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Articles 931 - 960 of 1029
Full-Text Articles in Medical Sciences
Localization And Function Of Electrogenic Na/Bicarbonate Cotransporter Nbce1 In Rat Brain, Debeshi Majumdar
Localization And Function Of Electrogenic Na/Bicarbonate Cotransporter Nbce1 In Rat Brain, Debeshi Majumdar
All ETDs from UAB
Na-Coupled Bicarbonate Transporters (NCBTs) are members of the bicarbonate transporter superfamily that play important roles in regulating intracellular pH (pHi) and extracellular pH (pHo) in the central nervous system. Electrogenic Na/bicarbonate Cotransporter 1 (NBCe1) is an NCBT that is expressed in different mammalian tissues including the brain. NBCe1 has three splice variants - NBCe1-A, -B and -C - that differ in the amino and carboxy termini. We have first performed a systematic characterization of the localization profiles of the three NBCe1 splice variants at mRNA and protein levels in rat brain. In these studies, we have used anti-sense probes and …
Mechanisms Of Growth Hormone Action In Skeletal Muscle, Mahendra Devaraj Mavalli
Mechanisms Of Growth Hormone Action In Skeletal Muscle, Mahendra Devaraj Mavalli
All ETDs from UAB
Growth hormone (GH) and insulin like growth factor-1 (IGF-1) exert profound growth promoting actions during pre and postnatal skeletal muscle development. GH and IGF-1 seem to promote their anabolic actions by influencing skeletal muscle cell prolif-eration and fusion. However, because GH stimulates the production of IGF-1 from the liver and other GH-responsive peripheral tissues, including skeletal muscle, the individual contributions of these two growth factors to anabolic responses in skeletal muscle remains poorly defined. In this dissertation research, I sought to distinguish the mechanisms responsible for growth hormone's (GH) anabolic actions in skeletal muscle. To accomplish this, I analyzed the …
Intracellular Trafficking Of The Hantaviral Nucleocapsid Protein And Its Function In Modulation Of Immune Signaling, Steven Joe Ontiveros
Intracellular Trafficking Of The Hantaviral Nucleocapsid Protein And Its Function In Modulation Of Immune Signaling, Steven Joe Ontiveros
All ETDs from UAB
Old World and New World hantaviruses, family Bunyaviridae, mature intracellularly within cellular compartments. Although it is generally accepted they assemble and bud in the Golgi apparatus the site remains controversial for New World hantaviruses, because some studies have raised the possibility of their maturation at the plasma membrane. Furthermore, the site of assembly hantaviruses still remains undetermined. The nucleocapsid (N) protein has been proposed to play a key role in facilitating assembly. To gain insight into the assembly pathways of Old World hantaviruses, we examine the intracellular trafficking of the Hantaan (HTN) virus N protein. We show progressive redistribution of …
Cystic Fibrosis Transmembrane Conductance Regulator (Cftr) Modulators And Their Mechanistic Basis: Relevance To Emerging Therapies For Cystic Fibrosis, Louise Clare Pyle
Cystic Fibrosis Transmembrane Conductance Regulator (Cftr) Modulators And Their Mechanistic Basis: Relevance To Emerging Therapies For Cystic Fibrosis, Louise Clare Pyle
All ETDs from UAB
Cystic fibrosis (CF) is a lethal genetic disorder leading to pulmonary decline and premature death. The gene responsible for CF, the cystic fibrosis transmembrane conductance regulator (CFTR), serves as a chloride and bicarbonate channel situated at the apical cell surface of epithelia. The discovery of small molecules that augment channel gating of mutant CFTR (so-called `potentiators') represents a major theme of CF research, and offers hope for new therapeutic interventions. High-throughput screening (HTS) provides a means to test millions of agents in an unbiased manner for CFTR potentiating properties. New agents identified by HTS have undergone extensive pre-clinical and clinical …
