Translational Medical Research Commons^™

Targeting Cox-2 And Rank In Aggressive Breast Cancers: Inflammatory Breast Cancer And Triple-Negative Breast Cancer, Monica Elizabeth Reyes

Dissertations and Theses (Open Access)

Inflammatory breast cancer (IBC) and triple-negative breast cancer (TNBC) are two highly aggressive breast cancer subtypes associated with a poor outcome. Despite sensitivity to current treatment, these breast cancers subtypes have a high recurrence rate and proclivity to metastasize early. The aggressiveness of IBC and TNBC have been linked to CSCs and epithelial to mesenchymal transition (EMT), which are critical features of breast cancer progression and metastasis. The clinical challenge faced in the treatment of IBC and TNBC is finding a treatment strategy to target the cancer stem-like (CSC) population to block metastasis. Cyclooxygenase-2 (COX-2) and receptor activator of nuclear …

Targeting Cox-2 And Rank In Aggressive Breast Cancers: Inflammatory Breast Cancer And Triple-Negative Breast Cancer, Monica E. Reyes

Dissertations and Theses (Open Access)

Inflammatory breast cancer (IBC) and triple-negative breast cancer (TNBC) are two highly aggressive breast cancer subtypes associated with a poor outcome. Despite sensitivity to current treatment, these breast cancers subtypes have a high recurrence rate and proclivity to metastasize early. The aggressiveness of IBC and TNBC have been linked to CSCs and epithelial to mesenchymal transition (EMT), which are critical features of breast cancer progression and metastasis. The clinical challenge faced in the treatment of IBC and TNBC is finding a treatment strategy to target the cancer stem-like (CSC) population to block metastasis. Cyclooxygenase-2 (COX-2) and receptor activator of nuclear …

Can Mhealth Improve Risk Assessment In Underserved Populations? Acceptability Of A Breast Health Questionnaire App In Ethnically Diverse, Older, Low-Income Women., Carolina Bravo, Cristina O’Donoghue, Celia P. Kaplan, Judith Luce, Elissa Ozanne

Journal of Health Disparities Research and Practice

Background: Use of mobile health (mHealth) tools has expanded rapidly but little research has been done on its acceptability by low-income, diverse, older patient populations.

Objective: To assess the attitudes of a diverse group of underserved women on the acceptability and usability of mHealth tools in a clinical setting using a breast health questionnaire application (app) at a public hospital mammography clinic.

Methods: Semi-structured interviews were conducted in a breast-imaging center of an urban safety net institution from July-August 2012. Interviews included pre- and post-questions. Women completed the Athena breast health questionnaire app on an iPad and were asked about …

Neglected Or Non-Compliant? Assessing The Difficulties Of Tuberculosis Patients In Salvador-Ba, Brazil, Erin Slatery

Independent Study Project (ISP) Collection

Objective: The aim of this study is to analyze how Instituto Brasileiro para Investigação da Tuberculose (IBIT), a philanthropic tuberculosis clinic in Salvador, Brazil, maintains treatment abandonment rates much lower than those of surrounding public clinics. This study also aims to evaluate how professionals conceptualize and address the difficulties faced by patients.

Methods: Interviews were conducted with 8 IBIT professionals and 16 patients in treatment for tuberculosis in the aforementioned institution via semi-structured and structured questionnaires, respectively. Participant observation guided the analysis of relationships between patients and professionals.

Results: Patients found varying aspects of treatment difficult depending on personal circumstances, …

Racial And Ethnic Disparities In Time To Cure Of Incontinence Present At Nursing Home Admission, Donna Z. Bliss, Olga Gurvich, Kay Savik, Lynn Eberly, Susan Harms, Jean F. Wyman

Journal of Health Disparities Research and Practice

Abstract

As many as half of older people that are admitted to nursing homes (NHs) are incontinent of urine and/or feces. Not much is known about the rate of cure of incontinence present at NH admission, but available reports suggest the rate is low. There have been racial and ethnic disparities in incontinence treatment, but the role of disparities in the cure of incontinence is understudied. Using the Peters-Belson method and multilevel predictors, our findings showed that there were disparities in the time to cure of incontinence for Hispanic NH admissions. A significantly smaller proportion of older Hispanic admissions were …

