Pharmacy and Pharmaceutical Sciences Commons^™

N-Glycosylation-Defective Splice Variants Of Neuropilin-1 Promote Metastasis By Activating Endosomal Signals, Xiuping Huang, Qing Ye, Min Chen, Aimin Li, Wenting Mi, Yuxin Fang, Yekaterina Y. Zaytseva, Kathleen L. O'Connor, Craig W. Vander Kooi, Side Liu, Qing-Bai She

Markey Cancer Center Faculty Publications

Neuropilin-1 (NRP1) is an essential transmembrane receptor with a variety of cellular functions. Here, we identify two human NRP1 splice variants resulting from the skipping of exon 4 and 5, respectively, in colorectal cancer (CRC). Both NRP1 variants exhibit increased endocytosis/recycling activity and decreased levels of degradation, leading to accumulation on endosomes. This increased endocytic trafficking of the two NRP1 variants, upon HGF stimulation, is due to loss of N-glycosylation at the Asn150 or Asn261 site, respectively. Moreover, these NRP1 variants enhance interactions with the Met and β1-integrin receptors, resulting in Met/β1-integrin co-internalization and co-accumulation on endosomes. This provides persistent …

Edb-Fn Targeted Peptide–Drug Conjugates For Use Against Prostate Cancer, Shang Eun Park, Kiumars Shamloo, Timothy A. Kristedja, Shaban Darwish, Marco Bisoffi, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Prostate cancer (PCa) is the most common malignancy in men and is the leading cause of cancer-related male mortality. A disulfide cyclic peptide ligand [CTVRTSADC] 1 has been previously found to target extra domain B of fibronectin (EDB-FN) in the extracellular matrix that can dierentiate aggressive PCa from benign prostatic hyperplasia. We synthesized and optimized the stability of ligand 1 by amide cyclization to obtain [KTVRTSADE] 8 using Fmoc/tBu solid-phase chemistry. Optimized targeting ligand 8 was found to be stable in phosphate buered saline (PBS, pH 6.5, 7.0, and 7.5) and under redox conditions, with a half-life longer than 8 …

Gangliosides: Treatment Avenues In Neurodegenerative Disease., Pierre J. Magistretti, Fred H. Geisler, Jay S. Schneider, P. Andy Li, Hubert Fiumelli, Simonetta Sipione

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Gangliosides are cell membrane components, most abundantly in the central nervous system (CNS) where they exert among others neuro-protective and -restorative functions. Clinical development of ganglioside replacement therapy for several neurodegenerative diseases was impeded by the BSE crisis in Europe during the 1990s. Nowadays, gangliosides are produced bovine-free and new pre-clinical and clinical data justify a reevaluation of their therapeutic potential in neurodegenerative diseases. Clinical experience is greatest with monosialo-tetrahexosyl-ganglioside (GM1) in the treatment of stroke. Fourteen randomized controlled trials (RCTs) in overall >2,000 patients revealed no difference in survival, but consistently superior neurological outcomes vs. placebo. GM1 was shown …

Marketing Channel Effectiveness Of New Medications/Medical Technology, Hadley Mccormick

Celebration of Learning

This research project will study what marketing platforms/channels are most effective in the dissemination of new medical product news. Many people like myself have an illness/disease that requires daily medication, or require the daily use of a medical device. Due to the increasing influence of Direct to Consumer advertising of pharmaceuticals and the constant development of new medications and devices, patients may now more often go to the doctor with perceptions of what they should do to manage their illness/disease. This study aims to look at how the developers of these medications/medical devices promote their products currently and how certain …

A 24-Week Double-Blind Placebo-Controlled Study Of The Efficacy And Safety Of The Ampa Modulator S47445 In Patients With Mild To Moderate Alzheimer's Disease And Depressive Symptoms, Eileen M. Bulger, Sylvie Gouttefangeas, Sylvie Bretin, Stéphanie Galtier, Philippe Robert, Vjera Holthoff-Detto, Jeffrey Cummings, Maria Pueyo

