Digital Commons Network^™

Serum Omentin As A Potential Biomarker For Complex Atypical Hyperplasia And Endometrioid Endometrial Adenocarcinoma, Laura L. Holman Md

Dissertations and Theses (Open Access)

Obesity is a significant risk factor for endometrial cancer, the most common gynecologic malignancy in the United States, but much remains unclear about the relationship between obesity-related factors and the development of endometrial cancer. Omentin, a recently discovered adipokine, has been shown to be present in lower levels in patients who are obese and/or insulin resistant. A case-control study was conducted using the serum of 140 women with endometrial cancer and 75 women with endometrial hyperplasia who were matched 1:1 based on body mass index (BMI) and menopausal status to women with no history of endometrial cancer (controls). The concentration …

Cancer Incidence In First And Second Degree Relatives Of Brca1 And Brca2 Mutation Carriers, Haley Streff

Dissertations and Theses (Open Access)

Mutations in the BRCA1 or BRCA2 genes are associated with increased risks for breast, ovarian, and several other cancers. The purpose of this study was to evaluate the incidence of cancers in first and second degree relatives of BRCA mutation carriers compared to the general population. A total of 1086 pedigrees of BRCA mutation carriers were obtained from a prospectively maintained, internal review board approved study of persons referred for clinical genetic counseling at The University of Texas MD Anderson Cancer Center. We identified 9032 first and second degree relatives from 784 pedigrees which demonstrated a clear indication of parental …

Increasing Adipocyte Lipoprotein Lipase Improves Glucose Metabolism In High Fat Diet-Induced Obesity, R. Grace Walton, Beibei Zhu, Resat Unal, Michael Spencer, Manjula Sunkara, Andrew J. Morris, Richard Charnigo, Wendy S. Katz, Alan Daugherty, Deborah A. Howatt, Philip A. Kern, Brian S. Finlin

Barnstable Brown Diabetes Center Faculty Publications

Lipid accumulation in liver and skeletal muscle contributes to co-morbidities associated with diabetes and obesity. We made a transgenic mouse in which the adiponectin (Adipoq) promoter drives expression of lipoprotein lipase (LPL) in adipocytes to potentially increase adipose tissue lipid storage. These mice (Adipoq-LPL) have improved glucose and insulin tolerance as well as increased energy expenditure when challenged with a high fat diet (HFD). To identify the mechanism(s) involved, we determined whether the Adipoq-LPL mice diverted dietary lipid to adipose tissue to reduce peripheral lipotoxicity, but we found no evidence for this. Instead, characterization …

Use Of Dietary And Herbal Supplements In Older Adults With Osteoarthritis, Sharon Denise Mcdonald

Dissertations

Over the past several decades, older adults with Osteoarthritis (OA) have increasingly used more natural products in an effort to manage chronic pain. The theoretical framework for this study was the Lazarus and Folkman transactional theory of stress and coping. This framework was chosen based on the belief that older adults with OA are taking natural products as an active problem solving coping strategy to manage the pain, disability, and alterations they experience in their health related quality life including functional status, physical symptoms, emotional health, and social functioning. Older adults also take prescription medications for Osteoarthritis and a variety …

Management Of Pediatric Headaches In The Emergency Department At Connecticut Children’S Medical Center, Chevaughn Wellington

Honors Scholar Theses

Headaches are a common complaint for children presenting to the Emergency Department (ED) at Connecticut Children’s Medical Center (CCMC). Currently, there is little published regarding a standard treatment plan for pediatric headaches. The purpose of this study is to determine which medications are most commonly utilized and which are most effective in managing pediatric headaches. Differences in management of acute and chronic headaches in the ED at CCMC were examined. A retrospective chart review was conducted of all children who presented to the ED from January 1 to March 31, 2013 with a chief complaint or discharge diagnosis of “headache” …

Transarterial Chemoembolization Is Ineffective For Neuroendocrine Tumors Metastatic To The Caudate Lobe: A Single Institution Review., Lawrence A Shirley, Megan Mcnally, Ravi Chokshi, Natalie Jones, Patrick Tassone, Gregory Guy, Hooman Khabiri, Carl Schmidt, Manisha Shah, Mark Bloomston

Oncology Articles

BACKGROUND: Caudate lobe liver metastases occur commonly in patients with neuroendocrine tumors. It is unknown, however, how these lesions respond to regional therapy and how their presence impacts outcomes. We reviewed our experience treating these lesions using transarterial chemoembolization (TACE).