Role Of The Ang-Tie2 Pathway In The Invasive Recurrence Of Gbm Following Anti-Vegf Therapy, Nahir Cortes Santiago

Dissertations and Theses (Open Access)

Strong pre-clinical and clinical data supporting the effectiveness of bevacizumab, a humanized monoclonal anti-VEGF antibody, for the treatment of gliomas led to its accelerated approval for the treatment of patients with recurrent glioma. However, despite strong anti-tumor effects, upon treatment with bevacizumab, patients will invariably recur with a tumor characterized by enhanced invasiveness and resistance to therapy. This study aims to elucidate the mechanisms leading to this enhanced malignancy with the hope of uncovering new potential therapeutic targets for combined treatment. Using tissue sections from U87-derived glioma bearing mice treated with or without aflibercept (another anti-VEGF antibody) we have gathered …

Targeting The Redox System To Overcome Mechanisms Of Drug Resistance In Chronic Lymphocytic Leukemia, Marcia A. Ogasawara

Dissertations and Theses (Open Access)

Chronic Lymphocytic Leukemia (CLL) is the most common form of leukemia diagnosed in Western countries and is characterized by clonal expansion of B cells. The clinical course of CLL is diverse and nearly 50% of patients present with chromosomal abnormalities. Deletion of the short arm on chromosome 17 (del17p) occurs in 5-7% of cases and presents with the shortest median survival time and often respond poorly to therapy. The tumor suppressor gene, TP53 is located on this region and it is well established that the p53 protein regulates multiple functions including: mitochondria biogenesis, response to DNA damage and redox balance. …

Targeting The Mdm2-P53 Axis For The Treatment Of Dedifferentiated Liposarcoma, Katelynn Bill

Dissertations and Theses (Open Access)

Dedifferentiated liposarcoma (DDLPS) is an aggressive malignancy characterized by a high rate of recurrence and dismal patient outcome. Minimal improvement in patient survival has been made in the last several decades, highlighting the crucial need for improved therapeutic strategies. A better understanding of the molecular deregulations underlying DDLPS would facilitate the discovery of improved therapeutic approaches. MDM2 is a well characterized oncoprotein and the most known negative regulator of p53. MDM2 amplification is considered the “hallmark” of DDLPS. Additionally, these tumors are known to harbor wild-type p53. We sought to take advantage of this knowledge and evaluate the role of …

Promoting Teamwork In Translational Medical Teams: Insights And Recommendations From Science And Practice, Lauren E. Benishek, Ashley M. Hughes, Megan E. Gregory, Shirley C. Sonesh, Eduardo Salas, Elizabeth H. Lazzara

Publications

Translational medical teams are transdisciplinary, highly collaborative, and operate within dynamic environments to solve time-sensitive and complex problems. These teams are tasked with turning observations in the laboratory and clinic into effective interventions that improve the health of individuals and the public. The nature of the problems they seek to solve requires coordination among clinicians, scientists, and experts from various scientific disciplines. Characteristically, translational medical teams have complex compositions, structure, and pluralistic goals, which pose significant challenges and barriers to enacting effective teamwork, compromising team performance. Given these challenges, it is imperative to glean insights from teams research and the …

Shape And Position Of The Node And Notochord Along The Bilateral Plane Of Symmetry Are Regulated By Cell-Extracellular Matrix Interactions., Maria Pulina, Dong Liang, Sophie Astrof

Center for Translational Medicine Faculty Papers

The node and notochord (and their equivalents in other species) are essential signaling centers, positioned along the plane of bilateral symmetry in developing vertebrate embryos. However, genes and mechanisms regulating morphogenesis of these structures and their placement along the embryonic midline are not well understood. In this work, we provide the first evidence that the position of the node and the notochord along the bilateral plane of symmetry are under genetic control and are regulated by integrin α5β1 and fibronectin in mice. We found that the shape of the node is often inverted in integrin α5-null and fibronectin-null mutants, and …

Pioglitazone Treatment Reduces Adipose Tissue Inflammation Through Reduction Of Mast Cell And Macrophage Number And By Improving Vascularity, Michael Spencer, Lin Yang, Akosua Adu, Brian S. Finlin, Beibei Zhu, Lindsey R. Shipp, Neda Rasouli, Charlotte A. Peterson, Philip A. Kern

Clinical and Translational Science Faculty Publications

Context and Objective: Adipose tissue in insulin resistant subjects contains inflammatory cells and extracellular matrix components. This study examined adipose pathology of insulin resistant subjects who were treated with pioglitazone or fish oil.

