Medical Specialties Commons^™

Emerging Novel Therapies For Heart Failure., Anthony M Szema, Sophia Dang, Jonathan C Li

Department of Medicine Faculty Papers

Heart function fails when the organ is unable to pump blood at a rate proportional to the body's need for oxygen or when this function leads to elevated cardiac chamber filling pressures (cardiogenic pulmonary edema). Despite our sophisticated knowledge of heart failure, even so-called ejection fraction-preserved heart failure has high rates of mortality and morbidity. So, novel therapies are sorely needed. This review discusses current standard therapies for heart failure and launches an exploration into emerging novel treatments on the heels of recently-approved sacubitril and ivbradine. For example, Vasoactive Intestinal Peptide (VIP) is protective of the heart, so in the …

Survival Outcome According To Kras Mutation Status In Newly Diagnosed Patients With Stage Iv Non-Small Cell Lung Cancer Treated With Platinum Doublet Chemotherapy., Anna K Brady, Jonathan D Mcneill, Brendan Judy, Joshua Bauml, Tracey L Evans, Roger B Cohen, Corey Langer, Anil Vachani, Charu Aggarwal

Department of Surgery Faculty Papers

INTRODUCTION: Mutations (MT) of the KRAS gene are the most common mutation in non-small cell lung cancer (NSCLC), seen in about 20-25% of all adenocarcinomas. Effect of KRAS MT on response to cytotoxic chemotherapy is unclear.

METHODS: We undertook a single-institution retrospective analysis of 93 consecutive patients with stage IV NSCLC adenocarcinoma with known KRAS and EGFR MT status to determine the association of KRAS MT with survival. All patients were treated between January 1, 2008 and December 31, 2011 with standard platinum based chemotherapy at the University of Pennsylvania. Overall and progression free survival were analyzed using Kaplan-Meier and …

Diagnostic Options And Challenges For Dengue And Chikungunya Viruses., Stacey K. Mardekian, Amity L. Roberts, Phd, D(Abmm)

Department of Medical Genetics Faculty Papers

Dengue virus (DENV) and Chikungunya virus (CHIKV) are arboviruses that share the same Aedes mosquito vectors and thus overlap in their endemic areas. These two viruses also cause similar clinical presentations, especially in the initial stages of infection, with neither virus possessing any specific distinguishing clinical features. Because the outcomes and management strategies for these two viruses are vastly different, early and accurate diagnosis is imperative. Diagnosis is also important for surveillance, outbreak control, and research related to vaccine and drug development. Available diagnostic tests are aimed at detection of the virus, its antigenic components, or the host immune antibody …

A Phase 3 Trial Of 2 Years Of Androgen Suppression And Radiation Therapy With Or Without Adjuvant Chemotherapy For High-Risk Prostate Cancer: Final Results Of Radiation Therapy Oncology Group Phase 3 Randomized Trial Nrg Oncology Rtog 9902., Seth A. Rosenthal, Daniel Hunt, A. Oliver Sartor, Kenneth J. Pienta, Leonard G. Gomella, David Grignon, Raghu Rajan, Kevin J. Kerlin, Christopher U. Jones, Michael Dobelbower, William U Shipley, Kenneth Zeitzer, Daniel A. Hamstra, Viroon Donavanik, Marvin Rotman, Alan C. Hartford, Jeffrey Michalski, Michael Seider, Harold Kim, Deborah A. Kuban, Jennifer Moughan, Howard Sandler

Department of Urology Faculty Papers

PURPOSE: Long-term (LT) androgen suppression (AS) with radiation therapy (RT) is a standard treatment of high-risk, localized prostate cancer (PCa). Radiation Therapy Oncology Group 9902 was a randomized trial testing the hypothesis that adjuvant combination chemotherapy (CT) with paclitaxel, estramustine, and oral etoposide plus LT AS plus RT would improve overall survival (OS).

