Digital Commons Network^™

Does The Use Of Intravenous Zoledronic Acid, In Combination With Chemotherapy Regimens, Arrest The Development And Spread Of Cancer Cells To Increase Disease-Free Survival In Breast Cancer Patients?, Dara Colasurdo

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not “Does the use of intravenous zoledronic acid, in combination with chemotherapy regimens, arrest the development and spread of cancer cells to increase disease-free survival in breast cancer patients.“

STUDY DESIGN: Review of three English language primary randomized controlled trials published between 2009 and 2010.

DATA SOURCES: Randomized controlled trials and open label, randomized, phase 2 trial comparing the use of zoledronic acid in combination with chemotherapy to the use of chemotherapy alone were found using Medline/PubMed and Cochrane Databases

OUTCOMES MEASURED: The outcomes measured were incidence …

Penile Enhancement Procedures With Simultaneous Penile Prosthesis Placement, Tariq S. Hakky, Jessica Suber, Gerard Henry, David Smith, Paul Bradley, Daniel Martinez, Rafael E. Carrion

Surgery Faculty Publications

Here we present an overview of various techniques performed concomitantly during penile prosthesis surgery to enhance penile length and girth. We report on the technique of ventral phalloplasty and its outcomes along with augmentation corporoplasty, suprapubic lipectomy, suspensory ligament release, and girth enhancement procedures. For the serious implanter, outcomes can be improved by combining the use of techniques for each scar incision. These adjuvant procedures are a key addition in the armamentarium for the serious implant surgeon

The Florida Melanoma Trial I: A Prospective Multicenter Phase I/Ii Trial Of Postoperative Hypofractionated Adjuvant Radiotherapy With Concurrent Interferon-Alfa-2b In The Treatment Of Advanced Stage Iii Melanoma With Long-Term Toxicity Follow-Up, Steven E. Finkelstein, Andy Trotti, Nikhil Rao, Douglas Reintgen, Wayne Cruse, Lynn Feun, Vernon Sondak, Daohai Yu, Weiwei Zhu, Clement Gwede, Ronald Deconti

Surgery Faculty Publications

Radiotherapy (RT) and interferon-alfa-2b (IFN α-2b) have individually been used for adjuvant therapy stage III melanoma with high-risk pathologic features. We hypothesized that concurrent adjuvant RT and IFN α-2b may decrease the risk of regional recurrence following surgery with acceptable toxicity. A prospective multicenter phase I/II study was conducted to evaluate hypofractionated RT with concurrent IFN. Induction IFN α-2b, 20 MU/m2/d, was administered IV ×5 consecutive days every week for 4 weeks. Next, RT 30 Gy in 5 fractions was given with concurrent IFN α-2b, 10 MU/m2 SQ 3 times per week on days alternating with …

Mobilizing Subdominant Hiv-Specific Ctls As A Novel Vaccine Strategy, Margaret Christina Costanzo

Open Access Theses & Dissertations

To overcome the extreme antigenic diversity of HIV, there is increasing interest in developing vaccines that target CD8 T cell responses to conserved regions of the viral proteome. Understanding the immunogenic potential of these domains is therefore critical for the success of this vaccine strategy. CD8 T cell responses to conserved domains restricted by the "neutral" and highly prevalent HLA-A2 allele have not been extensively characterized. Here we describe a novel essentially invariant 10-mer epitope in HIV Gag (p2414-23, RTLNAWVKVV (RV10)) in that it is expressed by the majority HIV isolates from all clades. Here we examined the character of …

Evaluation Of Protection Induced By Dna Vaccine Candidate Against Leishmania Mexicana In Balb/C Mice Model, Rosina Rodarte

Open Access Theses & Dissertations

Background and Significance. The leishmaniases are a diverse group of diseases with four major clinical manifestations: cutaneous, mucocutaneous, visceral, and diffuse. Approximately 21 Leishmania species and 30 sandfly vectors have been implicated in human leishmaniasis. Leishmaniasis is endemic in 88 countries, 72 are developing countries. Currently, 350 million people live in leishmaniasis-endemic areas around the world. The true incidence of the disease is not known. However, the estimated incidence for visceral leishmaniasis is 500,000 cases per year, and for cutaneous and mucocutaneous leishmaniasis 1.5-2 million cases per year. Visceral leishmaniasis causes 70,000 deaths each year. In the Americas region, …

