Translational Medical Research Commons^™

The Role Of Tbx3 In Early Breast Cancer Progression, Milica Krstic

Electronic Thesis and Dissertation Repository

TBX3 is a transcriptional regulator involved in embryonic development and in tumorigenesis of several cancer types. There are two isoforms of TBX3 (TBX3iso1 and TBX3iso2) with different DNA binding domains. The large-scale functional roles of TBX3iso1 and TBX3iso2 were characterized in a breast cancer context. Both TBX3 isoforms induced invasiveness and an epithelial-to-mesenchymal (EMT) phenotype. Coupling data from genome-wide ChIP-array and RNA-Seq studies provided a novel list of genes regulated by each isoform. Both TBX3 isoforms regulate expression of several EMT-related genes, including SLUG and TWIST1. Importantly, TBX3 is a direct regulator of SLUG, and SLUG expression is required for …

Innate Immunity, The Hepatic Extracellular Matrix, And Liver Injury: Mathematical Modeling Of Metastatic Potential And Tumor Development In Alcoholic Liver Disease., Shanice V. Hudson

Electronic Theses and Dissertations

The overarching goals of the current work are to fill key gaps in the current understanding of alcohol consumption and the risk of metastasis to the liver. Considering the evidence this research group has compiled confirming that the hepatic matrisome responds dynamically to injury, an altered extracellular matrix (ECM) profile appears to be a key feature of pre-fibrotic inflammatory injury in the liver. This group has demonstrated that the hepatic ECM responds dynamically to alcohol exposure, in particular, sensitizing the liver to LPS-induced inflammatory damage. Although the study of alcohol in its role as a contributing factor to oncogenesis and …

Nkx2-1-As1 Negatively Regulates Cd274/Pd-L1, Cell-Cell Interaction Genes, And Limits Human Lung Carcinoma Cell Migration., Hasmeena Kathuria, Guetchyn Millien, Liam Mcnally, Adam C. Gower, Jean-Bosco Tagne, Yuxia Cao, Maria I. Ramirez

Center for Translational Medicine Faculty Papers

The function of most long noncoding RNAs (lncRNAs) is unknown. However, recent studies reveal important roles of lncRNAs in regulating cancer-related pathways. Human antisense lncRNA-NKX2-1-AS1 partially overlaps the NKX2-1/TTF1 gene within chromosomal region 14q13.3. Amplification of this region and/or differential expression of genes therein are associated with cancer progression. Herein we show higher levels of NKX2-AS1 and NKX2-1 in lung adenocarcinomas relative to non-tumor controls but no correlation between NKX2-1-AS1 and NKX2-1 levels across specimens, or with amplification of the 14q13.3 region, suggesting that NKX2-1-AS1 and NKX2-1 are independently regulated. Loss-and-gain of function experiments showed that NKX2-1-AS1 does not regulate …

Intratumoral Sting Activation Sensitizes Poorly Immunogenic Cancers To Checkpoint Blockade Immunotherapy, Casey Ager

Dissertations & Theses (Open Access)

Unprecedented durable tumor regression can be achieved in patients with checkpoint blockade immunotherapy, yet these responses are rare and are not observed in all tumor types. Castration resistant prostate cancer (CRPC) and pancreatic adenocarcinoma (PDAC) are two common lethal cancers that remain refractory to checkpoint blockade, requiring development of new therapeutic approaches to promote responsivity in patients with these diseases. Both CRPC and PDAC are characterized by an immunosuppressive tumor milieu rich in cells of the myeloid lineage, which regulate T cell activity in many ways independent of the coinhibitory receptor axis. We investigated whether activation of acute inflammatory signaling …

Dual-Display Laparoscopic Laser Speckle Contrast Imaging For Real-Time Surgical Assistance, Jaepyeong Cha, Corey Zheng, Lung Wai Lau

Pediatrics Faculty Publications

Laser speckle contrast imaging (LSCI) utilizes the speckle pattern of a laser to determine the blood flow in tissues. The current approaches for its use in a clinical setting require a camera system with a laser source on a separate optical axis making it unsuitable for minimally invasive surgery (MIS). With blood flow visualization, bowel viability, for example, can be determined. Thus, LSCI can be a valuable tool in gastrointestinal surgery. In this work, we develop the first-of-its-kind dual-display laparoscopic vision system integrating LSCI with a commercially available 10mm rigid laparoscope where the laser has the same optical axis as …