METHODS AND MATERIALS: Patients with high-risk PCa (prostate-specific antigen 20-100 ng/mL and Gleason score [GS] ≥ 7 or clinical stage ≥ T2 and GS ≥ 8) were randomized to RT and AS (AS + RT) alone or with adjuvant CT (AS + RT + CT). CT was …

Orphan Nuclear Receptor Nur77 Inhibits Cardiac Hypertrophic Response To Beta-Adrenergic Stimulation., Guijun Yan, Ni Zhu, Shengdong Huang, Bing Yi, Xiying Shang, Ming Chen, Nadan Wang, Guan-Xin Zhang, Jennifer A Talarico, Douglas G Tilley, Erhe Gao, Jianxin Sun

Center for Translational Medicine Faculty Papers

The orphan nuclear receptor Nur77 plays critical roles in cardiovascular diseases, and its expression is markedly induced in the heart after beta-adrenergic receptor (β-AR) activation. However, the functional significance of Nur77 in β-AR signaling in the heart remains unclear. By using Northern blot, Western blot, and immunofluorescent staining assays, we showed that Nur77 expression was markedly upregulated in cardiomyocytes in response to multiple hypertrophic stimuli, including isoproterenol (ISO), phenylephrine (PE), and endothelin-1 (ET-1). In a time- and dose-dependent manner, ISO increases Nur77 expression in the nuclei of cardiomyocytes. Overexpression of Nur77 markedly inhibited ISO-induced cardiac hypertrophy by inducing nuclear translocation …

Increased Expression Of Napdh Oxidase 4 In Systemic Sclerosis Dermal Fibroblasts: Regulation By Transforming Growth Factor Β., Sonsoles Piera-Velazquez, Alma Makul, Sergio A. Jimenez

Department of Dermatology and Cutaneous Biology Faculty Papers

OBJECTIVE: Systemic sclerosis (SSc) is characterized by severe and often progressive fibrosis of the skin and multiple internal organs. The mechanisms responsible for these alterations remain obscure, although excessive reactive oxygen species (ROS)-mediated oxidative stress has been implicated. NOX-4 is 1 of 7 isoforms of NADPH oxidase responsible for the generation of ROS. The purpose of this study was to examine NOX-4 expression in skin and cultured dermal fibroblasts from SSc patients and to examine its regulation by transforming growth factor β1 (TGFβ1).

METHODS: NOX-4 was assessed in normal and SSc skin by immunohistologic analysis and in normal and SSc …

Iv And Ip Administration Of Rhodamine In Visualization Of Wbc-Bbb Interactions In Cerebral Vessels., Zachary Wilmer Reichenbach, Hongbo Li, John P. Gaughan, Melanie B. Elliott, Ronald Tuma

Department of Neurosurgery Faculty Papers

Epi-illuminescence intravital fluorescence microscopy has been employed to study leukocyte-endothelial interactions in a number of brain pathologies. Historically, dyes such as Rhodamine 6G have been injected intravenously. However, intravenous injections can predispose experimental animals to a multitude of complications and requires a high degree of technical skill. Here, we study the efficacy of injecting Rhodamine 6G into the peritoneum (IP) for the purpose of analyzing leukocyte-endothelial interactions through a cranial window during real time intravital microscopy. After examining the number of rolling and adherent leukocytes through a cranial window, we found no advantage to the intravenous injection (IV). Additionally, we …

Characterization Of 1577 Primary Prostate Cancers Reveals Novel Biological And Clinicopathologic Insights Into Molecular Subtypes., Scott A. Tomlins, Mohammed Alshalalfa, Elai Davicioni, Nicholas Erho, Kasra Yousefi, Shuang Zhao, Zaid Haddad, Robert B. Den, Adam P. Dicker, Bruce J. Trock, Angelo M. Demarzo, Ashley E. Ross, Edward M. Schaeffer, Eric A. Klein, Cristina Magi-Galluzzi, R. Jeffrey Karnes, Robert B. Jenkins, Felix Y. Feng

Department of Radiation Oncology Faculty Papers

BACKGROUND: Prostate cancer (PCa) molecular subtypes have been defined by essentially mutually exclusive events, including ETS gene fusions (most commonly involving ERG) and SPINK1 overexpression. Clinical assessment may aid in disease stratification, complementing available prognostic tests.

