Medical Specialties Commons^™

Expression And Function Of Pannexins In The Inner Ear And Hearing, Hong-Bo Zhao

Otolaryngology--Head & Neck Surgery Faculty Publications

Pannexin (Panx) is a gene family encoding gap junction proteins in vertebrates. So far, three isoforms (Panx1, 2 and 3) have been identified. All of three Panx isoforms express in the cochlea with distinct expression patterns. Panx1 expresses in the cochlea extensively, including the spiral limbus, the organ of Corti, and the cochlear lateral wall, whereas Panx2 and Panx3 restrict to the basal cells of the stria vascularis in the lateral wall and the cochlear bony structure, respectively. However, there is no pannexin expression in auditory sensory hair cells. Recent studies demonstrated that like connexin gap junction gene, Panx1 deficiency …

Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez

Biology: Student Scholarship & Creative Works

ABSTRACT: The HIV-1 pandemic continues to thrive due to ineffective HIV-1 vaccines. Historically, the world’s most infectious diseases, such as polio and smallpox, have been eradicated or have come close to eradication due to the advent of effective vaccines. Highly active antiretroviral therapy is able to delay the onset of AIDS but can neither rid the body of HIV-1 proviral DNA nor prevent further transmission. A prophylactic vaccine that prevents the various mechanisms HIV-1 has to evade and attack our immune system is needed to end the HIV-1 pandemic. Recent advances in engineered nuclease systems, like the CRISPR/Cas9 system, have …

Ubr3, A Novel Modulator Of Hh Signaling Affects The Degradation Of Costal-2 And Kif7 Through Poly-Ubiquitination, Tongchao Li, Junkai Fan, Bernardo Blanco-Sánchez, Nikolaos Giagtzoglou, Guang Lin, Shinya Yamamoto, Manish Jaiswal, Kuchuan Chen, Jie Zhang, Wei Wei, Michael T. Lewis, Andrew K. Groves, Monte Westerfield, Jianhang Jia, Hugo J. Bellen

Markey Cancer Center Faculty Publications

Hedgehog (Hh) signaling regulates multiple aspects of metazoan development and tissue homeostasis, and is constitutively active in numerous cancers. We identified Ubr3, an E3 ubiquitin ligase, as a novel, positive regulator of Hh signaling in Drosophila and vertebrates. Hh signaling regulates the Ubr3-mediated poly-ubiquitination and degradation of Cos2, a central component of Hh signaling. In developing Drosophila eye discs, loss of ubr3 leads to a delayed differentiation of photoreceptors and a reduction in Hh signaling. In zebrafish, loss of Ubr3 causes a decrease in Shh signaling in the developing eyes, somites, and sensory neurons. However, not all tissues that require …

Interaction Of Tau With The Rna-Binding Protein Tia1 Regulates Tau Pathophysiology And Toxicity, Tara Vanderweyde, Daniel J. Apicco, Katherine Youmans-Kidder, Peter E. A. Ash, Casey Cook, Edroaldo Lummertz Da Rocha, Karen Jansen-West, Alissa A. Frame, Allison Citro, John D. Leszyk, Pavel Ivanov, Jose F. Abisambra, Martin Steffen, Hu Li, Leonard Petrucelli, Benjamin Wolozin

Sanders-Brown Center on Aging Faculty Publications

Dendritic mislocalization of microtubule associated protein tau is a hallmark of tauopathies, but the role of dendritic tau is unknown. We now report that tau interacts with the RNA-binding protein (RBP) TIA1 in brain tissue, and we present the brain-protein interactome network for TIA1. Analysis of the TIA1 interactome in brain tissue from wild-type (WT) and tau knockout mice demonstrates that tau is required for normal interactions of TIA1 with proteins linked to RNA metabolism, including ribosomal proteins and RBPs. Expression studies show that tau regulates the distribution of TIA1, and tau accelerates stress granule (SG) formation. Conversely, TIA1 knockdown …

Norovirus Infection And Acquired Immunity In 8 Countries: Results From The Mal-Ed Study, Furqan Kabir, Adil Kalam, Pascal Bessong Pascal Bessong, Zulfiqar Ahmed Bhutta, Anita K. M. Zaidi, (Mal-Ed) Network Investigators, Imran Ahmed, Didar Alam, Syed Asad Ali, Shahida Qureshi, Muneera Rasheed, Sajid Bashir Soofi, Ali Turab, Aisha Khizar Yousafzai