School of Medicine Faculty Research

Introduction S47445 is a novel positive allosteric modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors that may emerge as a favorable candidate for the symptomatic treatment of cognitive and depressive disorders in patients suffering from Alzheimer's disease (AD) of mild to moderate severity and with depressive symptoms. Methods For this double-blind, placebo-controlled 24-week phase II trial, 520 outpatients aged between 55 and 85 years, with probable AD at mild to moderate stages (a Mini-Mental State Examination score of 24-15 inclusive) and exhibiting depressive symptoms (Cornell Scale for Depression in Dementia [CSDD] ≥ 8) were recruited in twelve countries and randomized to 3 doses …

Diagnosis, Treatment And Follow Up Of Acute Pulmonary Embolism: Consensus Practice From The Pert Consortium, Belinda Rivera-Lebron, Michael Mcdaniel, Kamran Ahrar, Abdulah Alrifai, David M. Dudzinski, Christina Fanola, Danielle Blais, David Janicke, Roman Melamed, Kerry Mohrien, Elizabeth Rozycki, Charles B. Ross, Andrew J. Klein, Parth Rali, Nicholas R. Teman, Leoara Yarboro, Eugene Ichinose, Aditya M. Sharma, Jason A. Bartos, Mahir Elder, Brent Keeling, Harold Palevsky, Soophia Naydenov, Parijat Sen, Nancy Amoroso, Josanna M. Rodriguez-Lopez, George A. Davis, Rachel Rosovsky, Kenneth Rosenfield, Christopher Kabrhel, James Horowitz, Jay S. Giri, Victor Tapson, Richard Channick, Pert Consortium

Pharmacy Practice and Science Faculty Publications

Pulmonary embolism (PE) is a life-threatening condition and a leading cause of morbidity and mortality. There have been many advances in the field of PE in the last few years, requiring a careful assessment of their impact on patient care. However, variations in recommendations by different clinical guidelines, as well as lack of robust clinical trials, make clinical decisions challenging. The Pulmonary Embolism Response Team Consortium is an international association created to advance the diagnosis, treatment, and outcomes of patients with PE. In this consensus practice document, we provide a comprehensive review of the diagnosis, treatment, and follow-up of acute …

A High-Throughput Screen Indicates Gemcitabine And Jak Inhibitors May Be Useful For Treating Pediatric Aml, Christina D. Drenberg, Anang Shelat, Jinjun Dang, Anitria Cotton, Shelley J. Orwick, Mengyu Li, Jae Yoon Jeon, Qiang Fu, Daelynn R. Buelow, Marissa Pioso, Shuiying Hu, Hiroto Inaba, Raul C. Ribeiro, Jeffrey E. Rubnitz, Tanja A. Gruber, R. Kiplin Guy, Sharyn D. Baker

Pharmaceutical Sciences Faculty Publications

Improvement in survival has been achieved for children and adolescents with AML but is largely attributed to enhanced supportive care as opposed to the development of better treatment regimens. High risk subtypes continue to have poor outcomes with event free survival rates < 40% despite the use of high intensity chemotherapy in combination with hematopoietic stem cell transplant. Here we combine high-throughput screening, intracellular accumulation assays, and in vivo efficacy studies to identify therapeutic strategies for pediatric AML. We report therapeutics not currently used to treat AML, gemcitabine and cabazitaxel, have broad anti-leukemic activity across subtypes and are more effective relative to the AML standard of care, cytarabine, both in vitro and in vivo. JAK inhibitors are selective for acute megakaryoblastic leukemia and significantly prolong survival in multiple preclinical models. Our approach provides advances in the development of treatment strategies for pediatric AML.

Effect Of Crohn’S Disease On Villous Length And Cyp3a4 Expression In The Pediatric Small Intestine, Brian D. Chapron

Research Days

No abstract provided.

Predictive Performance Of Existing Population Pharmacokinetic Models Of Tacrolimus In Pediatric Kidney Transplant Recipients, Alenka Chapron

Research Days

No abstract provided.