METHODS: We reviewed radiographic response to TACE in 86 patients with metastatic neuroendocrine tumors to the liver. We determined the impact of caudate lesions on outcomes in comparison to the cohort of patients without caudate lesions, as well as response of caudate lesions to TACE versus lesions elsewhere in the liver.

RESULTS: Caudate lesions were identified in 45 (52%) patients. …

Cancer Associated Fibroblast Derived Angiogenic Factor Mfap5 In Ovarian Cancer Progression, Sze Lee Cecilia Leung

Dissertations and Theses (Open Access)

Advanced stage ovarian cancer is the most lethal gynecologic malignancy. No major improvement on patient survival has been achieved in the past decade. Therefore, identification of predictive or prognostic markers and further understanding of the molecular mechanisms in ovarian cancer progression are of paramount importance.

While cancer cells have always been the targets for the identification of prognostic and predictive markers, the potential for developing new diagnosis and treatments based on the tumor supporting stromal microenvironment is relatively unexplored. Using transcriptome profiling analysis on microdissected stromal and epithelial components of normal and malignant ovarian tissues, we identified a gene signature …

Characterization Of Low Density Intracranial Lesions Using Dual-Energy Computed To Mography, Jessica L. Nute

Dissertations and Theses (Open Access)

Calcific and hemorrhagic foci of susceptibility are frequently encountered on routine brain MR studies. Both etiologies cause variations in local magnetic field strength, leading to dark regions on the MR images that cannot be classified. Single-energy CT (SECT) can be used to identify lesions with attenuation over 100 HU as calcific, however lesions with lower attenuation cannot be reliably identified. While calcific lesions are unlikely to cause harm, hemorrhagic lesions carry a risk of subsequent intracranial bleeding; as such, identification of hemorrhage is vital in preventing the inappropriate use of anticoagulant medications in patients with hemorrhagic lesions.

Given there currently …

Gene Set Analysis Of Post-Lactational Mammary Gland Involution Gene Signatures In Inflammatory And Triple Negative Breast Cancer, Arvind Bambhroliya

Dissertations and Theses (Open Access)

With each cycle of pregnancy and lactation, the mammary gland undergoes dramatic changes. Clarkson et al. (2004) and Stein et al. (2004) conducted a detailed analysis of these changes in the mouse mammary gland. Their results showed that tissue remodeling during post-lactational involution period mimics wound healing and tumorigenesis like pathological conditions. This indicates that post-lactational involution may create the microenvironment that initiates the development of precancerous mammary cells and promotes the progression of precancerous cells into cancer cells. Moreover, epidemiological studies have found that triple-negative (TN) breast cancer (BC) is associated with lower frequency and duration of breastfeeding compared …

Correlation Matrix Analysis Identifies Gene Signatures Of Immune Cell Subsets And Their Interactions In Follicular Lymphoma, Jason R. Westin

Dissertations and Theses (Open Access)

There are important but ill-defined interactions between benign immune cell subsets and neoplastic B cells within follicular lymphoma (FL). Using the novel technique of correlation matrix analysis (CMA) of publicly available FL whole-tumor gene expression profiling (GEP) data, we have identified signatures of immune cell subsets. Overall survival correlated most highly with a model using signatures of macrophages, T cells, and stroma, which was able to add significantly to existing clinical prognostic tools. From our own data of a cohort of 43 FL tumors sorted into B-cell and non-B cell (NB) fractions for GEP, CMA of the tumor infiltrating NB …

Flattening Filter-Free Accelerators: A Report From The Aapm Therapy Emerging Technology Assessment Work Group, Ying Xiao, Stephen F. Kry, Richard A. Poppel, Ellen D. Yorke, Niko Papanikolaou, Sotirios Stathakis, Ping Xia, Saiful Huq, John E. Bayouth, James Galvin Phd, Fang-Fang Yin

Department of Radiation Oncology Faculty Papers

No abstract provided.