Department of Paediatrics and Child Health

Background: Norovirus is an important cause of childhood diarrhea. We present data from a longitudinal, multicountry study describing norovirus epidemiology during the first 2 years of life.
Methods: A birth cohort of 1457 children across 8 countries contributed 7077 diarrheal stools for norovirus testing. A subset of 199 children contributed additional asymptomatic samples (2307) and diarrheal stools (770), which were used to derive incidence rates and evaluate evidence for acquired immunity.
Results: Across sites, 89% of children experienced at least 1 norovirus infection before 24 months, and 22.7% of all diarrheal stools were norovirus positive. Severity of norovirus-positive diarrhea was …

The Mysteries Of Your Blood, Alexandra J. Mauer

BU Well

Did you know that your blood type can be useful for determining disease susceptibility and even creating a diet that works best for your personal metabolism? The Mysteries of your Blood is an article that delves into the science behind the ABO blood types and explains why your body can handle certain foods, stress, and illness differently than someone with a different blood type. It proposes a new, perplexing way to determine how to avoid certain health problems while at the same time offering suggestions of what to eat or, rather, what to avoid eating.

Cardiac Remodeling And Dysfunction In Childhood Obesity: A Cardiovascular Magnetic Resonance Study, Linyuan Jing, Cassi M. Binkley, Jonathan D. Suever, Nivedita Umasankar, Christopher M. Haggerty, Jennifer Rich, Christopher D. Nevius, Gregory J. Wehner, Sean M. Hamlet, David K. Powell, Aurelia Radulescu, H. Lester Kirchner, Frederick H. Epstein, Brandon K. Fornwalt

Pediatrics Faculty Publications

Background: Obesity affects nearly one in five children and is associated with increased risk of premature death. Obesity-related heart disease contributes to premature death. We aimed to use cardiovascular magnetic resonance (CMR) to comprehensively characterize the changes in cardiac geometry and function in obese children.

Methods and results: Forty-one obese/overweight (age 12 ± 3 years, 56 % female) and 29 healthy weight children (age 14 ± 3 years, 41 % female) underwent CMR, including both standard cine imaging and displacement encoded imaging, for a complete assessment of left ventricular (LV) structure and function. After adjusting for age, LV mass index …

Tau And Aβ Imaging, Csf Measures, And Cognition In Alzheimer's Disease, Matthew R. Brier, Brian Gordon, Karl Friedrichsen, John E. Mccarthy, Ari Stern, Jon Christensen, Christopher Owen, Patricia Aldea, Yi Su, Jason Hassenstab, Nigel J. Cairns, David M. Holtzman, Anne M. Fagan, John C. Morris, Tammie L.S. Benzinger, Beau M. Ances

Mathematics Faculty Research

Alzheimer’s disease (AD) is characterized by two molecular pathologies: cerebral β-amyloidosis in the form of β-amyloid (Aβ) plaques and tauopathy in the form of neurofibrillary tangles, neuritic plaques, and neuropil threads. Until recently, only Aβ could be studied in humans using positron emission tomography (PET) imaging owing to a lack of tau PET imaging agents. Clinical pathological studies have linked tau pathology closely to the onset and progression of cognitive symptoms in patients with AD. We report PET imaging of tau and Aβ in a cohort of cognitively normal older adults and those with mild AD. Multivariate analyses identified unique …

Recurrent Mutations Of T-Cell Receptor And Co-Stimulatory Signaling Proteins In Peripheral T-Cell Lymphomas, Joseph Rohr

Theses & Dissertations

Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of mature T-cell neoplasms with a poor prognosis. Recently, mutations in TET2 and other epigenetic modifiers as well as RHOA have been identified in these diseases, particularly in angioimmunoblastic T-cell lymphoma (AITL). CD28 is the major co-stimulatory receptor in T-cells which, upon binding ligand, induces sustained T-cell proliferation and cytokine production when combined with T-cell receptor stimulation, through many signaling molecules including VAV1. This thesis identifies recurrent mutations in CD28 in PTCLs, as well as mutations in VAV1. Two residues of CD28 – D124 and T195 – were recurrently mutated in 11.3% …

The Tnfα-Transgenic Rat: Hippocampal Synaptic Integrity, Cognition, Function, And Post-Ischemic Cell Loss, L. Creed Pettigrew, Richard J. Kryscio, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