Characterization Of The Relative Contribution Of Cyp2d6 And Cyp3a4 To The Metabolism Of Pimozide, Brian D. Chapron

Research Days

No abstract provided.

Prospective Evaluation Of A Population Pharmacokinetic Model Of Pantoprazole For Obese Children, Alenka Chapron

Research Days

No abstract provided.

The Effect Of The Implementation Of A Quarterly Triad Tool In The Pain Clinic Setting On The Assessment And Mitigation Of Risks In Patients On Chronic Opioid Therapy, Caroline Asava

Evidence-Based Practice Project Reports

The concurrent use of opioids and benzodiazepines (BZDs poses a formidable challenge for clinicians who manage chronic pain. While the escalating use of opioid analgesics for the treatment of chronic pain and the concomitant rise in opioid-related abuse and misuse are widely recognized trends, the contribution of combination use of BZDs, alcohol, and/or other sedative agents to opioid-related morbidity and mortality is underappreciated, even when these agents are used appropriately. Patients with chronic pain who use opioid analgesics along with BZDs have a defined increase in rates of adverse events, overdose, and death, warranting close monitoring. To improve patient outcomes, …

Deregulation Of A Network Of Mrna And Mirna Genes Reveals That Ck2 And Mek Inhibitors May Synergize To Induce Apoptosis Kras-Active Nsclc, Madeline Krentz Gober, Robert M. Flight, Joshua W. Lambert, Hunter N. B. Moseley, Arnold Stromberg, Esther P. Black

Pharmaceutical Sciences Faculty Publications

KRAS-activation mutations occur in 25% to 40% of lung adenocarcinomas and are a known mechanism of epidermal growth factor receptor inhibitor (EGFRI) resistance. There are currently no targeted therapies approved specifically for the treatment of KRAS-active non–small cell lung cancers (NSCLC). Attempts to target mutant KRAS have failed in clinical studies leaving no targeted therapy option for these patients. To circumvent targeting KRAS directly, we hypothesized that targeting proteins connected to KRAS function rather than targeting KRAS directly could induce cell death in KRAS-active NSCLC cells. To identify potential targets, we leveraged 2 gene expression data sets derived from NSCLC …

Human Immunodeficiency Virus Theranostics, Christopher J. Woldstad

Theses & Dissertations

RATIONALE: Long-acting slow effective release antiretroviral therapy (LASER ART) was developed to improve patient regimen adherence, prevent new infections, and facilitate drug delivery to human immunodeficiency virus cell and tissue reservoirs. However, maintenance of sustained plasma drug levels, for weeks or months, after a single high-level dosing, could improve regimen adherence but, at the same time, affect systemic toxicities. Of these, the most troubling are those that affect the central nervous system (CNS) In an effort to facilitate LASER ART development, “multimodal imaging theranostic nanoprobes” were created. These allow combined bioimaging, drug pharmacokinetics and tissue biodistribution tests in animal …

Ethnic And Demographic Differences In Colectomy Rates And Timing For Ulcerative Colitis: 2007-2014, Daniel Bodek, Alana Persaud, Brian Blair, Ahlawat Sushil

Rowan-Virtua Research Day

Ulcerative Colitis (UC) is a chronic inflammatory disease of the bowel, with one third of patients requiring a colectomy for fulminant disease and tissue dysplasia. In 2007, infliximab was approved for induction and maintenance of remission in UC, with some evidence to suggest a potential reduction in colectomies. The aim of this study is to examine relative colectomy rates for UC among different ethnicities from 2007 to 2014 in order to evaluate for development of new trends or disparities.