Risks To Early Childhood Health And Development In The Postconflict Transition Of Northern Uganda, Theresa A. Mcelroy, Stella Atim, Charles P. Larson, Robert Armstrong

Paediatrics and Child Health, East Africa

Research from numerous fields of science has documented the critical importance of nurturing environments in shaping young children’s future health and development. We studied the environments of early childhood (birth to 3 years) during postconflict, post displacement transition in northern Uganda. The aim was to better understand perceived needs and risks in order to recommend targeted policy and interventions. Methods. Applied ethnography (interview, focus group discussion, case study, observational methods, document review) in 3 sites over 1 year. Results. Transition was a prolonged and deeply challenging phase for families. Young children were exposed to a myriad of risk factors. Participants …

Multimodal Imaging Evidence For Axonal And Myelin Deterioration In Amnestic Mild Cognitive Impairment, Brian T. Gold, Yang Jiang, David K. Powell, Charles D. Smith

Neuroscience Faculty Publications

White matter (WM) microstructural declines have been demonstrated in Alzheimer's disease and amnestic mild cognitive impairment (aMCI). However, the pattern of WM microstructural changes in aMCI after controlling for WM atrophy is unknown. Here, we address this issue through joint consideration of aMCI alterations in fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity, as well as macrostructural volume in WM and gray matter compartments. Participants were 18 individuals with aMCI and 24 healthy seniors. Voxelwise analyses of diffusion tensor imaging data was carried out using tract-based spatial statistics (TBSS) and voxelwise analyses of high-resolution structural data was conducted using …

Sexually Transmitted Diseases In Adolescence, Donald E. Greydanus, Jane Seyler, Hatim A. Omar, Colleen B. Dodich

Pediatrics Faculty Publications

High rates of unprotected sexual behavior in adolescents result in millions of sexually transmitted diseases (STDs) in the world. This paper reviews factors inducing high STD rates, specific STDs, and their management based on 2010 US Centers for Disease and Prevention (CDC) STD guidelines. Clinicians should screen all their sexually active adolescent patients for STDs and provide preventive education as well as treatment measures.

Mitochondrial Iron Uptake Through Mitoferrin2 Sensitizes Human Head And Neck Squamous Carcinoma Cells To Photodynamic Therapy, Hsin-I (Cindy) Hung

MUSC Theses and Dissertations

Photodynamic therapy (PDT) is an FDA-approved, minimally invasive treatment modality that utilizes light in the presence of oxygen to activate photosensitizing agents to produce cell death. Phthalocyanine 4 (Pc 4), a second generation photosensitizer has shown efficacy in vitro, in vivo and in a phase I clinical trial. Pc 4 localizes primarily to mitochondria and endoplasmic reticulum, where it causes apoptotic cell death during PDT. Previously, our laboratory showed that photo sensitizers that localize to lysosomes are more effective in killing cancer cells than ones directed to mitochondria after PDT. Here, we investigated the interactions between lysosomes and mitochondria in …

Extreme Sports: Are They Worth The Risk?, Angela Walin

3690: A Journal of First-Year Student Research Writing

Overview: Broken bones, head trauma, shark attacks, and casualties all while playing the sport you love. Is it worth it? With extreme sports come extreme risks. There are many controversies over these sports as to whether they are ethical or not and why anybody with the right mindset would consider participating in such events. These sports often involve high speed, great heights, a high level of physical exertion, and highly specialized gear or spectacular stunts. Some popular and quickly growing extreme sports in today’s society are snowboarding, speed and freestyle skiing, surfing, sky diving, mountain climbing, and wake boarding. Many …

Role Of The Immune System And Bioactive Lipids In Trafficking Bone Marrow-Derived Stem Cells In Patients With Ischemic Heart Disease, Ahmed Abdel-Latif

