Translational Medical Research Commons^™

Prostate Cancer Microparticles As A Next Generation Screening Tool For Prostate Cancer, Khurram M. Siddiqui

Electronic Thesis and Dissertation Repository

Currently available screening tests for prostate cancer (PCa) are neither very sensitive nor specific. Microparticles (MP) are submicron tumor cell fragments released by PCa cells into the circulation and offer a possible means of sampling the tumor. We evaluated the utility of a MP blood test using nanoscale flow cytometry to distinguish patients with PCa from patients with benign prostatic hyperplasia (BPH). We used monoclonal antibodies against prostate specific membrane antigen, gastrin releasing peptide receptor and ghrelin peptide ligand.

We found higher but statistically insignificant, PSMA and Ghrelin dual +ve MP counts in the BPH group. Our results show that …

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

Dissertations & 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 Elizabeth Reyes

Dissertations & 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 …

The Effects Of Temperature And Seasons On Subcutaneous White Adipose Tissue In Humans: Evidence For Thermogenic Gene Induction, Philip A. Kern, Brian S. Finlin, Beibei Zhu, Neda Rasouli, Robert E. Mcgehee Jr., Philip M. Westgate, Esther E. Dupont-Versteegden

Clinical and Translational Science Faculty Publications

Context: Although brown adipose tissue (BAT) activity is increased by a cold environment, little is known of the response of human white adipose tissue (WAT) to the cold.

Design: We examined both abdominal and thigh subcutaneous (SC) WAT from 71 subjects who were biopsied in the summer or winter, and adipose expression was assessed after an acute cold stimulus applied to the thigh of physically active young subjects.

Results: In winter, UCP1 and PGC1 α mRNA were increased 4 to 10-fold (p<0.05) and 1.5 to 2-fold, respectively, along with beige adipose markers, and UCP1 protein was 3-fold higher in the winter. The seasonal increase in abdominal SC WAT UCP1 mRNA was considerably diminished in subjects with a BMI > 30 kg/m², suggesting that dysfunctional WAT in obesity inhibits adipose thermogenesis. After applying an acute …

Sustained Adrenergic Signaling Promotes Cervical Cancer Progression, Nouara C. Sadaoui

Dissertations & Theses (Open Access)

Background: Chronic stress and sustained adrenergic signaling are known to promote tumor progression. The underlying mechanisms behind this process are not well understood. We examined the effects of sustained adrenergic signaling on cervical cancer progression through increased expression of HPV oncogenes, E6 and E7.

Materials and Methods: ADRβ expression levels were examined in patient-derived cervical cancer samples. We used an orthotopic model of cervical cancer to investigate the effects of restraint stress on tumor growth and metastasis. We evaluated the in vivo effects of a β-blocker, propranolol, and HPV E6/E7 siRNA. In vitro, ADRβ positive cervical cancer cells were …

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 …

Education And Career Development, Anthony Carruthers, Katherine Luzuriaga, Gyongyi Szabo

Gyongyi Szabo

This presentation describes educational programs for trainees and faculty that are offered through the UMCCTS.

Trends And Characteristics Associated With The Risk Of Re-Hospitalization In Patients Discharged From The Hospital After Acute Myocardial Infarction, Mayra Tisminetzky, Han-Yang Chen, Edgard A. Granillo, Joel M. Gore, Jorge L. Yarzebski, Darleen M. Lessard, Robert J. Goldberg

Jorge L. Yarzebski

BACKGROUND: Despite encouraging declines in short-term mortality in patients hospitalized with acute myocardial infarction (AMI), repeat hospitalizations among those discharged from the hospital after AMI remain a major clinical and public health concern. Few studies, however, have described the relatively contemporary magnitude, factors associated with, as well as decade long trends in repeat hospitalizations for cardiovascular disease (CVD) and other causes in patients discharged from the hospital after AMI. METHODS: We reviewed the medical records of 6,018 residents of the Worcester (MA) metropolitan area who were hospitalized for AMI in 6 biennial periods between 1999 and 2009. Re-hospitalizations for any …

Exosome-Mediated Delivery Of Rna Interference And Mirna Mimic, Fatemeh Momen-Heravi, Shashi Bala, Terence N. Bukong, Gyongyi Szabo

Gyongyi Szabo

Exosomes, membranous nanovesicles, naturally carry bio-macromolecules and play pivotal roles in both physiological intercellular crosstalk and disease pathogenesis. Here, we showed that B cell-derived exosomes can function as vehicles to deliver exogenous miRNA-155 mimic or inhibitor into hepatocytes or macrophages, respectively. Stimulation of B cells significantly increased exosome production. Unlike in parental cells, baseline level of miRNA-155 was very low in exosomes derived from stimulated B cells. Exosomes loaded with a miRNA-155 mimic significantly increased miRNA-155 levels in primary mouse hepatocytes and the liver of miRNA-155 knockout mice. Treatment of RAW macrophages with miRNA-155 inhibitor loaded exosomes resulted in statistically …