Discrepancies in colectomy rates and timing are seen in our models which mirror closely findings in a prior study from 1999-2003 …

Comparative Effectiveness Of Drugs Used To Constrict The Patent Ductus Arteriosus: A Secondary Analysis Of The Pda-Tolerate Trial (Nct01958320)., Melissa Liebowitz, Joseph Kaempf, Omer Erdeve, Ali Bulbul, Stellan Håkansson, Johanna Lindqvist, Aijaz Farooqi, Anup Katheria, Jason Sauberan, Jaideep Singh, Kelly Nelson, Andrea Wickremasinghe, Lawrence Dong, Denise C Hassinger, Susan W Aucott, Madoka Hayashi, Anne Marie Heuchan, William A Carey, Matthew Derrick, Ilene Sue Wolf, Amy Kimball, Meera Sankar, Tina Leone, Jorge Perez, Arturo Serize, Ronald I Clyman

Articles, Abstracts, and Reports

OBJECTIVE: To evaluate the effectiveness of drugs used to constrict patent ductus arteriosus (PDA) in newborns < 28 weeks.

METHODS: We performed a secondary analysis of the multi-center PDA-TOLERATE trial (NCT01958320). Infants with moderate-to-large PDAs were randomized 1:1 at 8.1 ± 2.1 days to either Drug treatment (n = 104) or Conservative management (n = 98). Drug treatments were assigned by center rather than within center (acetaminophen: 5 centers, 27 infants; ibuprofen: 7 centers, 38 infants; indomethacin: 7 centers, 39 infants).

RESULTS: Indomethacin produced the greatest constriction (compared with spontaneous constriction during Conservative management): RR (95% CI) = 3.21 (2.05-5.01)), followed by ibuprofen …

Extended Infusions Of Meropenem For Febrile Neutropenia, Daniel J. Przybylski, Pharmd, David J. Reeves, Pharmd, Bcop

BU Well

Background: Neutropenic fever is an oncologic emergency that requires quick intervention with anti-pseudomonal beta-lactam antibiotics, such as meropenem. Previous literature suggests that extended infusions of beta-lactam antibiotics may improve clinical outcomes. To date, there are 3 prior studies utilizing an extended infusion beta-lactam in this population; however, there is only one previous study investigating the use of extended infusion meropenem in patients with febrile neutropenia.

Objective: To describe the outcomes of eight patients receiving extended infusions of meropenem for the treatment of febrile neutropenia.

Methods: A retrospective chart review was completed including adult patients admitted to a community teaching hospital …

Aztreonam Lysine Inhalation Solution In Cystic Fibrosis., Claire Elson, Joel Mermis, Deepika Polineni, Christopher M. Oermann

Manuscripts, Articles, Book Chapters and Other Papers

Patients with cystic fibrosis (CF) develop pulmonary disease secondary to airway infection and dysregulated inflammation. Therapeutic innovations such as nebulized antimicrobial therapy targeting specific pathogens have resulted in improvements in quality of life and life expectancy. Aztreonam lysine for inhalation (AZLI) solution was initially approved to improve respiratory symptoms in CF patients with Pseudomonas aeruginosa (PA) in 2010 by the Food and Drug Administration. Since then, research broadening labeling and clinical application has been developed. In this review, we analyze published and ongoing research regarding AZLI therapy in CF. A search of the Cochrane Database of Systematic Reviews and the …

Evidence-Based Toolkit For Reduction Of Overdose Risk In Primary Care Patients On Opioid Therapy, Katelin A. Aris

Doctoral Projects

Introduction: Opioids are powerful pain killing medications that can be highly addictive and can cause risk for overdose and even death (Michigan Prescription Drug and Opioid Task Force, 2015). Many primary care providers treat patients with acute and chronic pain, although it is recognized that many receive inadequate training in pain management and feel unprepared in the complexities of caring for these patients (Becker, Bair, Picchioni, Starrels, and Frank, 2018). To treat these patients safely, provider education and adherence to guidelines put forward by these initiatives is essential.

Methods: An evidence-based prescribing toolkit was devised using guidance from the literature …

The Pharmabiotic For Phenylketonuria: Development Of A Novel Therapeutic, Chloé Elizabeth Lebegue

Senior Theses

Phenylketonuria, now known as phenylalanine hydroxylase (PAH) deficiency, is a genetic disorder of metabolism affecting approximately one in every 15,000 infants born in the United States. Patients have nonfunctional PAH enzyme secondary to one or more genetic mutations. The enzyme deficit results in destructive supraphysiologic blood phenylalanine levels upon consumption of the essential dietary amino acid phenylalanine. Current standards of care mitigate signs and symptoms of the disorder, but do not approach a cure. The methods for creating a prototype pharmabiotic as an innovative treatment strategy for PAH deficiency are described herein.

