatocellular carcinoma (HCC) as well as 26 additional …

Pi3k- And Mtor-Dependent Mechanisms Of Lapatinib Resistance And Resulting Therapeutic Opportunities, Samuel Brady

Dissertations and Theses (Open Access)

Breast cancers with HER2 amplification represent 20-25% of breast cancer cases and are frequently responsive to the HER2 kinase inhibitor lapatinib, but generally for only short duration. We aimed to understand how breast cancers with HER2 amplification become resistant to lapatinib, in order to identify potential therapies that can overcome lapatinib resistance. To establish lapatinib resistance models we treated three HER2+ breast cancer cell lines with lapatinib for several months until they became lapatinib-resistant. We then compared lapatinib-sensitive (parental) cells with their lapatinib-resistant (LapR) counterparts to identify changes conferring lapatinib resistance. We found that activation of PI3K, specifically the p110α …

Characterization Of The Vascular Pathology In The Acta2 R258c Mouse Model And Cerebrovascular Characterization Of The Acta2 Null Mouse, Carlos A. Villamizar

Dissertations and Theses (Open Access)

Mutations in ACTA2, the gene encoding for smooth muscle α-actin, predispose patients to a wide range of vascular diseases and is most commonly associated with thoracic aortic aneurysms (TAAD) and dissections (TAAD) and strokes. TAAD in patients is characterized by aortic media degeneration and loss in contractile force generation followed by aortic enlargement and subsequent rupture. Most stroke cases associated with ACTA2 are described as moyamoya-like cerebrovascular incidents characterized by distal occlusion of the internal carotid artery, stenosis of arteries in the Circle of Willis, and straightening of cerebral arteries. Patient samples are scarcely available for analysis, and the few …

Notch Signaling Inhibited By Ikaros1 In Human T-Cell Acute Lymphoblastic Leukemia, Camille W. Graham

Dissertations and Theses (Open Access)

The highly conserved Notch signaling pathway regulates cell growth, differentiation, survival and apoptosis. In hematopoiesis, Notch signaling drives commitment to the T-cell fate and promotes differentiation, T-cell receptor signaling and immune function. In T-cells, Notch signaling is oncogenic when constitutively active, promoting proliferation and survival while inhibiting differentiation. The majority of patients with T-cell acute lymphoblastic leukemia (TALL) have activating Notch mutations. Similarly, Notch activation is present in more than 75% of murine T-ALL models. In murine T-ALL, loss of Ikaros, a zinc finger transcriptional regulator, leads to disrupted differentiation and also cooperates with activated Notch signaling to promote T-ALL. …

Regulators Of Bacterial Cell Division: Investigations Of Min Oscillation And Ftsa Activity, Jennifer R. Herricks

Dissertations and Theses (Open Access)

Cytokinesis is a fundamental process that is essential for bacterial proliferation. The cytokinetic machinery in bacteria is termed the “divisome”. The divisome is a complex of proteins that forms a ring at midcell over dividing nucleoids. In order for daughter cells to form, the divisome must constrict. As constriction occurs, two new cell poles are formed, one for each daughter cell. The first step in divisome formation is the assembly of FtsZ into a Z ring. The work presented in this dissertation focuses on two proteins that regulate the Z ring: MinD, which is a part of the Min system …

Potential Roles Of Peroxidases In Caenorhabditis Elegans Innate Immunity, George R. Tiller, George R. Tiller

Dissertations and Theses (Open Access)

The production of ROS (reactive oxygen species) in response to pathogen detection is a rapid, nonspecific response that is evolutionarily conserved from nematodes to humans. ROS serve as direct and indirect effectors of innate and adaptive immunity. In Caenorhabditis elegans, a ROS burst is observed during infection and is mediated by the dual oxidase BLI-3, which produces H₂O₂. RNAi (RNA interference) to reduce the amount of BLI-3 results in a significant increase in susceptibility to pathogens, suggesting BLI-3 has a role in the immune response. However, H₂O₂ by itself is not a …

Targeting The Redox System To Overcome Mechanisms Of Drug Resistance In Chronic Lymphocytic Leukemia, Marcia A. Ogasawara

Dissertations and Theses (Open Access)

Chronic Lymphocytic Leukemia (CLL) is the most common form of leukemia diagnosed in Western countries and is characterized by clonal expansion of B cells. The clinical course of CLL is diverse and nearly 50% of patients present with chromosomal abnormalities. Deletion of the short arm on chromosome 17 (del17p) occurs in 5-7% of cases and presents with the shortest median survival time and often respond poorly to therapy. The tumor suppressor gene, TP53 is located on this region and it is well established that the p53 protein regulates multiple functions including: mitochondria biogenesis, response to DNA damage and redox balance. …