The cytokine, tumor necrosis factor α (TNFα), is a key regulator of neuroinflammation linked to numerous neurodegenerative conditions and diseases. The present study used transgenic rats that overexpress a murine TNFα gene, under the control of its own promoter, to investigate the impact of chronically elevated TNFα on hippocampal synaptic function. Neuronal viability and cognitive recovery in TNFα Tg rats were also determined following an ischemic insult arising from reversible middle cerebral artery occlusion (MCAO). Basal CA3-CA1 synaptic strength, recorded in acute brain slices, was not significantly different between eight-week-old TNFα Tg rats and non-Tg rats. In contrast, slices from …

Fbxo30 Regulates Mammopoiesis By Targeting The Bipolar Mitotic Kinesin Eg5., Yan Liu, Yin Wang, Zhanwen Du, Xiaoli Yan, Pan Zheng, Yang Liu

Pediatrics Faculty Publications

Fbxo30 is an orphan member of the F-box protein family with no known substrate or function. Here we report that, while Fbxo30^−/− mice exhibit normal development, growth, lifespan, and fertility, the females fail to nurture their offspring as a result of defective mammopoiesis. Mass spectrometry analysis of Fbxo30-associated proteins revealed that Fbxo30 specifically interacts with the bipolar spindle kinesin EG5 (encoded byKif11). As a result, Fbxo30 targets Eg5 for ubiquitinylation and controls its oscillation during the cell cycle. Correlated with EG5 dysregulation, Fbxo30^−/− mammary epithelial cells exhibit multiple defects in centrosome homeostasis, mitotic spindle …

Acth Prevents Deficits In Fear Extinction Associated With Early Life Seizures, Andrew T. Massey, David K. Lerner, Gregory L. Holmes, Rod C. Scott, Amanda Hernan

Dartmouth Scholarship

Objective: Early life seizures (ELS) are often associated with cognitive and psychiatric comorbidities that are detrimental to quality of life. In a rat model of ELS, we explored long-term cognitive outcomes in adult rats. Using ACTH, an endogeneous HPA-axis hormone given to children with severe epilepsy, we sought to prevent cognitive deficits. Through comparisons with dexamethasone, we sought to dissociate the corticosteroid effects of ACTH from other potential mechanisms of action.

Results: Although rats with a history of ELS were able to acquire a conditioned fear learning paradigm and controls, these rats had significant deficits in their ability to extinguish …

A Single Exercise Bout Enhances The Manufacture Of Viral-Specific T-Cells From Healthy Donors: Implications For Allogeneic Adoptive Transfer Immunotherapy, Guillaume Spielmann, Catherine Bollard, Hawley Kunz, Patrick J. Hanley, Richard J. Simpson

Pediatrics Faculty Publications

Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The adoptive transfer of donor-derived viral-specific cytotoxic T-cells (VSTs) is an effective treatment for controlling CMV and EBV infections after HSCT; however, new practical methods are required to augment the ex vivo manufacture of multi-VSTs from healthy donors. This study investigated the effects of a single exercise bout on the ex vivo manufacture of multi-VSTs. PBMCs isolated from healthy CMV/EBV seropositive participants before (PRE) and immediately after (POST) 30-minutes of cycling exercise were stimulated with CMV (pp65 and …

Characterization Of Bacterial Pathogens Involved In Aerobic Vaginitis: Prevalence, Strain Characterization And Sequelae, Leslie A. Lafferty

Graduate School of Biomedical Sciences Theses and Dissertations

Aerobic vaginitis (AV) is a more recently defined infection that involves aerobic pathogenic bacteria that replace the normal flora of the vaginal tract. It is commonly mistaken for other vaginal infections, such as bacterial vaginosis (BV), because they share many common symptoms. AV leads to complications during pregnancy, such as premature delivery and amnion infection, and is diagnosed by indications that range from vaginal discharge to inflammation. Because this infection is difficult to diagnose differentially from other vaginal infections, it is important to determine what pathogens are involved in AV so that we may have the ability to detect them. …

Immune Modulating Functions By Soypeptide Lunasin In Cancer Immunotherapy, Chun-Yu Tung