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Acute myocardial infarction (AMI) triggers the mobilization of stem/progenitor cells from bone marrow (BMSPCs) into peripheral blood (PB). The underlying mechanisms orchestrating this mobilization and subsequent homing of BMSPCs to the myocardium are poorly understood. While the role of traditional chemokines in the mobilization and homing of hematopoietic stem cell (HSCs) to BM niches is undisputed, their role in directing BMSPCs to the highly proteolytic environment of the ischemic myocardium is debatable and other redundant mechanism may exist. Based on our observation that bioactive lipids, such as sphingosine-1 phosphate (S1P) and ceramide-1 phosphate (C1P), play an important role in regulating …

Influence Of Oncotype Dx® On Chemotherapy Prescribing In Early Stage Breast Cancer Patients: A Claims-Based Evaluation Of Utilization In The Real World, Kenneth Neil Kennedy

Theses and Dissertations--Pharmacy

The decision for adjuvant therapy in women with early stage breast cancer (ESBC) has historically been guided by the presence or absence of specific biological markers (hormone and HER2 receptors), age, and extent of nodal involvement. Oncotype DX® is a validated assay that quantifies protein expression that can predict the risk of cancer recurrence. This study evaluates if the use of Oncotype DX® impacts chemotherapy prescribing in ESBC. This retrospective, cohort study identified patients with ESBC from a large commercially insured population from January 2007 through June 2009. Patients were identified as having ESBC by utilizing procedure and diagnosis codes …

Short-Term Plasticity At The Schaffer Collateral: A New Model With Implications For Hippocampal Processing, Andrew Hamilton Toland

Dissertations and Theses

A new mathematical model of short-term synaptic plasticity (STP) at the Schaffer collateral is introduced. Like other models of STP, the new model relates short-term synaptic plasticity to an interaction between facilitative and depressive dynamic influences. Unlike previous models, the new model successfully simulates facilitative and depressive dynamics within the framework of the synaptic vesicle cycle. The novelty of the model lies in the description of a competitive interaction between calcium-sensitive proteins for binding sites on the vesicle release machinery. By attributing specific molecular causes to observable presynaptic effects, the new model of STP can predict the effects of specific …

An Evaluation Of Warfarin Use And 30-Day Hemorrhage In Bariatric Surgery, Amanda M. Curry, Richard Boorse Md, Peter J. Bechtel Md, Cathy Fuhrman Rn, Msn, Cathleen Webber Rn, Mshs, Suzanne L. Smith Mba, Rrt, Tas

Department of Surgery

No abstract provided.

Attenuation Of Corneal Myofibroblast Development Through Nanoparticle-Mediated Soluble Transforming Growth Factor-Β Type Ii Receptor (Stgfβrii) Gene Transfer, Ajay Sharma, Jason T. Rodier, Ashish Tandon, Alexander M. Klibanov, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Purpose: To explore (i) the potential of polyethylenimine (PEI)-DNA nanoparticles as a vector for delivering genes into human corneal fibroblasts, and (ii) whether the nanoparticle-mediated soluble extracellular domain of the transforming growth factor–β type II receptor (sTGFβRII) gene therapy could be used to reduce myofibroblasts and fibrosis in the cornea using an in vitro model.

Methods: PEI-DNA nanoparticles were prepared at a nitrogen-to-phosphate ratio of 30 by mixing linear PEI and a plasmid encoding sTGFβRII conjugated to the fragment crystallizable (Fc) portion of human immunoglobulin. The PEI-DNA polyplex formation was confirmed through gel retardation assay. Human corneal fibroblasts (HCFs) were …

Mild Cognitive Impairment: Statistical Models Of Transition Using Longitudinal Clinical Data, Erin L. Abner, Richard J. Kryscio, Gregory E. Cooper, David W. Fardo, Gregory A. Jicha, Marta S. Mendiondo, Peter T. Nelson, Charles D. Smith, Linda J. Van Eldik, Lijie Wan, Frederick A. Schmitt