Local Modulation And Measurement Of Macrophage-Derived Bioactive Proteins From Implanted Biomaterials In Rat, Geetika Bajpai

Graduate Theses and Dissertations

Fibrosis around the implanted medical devices is a severe problem that can plague long-term device reliability. Activation of macrophage phenotype (macrophage polarization) has emerged as a new and possible means for reducing fibrosis in the fields of biomaterials and regenerative medicine. Macrophages are phagocytic cells that respond to microenvironmental cues that direct their phenotype. Macrophage activation has been widely studied in mouse and human in the context of tumor biology, yet little information is available regarding how macrophage activation could be used in a biomaterials context. Further, rats rather than mice are the common subjects in biomaterials experiments. A significant …

Killer Cell Activation By A Novel Multifunctional Protein: An Immuno/Gene Therapy For Cancer, Ashlee Tietje

All Dissertations

One of the characteristics of advanced tumors is the evasion of the immune system. There are multiple methods that tumor cells employ to achieve this including reducing the expression of activating ligands on the cell surface and a shift in the tumor microenvironment toward pro-tumor cytokines. The purpose of this research is to develop a novel bifunctional fusion protein that will target these two deficiencies in the tumor microenvironment and activate killer cells that are already present. The proposed protein combines the extracellular domain of a ligand for the killer cell activating receptor NKG2D and Interleukin-12 (IL-12). It is hypothesized …

Urinary Phthalate Metabolite Concentrations And Blood Glucose Levels During Pregnancy, Candace A. Robledo, Jennifer D. Peck, Julie A. Stoner, Antonia M. Calafat, Hélène Carabin, Linda Cowan, Jean R. Goodman

School of Medicine Publications

Purpose: To examine associations between phthalate metabolite urinary concentrations during early pregnancy and blood glucose levels obtained at the time of screening for gestational diabetes mellitus (GDM).

Methods: Upon initiation of prenatal care, women with a mean gestational age of 12.8 weeks were recruited for a study of environmental chemical exposures (n = 110) and provided a spot urinary specimen. Blood glucose concentrations (mg/dl) were obtained from the electronic medical record for those patients who did not experience a pregnancy loss and did not transfer care to another facility prior to glucose screening (n = 72). Urinary concentrations of nine …

Compensatory Fetal Membrane Mechanisms Between Biglycan And Decorin In Inflammation., Luciana Batalha De Miranda De Araujo, Casie E Horgan, Abraham Aron, Renato V. Iozzo, Beatrice E Lechner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Preterm premature rupture of fetal membranes (PPROM) is associated with infection, and is one of the most common causes of preterm birth. Abnormal expression of biglycan and decorin, two extracellular matrix proteoglycans, leads to preterm birth and aberrant fetal membrane morphology and signaling in the mouse. In humans and mice, decorin dysregulation is associated with inflammation in PPROM. We therefore investigated the link between biglycan and decorin and inflammation in fetal membranes using mouse models of intraperitoneal Escherichia coli injections superimposed on genetic biglycan and decorin deficiencies. We assessed outcomes in vivo as well as in vitro using quantitative PCR, …

Comparing Before-And After-School Neurocognitive Performance In High School Athletes: Implications For Concussion Management, Anderson Morgan

Health, Human Performance and Recreation Undergraduate Honors Theses

Abstract Background: Sport-related concussion (SRC) continues be a hot topic in sports medicine. Computerized Neurocognitive Testing (CNT) provides researchers and sports medicine professionals an objective way to manage SRC. Administering CNT comes at the convenience of the student athlete and the sports medicine professional working at the school, which usually results in CNT being administered in the afternoon, or after school. However, little is known how the cognitive fatigue of attending a full day of school influences CNT performance. Purpose: The purpose of this study was to compare before school CNT performance to after school CNT performance in a sample …