The Role Of Mitochondria And Plasma Membrane Ca2+ Transport Systems In Ca2+-Dependent Glutamate Release From Rat Cortical Astrocytes, Reno Cervo Reyes
The Role Of Mitochondria And Plasma Membrane Ca2+ Transport Systems In Ca2+-Dependent Glutamate Release From Rat Cortical Astrocytes, Reno Cervo Reyes
All ETDs from UAB
Astrocytes, a type of glial cell in the central nervous system, are recognized for their support roles to neurons. They supply neurons with metabolites, maintain ion homeostasis and clear the synaptic space of neurotransmitters. However, it has been found that some astrocytes have receptors for neurotransmitter and neuroligands, exhibit Ca2+ excitability when stimulated via these receptors, and secrete gliotransmitters as an output of this Ca2+ excitability. In the Ca2+-dependent release of glutamate, it has been shown that the endoplasmic reticulum is the predominant source and the extracellular space is the auxiliary source of free Ca2+ necessary for triggering exocytosis. Because …
Neuroinflammation And Fragile X Syndrome: Regulation By Glycogen Synthase Kinase-3, Christopher Joseph Yuskaitis
Neuroinflammation And Fragile X Syndrome: Regulation By Glycogen Synthase Kinase-3, Christopher Joseph Yuskaitis
All ETDs from UAB
Neuroinflammation and Fragile X syndrome (FXS) are two particularly devastating neurologic conditions for which no adequate treatment exists and much is still unknown about the underlying cellular and molecular processes. Neuroinflammation contributes to the pathogenesis of many neurologic and psychiatric disorders, thus treatment of the underlying inflammation has broad implications. FXS is the most common cause of inherited intellectual and developmental delay and one of the few known genetic causes of autism. Neuroinflammation and FXS have potential links with glycogen synthase kinase-3 (GSK3) and its inhibitor, lithium. Therefore, the overall goal of this research was to examine the role of …
Involvement Of Reactive Oxygen Species In The Acute Development Of Insulin Resistance Following Trauma And Hemorrhage, Lidong Zhai
Involvement Of Reactive Oxygen Species In The Acute Development Of Insulin Resistance Following Trauma And Hemorrhage, Lidong Zhai
All ETDs from UAB
Hyperglycemia develops in the intensive care unit in many patients following injury, infection and critical illness. However, little is known about the mechanism of acute development of insulin resistance that causes this hyperglycemia, even though reducing or normalizing the elevated glucose levels has become a major therapeutic target in many ICUs. Using rodent models of injury, acute hepatic insulin resistance occurs within minutes and continues for at least several hours even following fluid resuscitation. We have previously reported that TNF-alpha; is necessary for the hepatic insulin resistance in the rat following resuscitation. However, whether TNF-alpha; plays a role in the …
Exopolysaccharides Of Mycoplasma Pulmonis, James Michael Daubenspeck
Exopolysaccharides Of Mycoplasma Pulmonis, James Michael Daubenspeck
All ETDs from UAB
Capsule has been associated with virulence in numerous bacterial pathogens. The Mollicutes are a host-specific group of pathogens that cause a variety of economically relevant diseases important to man. Mycoplasma pneumoniae is responsible for 2 million cases of atypical pneumonia and 100,000 hospitalizations every year in the United States (Atkinson et al., 2008) (Krause and Taylor-Robinson, 1992). There was a toxic galactan molecule described as early as 1958 in Mycoplasma mycoides subsp. mycoides (Plackett and Buttery, 1958), although no evidence was presented that it was produced by the bacteria. Over the intervening fifty years the evidence to support the production …
Diffusion Pathways Through The Outer Membrane Of Mycobacteria, Olga Danilchanka
Diffusion Pathways Through The Outer Membrane Of Mycobacteria, Olga Danilchanka
All ETDs from UAB