Direct Crystal Formation From Micronized Bone And Lactic Acid: The Writing On The Wall For Calcium-Containing Crystal Pathogenesis In Osteoarthritis?, Anna A. Bulysheva, Nardos Sori, Michael P. Francis

Bioelectrics Publications

Introduction

Pathological calcium-containing crystals accumulating in the joints, synovial fluid, and soft tissues are noted in most elderly patients, yet arthritic crystal formation remains idiopathic. Interestingly, elevated lactic acid and bone erosion are frequently among the comorbidities and clinical features of patients with highest incidence of crystal arthropathies. This work shows that bone particulates (modeling bone erosion) dissolve in lactic acid and directly generate crystals, possibly presenting a mechanism for crystal accumulation in osteoarthritis.

Methods and results

Micronized human bone (average particle size of 160 μm x 79 μm ) completely dissolved in lactic acid in 48 hours, and in …

The Anti-Cancer Effect Of Retinoic Acid Signaling In Crc Occurs Via Decreased Growth Of Aldh+ Colon Cancer Stem Cells And Increased Differentiation Of Stem Cells, Shirin R. Modarai, Anindita Gupta, Lynn M. Opdenaker, Ryan Kowash, Gabriel Masters, Vignesh Viswanathan, Tao Zhang, Jeremy Z. Fields, Bruce M. Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Background: Tumorigenesis is driven by stem cell (SC) overpopulation. BecauseALDH is both a marker for SCs in many tissues and a key enzyme in retinoid acid (RA)signaling, we studied RA signaling in normal and malignant colonic SCs.Hypothesis: RA signaling regulates growth and differentiation of ALDH+ colonicSCs dysregulation of RA signaling contributes to SC overpopulation and colorectalcancer (CRC) development.Methods: We analyzed normal and malignant colonic tissues and CRC cell linesto see if retinoid receptors (RXR &RAR) are exclusively expressed in ALDH+ SCs,and if RA signaling changes during CRC development. We determined whether RAsignaling regulates cancer SC (CSC) proliferation, differentiation, sphere formation,and …

Non-St-Segment Elevation Acute Coronary Syndrome: Early Versus Delayed Cardiac Catheterization, Teresa Colelli, Adrianna Clapp, Rudy Wenner, Blake J. Arthurs

Clinical Research in Practice: The Journal of Team Hippocrates

An informed consent conversation regarding early vs. delayed cardiac catheterization for patients with NSTEMI.

Editorial: Clinical Practice Can Save Evidence-Based Medicine From Itself, James Peter Meza, Nicholus Yee

Clinical Research in Practice: The Journal of Team Hippocrates

Although imperfect, the structure of this journal and its publications are demonstrations of clinicians attempting to actualize the wisdom of these foundational thinkers. We need to leave examples and guideposts to the next generation of clinicians of how to fulfill this vision of being excellent clinicians, through both formal education and role modeling.

Pneumatic Balloon Dilation Versus Myotomy For The Treatment Of Achalsia, Benjamin E. Ueberroth

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Moonen A, Annese V, Belmans A, et al. Long-term results of the European achalasia trial: A multicentre randomised controlled trial comparing pneumatic dilation versus laparoscopic Heller myotomy. Gut. 2016 May;65(5):732-9. doi: 10.1136/gutjnl-2015-310602.

Fecal Transplant Is Superior To Oral Vancomycin For Treatment Of Recurrent Clostridium Difficile, Kassandra J. Weber

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013;368(5):407-415. doi: 10.1056/NEJMoa1205037.

Equal Efficacy Of Clopidogrel Versus Ticagrelor As Monotherapy In Peripheral Artery Disease, Aimee L. Vos

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Hiatt H, Fowkes G, Heizer G, et al. Ticagrelor versus clopidogrel in symptomatic peripheral artery disease. N Engl J Med. 2017;376:32-40. doi: 10.1056/NEJMoa1611688.

Lurasidone Is Not Associated With Risk Of Qtc Prolongation, Halimah Y. Oral

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Meltzer HY, Cucchiaro J, Silva R, Ogasa M, Phillips D, Xu J, Kalali AH, Scheizer E, Pikalov A, Loebel A. Lurasidone in the treatment of schizophrenia: a randomized, double-blind, placebo- and olanzapine-controlled study. Am J Psychiatry. 2011 Sep;168(9):957-67. doi: https://doi.org/10.1176/appi.ajp.2011.10060907.