Open Access Dissertations

Chemotherapy is currently the mainstay of treatment for most cancer patients. Despite its efficacy in eliminating cancer cells, a high percentage of chemotherapy patients eventually relapse or suffer progression of the disease. Immunosurveillance is capable of recognizing and eliminating continuously arising transformed mutant cells, and thus cancer immunotherapy is one of the emerging therapeutic strategies that harnesses the power of the immune system to eradicate chemotherapy-resistant cancerous cells. However, the adverse side effects of chemotherapy impede the therapeutic effects of immunotherapy. Our previous studies demonstrate that lymphoma patients are refractory to clinical immunotherapy because of chemotherapy-induced immune dysfunction. In addition, …

A Prediction Model For Acute Core And Lower Extremity Injuries In Division 1 Collegiate Football Players, Alexandra Aline Mcdonald

Graduate Theses and Dissertations

Context: Various intrinsic factors such as high exposure, poor endurance of core muscles, previous injury, strength deficits, suboptimal neurocognitive function, and orthopedic abnormalities have been found as predictors for sprains and strains among collegiate football players. Objective: Assess the applicability of pre-participation assessments as predictors of core or lower extremity injury. Design: Cohort Study. Setting: National Collegiate Athletic Association Division I football program. Patients or Other Participants: Athletes who underwent mandatory pre-participation examinations before preseason football training over two consecutive seasons (n=225). Main Outcome Measure(s): Associations between preseason protocols and injury incidence for core and lower extremity injuries were established …

The Effects Of Pulmonary Hypertension In Diabetic Zucker Rats On Pulmonary Vascular Contraction And Right Ventricular Size, Michael Franzetti

Biological Sciences Undergraduate Honors Theses

Pulmonary hypertension is a life-threatening disease that is identified by a resting mean pulmonary arterial pressure over 25 mmHg and established by right heart catheterization (Saglam et al., 2015). The symptoms commonly associated with pulmonary hypertension include fatigue, dyspnea, syncope, and chest pain, which severely limit quality of life in diagnosed patients (Saglam et al., 2015). According to recent studies in patients with pulmonary hypertension, the one, three and five year mortality rates are 8%, 25%, and 34%, respectively (Burudpakdee, Shah, Joish, Divers, & Yaldo, 2014). Although some advances have been made in therapies for pulmonary hypertension, the prognosis is …

Stabilization Of Gp120 Outer Domain For Hiv-1-1 Vaccine Immunogen Design, Duoyi Hu

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The sole envelope glycoprotein spike on the surface of Human Immunodeficiency Virus (HIV-1) is composed of two subunits: gp120 and gp41. The gp120 consists of three domains: the inner domain, outer domain and bridging sheet, to which the viral primary receptor CD4 binds and induces a conformational change in gp120 to expose the co-receptor binding site. Previous studies have found that the outer domain of gp120 is relatively more stable than the inner domain and bridging sheet. When superimposed, the co-crystal structures of CD4-gp120 complex and VRC01-gp120 complex revealed that the CD4-binding site (CD4-BS) antibody VRC01 actually mainly bound to …

Programming Heart Disease: Does Poor Maternal Nutrition Alter Expression Of Cardiac Markers Of Proliferation, Hypertrophy, And Fibrosis In Offspring?, Cathy Chun

Honors Scholar Theses

Maternal malnutrition can affect fetal organogenesis, metabolic processes, and factors involved in developmental regulation. Of the many physiological effects poor maternal nutrition can induce in offspring, one of the most important organs affected is the heart. Cardiovascular disease has been associated with poor maternal diet. It also been suggested that hypertension can originate during impaired intrauterine growth and development. Hypertension can trigger hypertensive heart disease and is associated with numerous heart complications. We hypothesized that poor maternal nutrition would alter critical growth factors associated with normal heart development, specifically, insulin-like growth factor (IGF)-1, IGF-2, transforming growth factor (TGF)β, and connective …

Sa-4-1bbl As A Modulator Of Innate, Adaptive, And Regulatory Immunity : Implications For Cancer Prevention And Treatment., Hampartsoum Barsoumian

Electronic Theses and Dissertations

SA-4-1BBL is a recombinant costimulatory molecule that is active in its soluble form and has pleiotropic effects on the functions of innate, adaptive, and regulatory immune cells. We have previously shown that SA-4-1BBL makes CD4+ T conventional cells (Tconvs) resistant to suppression by CD4+CD25+Foxp3+ T regulatory cells (Tregs). The mechanistic basis of this observation is the subject of this study. We demonstrate that Tconvs, but not Tregs, are the direct targets of SA-4-1BBL-mediated evasion of Treg suppression without contribution from antigen presenting cells (APCs). SA-4-1BBL engagement with its receptor, 4-1BB, on Tconvs resulted in the production of high levels of …