DNA molecular cloning techniques were utilized to engineer …

Long-Term Use Of Antibiotics And Risk Of Colorectal Adenoma, Yin Cao, Kana Wu, Raaj Mehta, David A. Drew, Mingyang Song, Paul Lochhead, Long H. Nguyen, Jacques Izard, Charles S. Fuchs, Wendy S. Garrett, Curtis Huttenhower, Shuji Ogino, Edward L. Giovannucci, Andrew T. Chan

Department of Food Science and Technology: Faculty Publications

Objective: Recent evidence suggests that antibiotic use, which alters the gut microbiome, is associated with an increased risk of colorectal cancer. However, the association between antibiotic use and risk of colorectal adenoma, the precursor for the majority of colorectal cancers, has not been investigated.

Design: We prospectively evaluated the association between antibiotic use at age 20–39 and 40–59 (assessed in 2004) and recent antibiotic use (assessed in 2008) with risk of subsequent colorectal adenoma among 16,642 women aged ≥ 60 enrolled in the Nurses’ Health Study who underwent at least one colonoscopy through 2010. We used multivariate logistic …

The Role Of Thyroglobulin In Thyroid Hormonogenesis, Cintia E. Citterio, Héctor M. Targovnik, Peter Arvan

Pharmacy Faculty Articles and Research

In humans, the thyroid hormones T₃ and T₄ are synthesized in the thyroid gland in a process that crucially involves the iodoglycoprotein thyroglobulin. The overall structure of thyroglobulin is conserved in all vertebrates. Upon thyroglobulin delivery from thyrocytes to the follicular lumen of the thyroid gland via the secretory pathway, multiple tyrosine residues can become iodinated to form mono-iodotyrosine (MIT) and/or di-iodotyrosine (DIT); however, selective tyrosine residues lead to preferential formation of T₄ and T₃ at distinct sites. T₄ formation involves oxidative coupling between two DIT side chains, and de novo T₃ formation involves …

Safety And Efficacy Of Very High Dose Furosemide Continuous Infusions, Jessica Wilczynski, Pharmd, Matthew Decaro, Md, Facc, Facp, Gregary Marhefka, Md, Facc, Facp, Brandi Thoma, Pharmd, Bcps, Bccp, Susan Varghese, Pharmd, Bcps, Ryan Watson, Md, Ilya Danelich, Pharmd, Bcps, Bccp

Division of Cardiology Posters

• Fluid overload is treated with loop diuretics in patients with heart failure and in patients with acute kidney injury1,2
• There are sparse data regarding use of very high dose continuous loop diuretic infusions. In some studies, very high doses were only used in outlying patients (maximum160 mg/hour)3, 4
• The use of very high dose furosemide continuous infusions at Thomas Jefferson University Hospital is a rare practice. These infusions range in dose from 40-240 mg/hour, with no limitation on the duration
• The purpose of this study is to examine the efficacy and safety of very high dose furosemide continuous infusions

Systematic Literature Review Of Quetiapine For The Treatment Of Psychosis In Patients With Parkinsonism, Jack J. Chen, Henry Hua, Lilian Massihi, Ivan Portillo, Azita Alipour, William Ondo, Khashayar Dashtipour

Library Articles and Research

Objective:

The purpose of this article was to determine the efficacy and tolerability of quetiapine compared with placebo or other interventions for psychosis in parkinsonism.

Methods:

Participants with a diagnosis of parkinsonism participated in randomized controlled trials (RCTs) investigating the efficacy and tolerability of quetiapine for psychotic symptoms within a defined follow-up period. The authors conducted searches on PubMed, Cochrane Controlled Register of Trials, and EMBASE for articles published from January 1991 to October 2017. Study methodology and patient- and treatment-level data were independently extracted and summarized by using descriptive statistics. Studies underwent quality assessment for risk of bias.