Sanders-Brown Center on Aging Faculty Publications

Mild cognitive impairment (MCI) refers to the clinical state between normal cognition and probable Alzheimer's disease (AD), but persons diagnosed with MCI may progress to non-AD forms of dementia, remain MCI until death, or recover to normal cognition. Risk factors for these various clinical changes, which we term "transitions," may provide targets for therapeutic interventions. Therefore, it is useful to develop new approaches to assess risk factors for these transitions. Markov models have been used to investigate the transient nature of MCI represented by amnestic single-domain and mixed MCI states, where mixed MCI comprised all other MCI subtypes based on …

Biochemical Links Between Hormonal Mediators Of Psychological Stress And The Expression Of Muc1 In Prostate Cancer Cells, Kristina Andrijauskaite

MUSC Theses and Dissertations

A growing body of scientific evidence has demonstrated that chronic psychological stress can not only increase the growth and metastasis of tumors through a number of mechanisms, such as by an increase of VEGF and Bcl-2, but also can decrease the survival of cancer patients. However, no studies have reported the effect of psychological stress with respect to the tumor marker MUC1. Therefore, building upon previous research, the purpose of the present study was to investigate the effect of the stress hormones cortisol and norepinephrine on the tumor marker MUC1, which is highly associated with tumor cell metastasis and is …

Critical Issues For Integrating Srh And Hiv/Aids Services To Provide Dual Protection Against Unintended Pregnancy And Hiv/Sti Acquisition, Population Council

Reproductive Health

This document reports on a one-day symposium that was held by the STEP UP (Strengthening Evidence for Programming on Unintended Pregnancy) Research Program Consortium, coordinated by the Population Council. STEP UP generates policy-relevant research to promote an evidence-based approach for improving access to family planning and safe abortion in Bangladesh, Ghana, India, Kenya, and Senegal. The symposium’s objectives were to review and discuss critical and emerging issues around integrating SRH and HIV and AIDS services to enable dual protection, including new directions in dual protection technology and behaviour change interventions. The meeting also provided an opportunity to discuss the programmatic …

Investigating The Impact Of Cd147 And Its Expression On Neurodegenaration And Alzheimer's Disease (Ad), Limbikani J. Kanyenda

Theses: Doctorates and Masters

CD147, also known as basigin, extracellular matrix metalloproteinase inducer, neurothelin, tumour cell-derived collagenase stimulatory factor, M6, HT7, OX47 or gp42, is a transmembrane glycoprotein of the immunoglobulin super-family. It is expressed in many neuronal and non-neuronal tissues with high expression in the hippocampus, pre-frontal cortex, thyroid, heart, early erythroid, amygdala and placenta. This protein is involved in various cellular and biological functions such as lymphocyte migration and maturation, tissue repair, cancer progression, T and B lymphocyte activation and induction of extracellular matrix metalloproteinase. The CD147 protein interacts with with cyclophilin A, cyclophilin B, sterol carrier protein, caveolin-1 and integrins, and …

The Effectiveness Of Airway Management In The Pre Hospital Treatment Of Traumatic Brain Injury : A Retrospective, Observational Study Of Pre Hospital Treatment Of Traumatic Brain Injury (Tbi) In The Western Australian Ambulance Service, Joseph Cuthbertson

Theses: Doctorates and Masters

There is concern over mortality and the potential for secondary brain injury in the head-injured patient. The use of advanced airway management and rapid sequence intubation in the pre hospital treatment of patients with Traumatic Brain Injury is controversial. Currently in St John Ambulance Service Australia (WA) Inc. three forms of pre hospital treatment are utilized to manage the airway of the adult head-injured patient. If attended by on-road paramedic staff, basic airway management is utilized unless the patient is unconscious and areflexic, in which case advanced airway management utilising endotracheal intubation or laryngeal mask insertion is authorised. In the …

A Mathematical Model For Cell Cycle-Specific Cancer Virotherapy, Joanna R. Wares, Joseph J. Crivelli, Juraj Földes, Peter S. Kim