Massteri: Promoting Translational Research And Entrepreneurship At The University Of Massachusetts Medical School, Melissa J. Moore, Celia A. Schiffer, Anastasia Khvorova, Anita Ballesteros, Cynthia Fuhrmann, Jean A. King, Margaret Koziel, Thomas Mccullough, Linda Plano

Celia A. Schiffer

MassTERi is a faculty-led initiative to foster entrepreneurship among UMass Medical School students, postdocs and faculty, and facilitate translation of UMMS discoveries into drugs, products, technologies and companies. The mission of MassTERi is to; foster a culture of entrepreneurship at UMass Medical School and facilitate dynamic partnerships with industry; bridge the gap between UMMS discoveries and their development into drugs, products, technologies and companies; educate and nurture the next generation of translational scientists and entrepreneurs; benefit the public good through development and commercialization of new therapies and creation of high-value life science jobs. We will present information about MassTERi and …

In-Hospital Depression Predicts Early Hospital Readmission After An Acute Coronary Syndrome: Preliminary Data From Trace-Core, David Mcmanus, Jane Saczynski, Molly Waring, Milena Anatchkova, Richard Mcmanus, Robert Goldberg, Jeroan Allison, David Parish, Hamza Awad, Jerry Gurwitz, Arlene Ash, Catarina Kiefe

Richard H. McManus

Background: Hospital systems, patients and providers seek to avert rehospitalizations within 30 days for patients admitted with an acute coronary syndrome (ACS). Rehospitalizations within 30 days of discharge are often considered preventable and to reflect poor in-hospital management or discharge practices. However, independent associations of psychosocial factors with early rehospitalization in patients admitted with an ACS have not been examined. Methods: A multi-racial cohort of 1,540 patients admitted with an ACS reported psychosocial factors via standardized questionnaires in an in-hospital interview. One month following discharge, patients were interviewed via phone and reported hospital readmissions. We used logistic regression models to …

Associations Of Adipose Tissue Architecture, Adipokines And Inflammatory Markers With Body Mass Index And Gestational Weight Gain In Non-Diabetic Pregnancies, Tiffany A. Moore Simas, Crina Boeras, Ningning Zhang, Olga Gaelikman, Katherine G. Leung, Nicole M. Wedick, Laura Robidoux, Jodi Adams Puleo, Mary M. Lee, Silvia Corvera, Milagros C. Rosal

Mary M. Lee

Background: Some pregnancy weight gain is stored as adipose tissue (AT). Human AT depots vary in their capacity for expansion. Data suggests that subcutaneous (SQ) is adapted for healthy lipid storage. Conversely visceral (V) accumulation is associated with inflammation, obesity-related co-morbidities and Type 2 diabetes (T2DM) risk. We investigated SQ and VAT histologic architecture along with insulin, adipokines and inflammatory markers in relationship to prepregnancy BMI and gestational weight gain (GWG). Methods: Subset of non-diabetic singleton gravidas from the Pregnancy & Postpartum Observational Dietary Study (PPODS), undergoing Cesareans and consenting to SQ & VAT biopsies were included. Average adipocyte size …

Keynote Speaker Presentations: 5th Annual Umass Center For Clinical And Translational Research Retreat (Video), Robert H. Brown Jr., Thomas Grisso

Thomas Grisso

This video features the full keynote presentations from the 5th Annual UMass Center for Clinical and Translational Science Research Retreat at the University of Massachusetts Medical School (UMMS) in Worcester, MA, on May 20, 2014.

Beginning at 12:40

1st Keynote Speaker: Robert H. Brown, Jr., MD, D.Phil, Chair, Department of Neurology, UMMS. “Lou Gehrig Disease: From Mapping to Medicines”

Beginning at 1:22:19

2nd Keynote Speaker: Thomas Grisso, PhD, Director, Law and Psychiatry Program and Professor, Department of Psychiatry, UMMS. Recipient, Chancellor’s Medal for Distinguished Scholarship. “Translational Research in Law and Psychiatry”

Also included is a brief introductory presentation with updates …

Does Functional Gain And Pain Relief After Tkr And Thr Differ By Patient Obese Status?, Wenjun Li, Jeffrey Lange, Leslie R. Harrold, Jeroan J. Allison, Courtland Lewis, Thomas Bowen, David C. Ayers, Patricia D. Franklin

Jeroan J. Allison

Introduction: Obesity is an important predictor of functional status and pain after total knee (TKR) and total hip (THR) replacement. However, variations in pre-post TKR and THR changes in function and pain by obesity status remain to be examined.