The Roles Of Malt1 In Nf-Κb Activation And Solid Tumor Progression, Deng Pan

Dissertations and Theses (Open Access)

The transcription factor NF-κB plays a central role in many aspects of biological processes and diseases, such as inflammation and cancer. Although it has been suggested thatNF-κB is critical in tumorigenesis and tumor progression, the molecular mechanism by which NF-κB is activated in solid tumor remains largely unknown. In the current work, we focus on growth factor receptor-induced NF-κB activation and tumor progression, including epidermal growth factor receptor (EGFR)-induced NF-κB in lung cancer and heregulin receptor (HER2)-induced NF-κB in breast cancer. We found that Mucosa-associated lymphoma translocation protein 1 (MALT1), also known as paracaspase, is required for EGFR-induced NF-κB activation …

Cll Metabolism Is Regulated By Prognostic Factors, Modulated By Stroma And Abrogated By Pi3k Inhibition, Hima Vangapandu

Dissertations and Theses (Open Access)

Metabolism of chronic lymphocytic leukemia (CLL), a disease characterized by the relentless accumulation of mature B cells has been little explored. Bone marrow stromal cells provide a survival benefit to CLL cells, in part through PI3K/AKT pathway. Compared with proliferative B-cell lines, metabolic fluxes of oxygen and lactate were low in quiescent malignant B lymphocytes from CLL patients. Glycolysis (extracellular acidification rate, ECAR) was consistently low in CLL samples, but oxygen consumption (OCR) varied considerably. Higher OCR was associated with poor prognostic factors such as ZAP 70 positivity, unmutated IgVH, high β2M levels, and higher Rai stage. Co-culture with the …

Nipt Results Indicative Of Maternal Neoplasms: Genetic Counselors' Preferences And Attitudes, Meagan E. Giles

Dissertations and Theses (Open Access)

Performing non-invasive prenatal testing (NIPT) on a pregnant woman with a chromosomally abnormal neoplasm may incidentally lead to the diagnosis of cancer due to the coexistence of circulating tumor and placental DNA. Published information regarding NIPT’s accuracy for neoplasm screening is limited, and guidance for patient management is currently lacking. This challenges clinicians’ ability to counsel patients regarding the implications of these results, which often is the responsibility of a genetic counselor. Over three hundred board-eligible/certified genetic counselors were surveyed regarding their awareness, preferences, and attitudes towards NIPT’s ability to indicate maternal neoplasms. Despite 95% of this cohort being aware …

Evaluation Of The Effects Of Radiation On The Positioning Of Histones And Other Proteins, Ashley Elizabeth Foster

School of Biological Sciences: Dissertations, Theses, and Student Research

Nucleosomes and the secondary structure of DNA play an important role in many cellular processes that are contingent on DNA accessibility, such as replication, transcriptional regulation, and DNA repair. Recently, there is also growing evidence that the association of histones and DNA to form a nucleosome offers protection from DNA degradation. Specifically, that the inherent structural properties of DNA organization can help protect DNA from exogenous damage such as radiation. In this study, we sought to evaluate the effects of radiation on the positioning of histones and other proteins.

In this experiment, we optimized established protein protocols in Saccharomyces cerevisiae. …

Improving Access To Care For Arkansas Youth Athletes With Sport-Related Concussion: Establishing “Teleconcussion” In Arkansas, Kristin Maxey

Health, Human Performance and Recreation Undergraduate Honors Theses

Background: Proper management of sport-related concussion (SRC) is critical for improved recovery outcomes in youth athletes. Several barriers exist to improving the standard of care for youth athletes with SRC. Many rural areas lack medical professionals with specialized training in SRC. Innovative methods for providing specialized healthcare to youth athletes with SRC are needed. Telehealth may be an effective means of providing specialized care for youth athletes with SRC located in underserved areas that have a shortage of healthcare providers specializing in SRC.

Purpose: The purpose of this study was to compare patient, caregiver, and provider ratings of the therapeutic …

Stop Stunting: Situation And Way Forward To Improve Maternal, Child And Adolescent Nutrition In Afghanistan, Ariel Higgins Steele, Piyali Mustaphi, Sherin Varkey, Humayoun Ludin, Najibullah Safi, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

No abstract provided.

