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Articles 1 - 23 of 23
Full-Text Articles in Medicine and Health Sciences
Epacs: Epigenetic Regulators That Affect Cell Survival In Cancer., Catherine Murari
Epacs: Epigenetic Regulators That Affect Cell Survival In Cancer., Catherine Murari
Theses & Dissertations
Cyclic adenosine monophosphate (cAMP) is a second messenger responsive to many external stimuli, playing an important role in cellular gene expression, metabolism, migration, differentiation, hypertrophy, apoptosis and secretion. All of these cellular functions are important in many diseases including cancer. Most of its effects were initially attributed to the classical protein kinase A (PKA) protein, but cellular functions such as proliferation and migration were found to be PKA independent and dependent on the newly discovered exchange proteins directly activated by cAMP (EPACs). EPACs are single polypeptides that primarily function as guanine exchange factors (GEFs) for Rap proteins that allow the …
How The Manipulation Of The Ras Homolog Enriched In Striatum Alters The Behavioral And Molecular Progression Of Huntington’S Disease, Franklin A. Lee
How The Manipulation Of The Ras Homolog Enriched In Striatum Alters The Behavioral And Molecular Progression Of Huntington’S Disease, Franklin A. Lee
University of New Orleans Theses and Dissertations
Huntington’s disease is an incurable, progressive neurological disorder characterized by loss of motor control, psychiatric dysfunction, and eventual dystonia leading to death. Despite the fact that this disorder is caused by a mutation in one single gene, there is no cure. The mutant Huntingtin (mHtt) protein is expressed ubiquitously throughout the brain but frank cell death is limited to the striatum. Recent work has suggested that Rhes, Ras homolog enriched in striatum, which is selectively expressed in the striatum, may play a role in Huntington’s disease neuropathology. In vitro studies have shown Rhes to be an E3 ligase for the …
Intracellular Trafficking Governs The Processing Of The Amyloid Precursor Protein And The Secretion Of Beta-Amyloid, Joshua Hoi Ki Tam
Intracellular Trafficking Governs The Processing Of The Amyloid Precursor Protein And The Secretion Of Beta-Amyloid, Joshua Hoi Ki Tam
Electronic Thesis and Dissertation Repository
One of the hallmarks of Alzheimer’s disease (AD) is the pathological accumulation of β-amyloid (Aβ) in the brains of AD patients. Oligomeric and fibrillar aggregates of Aβ have been shown to be neurotoxic to neurons and hippocampal slices. Therefore, limiting Aβ production is an important area of research in order to delay or stop AD progression. Aβ is produced by amyloidogenic cleavage of amyloid precursor protein (APP). Amyloidogenic cleavage requires ectodomain removal by β-secretase and intramembrane γ-cleavage by γ-secretase to release Aβ products ranging from 38-43 residues. Work from our lab has shown that APP and γ-secretase are resident proteins …
The Role Of Cytoplasmic Polyadenylation Element Binding Protein-2 (Cpeb-2) In Breast Cancer, Asma Hasan
The Role Of Cytoplasmic Polyadenylation Element Binding Protein-2 (Cpeb-2) In Breast Cancer, Asma Hasan
Electronic Thesis and Dissertation Repository
Over-expression of inflammation associated enzyme cyclo-oxygenase (COX)-2 promotes breast cancer progression, metastasis and sustains cancer stem-like cells (SLCs) by activating prostaglandin E2 receptor EP4. Two COX-2 induced oncogenic miRNAs, miR-655 and miR-526b, target and down-regulate the cytoplasmic polyadenylation element binding protein (CPEB)-2. Hypothesis: Down-regulation of CPEB2 promotes an aggressive breast cancer phenotype through SLC induction and epithelial to mesenchymal transition (EMT). We found that high COX-2/miRNA expressing cell lines MDAMB231 and MCF7-COX-2 had significantly lower expression of CPEB2 than MCF7 cells (low COX-2/miRNA). CPEB2 knockdown in CPEB2-high MCF7 cell line resulted in increased migratory and invasive capacity in …
The Role Of Glutaminase 1 In Hiv-1 Associated Neurocognitive Disorders And In Brain Development, Yi Wang
The Role Of Glutaminase 1 In Hiv-1 Associated Neurocognitive Disorders And In Brain Development, Yi Wang
Theses & Dissertations