The extraordinary capacity of Mycobacterium tuberculosis (Mtb) to adapt to environmental changes during infection contributes to its success as a pathogen. While the unique outer membrane (OM) of mycobacteria functions as a permeability barrier for toxic molecules, uptake of nutrients is required to sustain viability of Mtb. Whereas hydrophobic molecules can diffuse through membranes, uptake of small hydrophilic compounds is mediated by water-filled channels, porins. For example, Msp-like porins of M. smegmatis (Ms) were shown to be required for uptake of hydrophilic beta-lactam antibiotics, which are also known to diffuse through porins in gram-negative bacteria. Because the structure of the …
Mechanisms And Countermeasures Of Microgravity Induced Bone Loss: In Vitro And In Vivo Model Systems, Ritu Saxena
Mechanisms And Countermeasures Of Microgravity Induced Bone Loss: In Vitro And In Vivo Model Systems, Ritu Saxena
All ETDs from UAB
Rapid bone loss occurs during prolonged periods of weightlessness experienced by astronauts during spaceflights which leads to osteopenia and increased fracture risk upon return to earth. Spaceflight studies have shown that the bone loss occurs as a result of both a decrease in bone formation and an increase in bone resorption, however, the molecular mechanisms still need to be elucidated. Previous studies from our laboratory and other groups have indicated that modeled microgravity leads to inhibition of osteoblastogenesis and a stimulation of adipogenesis of human mesenchymal stem cells in osteogenic medium which is most likely mediated by a decrease in …
Biological Characterization Of Fc Receptor-Like 6 (Fcrl6), Daniel M. Schreeder
Biological Characterization Of Fc Receptor-Like 6 (Fcrl6), Daniel M. Schreeder
All ETDs from UAB
Members of the Fc receptor-like (FCRL) family are cell-surface proteins with ancient conservation, distinct lymphocyte expression patterns, and tyrosine-based signaling capa-bilities that imply a fundamental role for them in modulating immune responses. Though they share many features with the Fc receptors (FCR) for IgG and IgE, FCRLs have not been found to bind immunoglobulin. In these studies, we sought to characterize the cellu-lar expression pattern, binding partner, and function of a recently identified FCRL family member, human FCRL6. By developing specific monoclonal antibodies (mAbs) we determined that FCRL6 is dis-tinctly expressed by cytotoxic lymphocytes, namely NK cells, CD8+ T cells, …
Role Of Variant Sialylation In Regulating Tumor Cell Behavior, Faheem M. Shaikh
Role Of Variant Sialylation In Regulating Tumor Cell Behavior, Faheem M. Shaikh
All ETDs from UAB
Many different tumors have been documented to have elevated levels of the enzyme ST6Gal I, a Golgi glycosyltransferase that adds α2-6 sialic acids to glycoproteins. Concurrently, upregulated ST6Gal I is associated with metastasis and poor patient prognosis. We initially showed that HD3 colonocytes made to express oncogenic-ras, a common mutation in colon carcinoma, have increased expression of ST6Gal I and elevated α2-6 sialylated integrins. Having established that ras regulates ST6Gal I expression in colon epithelial cells, we found that colonocytes carrying hyper α2-6 sialylated β1 integrins exhibit increased adhesion to and migration toward collagen I. Further, we found that β1 …
Effects Of Hexosamine Biosynthesis On An In Vitro Model Of Cardiacischemia, Voraratt Champattanachai
Effects Of Hexosamine Biosynthesis On An In Vitro Model Of Cardiacischemia, Voraratt Champattanachai
All ETDs from UAB
Increased levels of protein O-linked-N-acetylglucosamine (O-GlcNAc) have been correlated with increased cell survival following stress. Therefore the goal of this study was to determine whether enhanced flux through the hexosamine biosynthesis pathway (HBP), which leads to elevated levels of O-GlcNAc, improved the tolerance of isolated neonatal rat ventricular myocytes (NRVMs) to ischemia/reperfusion (I/R) injury. NRVMs were exposed to hypoxic medium for 4 hours, followed by oxygenated complete medium for 16 hours. Acute treatment with 5 mM glucosamine showed an increase in viability and decreased both necrosis and apoptosis following I/R. Glucosamine increased O-GlcNAc levels maximally at 2 hours and went …