Department of Math & Statistics Faculty Publications

Oncolytic viruses preferentially infect and replicate in cancerous cells, leading to elimination of tumour populations, while sparing most healthy cells. Here, we study the cell cycle-specific activity of viruses such as vesicular stomatitis virus (VSV). In spite of its capacity as a robust cytolytic agent,VSVcannot effectively attack certain tumour cell types during the quiescent, or resting, phase of the cell cycle. In an effort to understand the interplay between the time course of the cell cycle and the specificity of VSV, we develop a mathematical model for cycle-specific virus therapeutics. We incorporate the minimum biologically required time spent in the …

Long Term Weight Variability In Adults Of Adventist Health Study 1 And 2, Namgyal Lhawang Kyulo

Loma Linda University Electronic Theses, Dissertations & Projects

Background: The effect of overweight and obesity on the risk of fatal disease tends to attenuate with age. One plausible explanation is that a proportion of elderly people in the ideal weight category (19 to 25 kg/m ) experienced disease-related weight loss - an effect that will attenuate health risk related to overweight and obesity. One potential approach to controlling for this bias would be to examine fluctuations in weight during the adult lifespan by considering multiple measures of weight or recall of body weight during adulthood. Some of these measures are available in the Adventist Health Study cohorts and …

Mir-128 Inhibits Tumor Growth And Angiogenesis By Targeting P70s6k1., Zhu-Mei Shi, Jing Wang, Zhiping Yan, Yong-Ping You, Chong-Yong Li, Xu Qian, Yu Yin, Peng Zhao, Ying-Ying Wang, Xie-Feng Wang, Ming-Na Li, Ling-Zhi Liu, Ning Liu, Bing-Hua Jiang

Kimmel Cancer Center Faculty Papers

MicroRNAs are a class of small noncoding RNAs that function as critical gene regulators through targeting mRNAs for translational repression or degradation. In this study, we showed that miR-128 expression levels were decreased in glioma, and identified p70S6K1 as a novel direct target of miR-128. Overexpression of miR-128 suppressed p70S6K1 and its downstream signaling molecules such as HIF-1 and VEGF expression, and attenuated cell proliferation, tumor growth and angiogenesis. Forced expression of p70S6K1 can partly rescue the inhibitory effect of miR-128 in the cells. Taken together, these findings will shed light to the role and mechanism of miR-128 in regulating …

A Novel Survival-Based Tissue Microarray Of Pancreatic Cancer Validates Muc1 And Mesothelin As Biomarkers., Jordan M Winter, Laura H Tang, David S Klimstra, Murray F Brennan, Jonathan R Brody, Flavio G Rocha, Xiaoyu Jia, Li-Xuan Qin, Michael I D'Angelica, Ronald P Dematteo, Yuman Fong, William R Jarnagin, Eileen M O'Reilly, Peter J Allen

Department of Surgery Faculty Papers

BACKGROUND: One-fifth of patients with seemingly 'curable' pancreatic ductal adenocarcinoma (PDA) experience an early recurrence and death, receiving no definable benefit from a major operation. Some patients with advanced stage tumors are deemed 'unresectable' by conventional staging criteria (e.g. liver metastasis), yet progress slowly. Effective biomarkers that stratify PDA based on biologic behavior are needed. To help researchers sort through the maze of biomarker data, a compendium of ∼2500 published candidate biomarkers in PDA was compiled (PLoS Med, 2009. 6(4) p. e1000046).

METHODS AND FINDINGS: Building on this compendium, we constructed a survival tissue microarray (termed s-TMA) comprised of short-term …

Early Versus Delayed Decompression For Traumatic Cervical Spinal Cord Injury: Results Of The Surgical Timing In Acute Spinal Cord Injury Study (Stascis)., Michael G Fehlings, Alex R. Vaccaro, Jefferson R Wilson, Anoushka Singh, David W Cadotte, James Harrop, Bizhan Aarabi, Christopher Shaffrey, Marcel Dvorak, Charles Fisher, Paul Arnold, Eric M Massicotte, Stephen Lewis, Raja Rampersaud

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: There is convincing preclinical evidence that early decompression in the setting of spinal cord injury (SCI) improves neurologic outcomes. However, the effect of early surgical decompression in patients with acute SCI remains uncertain. Our objective was to evaluate the relative effectiveness of early (injury) versus late (≥ 24 hours after injury) decompressive surgery after traumatic cervical SCI.