Material & Methods: Pre- and 6 month post surgery data were collected on 2,964 primary TKR and 2,040 primary THR patients between 5/2011 and 3/2013. Data included demographics, comorbidities, operative joint pain severity based on the Knee Injury or Hip Disability and Osteoarthritis Outcome Score (KOOS/HOOS), WOMAC pain (higher is better), physical function (SF-36 PCS, higher is better), mental health (SF-36 …

An Electronic Health Record-Based Intervention To Increase Follow-Up Office Visits And Decrease Rehospitalization In Older Adults, Jerry Gurwitz, Terry Field, Jessica Ogarek, Jennifer Tjia, Sarah Cutrona, Leslie Harrold, Shawn Gagne, Peggy Preusse, Jennifer Donovan, Abir Kanaan, George Reed, Lawrence Garber

Jennifer Tjia

OBJECTIVES: To assess the effect of an electronic health record-based transitional care intervention involving automated alerts to primary care providers and staff when older adults were discharged from the hospital.

DESIGN: Randomized controlled trial.

SETTING: Large multispecialty group practice.

PARTICIPANTS: Individuals aged 65 and older discharged from hospital to home.

INTERVENTION: In addition to notifying primary care providers about the individual's recent discharge, the system provided information about new drugs added during the inpatient stay, warnings about drug-drug interactions, recommendations for dose changes and laboratory monitoring of high-risk medications, and alerts to the primary care provider's support staff to schedule …

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, …

Long-Term Survival For Patients With Acute Decompensated Heart Failure According To Ejection Fraction Findings, Andrew Coles, Kimberly Fisher, Chad Darling, Jorge Yarzebski, David Mcmanus, Joel Gore, Darleen Lessard, Robert Goldberg

Jorge L. Yarzebski

Limited data exist about the long-term prognosis of patients with acute decompensated heart failure (ADHF) further stratified according to ejection fraction (EF) findings. The primary objective of this population-based observational study was to characterize and compare trends in long-term prognosis after an episode of ADHF across 3 EF strata. Hospital medical records were reviewed for 3,604 residents of the Worcester, Massachusetts, metropolitan area who were discharged after ADHF from all 11 medical centers in central Massachusetts during 1995, 2000, 2002, and 2004 and had EF measurements during their index hospitalizations. The average age of this population was 75 years, most …

Cluster Randomized Trials And Statistical Power, Stephen A. Lauer, Nicholas G. Reich

Nicholas G Reich

The cluster-randomized trial (CRT) is a common study design in public health research. In situations where dividing a group of individuals into treatment and controls is unethical or impossible, a CRT design maintains the strengths of a randomized study design. By comparing the outcomes of small populations (clusters), we can observe the impacts of interventions on the community as a whole. Public health researchers around the world have utilized CRTs to measure the effect of, for example, de-worming medication on school attendance, financial incentives on doctor absenteeism, and providing chlorine to waterholes. The CRT can be a potent tool, however …

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 …

The Clinic Narrative: A Multiple Case Study Of Integrated Knowledge Translation And Equity-Oriented Primary Health Care, Christine A. Garinger

Electronic Thesis and Dissertation Repository

Understanding how PHC organizations implement changes to achieve equity-oriented care will add to the knowledge base regarding primary care renewal. Implementation science or knowledge translation (KT) has emerged, with the goal of enhancing evidence-based practice by implementing strategies of knowledge mobilization. Questions in this qualitative multiple case study were: 1) How does a new knowledge product, a ‘clinic narrative’, co-created by the researchers and the clinic leads, influence practices in the clinic specific to equity-oriented care?, 2) What facilitates or constrains the use of the narrative? and, 3) What are the novel uses of the narrative for organizational goals? The …

Knowledge Translation And The Governance Of Health Research In Canada: A Critical Discourse Analysis, Kathleen S. Ellis

Electronic Thesis and Dissertation Repository

Knowledge translation (KT) is a dominant discourse in the governance of health research in Canada. I critically examine the KT discourse of the Canadian Institutes of Health Research (CIHR), Canada’s major health research funder. Informed by a governmentality perspective, I explore how the KT discourse operates to shape the directions of health research and the activities of health researchers using critical discourse analysis with a sample of publicly available CIHR documents.

This KT discourse is constructed through three rationales: a “gap” between knowledge creation and its application; financial and health care accountabilities for public investment in health research; and, the …

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

Dissertations & 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 …

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

Dissertations & 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. …

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

Dissertations & 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 …

The Demethylating Agent 5-Aza Reduces The Growth, Invasiveness, And Clonogenicity Of Uveal And Cutaneous Melanoma, F. Rajaii, L. Asnaghi, Raymond Enke, S. Merbs, J. Handa, C. Eberhart

Ray Enke Ph.D.

No abstract provided.

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 …

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 …

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 …