The Developmental Functions Of Bdnf And Mecp2 On Dendritic And Synaptic Structure, Christopher A. Chapleau
The Developmental Functions Of Bdnf And Mecp2 On Dendritic And Synaptic Structure, Christopher A. Chapleau
All ETDs from UAB
Mutations in the transcriptional repressor MeCP2 cause Rett Syndrome (RTT), a mental retardation disease associated with reduced dendritic architecture of cortical pyramidal neurons, in addition to a decrease in the number of dendritic spines. I present the first quantification analysis of spine density in postmortem human brain tissue, demonstrating that hippocampal CA1 pyramidal neurons have reduced spine densities in RTT patients throughout their lives. One gene that MeCP2 regulates is BDNF, an important developmental factor that modulates synaptic transmission and plasticity, as well as spine formation and maturation. In immature cultured hippocampal neurons, cell-autonomous expression of BDNF accelerates the differentiation …
Microbial Biofilm Attachment To Caenorhabditis Elegans, Kevin Drace
Microbial Biofilm Attachment To Caenorhabditis Elegans, Kevin Drace
All ETDs from UAB
The closely related bacterial species Xenorhabdus nematophila, Yersinia pestis and Y. pseudotuberculosis make biofilms capable of adhering to the head of the model nematode Caenorhabditis elegans. Y. pestis uses biofilms to block the digestive tract of its vector, the flea, in order to enhance its efficiency of transmission. I investigated the role of biofilms in X. nematophila and found that, like its Yersinia sp. counterparts, production of biofilm requires a four-gene operon: hmsHFRS. X. nematophila is an insect pathogen and an obligate symbiont of the nematode Steinernema carpocapsae. However, an X. nematophila hmsH mutant that failed to make biofilms on …
Analysis Of The Role Of Fcrl5 And Figlers In B Cell Development, Signaling, And Malignancy, Christopher L. Haga
Analysis Of The Role Of Fcrl5 And Figlers In B Cell Development, Signaling, And Malignancy, Christopher L. Haga
All ETDs from UAB
The regulation of signaling and migration is critical to B lymphocyte development, activation, and proliferation. This dissertation reports a functional role for Fc receptor-like molecule 5 (FCRL5), a B cell specific member of the Fc receptor-like family of molecules, and the discovery of a novel family of conserved transmembrane proteins with fibronectin, immunoglobulin, and leucine-rich repeat domains (FIGLER) expressed in bone marrow and B lineage cells. Until now, the signaling potential of FCRL5 was unknown. A panel of FcRIIB/FCRL5 chimeric receptors were created and expressed in a B cell line lacking endogenous FcRIIB. Coligation of the chimeric receptor with the …
Role Of The Gm/Gn Glycoprotein Complex In The Final Assembly And Egress Of The Human Cytomegalovirus (Hcmv), Magdalena Anna Krzyzaniak
Role Of The Gm/Gn Glycoprotein Complex In The Final Assembly And Egress Of The Human Cytomegalovirus (Hcmv), Magdalena Anna Krzyzaniak
All ETDs from UAB
HCMV consists of a dsDNA genome enclosed by, an icosahedral capsid surrounded by a layer of tegument proteins; the virion structure is enclosed in a lipid envelope rich in virus expressed glycoproteins. The HCMV envelope contains an incompletely defined number of glycoproteins. The glycoprotein M (gM) and glycoprotein N (gN) form a gM/gN protein complex which is the most abundant protein component of the HCMV envelope. Recent studies have indicated that deletion of the viral gene encoding either gM or gN is lethal for HCMV. The gM C-terminal cytoplasmic tail (gM-CT) revealed an acidic cluster and a tyrosine-based trafficking motifs. …
Mechanism Of Interferon-Beta-Mediated Inhibition Of Il-8 Gene Expression, Travis Laver
Mechanism Of Interferon-Beta-Mediated Inhibition Of Il-8 Gene Expression, Travis Laver
All ETDs from UAB