Long-Term Antibiotic Therapy Is Just As Effective As Amputation For Foot Osteomyelitis In Diabetics Without Peripheral Arterial Disease, Christopher Hopper

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Lázaro-Martínez JL, Aragón-Sánchez J, García-Morales E. Antibiotics versus conservative surgery for treating diabetic foot osteomyelitis: a randomized comparative trial. Diabetes Care. 2014;37(3):789-95. doi: 10.2337/dc13-1526.

Ssri Maintenance Therapy Reduces Rate Of Recurrence For Elderly Patients With First Episode Of Major Depression, Blake J. Arthurs

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Reynolds CF 3rd, Dew MA, Pollock BG, et al. Maintenance treatment of major depression in old age. N Engl J Med. 2006 Mar 16;354(11):1130-8. doi: 10.1056/NEJMoa052619. Based on the appraisal, long term SSRI maintenance therapy is recommended for elderly patients suffering from first episode of major depression.

My Patient Chose To Not Use Daily Azithromycin To Prevent Exacerbation Of Copd, Jacob Oblak

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Albert RK, Connett J, Bailey WC, et al. Azithromycin for prevention of exacerbations of COPD. New Eng J Med. 2011;365:689-698. doi: 10.1056/NEJMoa1104623.

Abstinence From Alcohol Improves Survival In Decompensated Cirrhotic Patients, Perry Zong

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Alvarez MA, Cirera I, Solà R, Bargalló A, Morillas RM, Planas R. Long-term clinical course of decompensated alcoholic cirrhosis. Journal of Clinical Gastroenterology. 2011;45(10):906-911. doi: 10.1097/mcg.0b013e3182284e13.

Therapeutic Hypothermia For Children After In-Hospital Cardiac Arrest Not Helpful, Bradley Kolb

Clinical Research in Practice: The Journal of Team Hippocrates

An informed consent discussion regarding the merits of therapeutic hypothermia in a comatose pediatric patient following in-hospital cardiac arrest and return of spontaneous circulation.

Institutional Protocols Can Improve Ivc Filter Retrieval Rates, Madeline Ross, Gong He, Veronica Santana-Ufret, Anjali Sundar

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Lynch FC. A method for following patients with retrievable inferior vena cava filters: results and lessons learned from the first 1100 patients. J Vasc Interv Radiol. 2011;22:1507–1512. doi: 10.1016/j.jvir.2011.07.019

Pepducin-Mediated Cardioprotection Via Β-Arrestin-Biased Β2-Adrenergic Receptor-Specific Signaling, Laurel A. Grisanti, Toby P. Thomas, Rhonda L. Carter, Claudio De Lucia, Erhe Gao, Walter J. Koch, Jeffrey L. Benovic, Douglas G. Tilley

Department of Biochemistry and Molecular Biology Faculty Papers

Reperfusion as a therapeutic intervention for acute myocardial infarction-induced cardiac injury itself induces further cardiomyocyte death. β-arrestin (βarr)-biased β-adrenergic receptor (βAR) activation promotes survival signaling responses in vitro; thus, we hypothesize that this pathway can mitigate cardiomyocyte death at the time of reperfusion to better preserve function. However, a lack of efficacious βarr-biased orthosteric small molecules has prevented investigation into whether this pathway relays protection against ischemic injury in vivo. We recently demonstrated that the pepducin ICL1-9, a small lipidated peptide fragment designed from the first intracellular loop of β2AR, allosterically engaged pro-survival signaling cascades in a βarr-dependent manner in …

Autologous Blood Patch After Ct-Guided Lung Biopsy Might Reduce Pneumothorax Requiring Chest Tube Placement, Tiffani Strickland

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Malone LJ, Stanfill RM, Wang H, Fahey KM, Bertino RE. Effect of intraparenchymal blood patch on rates of pneumothorax and pneumothorax requiring chest tube placement after percutaneous lung biopsy. American Journal of Roentgenology. 2013;200(6):1238-1243. doi: 10.2214/ajr.12.8980.