Glutaminase is the enzyme that converts glutamine into glutamate, which serves as a key excitatory neurotransmitter and one of the energy providers for cellular metabolism. Glutamate is essential for proper brain functioning but at excess levels, it is neurotoxic and has a key role in the pathogenesis of various neurodegenerative diseases, including HIV-1 associated neurocognitive disorders (HAND). However, the detailed mechanism of glutamate-mediated neurotoxicity remains unclear. In part I, we identified the regulation of glutaminase 1 (GLS1) in the central nervous system (CNS) of HAND animal models including HIV-Tat transgenic (Tg) mouse and HIVE-SCID mouse, since GLS1 is the dominant …
Characterization Of The Nicotine-Induced Endoplasmic Reticulum Stress Response In The Rat Placenta In Vivo And In Vitro, Michael Ka Chun Wong
Characterization Of The Nicotine-Induced Endoplasmic Reticulum Stress Response In The Rat Placenta In Vivo And In Vitro, Michael Ka Chun Wong
Electronic Thesis and Dissertation Repository
Nicotine exposure during pregnancy leads to adverse health outcomes, including compromised placental development. Although the molecular mechanisms remain elusive, recent studies identified that endoplasmic reticulum (ER) stress may underlie poor placentation. Therefore, we were interested in investigating the effects of nicotine exposure on the ER stress response in the placenta. A well-established maternal nicotine exposure rat model and Rcho-1 trophoblast giant cell model were utilized to address the research questions. Maternal nicotine exposure in vivo led to elevated ER stress in association with impaired disulfide bond formation and hypoxia. Nicotine exposure in vitro further differentiated that ER stress may be …
Methylation Of Egfr By Arginine Methyltransferase Prmt1 Enhances Egfr Signaling And Cetuximab Resistance, Hsin-Wei Liao
Methylation Of Egfr By Arginine Methyltransferase Prmt1 Enhances Egfr Signaling And Cetuximab Resistance, Hsin-Wei Liao
Dissertations & Theses (Open Access)
Protein modifications of epidermal growth factor receptor (EGFR) intracellular domain are well known regulators of EGFR functions whereas those of its extracellular domain remain relatively unexplored. Here, we report that methylation at R198 and R200 of EGFR extracellular domain by protein arginine methyltransferase 1 (PRMT1) upregulates its binding to EGF and subsequent receptor dimerization and signaling activation. Methylation-defective EGFR mutant reduced tumor growth in mouse orthotopic xenograft model. Importantly, increased EGFR methylation sustains its signaling activation and cell proliferation in the presence of therapeutic EGFR monoclonal antibody, cetuximab. EGFR methylation level also correlates with higher recurrence rate after cetuximab treatment …
Numerical Simulation Of Terahertz Wave Interaction With Breast Cancer Tumor Tissue Sections, Abayomi Omotola Omolewu
Numerical Simulation Of Terahertz Wave Interaction With Breast Cancer Tumor Tissue Sections, Abayomi Omotola Omolewu
Graduate Theses and Dissertations
This thesis presents numerical simulation of terahertz (THz) wave interaction with breast cancer tumor tissue sections. The obtained results are expressed in THz images of heterogeneous material that mimics the excised breast cancer tissue sections. The finite-element software package ANSYS High Frequency Structural Simulator (HFSS) was used in this work. HFSS is a full wave frequency domain three-dimensional (3D) electromagnetic simulation package. In this work, four breast cancer tissue models based on pathology images were simulated and images of the models were obtained at 1 THz. An incident Gaussian beam was raster scanned over tissue model configurations and the reflected …
The Role Of Bone-Derived Osteopontin In The Migration And Stem-Like Behavior Of Breast Cancer Cells, Graciella Pio
The Role Of Bone-Derived Osteopontin In The Migration And Stem-Like Behavior Of Breast Cancer Cells, Graciella Pio
Electronic Thesis and Dissertation Repository