Interleukin-8 (IL-8) is a potent chemoattractant of numerous cells, particularly neutrophils, in the innate immune response. In addition to immune functions, IL-8 is known to contribute to the pathogenesis of a number of diseases, including cancer. Interferon-β (IFN-β), a Type I interferon, inhibits the expression of IL-8, but the details of this effect are not known. In this study we investigate transcriptional control of the IL- 8 gene and the mechanism by which IFN-β exerts inhibitory effects on IL-8. Herein we show that stimulation of U87-MG glioma cells with phorbol 12-myristate 13-acetate (PMA) results in a rapid recruitment of NF-κB …
Transcriptional Regulation Of Cd40 And Class Ii Mhc Molecules In Macrophages And Microglia By Statins, Sun Jung Lee
Transcriptional Regulation Of Cd40 And Class Ii Mhc Molecules In Macrophages And Microglia By Statins, Sun Jung Lee
All ETDs from UAB
Microglia/macrophages are the main intrinsic immune effector cells and the first cell types that respond to a variety of CNS injures. They have important functions including secretion of cytokines/chemokines and antigen presentation, thereby regulating immune responses. Interferon-γ (IFN-γ) is a cytokine involved in many aspects of the immune response, and activates microglia/macrophages to express cell surface antigens such as class II MHC, and co-stimulatory molecules such as CD40. CD40 and class II MHC molecules play a critical role in immune reactivity such as antigen presentation and subsequent T cell activation. However, aberrant CD40 and class II MHC expression have been …
The Au-Rich Element Mrna Decay-Promoting Activity Of Brf1 Is Regulated By Mitogen-Activated Protein Kinase Activated Protein Kinase 2, Sushmit Maitra
The Au-Rich Element Mrna Decay-Promoting Activity Of Brf1 Is Regulated By Mitogen-Activated Protein Kinase Activated Protein Kinase 2, Sushmit Maitra
All ETDs from UAB
Regulated mRNA decay is a highly important process for the tight control of gene expression. Inherently unstable mRNAs contain AU-rich elements (AREs) in the 3’ untranslated regions that direct rapid mRNA decay by interaction with decay-promoting ARE-binding proteins (ARE-BPs). The decay of ARE-containing mRNAs is regulated by signaling pathways, which are believed to directly target ARE-BPs. Here, we show that BRF1 involved in ARE-mediated mRNA decay (AMD) is phosphorylated by MAPK-activated protein kinase 2, MK2. In vitro kinase assays using different BRF1 fragments suggest that MK2 phosphorylates BRF1 at four distinct sites, S54, S92, S203, and an unidentified site at …
Modulation Of Transforming Growth Factor (Tgf)-Ss1 And Its Implications In Breast Cancer Metastasis, Lakisha Dionne Moore
Modulation Of Transforming Growth Factor (Tgf)-Ss1 And Its Implications In Breast Cancer Metastasis, Lakisha Dionne Moore
All ETDs from UAB
Overexpresssion of transforming growth factor (TGF)-β has been implicated in promoting immune suppression, tumor angiogenesis, tumor cell migration, and invasion in many cancers including carcinoma of the breast. Thus, targeted downregulation of TGF-β1 expression in breast cancer in situ and determination of its implications potentially could provide new treatment approaches for disease management. siRNA constructs targeting TGF-β1 were validated and used to develop clonal derivatives of the MDA-MB-435 metastatic breast cancer cell line. Inhibition of TGF-β1 expression in MDA-MB-435 cells showed decrease in migration and invasion in vitro with an increase in proliferation. In vivo analysis indicated a 90% decrease …
The Role Of Centaurin Alpha-1 In The Regulation Of Neuron Al Differentiation, Carlene Drucilla Moore
The Role Of Centaurin Alpha-1 In The Regulation Of Neuron Al Differentiation, Carlene Drucilla Moore
All ETDs from UAB