Design, Setting and Participants: Adipose biopsies were examined from nine insulin resistant subjects before/after treatment with pioglitazone 45 mg/day for 12 weeks and also from 19 subjects who were treated with fish oil (1,860 mg EPA, 1,500 mg DHA daily). These studies were performed in a clinical research center setting.

Results: Pioglitazone treatment increased the cross-sectional area of adipocytes by 18% (p = 0.01), and also increased …

The Association Between Health Literacy And Diet Adherence Among Primary Care Patients With Hypertension, Jenny A. Hutchison Ms., Jan Warren-Findlow Dr., Michael Dulin Dr., Hazel Tapp Dr., Lindsay Kuhn

Journal of Health Disparities Research and Practice

This study examines the association between health literacy and adherence to low-salt diet practices among individuals with hypertension. Health literacy is the ability of individuals to understand and utilize health information. We surveyed 238 patients with hypertension from a primary care clinic in Charlotte, NC. We assessed health literacy and self-reported low-salt diet. Logistic regression was used to model the relationship between health literacy and low-salt diet adherence. Respondents were primarily female (67.3%) and black (80%). Black Americans were less likely to have adequate health literacy as compared to white Americans (21.8% vs. 55.8%). The study found no association between …

A Transdisciplinary Approach To Eliminate Cancer Disparities: An Overview Of Community Engagement And Outreach Efforts In An National Institute Of Health Center For Excellence, Maisha Standifer, Mph, Julie Baldwin, Phd, Jenna Davis, Mph, Clemente Gwede, Phd, Coni Williams, Ma, Lolita Dash-Pitts, Johnetta Goldsmith, Ms, Thometta Cozart Brooks Ms, Mph, Deanna Wathington, Md, B. Lee Green, Phd, Kevin Sneed, Phamd

Journal of Health Disparities Research and Practice

Creating health equity and eliminating health disparities are considered national priorities for improving the health of Americans (U.S. Department of Health and Human Services, n.d.). Health disparities are a primary public health concern, yet are complex phenomena and challenging to research (Harper & Lynch, 2005). The National Institute on Minority Health and Health Disparities (NIMHD), under the National Institute of Health (NIH), is committed to finding solutions to achieve this goal through the creation of interdisciplinary Centers of Excellence. In 2009, the University of South Florida (USF) and Moffitt Cancer Center (Moffitt) received a NIMHD Exploratory Center of Excellence award …

Statement Before The House Of Representatives Subcommittee On Health Of The Committee On Energy And Commerce, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

Statement of Fred David Ledley, M.D.
Director, Center for Integration of Science and Industry
Professor, Natural and Applied Sciences and Management
Bentley University, Waltham, MA

Before the House of Representatives
Subcommittee on Health of the
Committee on Energy and Commerce

Hearing: 21st Century Cures: Examining the Role of Incentives in Advancing Treatments and Cures for Patients

June 11, 2014

Why Does Society Support Science? And How To Meet The Expectations?, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

Public support for science is related less to the wonder of scientific discovery than the expectation that scientific and technological advances will lead to new product, jobs, and economic growth. Recent evidence suggests that these outcomes are not certain. Fred Ledley argues that the public is often promised the benefits of scientific discoveries without adequate consideration of the business challenges inherent in translating science for public benefit.

How To Lie With (Fda) Statistics, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

The FDA approved 27 new drugs in 2013. Is this a downward trend? Is it an upward trend? Does it suggest that the pharmaceutical industry is failing, or that genomics is finally paying dividends? We revisit Darrell Huff’s 1954 classic How to Lie with Statistics for insights into these pressing questions.