The majority of breast cancer deaths occur due to metastasis, with the most common site of breast cancer metastasis being bone. Previous work in our laboratory has established that stem-like breast cancer cells with high aldehyde dehydrogenase (ALDH) activity and expression of a CD44+CD24- phenotype have enhanced metastatic capacity. This study tested the hypothesis that bone-derived osteopontin (OPN) promotes the migration and stem-like behavior of breast cancer cells. We demonstrate that bone- derived OPN promotes migration, tumorsphere-forming ability and colony-forming ability of whole population and ALDHhiCD44+CD24- breast cancer cells in bone marrow- …
Inhibition Of Elongation Factor 1a-1 Activity And Hepatic Lipotoxicity, Alexandra Margaret Anne Hetherington
Inhibition Of Elongation Factor 1a-1 Activity And Hepatic Lipotoxicity, Alexandra Margaret Anne Hetherington
Electronic Thesis and Dissertation Repository
Elongation factor 1A-1 (eEF1A-1) was previously identified as a mediator of fatty acid-induced cell death (lipotoxicity) downstream of endoplasmic reticulum (ER) stress. Furthermore, inhibition of the peptide elongation activity of eEF1A-1 with the cyclic depsipeptide didemnin B (DB) diminishes ER stress and lipotoxicity in cultured hepatocytes. Since ER stress is involved in nonalcoholic fatty liver disease (NAFLD), it was hypothesized that administration of DB to obese mice with NAFLD would reduce hepatic lipotoxicity. Treatment with DB for one week improved several parameters associated with hepatic lipotoxicity and modestly decreased food intake without evidence of illness. Liver triglycerides and protein markers …
Nicotinamide Riboside Delivery Generates Nad+ Reserves To Protect Vascular Cells Against Oxidative Damage, Krista M. Hawrylyshyn
Nicotinamide Riboside Delivery Generates Nad+ Reserves To Protect Vascular Cells Against Oxidative Damage, Krista M. Hawrylyshyn
Electronic Thesis and Dissertation Repository
The ability of vascular cells to withstand oxidative insults is critical to vascular health. NAD+, which drives poly (ADP-ribose) polymerase (PARP) and sirtuin (SIRT) reactions, can be compromised and strategies for overcoming this limitation in the vasculature do not exist. This study determines if nicotinamide riboside (NR) delivery can augment NAD+ stores and fuel resistance to oxidative stress. I established that oxidative-stress insult on vascular cells decreased NAD+ levels, accompanied by a striking increase in nuclear PAR-chain accumulation. PARP inhibition abolished PAR-chain formation and preserved NAD+ levels, establishing PARP in NAD+ consumption in this …
Investigating The Role Of Hydrogen Sulfide In The Survival, Growth And Angiogenic Potential Of Clear Cell Renal Cell Carcinoma Cell Lines And Xenografts, Eric Sonke
Electronic Thesis and Dissertation Repository
Clear cell renal cell carcinoma (ccRCC) is characterized by Von Hippel-Lindau (VHL)-deficiency, resulting in pseudohypoxic, angiogenic and glycolytic tumours. Hydrogen sulfide (H2S) is an endogenously-produced gasotransmitter that accumulates under hypoxia and has been shown to be pro-angiogenic and cytoprotective in cancer. It was hypothesized that H2S levels are elevated in VHL-deficient ccRCC, contributing to survival, metabolism, and angiogenesis. Using H2S-specific probes, it was found that H2S levels were higher in VHL-deficient ccRCC cell lines compared to cells with wild-type VHL. Inhibition of H2S-producing enzymes could reduce the proliferation, metabolism …
Granulocyte Colony-Stimulating Factor: Its Role In Gut-Homing Macrophage Generation And Colitis, And Production By Probiotics, Shahab Meshkibaf
Granulocyte Colony-Stimulating Factor: Its Role In Gut-Homing Macrophage Generation And Colitis, And Production By Probiotics, Shahab Meshkibaf
Electronic Thesis and Dissertation Repository
The pleiotropic cytokine granulocyte-colony stimulatory factor (G-CSF) is mainly required for the generation of neutrophils, but its role in macrophage generation has also been reported. In addition, G-CSF is effective for the down-regulation of inflammatory cytokines and ameliorating gut disorders, such as colitis. However, the G-CSF function in macrophage generation and gut immunity remains unclear. The first focus of this thesis was to assess the role of G-CSF in macrophage generation and its contribution to gut immunity. G-CSF was found to promote the generation of Gr-1high/F4/80+ macrophages in macrophage (M)-CSF-treated bone marrow cells, most likely through suppressing cell death. Gr-1high …