In the nervous system, PI 3-kinase has been implicated in neuronal differentiation. My studies have focused on a candidate neuronal PI 3-kinase target centaurin alpha-1, which binds PtdIns(3,4,5)P3, and is an Arf6 GAP. Centaurin alpha-1 is localized in dendrites, dendritic spines and synapses, and is required for neuronal differentiation and spine morphogenesis. In dissociated neuronal cultures, expression of centaurin alpha-1 enhances dendritic branching, and increases dendritic filopodia, lamellipodia and spine-like protrusions. Expression of centaurin alpha-1 GAP inactive mutant or knocking down centaurin alpha-1 levels using siRNA leads to inhibition of dendritic outgrowth and branching. Manipulations of centaurin alpha-1 also disrupt …
Calmodulin Binding To Cellular Flice Like Inhibitory Protein Modulates Fas-Induced Signaling And Tumorigenesis In Cholangiocarcinoma, Pritish Subhash Pawar
Calmodulin Binding To Cellular Flice Like Inhibitory Protein Modulates Fas-Induced Signaling And Tumorigenesis In Cholangiocarcinoma, Pritish Subhash Pawar
All ETDs from UAB
Cholangiocarcinoma, a fatal tumor arising from biliary epithelium, has very poor 5-year survival rate due to lack of early diagnosis and effective therapies. Induction of the Fas-mediated apoptosis is a promising therapeutic target in this tumor. Studies from our group and others have indicated that Fas-expression correlates inversely with disease progression and that CaM-antagonists induce apoptosis in cholangiocarcinoma cells in a Fas related manner. Further, we reported a direct and dynamic interaction of CaM and Fas and that CaM is recruited into the Fas-stimulated death inducing signaling complex (DISC), suggesting a cross talk between Fas and CaM pathways. The studies …
Investigation Of Lipoteichoic Acid Structure And Function To Establish Its Role In Gram-Positive Bacterial Infections, Ho Seong Seo
Investigation Of Lipoteichoic Acid Structure And Function To Establish Its Role In Gram-Positive Bacterial Infections, Ho Seong Seo
All ETDs from UAB
Lipoteichoic acid (LTA) is an essential bacterial membrane polysaccharide (cell wall component) that is linked to a glycerol backbone with two acyl chains. Since an antibody to LTA has been shown to protect from Gr+ bacterial infections or colonization, and the mutant Gr+ bacteria which produce less amount of LTA have less pathogenic than WT, LTA may be an important role in Gr+ bacterial infection and inflammation. The currently accepted structure of pneumococcal LTA has the pentameric repeating unit bound to the lipid anchor {Glc(β1��3)AATGal(β1��3)Glc(α1��3)-acyl2Gro}. Unlike the lipid anchor of other Gr+ bacterial LTA, this pneumococcal LTA lipid anchor has …
Changes In Short-Term Facilitation Are Opposite At Schaffer Collateral And Temporoammonic Ca1 Synapses In The Developing Rat Hippocampus, Haley E. Speed
Changes In Short-Term Facilitation Are Opposite At Schaffer Collateral And Temporoammonic Ca1 Synapses In The Developing Rat Hippocampus, Haley E. Speed
All ETDs from UAB
Hippocampal CA1 pyramidal neurons integrate and filter spatial, temporal, and sensory information from the entorhinal cortex (EC) for memory storage. Synaptic transmission mediates the processing of incoming information, and recent studies have demonstrated that long-term changes in synaptic strength at CA1 synapses are important for learning and memory. Short-term changes in synaptic strength, occurring on a timescale of milliseconds to minutes, do not require lasting modifications and are rapidly reversible. Termed short-term plasticity, it is known to be important for dynamic gain control of synaptic transmission and neural computation. During late postnatal development, there are extensive developmental changes in rat …
Analysis Of The Hedgehog Pathway In Pancreatic Adenocarcinoma, Adam Steg
Analysis Of The Hedgehog Pathway In Pancreatic Adenocarcinoma, Adam Steg
All ETDs from UAB