Isolation Frequency And Susceptibility Pattern Of Non-O1 And Non-O139 Vibrio Cholerae In A Tertiary Health Care Laboratory, 1999-2012, S Irfan, N Fasih, N K. Ghanchi, Erum Khan

Department of Pathology and Laboratory Medicine

In the past decade the importance of non-O1 and non-O139 strains of Vibrio cholerae has been highlighted globally. This study aimed to evaluate the frequency and antimicrobial susceptibility profile of non-O1 and non-O139 V. cholerae in Pakistan. Data of stool specimens yielding growth of non-O1 and non-O139 V. cholerae isolated at a national referral laboratory from 1999 to 2012 were retrospectively analysed and evaluated for resistance to ampicillin, tetracycline, chloramphenicol, co-trimoxazole and ofloxacin. A total of 95 800 stool samples submitted over 1999-2012 yielded 3668 strains of V. cholerae, of which 6% were non-O1 and non-O139 V. cholerae. A high …

Network-Driven Plasma Proteomics Expose Molecular Changes In The Alzheimer's Brain, Philipp A. Jaeger, Kurt M. Lucin, Markus Britschgi, Badri Vardarajan, Ruo-Pan Huang, Elizabeth D. Kirby, Rachelle Abbey, Bradley F. Boeve, Adam L. Boxer, Lindsay A. Farrer, Nicole Finch, Neill R. Graff-Radford, Elizabeth Head, Matan Hofree, Ruochun Huang, Hudson Johns, Anna Karydas, David S. Knopman, Andrey Loboda, Eliezer Masliah, Ramya Narasimhan, Ronald C. Petersen, Alexei Podtelezhnikov, Suraj Pradhan, Rosa Rademakers, Chung-Huan Sun, Steven G. Younkin, Bruce L. Miller, Trey Ideker, Tony Wyss-Coray

Pharmacology and Nutritional Sciences Faculty Publications

Background: Biological pathways that significantly contribute to sporadic Alzheimer’s disease are largely unknown and cannot be observed directly. Cognitive symptoms appear only decades after the molecular disease onset, further complicating analyses. As a consequence, molecular research is often restricted to late-stage post-mortem studies of brain tissue. However, the disease process is expected to trigger numerous cellular signaling pathways and modulate the local and systemic environment, and resulting changes in secreted signaling molecules carry information about otherwise inaccessible pathological processes.

Results: To access this information we probed relative levels of close to 600 secreted signaling proteins from patients’ blood samples using …

The Effects Of Iron Deficiency Anemia And Iron Supplementation In Pregnancy, Anna J. Cox

Senior Honors Theses

Iron deficiency anemia (IDA) is a condition that occurs in both underdeveloped and developed countries worldwide. This disorder is diagnosed in an individual who presents the common signs and symptoms of anemia along with consistently low clinical markers of stored iron. Iron deficiency (ID) usually precedes a diagnosis of IDA as the insufficient amount of iron often goes undetected until one’s quality of life is diminished. Certain populations, such as women who are pregnant or of reproductive age, are particularly at risk for ID and the development of IDA. During pregnancy, the recommended dietary allowance (RDA) for iron is greater …

S100a4 Drives Non-Small Cell Lung Cancer Invasion, Associates With Poor Prognosis, And Is Effectively Targeted By The Fda-Approved Anti-Helminthic Agent Niclosamide, Rachel L. Stewart, Brittany L. Carpenter, Dava S. West, Teresa Knifley, Lili Liu, Chi Wang, Heidi L. Weiss, Tamas S. Gal, Eric B. Durbin, Susanne M. Arnold, Kathleen L. O'Connor, Min Chen

Markey Cancer Center Faculty Publications

S100A4 (metastasin-1), a metastasis-associated protein and marker of the epithelial to mesenchymal transition, contributes to several hallmarks of cancer and has been implicated in the progression of several types of cancer. However, the impacts of S100A4 signaling in lung cancer progression and its potential use as a target for therapy in lung cancer have not been properly explored. Using established lung cancer cell lines, we demonstrate that S100A4 knockdown reduces cell proliferation, invasion and three-dimensional invasive growth, while overexpression of S100A4 increases invasive potential. In patient-derived tissues, S100A4 is preferentially elevated in lung adenocarcinoma. This elevation is associated with lymphovascular …