Structural And Functional Interactions Between Bro1 Domain Of Human Alix Protein And Nucleocapsid Packaging Rna Complex From Hiv, Scott Gross
Graduate School of Biomedical Sciences Theses and Dissertations
A virus is only as powerful as its ability to spread. Enveloped retroviruses, namely HIV-1, use exocytosis pathways that normal host cells use to release particles from the plasma membrane. The main pathways of interest in this study are the Endosomal Sorting Complex Required for Transport (ESCRT) and adjacent ALIX pathways. The ESCRT pathway is especially important for degradation of receptor/cargo complexes that form Multi-Vesicular Bodies (MVBs). Currently, there is no known therapy that targets this endosomal pathway, which would prevent the spread of the virus to other cells. The virus has adapted to jump from pathway to pathway when …
Multilevel Deregulation Of Survival Mechanisms In Npm-Alk+ T-Cell Lymphoma, Deeksha Vishwamitra
Multilevel Deregulation Of Survival Mechanisms In Npm-Alk+ T-Cell Lymphoma, Deeksha Vishwamitra
Dissertations & Theses (Open Access)
The anaplastic lymphoma kinase (ALK) is a single chain transmembrane receptor tyrosine kinase that belongs to the insulin receptor superfamily. Other members of this superfamily include the insulin receptor (IR), type I insulin-like growth factor receptor (IGF-IR), and the leukocyte tyrosine kinase. The common structural finding among these tyrosine kinases is the YXXXYY motif present within their respective tyrosine kinase domains. Binding of its ligands causes ALK receptor homodimerization and protein kinase activation. ALK has been previously shown to play a significant role during early developmental stages. In human embryos, the expression of ALK is mainly seen in …
Structural-Based Investigation Of Fak And P130cas In Focal Adhesion, Chi Zhang
Structural-Based Investigation Of Fak And P130cas In Focal Adhesion, Chi Zhang
Theses and Dissertations (ETD)
Cell migration is an integrated multistep process accompanying us throughout life, from birth to death. It contributes to a variety of biological activities and has been implicated in many pathological conditions, including cancer, primary immunodeficiency diseases, vascular diseases, and mental retardation. Cell migration has been considered to be a three-step cyclic process including polarization, protrusion and retraction. The initiation and extension of the protrusion is driven by actin polymerization, and is stabilized by attaching to the extracellular matrix (ECM) or adjacent cells. The cell-ECM attachment sites are named focal adhesions (FAs), which are dynamic, large protein complexes containing more than …
Diabetic Bone Marrow & Stem Cell Dysfunction, Meghan A. Piccinin
Diabetic Bone Marrow & Stem Cell Dysfunction, Meghan A. Piccinin
Electronic Thesis and Dissertation Repository
ii Abstract Abstract Defects in the proliferation, differentiation, and activity of bone marrow (BM)-derived vasculogenic/vascular stem cells (VSCs) have been observed in diabetes and contribute to the development of vascular complications. Diabetes leads to enhanced bone marrow adipogenesis, altering the composition of the BM stem cell (SC) niche and potentially disrupting the normal functioning of resident VSCs. Here, I establish that adipocytes have a negative influence on SC survival in culture. I also show that adipocytes and osteoblasts are responsible for the creation of distinct extracellular microenvironments, with unique expression patterns of several pro- and anti-angiogenic factors with known effects …
Timp3 Regulation Of Macrophage Activation And Apoptosis, Michael S. Brock
Timp3 Regulation Of Macrophage Activation And Apoptosis, Michael S. Brock
Electronic Thesis and Dissertation Repository
Acute respiratory distress syndrome (ARDS) is a lung disease involving profound inflammation. Origins of persistent inflammation in select cases of ARDS are poorly understood, and we propose persistent inflammatory macrophages may be one of its mechanisms. Macrophages polarize to either promote inflammation, or suppress inflammation. Tissue inhibitor of metalloproteinases 3 (TIMP3) reduces the pro-inflammatory polarization in macrophages. Additionally, studies have shown TIMP3 promotes apoptosis, and its absence delays recovery from bleomycin-induced lung injury.