Evaluation Of Tulane Virus As A Surrogate For The Study Of Human Norovirus, Sabastine Eugene Arthur

Graduate Theses and Dissertations

Among all known causes of acute gastroenteritis, human noroviruses (HuNoV) are the primary cause (68%) of outbreaks and are associated with 78% of illnesses, 46% of hospitalizations, and 86% of deaths. The main obstacle to studying the pathogenesis of HuNoV is the lack of cell culture system and small animal model. Murine norovirus (MNV) and feline calicivirus (FCV) have been utilized as model surrogate viruses to study HuNoV. In this research, a more recent surrogate virus, Tulane virus (TV), was evaluated for physicochemical stability and environmental persistence. The primary goal was to determine the suitability of TV as a surrogate …

Characterization And Investigation Of Fungi Inhabiting The Gastrointestinal Tract Of Healthy And Diseased Humans, Mallory J. Suhr

Department of Food Science and Technology: Dissertations, Theses, and Student Research

Gastrointestinal microbiome studies have failed to include fungi in total community analyses. As a result, their diversity and function in the gut is poorly understood. Recent work has begun to uncover the role intestinal fungi play in diet, immune system development, interactions with other microorganisms in the gut, and pathogenesis of diseases. Advances in sequencing technologies allow for the ability to profile the fungal gut microbiome (“mycobiome”) in healthy and diseased states. This thesis explores the mycobiome in 1) healthy humans with a vegetarian diet and 2) pediatric small bowel transplant recipients that develop fungal bloodstream infections.

The gut mycobiome …

Powerful Anti-Tumor And Anti-Angiogenic Activity Of A New Anti-Vascular Endothelial Growth Factor Receptor 1 Peptide In Colorectal Cancer Models, Valeria Cicatiello, Ivana Apicella, Laura Tudisco, Valeria Tarallo, Luigi Formisano, Annamaria Sandomenico, Younghee Kim, Ana Bastos-Carvalho, Augusto Orlandi, Jayakrishna Ambati, Menotti Ruvo, Roberto Bianco, Sandro De Falco

Ophthalmology and Visual Science Faculty Publications

To assess the therapeutic outcome of selective block of VEGFR1, we have evaluated the activity of a new specific antagonist of VEGFR1, named iVR1 (inhibitor of VEGFR1), in syngenic and xenograft colorectal cancer models, in an artificial model of metastatization, and in laser-induced choroid neovascularization. iVR1 inhibited tumor growth and neoangiogenesis in both models of colorectal cancer, with an extent similar to that of bevacizumab, a monoclonal antibody anti-VEGF-A. It potently inhibited VEGFR1 phosphorylation in vivo, determining a strong inhibition of the recruitment of monocyte-macrophages and of mural cells as confirmed, in vitro, by the ability to inhibit …

Inflammatory Muscle Diseases., Marinos C Dalakas

Department of Neurology Faculty Papers

No abstract provided.

Site-Specific Immunomodulator: A Novel Treatment For Crohn's Disease, Brian Bressler, Kevin P. Bethel, Ralf Kleef, Sophie L. Reynolds, Simon Sutcliffe, David W. Mullins, Hal Gunn

Dartmouth Scholarship

We investigated the mechanism of action, safety, and efficacy of the Site-Specific Immunomodulator (SSI) QBECO, a novel immunotherapy for Crohn’s disease (CD). Using human monocytic THP-1 cells, we demonstrate that SSI QBECO (derived from the common colon bacteria E. coli) activates macrophages to an M1 phenotype (associated with enhanced capacity to eliminate bacteria and activate innate immune responses). We assessed SSI QBECO in a compassionate use protocol of ten adult patients with active CD. Patients with moderate to severe clinical symptoms receiving conventional CD treatments and/or complementary therapies were included, except patients receiving anti-TNF medications. SSI QBECO was self-administered subcutaneously …