Pancreatic adenocarcinoma (PAC) is the fourth leading cause of cancer mortality in the United States. Despite the use of highly aggressive treatment regimens (surgery, chemotherapy and radiation), almost all patients succumb to metastatic disease within 6-10 months of diagnosis. The hedgehog (HH) signaling pathway was originally discov-ered to play a critical role in mammalian embryological development. Interestingly, re-cent studies have suggested that aberrant expression of this pathway is involved in the initiation and continued growth of PAC. Small molecules that antagonize the transmem-brane protein Smoothened (Smo), a critical signaling component of the HH pathway, have proven effective in decreasing PAC …
Mapks Regulate Nuclear Import Of Human Papillomavirus Type 11 Replicative Helicase E1, Jei-Hwa Yu
Mapks Regulate Nuclear Import Of Human Papillomavirus Type 11 Replicative Helicase E1, Jei-Hwa Yu
All ETDs from UAB
Papillomaviruses (PV) are prevalent pathogens that infect human or animal squamous epithelia. Its genome is a double strand circular DNA of approximately 7.9 kb. It contains origin of replication (ori) and encodes early viral proteins for viral DNA amplication, and late capsid proteins for packaging viron. The viral DNA replicates as extrachromosomal nuclear plasmid in the host cell. Infections by low risk virus, such as HPV-6 and -11, can result in benign papillomas, condylomata, and low grade squamous intraepithelial dysplasias (SIL), whereas infection by high risk virus, such as HPV-16 and -18, can progress to high grade SIL, carcinoma in …
A Dual-Action, Armed Replicating Adenovirus For The Treatment Of Bone Metastases Of Breast Cancer, James Joseph Cody
A Dual-Action, Armed Replicating Adenovirus For The Treatment Of Bone Metastases Of Breast Cancer, James Joseph Cody
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Most patients with advanced breast cancer develop osteolytic bone metastases, which have numerous complications. Because current therapies are not curative, new treatments are needed. Conditionally replicating adenoviruses (CRAds) are anti-cancer agents designed to infect and lyse tumor cells. For increased efficacy, CRAds have been armed with therapeutic transgenes. Osteoprotegerin (OPG), an inhibitor of osteoclastic bone resorption, represents a promising candidate with which to arm a CRAd intended to treat osteolytic bone metastases. We hypothesize that a CRAd armed with OPG will inhibit breast cancer bone metastasis and reduce tumor burden in the bone by directly lysing tumor cells and by …
Thrombospondin Type-1 Repeats And Their Potential Role In Inhibiting Glioblastoma Angiogenesis, Joshua C. Anderson
Thrombospondin Type-1 Repeats And Their Potential Role In Inhibiting Glioblastoma Angiogenesis, Joshua C. Anderson
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Thrombospondin-1 (TSP-1) is a 420 kilodalton homotrimeric protein; it is one of the first identified anti-angiogenic proteins found to be expressed in some normal tissues. Peptides derived from the type-1 repeat (TSR) domains of full length TSP-1 have been shown to have anti-angiogenic activity, and thus anti-tumor activity in some non-glioma tumor models. I hypothesized that peptides derived from the TSRs of TSP-1, such as ABT-510, could inhibit angiogenesis and thus malignant glioma tumor growth in vivo. I found that ABT-510 inhibited angiogenesis of the human brain microvascular endothelial cell (MvEC) in an in vitro tubulomorphogenesis assay. To determine the …
Human Papillomavirus: Segregation And Replication, Luan D. Dao
Human Papillomavirus: Segregation And Replication, Luan D. Dao
All ETDs from UAB
Human papillomavirus are small DNA tumor viruses. The viral genome is a small circular double stranded DNA that replicates autonomously as an extrachromosomal plasmid. Occasionally infections by the high risk HPV viruses can lead to DNA integration and progression to cancer. How the HPV DNA is maintained and becomes established in the dividing host cells is not well understood. Additionally, as a double-stranded DNA virus it is likely that double-stranded DNA breaks in the viral genome, either from replication or random damage, will trigger a DNA repair response from the host cell. Such responses have been alternatively reported to be …