Results: …

The Opioid Crisis: Exploring The Effects On First Responders And Healthcare Professionals, Rachel Lubischer, Dawne Frain

UNO Student Research and Creative Activity Fair

In 2017, the National Department of Health and Human Services declared the opioid crisis a public health emergency (The White House, 2018). Although Nebraska ranks among the states with the lowest number of drug overdose deaths, rising opioid use creates safety concerns for first responders and healthcare professionals, and leads to strained resources in many jurisdictions. We hope to increase our audience’s knowledge on the opioid crisis, how it effects first responders and healthcare professionals, and pertinent policies and initiatives in Nebraska. Our audience will leave this presentation better equipped to initiate discussions with friends, family, and community members about …

Icatibant Is Not Helpful For The Treatment Of Ace Inhibitor-Induced Angioedema, Samantha R. Schwartz

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Sinert R, 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): 1402-1409. doi: 10.1016/j.jaip.2017.03.003.

Assessing The Use Of Pre-Treatment Medications In The Management Of Infusion-Related Reactions In An Outpatient Infusion Center, Alyssa Boesche, Alyssa Augst, Bill Kuhlman

Pharmacy Posters

Introduction

• Infusion-related reactions (IRRs) are well-known adverse drug reactions of many biological agents and antineoplastic medications
• While typically mild-to-moderate in intensity, IRRs can be severe, with potentially life-threatening consequences requiring urgent interventions
• Appropriate use of pre-treatment medications, such as corticosteroids, antihistamines, intravenous fluids, and antiemetics reduces the incidence and severity of IRRs

Purpose

• Evaluate the use of pre-treatment medications in patients with experienced IRRs at an outpatient infusion center
• Identify opportunities to improve treatment plans and reduce the occurrence of IRRs

Inhibition Of Cancer Stem Cells By Glycosaminoglycan Mimetics, Connor P. O'Hara

Theses and Dissertations

Connor O’Hara July 29, 2019

Inhibition of Cancer Stem Cells by Glycosaminoglycan Mimetics

In the United States cancer is the second leading cause of death, with colorectal cancer (CRC) being the third deadliest cancer and expected to cause over 51,000 fatalities in 2019 alone.¹ The current standard of care for CRC depends largely on the staging, location, and presence of metastasis.² As the tumor grows and invades nearby lymph tissue and blood vessels, CRC has the opportunity to invade not only nearby tissue but also metastasize into the liver and lung (most commonly).³ The 5-year survival rate …

Diuretic, Natriuretic, And Vasodepressor Activity Of A Lipid Fraction Enhanced In Medium Of Cultured Mouse Medullary Interstitial Cells By A Selective Faah Inhibitor, Zdravka P. Daneva

Theses and Dissertations

The relationship between the endocannabinoid system in the renal medulla and the long-term regulation of blood pressure is not well understood. To investigate the possible role of the endocannabinoid system in renomedullary interstitial cells, mouse medullary interstitial cells (MMICs) were obtained, cultured and characterized for their responses to treatment with a selective inhibitor of fatty acid amide hydrolase (FAAH), PF-3845. Treatment of MMICs with PF-3845 increased cytoplasmic lipid granules detected by Sudan Black B staining and multilamellar bodies identified by transmission electron microscopy. HPLC analyses of lipid extracts of MMIC culture medium revealed a 205nm-absorbing peak that showed responsiveness to …

Are Patients Living With Hiv Infection At Risk For Not Receiving Statin Medications For Cardiovascular Disease Risk Reduction?, Nick Hastain, Pharmd Candidate, Roshni S. Patel, Pharmd, Bcps, Jason J. Schafer, Pharmd, Mph, Bcps, Aahivp

College of Pharmacy Posters

Objective

To determine the prevalence of appropriate statin prescribing for ASCVD risk reduction in PLWH