Association Between Inflammation And Cardiac Geometry In Chronic Kidney Disease: Findings From The Cric Study., Jayanta Gupta, Elizabeth Dominic, Jeffrey C. Fink, Akinlolu O. Ojo, Ian R. Barrows, Muredach Reilly, Raymond R. Townsend, Marshall Joffe, Sylvia Rosas, Melanie Wolman, Samir Patel, Martin Keane, Harold I. Feldman, John W. Kusek, Dominic S. Raj

Medicine Faculty Publications

Background

Left ventricular hypertrophy (LVH) and myocardial contractile dysfunction are independent predictors of mortality in patients with chronic kidney disease (CKD). The association between inflammatory biomarkers and cardiac geometry has not yet been studied in a large cohort of CKD patients with a wide range of kidney function.

Methods

Plasma levels of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, high-sensitivity C-Reactive protein (hs-CRP), fibrinogen and serum albumin were measured in 3,939 Chronic Renal Insufficiency Cohort study participants. Echocardiography was performed according to the recommendations of the American Society of Echocardiography and interpreted …

Role Of Il-16 In Cd4(+) T Cell-Mediated Regulation Of Relapsing Multiple Sclerosis, Dusanka S. Skundric, William W. Cruikshank, Jelena Drulovic

Neurology Faculty Publications

In an important article published in Nature Medicine, Liu and colleagues described a novel CD4⁺ FoxA1⁺ regulatory T (Treg) cell population as distinct regulators of relapsing-remitting multiple sclerosis (RRMS) and experimental autoimmune encephalomyelitis (EAE). CD4⁺ FoxA1⁺ Treg cells appear as key regulators of responsiveness to therapy with interferon beta (IFN-β) in RRMS patients. Data indicate that CD4⁺ FoxA1⁺ FOXP3⁻ Treg cells develop within the central nervous system (CNS), and a potential of cerebellar granule neurons (CGN) in generation of CD4⁺ FoxA1⁺ PD-L1^hiFOXP3⁻ Treg cells from encephalitogenic CD4^{+ …}

The Effects Of Adderall On Maternal And Fetal Health, Alyson Brady

Honors Theses

Information available for woman prescribed Adderall to treat ADHD and the effects that it may have on her fetus is limited. However, Adderall and methamphetamine have similar pharmacological and addictive qualities. This paper is concerned with whether there is an adequate approach to treatment that balances the needs of the mother and the fetus. With Adderall use becoming more prevalent, it is essential that society is aware of the physiology and pharmacology of this drug, as well as, the need for more research on this subject to be produced.

Diabetes Self-Management Education For Adolescent Patients: The Importance Of A Developmentally Sensitive Approach, Laura Mumme

Senior Honors Theses

The attention of healthcare providers to the developmental level of adolescent patients with type one diabetes (T1D) maximizes effective patient education and glycemic control. Due to the dynamic changes that occur in the mind and body during adolescence, self-care for adolescent T1D patients is overwhelming as it envelopes activities of everyday life. The disease process and the unique aspects of adolescence in relation to T1D are important for caregivers to consider. Developmentally appropriate teaching during the initial onset of the disease must inform the patient and the patient’s family of the basics of the disease process and the daily care …

Elevated Serum Bicarbonate Concentration In Chronic Kidney Disease: A Call To Find The Cause, Zeid J. Khitan

Internal Medicine

In this issue, Dobre et al1 reported an observational study looking at results of annually measured serum bicarbonate concentration in participants with chronic kidney disease (CKD) enrolled in the Chronic Renal Insufficiency Cohort (CRIC) using the marginal structural model, a validated statistical method,2 to estimate the cumulative effect over the period of the study and their effects on adjudicated heart failure events, atherosclerotic events, renal disease progression, and mortality. In their analysis, they included patients aged 21 to 74 years with estimated glomerular filtration rate of 20 to 70 mL/min per 1.73 m2 and excluded patients with NYHA Class III/IV …