METHODS: We performed a multicenter, international, prospective cohort study (Surgical Timing In Acute Spinal Cord Injury Study: STASCIS) in adults aged 16-80 with cervical SCI. Enrolment occurred between 2002 and 2009 at 6 North American centers. The primary outcome was ordinal change …

Fiber And Bulking Agents For The Treatment Of Chronic Constipation, Kashmira Nanji, Bilal Ahmed, Safia Awan, Waris Qidwai, Saeed Hamid

Department of Family Medicine

No abstract provided.

Role Of Human Protein Disulfide Isomerase (Pdi) In The Redox Regulation Of Anthrax Receptor 2 (Antxr2), Naima Mohamed Alshrif

Open Access Theses & Dissertations

Anthrax is an acute infectious disease caused by B. anthracis, a gram-positive and spore-forming bacterium. Anthrax toxin is a tripartite AB toxin composed of a receptor binding/pore-forming moiety, protective antigen (PA), and two catalytic moieties, edema factor (EF) and lethal factor (LF). Anthrax toxin PA binds to cell-surface receptors, where it gets activated by furin, and assembles into a ring-like heptameric structure. The toxin-receptor complex is internalized into endosomes where the acidic pH triggers PA pore formation on the endosomal membrane that translocates the toxin catalytic moieties. Recent study has shown that anthrax toxin receptors play a critical role in …

Orphan Nuclear Receptor Nur77 Regulates Androgen Receptor Gene Expression In Mouse Ovary., Anyi Dai, Guijun Yan, Qinyuan He, Yue Jiang, Qun Zhang, Ting Fang, Lijun Ding, Jianxin Sun, Haixiang Sun, Yali Hu

Center for Translational Medicine Faculty Papers

The androgen receptor (AR) is a nuclear receptor that is expressed in growing follicles and involved in folliculogenesis and follicle growth. The orphan nuclear receptor, Nur77, also has an important role in steroid signaling and follicle maturation. We hypothesized that AR levels and androgen signaling through AR are regulated by Nur77 in the ovary. In the ovaries of Nur77 knockout mice (n = 5), real-time PCR results showed that the mRNA levels of AR and an androgen signaling target gene, Kitl, were decreased by 35% and 24%, respectively, relative to wild-type mice (n = 5), which suggested transcriptional regulation of …

Identifying Sm22 As A Key Player In Arterial Diseases, Jianbin Shen

Wayne State University Dissertations

Background : Expression of vascular smooth muscle cell (VSMC) cytoskeleton markers including SM22 is down-regulated in arterial diseases including atherosclerosis where inflammation and osteochondrogenesis are present. However, the role of this downregulation in arterial pathogenesis is unknown. Hypothesis : Downregulation of SM22 may actively contribute to arterial pathogenesis. Methods : Five Sm22 knockout (Sm22^-/-) mice and their wild type littermates were subjected to carotid artery denudation, an artery injury model. Analyses were conducted on carotid arteries 2 weeks after injury. Primary VSMCs were isolated from mouse aortas and investigated individually at passage 2 to 4. Sm22 knockdown was …

Role Of Thromboxane Receptor-Alpha In Prostate Cancer Progression, Prasanna Ekambaram

Wayne State University Dissertations

Thromboxane A2 (TXA2) is a major arachidonic acid metabolite that signals through TXA2 receptors (TP) to induce platelet aggregation and smooth muscle contraction. TXA2 receptors are expressed as two different isoforms in humans, namely TP-alpha (TPα) and TP-beta (TPβ), which have common and distinct signaling pathways. Of the two TP receptor isoforms, studies have shown that TPα impacts tumor growth and progression of lung cancer. Previously our studies demonstrated that activation of Thromboxane receptor by TXA2 agonists could regulate prostate cancer (PCa) cell motility and cytoskeletal reorganization through activation of Rho-A. The primary objective of this study is to investigate …