Icatibant Is Not An Appropriate Treatment Option For Ace-Inhibitor Induced Angioedema Of The Head And Neck, Faiz Khaja

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Sinert T, Levy P, Bernstein JA, et al. Randomized trial of icatibant for angiotensin-converting enzyme inhibitor-induced upper airway angioedema. J Allergy Clin Immunol Pract. 2017;5(5):1402-9. doi: 10.1016/j.jaip.2017.03.003

Transcriptional Up-Regulation Of Relaxin-3 By Nur77 Attenuates Β-Adrenergic Agonist-Induced Apoptosis In Cardiomyocytes., Xiaohua You, Zhifu Guo, Fang Cheng, Bing Yi, Fan Yang, Xinzhu Liu, Ni Zhu, Xianxian Zhao, Guijun Yan, Xin-Liang Ma, Jianxin Sun

Center for Translational Medicine Faculty Papers

The relaxin family peptides have been shown to exert several beneficial effects on the heart, including anti-apoptosis, anti-fibrosis, and anti-hypertrophy activity. Understanding their regulation might provide new opportunities for therapeutic interventions, but the molecular mechanism(s) coordinating relaxin expression in the heart remain largely obscured. Previous work demonstrated a role for the orphan nuclear receptor Nur77 in regulating cardiomyocyte apoptosis. We therefore investigated Nur77 in the hopes of identifying novel relaxin regulators. Quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) data indicated that ectopic expression of orphan nuclear receptor Nur77 markedly increased the expression of latexin-3 (RLN3), but not relaxin-1 …

Anidulafungin: A Noninferior Alternative To Fluconazole For Treatment Of Esophageal Candidiasis, Blake S. Sanford

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Krause DS, Simjee AE, van Rensburg C, et al. A randomized, double-blind trial of anidulafungin versus fluconazole for the treatment of esophageal candidiasis. Clin Infect Dis. 2004;39(6):770-775. doi: 10.1086/423378.

Sertraline Is An Effective Management Option For Cholestatic Pruritus, Rudy W. Wenner

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Mayo MJ, Handem I, Saldana S, Jacobe H, Getachew Y, Rush AJ. Sertraline as a first-line treatment for cholestatic pruritus. Hepatology. 2007 Mar;45(3):666-74. doi: 10.1002/hep.21553

Intravenous Glucocorticoids Provide No Additional Benefit Over Oral Glucocorticoids In Chronic Obstructive Pulmonary Disease Exacerbation, Alexander C. Waselewski

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of de Jong YP, Uil SM, Grotjohan HP, Postma DS, Kerstjens HA, van den Berg JW. Oral or IV prednisolone in the treatment of COPD exacerbations: a randomized, controlled, double-blind study. Chest. 2007;132(6):1741-1747. doi: 10.1378/chest.07-0208

Pulmonary Aspergillosis: A Review On Diagnosis And Management, Bilal A. Jalil, Juan M. Galvis, Karim A. El Kersh, Mohamed Saad, Mostafa M. Fraig, Juan J. Guardiola Ii

The University of Louisville Journal of Respiratory Infections

Aspergillosis is acquired by inhalation of spores of Aspergillus, a ubiquitous species in the environment. In normal hosts, spore inhalation rarely causes lung disease.

Pulmonary aspergillosis covers a wide spectrum of clinical syndromes depending on the interaction between Aspergillus and the host (immune-status, prior bronchopulmonary disease). It runs the gamut from invasive aspergillosis to Aspergillus bronchitis and colonization.

Invasive aspergillosis occurs in severely immunocompromised patients, typically with neutropenia. Chronic pulmonary aspergillosis affects patients with chronic structural lung disease such as chronic obstructive pulmonary disease, mycobacterial lung disease, but without significant immunocompromise. Aspergillus bronchitis affects patients with bronchial disease such …

A Continuum Of Disease From Community-Acquired Pneumonia To Multiple Organ Dysfunction Syndrome, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Characteristics And Clinical Outcomes Of Hospitalized Patients With Community-Acquired Pneumonia Who Are Active Intravenous Drug Users, Vidyulata Salunkhe, Paula Peyrani, Leslie A. Beavin, Stephen P. Furmanek, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Background: Intravenous drug users (IVDU) have a 10-fold increased risk of community-acquired pneumonia (CAP) compared to the general population. There is scarce data available evaluating the clinical outcomes of IVDU hospitalized patients with CAP and that data mostly focuses on mortality. The objective of this study was to evaluate the clinical characteristics, incidence and outcomes of hospitalized patients with CAP in active intravenous drug users in Louisville, Kentucky.

Methods: This was a secondary data analysis of the University of Louisville Pneumonia study. IVDU patients were propensity score matched to a non-IVDU group. Study outcomes were time to clinical stability (TCS), …

Coping With Chronic Fungal Rhinosinusitis: Diagnosis To Therapy, Veronica Corcino, Leslie Beavin, Shengli Lu, Ashley Ross, Carmen V. Sciortino Jr.

The University of Louisville Journal of Respiratory Infections

No abstract provided.