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

University Scholar Projects

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Latinos' Health Perceptions: A Cross-Cultural Analyisis, Elizabeth Pappenfus

Undergraduate Research Symposium 2014

The purpose of my study is to examine how Latinos’ cultural health beliefs impact their illness behaviors in a rural setting in comparison to White individuals. Illness behavior is defined as the manner in which a person monitors their body, interprets their symptoms, and their reactions to those symptoms. Although Latino immigrants suffer from higher rates of treatable diseases, they are largely underutilizing the healthcare system in the U.S. The Andersen model of healthcare utilization is the most commonly used model for predicting utilization based on the person's environment (i.e. healthcare system) and personal characteristics (i.e. personal need, available resources, …

Brain Blast 2014 Poster, Annie Leslie

Brain Blast

Announcement poster for UNE's Brain Blast 2014, a pechakucha-style brain health and safety awareness and learning event.

Between The Lines: Somali Women And Medical Interpretation Experiences, Amin Sheikh

Muskie School Capstones and Dissertations

Many studies have investigated the health care experiences of Somali women. However, there is little research that looks at Somali women’s experiences with language barriers and their language preferences. In my capstone, I explore language barriers in the health care system from the perspective of non-English speaking immigrant Somali women with children living in the Lewiston-Auburn area.

Brain Blast 2014 Speakers Poster, Annie Leslie

Brain Blast

Poster from UNE's Brain Blast 2014 listing the presenters at this event.

Research Annual Report Fy2014, Children's Mercy Hospital

Research Annual Reports

Annual report of the research at Children's Mercy Hospital in Kansas City MO, a pediatric medical center.

African Primary Care Research: Current Situation, Priorities And Capacity Building, Robert Mash, Akye Essuman, Riaz Ratansi, Felicity Goodyear-Smith, Klaus Von Pressentin, Zelra Malan, Marianne Van Lancker, Jan De Maeseneer

Faculty of Health Sciences, East Africa

The Sixth PRIMAFAMED (Primary Health Care/Family Medicine Education Network) workshop on ‘Capacity Building and Priorities in Primary Care Research’ was held in Pretoria, South Africa (SA), from 22 to 24 June 2014. Delegates from the following countries attended the workshop: Ghana, Nigeria, Uganda, Kenya, Tanzania, Sudan, Malawi, Zimbabwe, Botswana, Namibia, SA, Zambia, Ethiopia, Rwanda, Mozambique, Swaziland, Belgium, and Denmark (Figure 1). Delegates were from established or emerging departments of family medicine and primary care in these countries. The central theme of the workshop was primary care research – the current situation, the priorities for research and the need for capacity …

Primary And Secondary Prevention Of Hepatitis C Virus Among Rural Appalachian People Who Use Drugs, Dustin B. Stephens

Theses and Dissertations--Clinical and Translational Science

Hepatitis C virus (HCV) remains a major cause of morbidity and mortality worldwide, with 3% of the global population chronically infected. Clinical impacts in the United States are projected to increase for two decades, and mortality attributed to HCV now exceeds HIV. Injection drug use (IDU) is the most common route of transmission in the developed world. Advances in treatment offer hope of mitigating HCV impacts, but substantial barriers obstruct people who inject drugs (PWID) from receiving care, particularly in medically underserved regions including Central Appalachia. This study assessed IDU paraphernalia sharing longitudinally over 24 months in a sample of …

Receptor Of Advanced Glycation Endproducts (Rage) Is Positively Correlated With Tumor Necrosis Factor-Α In Adolescents With Obesity, Tasnim Rahman, Daniel H. Conrad, Anshu Gupta

Undergraduate Research Posters

Introduction: Obesity in childhood is associated with an increased prevalence of diabetes and other traditional cardiometabolic risk factors, suggesting an epidemic of premature cardiovascular disease among today’s youth. Glycotoxins, known as advanced glycationend products (AGE’s), activating via the membrane-bound receptors (mRAGE), have been implicated in the pathophysiology of inflammation, (increased tumor necrosis factor-α [TNF-α ]), insulin resistance and vascular dysfunction in adults, but the role of RAGE in the early stages of metabolic disorders is unknown. In this study, we assessed relationship of cardiometabolicrisk factors, mRNA expression of TNF-α and RAGE in peripheral monocytes in adolescents with obesity.