Kinase-Independent Role Of Cyclin D1 In Chromosomal Instability And Mammary Tumorigenesis., Mathew C Casimiro, Gabriele Disante, Marco Crosariol, Emanuele Loro, William Dampier, Adam Ertel, Zuoren Yu, Elizabeth A Saria, Alexandros Papanikolaou, Z Li, Chenguang Wang, Sankar Addya, Michael P. Lisanti, Paolo Fortina, Robert D Cardiff, Aydin Tozeren, Erik S Knudsen, Andrew Arnold, Richard Pestell

Department of Cancer Biology Faculty Papers

Cyclin D1 is an important molecular driver of human breast cancer but better understanding of its oncogenic mechanisms is needed, especially to enhance efforts in targeted therapeutics. Currently, pharmaceutical initiatives to inhibit cyclin D1 are focused on the catalytic component since the transforming capacity is thought to reside in the cyclin D1/CDK activity. We initiated the following study to directly test the oncogenic potential of catalytically inactive cyclin D1 in an in vivo mouse model that is relevant to breast cancer. Herein, transduction of cyclin D1-/- mouse embryonic fibroblasts (MEFs) with the kinase dead KE mutant of cyclin D1 led …

Translation Initiation Complex Eif4f Is A Therapeutic Target For Dual Mtor Kinase Inhibitors In Non-Hodgkin Lymphoma., Christos Demosthenous, Jing Jing Han, Mary J Stenson, Matthew J Maurer, Linda E Wellik, Brian Link, Kristen Hege, Ahmet Dogan, Eduardo Sotomayor, Thomas Witzig, Mamta Gupta

Medicine Faculty Publications

Deregulated mRNA translation has been implicated in disease development and in part is controlled by a eukaryotic initiation complex eIF4F (composed of eIF4E, eIF4G and eIF4A). We demonstrate here that the cap bound fraction from lymphoma cells was enriched with eIF4G and eIF4E indicating that lymphoma cells exist in an activated translational state. Moreover, 77% (110/142) of diffuse large B cell lymphoma tumors expressed eIF4E and this was associated with an inferior event free survival. Over-expression of wild-type eIF4E (eIF4E(WT)) but not cap-mutant eIF4E (eIF4E(cap mutant)) increased the activation of the eIF4F complex. Treatment with the active-site dual mTOR inhibitor …

Implementation Of An Advance Directive Protocol In A Primary Care Setting, Gloria Dillman

Evidence-Based Practice Project Reports

Despite the passage of the Patient Self-Determination Act in 1992, only 15% of the United States population has completed an advance directive (AD). This statistic will be exaggerated with the future growth of older adults in the year 2030, at which time this portion of the population is expected to double to 72.1 million people. Without an AD, patients lose their autonomy and may be subjected to costly, life prolonging treatments that they would never choose for themselves. The unnecessary costs and unwanted treatment are preventable with an AD, and primary care providers are in a prime position to initiate …

Phylogenetic Tree Construction And “Truncal Loss” Analysis Reveal Hidden Associations Between Loss Of Protein Expression In Swi/Snf Complex Components And Tumor Stage And Survival In Clear Cell Renal Cell Carcinoma (Ccrcc), Wei Jiang, Md, Phd, Essel Dulaimi, Karthik Devarajan, Qiong Wang, Raymond O'Neill, Charalambos C. Solomides, Md, Stephen C Peiper, Phd, Robert Uzzo, Joseph R. Testa, Haifeng Yang, Phd

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background

Polybromo-1 (PBRM1), a targeting subunit of the SWI/SNF chromatin remodeling complex, is mutated at a rate of ~40% in clear cell Renal Cell Carcinoma (ccRCC), second only to VHL. Whether its mutation is correlated with tumor stage is controversial. As other components of the SWI/SNF complex were also reported to be mutated in ccRCC, we aim to examine the protein expression patterns of PBRM1, ARID1A, BRG1, and BRM in ccRCC, and to investigate possible association between their loss of expression and tumor stage, as well as survival. We also included a histone modifier, SETD2, which is recently discovered to …