We hypothesize that TIMP3 promotes apoptosis of murine macrophages through inhibition of metalloproteinase activity and stabilization of FAS on the cell surface. Pro-inflammatory Timp3-/- bone marrow-derived …
Towards A Structural Understanding Of Spore Germination In Clostridium Difficile, Chloe M. Adams
Towards A Structural Understanding Of Spore Germination In Clostridium Difficile, Chloe M. Adams
Graduate College Dissertations and Theses
Clostridium difficile is a Gram-positive bacterium that causes a toxin-mediated disease, typically in individuals whose normal intestinal flora has been compromised by antibiotic therapy. C. difficile is naturally resistant to many antibiotics and produces spores that can withstand harsh environmental conditions and many disinfectants, making the infection difficult to clear and easy to spread. The infection begins when spores from the environment are ingested and germinate upon exposure to taurocholate and glycine in the digestive tract. This germination process is required to initiate infection and thus represents a good target for the development of novel therapeutics. Although spore germination is …
Investigation Of Ultrasound Targeted Microbubbles As A Therapeutic Gene Delivery System For Prostate Cancer, Rounak Paramjeet Nande
Investigation Of Ultrasound Targeted Microbubbles As A Therapeutic Gene Delivery System For Prostate Cancer, Rounak Paramjeet Nande
Theses, Dissertations and Capstones
A major challenge for effective gene therapy is systemic delivery of viruses carrying therapeutic genes into affected tissue. The immunogenic nature of human adenoviruses (Ads) limits their use for intratumoral (IT) injection in gene therapy. Ads transfection is further hampered by the fluctuating presence of Coxsackie and Adenovirus Receptor (CAR) and integrins on the cells’ surface. To circumvent these limitations we developed a novel approach wherein Ads are encapsulated inside the shell of lyophilized, lipid-encapsulated, perfluorocarbon microbubbles (MBs)/ultrasound (US) contrast agents, which act as delivery vehicles for a sitespecific gene transfer system.
We performed infection studies with Ad.GFP (Green Fluorescent …
Dual Pi3k/Mtor Inhibition With Bez235 Augments The Therapeutic Efficacy Of Doxorubicin In Cancer Without Influencing Cardiac Function, David E. Durrant
Dual Pi3k/Mtor Inhibition With Bez235 Augments The Therapeutic Efficacy Of Doxorubicin In Cancer Without Influencing Cardiac Function, David E. Durrant
Theses and Dissertations
Cancer continues to be a leading cause death in the United States despite improved treatments. Cancerous lesions form after acquiring oncogenic driver mutations or losing tumor suppressor function in normal cells. Traditional therapies have included use of genotoxic substances that take advantage of the increased growth rate and loss of tumor suppressor function to cause cell death. One such drug is the anthracycline antibiotic doxorubicin (DOX). DOX interchelates into DNA and disrupts transcriptional machinery while also poisoning topoisomerase II. This results in single and double stranded DNA breaks, which if severe enough leads to either necrotic or apoptotic cell death. …
The Use Of Rna Interference To Mitigate Pulmonary Fibrosis In Response To Asbestos Exposure, Sarah Kinsey
The Use Of Rna Interference To Mitigate Pulmonary Fibrosis In Response To Asbestos Exposure, Sarah Kinsey
Undergraduate Theses, Professional Papers, and Capstone Artifacts
The adverse health effects of exposure to asbestos are widely known and have been well documented. When a person is diagnosed with asbestosis, a chronic lung disease caused by inhaling asbestos fibers, few treatment options exist, none of which halt or reverse the progression of the disease. The rapidly growing field of gene therapy offers new avenues for potential treatments worthy of investigation. The detrimental effects of asbestos exposure are due to the physiological response of the lungs to asbestos fibers in the form of fibrosis, a result of excess extracellular collagen deposition. A protein called SPARC (Secreted Protein Acidic …
Interaction Between Atm Kinase And P53 In Determining Glioma Radiosensitivity, Syed F. Ahmad
Interaction Between Atm Kinase And P53 In Determining Glioma Radiosensitivity, Syed F. Ahmad
Theses and Dissertations
Glioblastoma multiforme (GBM) is the most common primary brain tumor. Studies have shown that targeting the DNA damage response can sensitize cancer cells to DNA damaging agents. Ataxia telangiectasia mutated (ATM) is involved in signaling DNA double strand breaks. Our group has previously shown that ATM inhibitors (ATMi) sensitize GBM cells and tumors to ionizing radiation. This effect is greater when the tumor suppressor p53 is mutated.
The goals of this work include validation of a new ATM inhibitor, AZ32, and elucidation of how ATMi and p53 status interact to promote cell death after radiation. We propose that ATMi and …