Methods: Thirty …

Emergency Nurses' Knowledge Of Pediatric Complaints, Kari J. Blackburn

DNP Projects

Each year there are more than 25 million pediatric emergency department (ED) visits, with 37-60% of the complaints being non-urgent (Brosseau, Hoffman, Nattinger, Flores, Zhang and Gorelick, 2007). Injury is the number one reason children present to the ED and is strongly associated with a complaint of pain (AHRQ, 2013). While pain is a high volume reason for visiting the ED, there are other presentation causes that may pose a high risk to pediatric patients. Nausea and vomiting is not typically viewed as a high risk complaint, yet there are some high risk etiologies resulting in nausea and vomiting that …

A Systems Biology Approach To Detect Eqtls Associated With Mirna And Mrna Co-Expression Networks In The Nucleus Accumbens Of Chronic Alcoholic Patients, Mohammed Mamdani

Theses and Dissertations

Alcohol Dependence (AD) is a chronic substance use disorder with moderate heritability (60%). Linkage and genome-wide association studies (GWAS) have implicated a number of loci; however, the molecular mechanisms underlying AD are unclear. Advances in systems biology allow genome-wide expression data to be integrated with genetic data to detect expression quantitative trait loci (eQTL), polymorphisms that regulate gene expression levels, influence phenotypes and are significantly enriched among validated genetic signals for many commonly studied traits including AD.

We integrated genome-wide mRNA and miRNA expression data with genotypic data from the nucleus accumbens (NAc), a major addiction-related brain region, of 36 …

Novel Therapeutic Strategies For Pancreatic Cancer, Bridget A. Quinn

Theses and Dissertations

Pancreatic cancer is a devastating disease that leaves patients with a very poor prognosis and few therapeutic options. Many of the treatment options available are the same that have been used for almost 2 decades. There is a dire need for both novel treatments for this disease as well as novel strategies of treatment. This body of work will introduce and provide evidence in support of a novel combination therapy for pancreatic cancer treatment, a novel strategy of modifying currently used chemotherapeutics for pancreatic cancer therapy, and a novel transgenic preclinical mouse model of pancreatic cancer. Sabutoclax, an antagonist of …

Sildenafil And Celecoxib Interact To Kill Breast Cancer Cells, Brittany Binion

Theses and Dissertations

Breast cancer is the second most commonly diagnosed cancer among American women and is responsible for the second highest number of cancer-related deaths. Targeted therapeutic agents sildenafil, a phosphodiesterase type 5 inhibitor, and celecoxib, a cyclooxygenase-2 inhibitor, have been used individually in conjunction with other chemotherapeutic agents to enhance cell killing in a variety of cancers. Sildenafil when combined with traditional chemotherapeutic drugs, such as the taxanes and anthracyclines, or celecoxib combined with traditional hormone therapies have been used to increase cytotoxicity and cell killing. The data presented here demonstrates that the novel combination of sildenafil and celecoxib work together …

Regulation Of Pten Inhibition By The Pleckstrin Homology Domain Of P-Rex2 During Insulin Signaling And Glucose Homeostasis, Cindy Hodakoski, Benjamin D. Hopkins, Douglas Barrows, Sarah M. Mense, Megan Keniry, Karen E. Anderson, Philip A. Kern, Phillip T. Hawkins, Len R. Stephens, Ramon Parsons

Clinical and Translational Science Faculty Publications

Insulin activation of phosphoinositide 3-kinase (PI3K) signaling regulates glucose homeostasis through the production of phosphatidylinositol 3,4,5-trisphosphate (PIP3). The dual-specificity phosphatase and tensin homolog deleted on chromosome 10 (PTEN) blocks PI3K signaling by dephosphorylating PIP3, and is inhibited through its interaction with phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 2 (P-REX2). The mechanism of inhibition and its physiological significance are not known. Here, we report that P-REX2 interacts with PTEN via two interfaces. The pleckstrin homology (PH) domain of P-REX2 inhibits PTEN by interacting with the catalytic region of PTEN, and the inositol polyphosphate 4-phosphatase domain of P-REX2 provides high-affinity binding to the postsynaptic …