OBJECTIVE: To determine the analytical validity and clinicopatholgic associations of microarray-based molecular subtyping.

DESIGN, SETTING, AND PARTICIPANTS: We analyzed Affymetrix GeneChip expression profiles for 1577 patients from eight radical prostatectomy cohorts, including 1351 cases assessed using the Decipher prognostic assay (GenomeDx Biosciences, San Diego, CA, USA) performed in a laboratory with Clinical Laboratory Improvements Amendment certification. A microarray-based (m-) random forest ERG classification model …

Simple New Risk Score Model For Adult Cardiac Extracorporeal Membrane Oxygenation: Simple Cardiac Ecmo Score., Graham Peigh, Nicholas Cavarocchi, Scott W. Keith, Hitoshi Hirose

Department of Surgery Faculty Papers

BACKGROUND: Although the use of cardiac extracorporeal membrane oxygenation (ECMO) is increasing in adult patients, the field lacks understanding of associated risk factors. While standard intensive care unit risk scores such as SAPS II (simplified acute physiology score II), SOFA (sequential organ failure assessment), and APACHE II (acute physiology and chronic health evaluation II), or disease-specific scores such as MELD (model for end-stage liver disease) and RIFLE (kidney risk, injury, failure, loss of function, ESRD) exist, they may not apply to adult cardiac ECMO patients as their risk factors differ from variables used in these scores.

METHODS: Between 2010 and …

Caffeine And Progression Of Parkinson Disease: A Deleterious Interaction With Creatine., David K. Simon, Cai Wu, Barbara C. Tilley, Anne-Marie Wills, Michael J. Aminoff, Jacquelyn Bainbridge, Robert A. Hauser, Jay S. Schneider, Saloni Sharma, Carlos Singer, Caroline M. Tanner, Daniel Truong, Pei Shieen Wong

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

OBJECTIVE: Increased caffeine intake is associated with a lower risk of Parkinson disease (PD) and is neuroprotective in mouse models of PD. However, in a previous study, an exploratory analysis suggested that, in patients taking creatine, caffeine intake was associated with a faster rate of progression. In the current study, we investigated the association of caffeine with the rate of progression of PD and the interaction of this association with creatine intake.

METHODS: Data were analyzed from a large phase 3 placebo-controlled clinical study of creatine as a potentially disease-modifying agent in PD. Subjects were recruited for this study from …

Fsd-C10: A More Promising Novel Rock Inhibitor Than Fasudil For Treatment Of Cns Autoimmunity., Yan-Le Xin, Jie-Zhong Yu, Xin-Wang Yang, Chun-Yun Liu, Yan-Hua Li, Ling Feng, Zhi Chai, Wan-Fang Yang, Qing Wang, Wei-Jia Jiang, Guang-Xian Zhang, Bao-Guo Xiao, Cun-Gen Ma

Department of Neurology Faculty Papers

Rho-Rho kinase (Rho-ROCK) triggers an intracellular signalling cascade that regulates cell survival, death, adhesion, migration, neurite outgrowth and retraction and influences the generation and development of several neurological disorders. Although Fasudil, a ROCK inhibitor, effectively suppressed encephalomyelitis (EAE), certain side effects may limit its clinical use. A novel and efficient ROCK inhibitor, FSD-C10, has been explored. In the present study, we present chemical synthesis and structure of FSD-C10, as well as the relationship between compound concentration and ROCK inhibition. We compared the inhibitory efficiency of ROCKI and ROCK II, the cell cytotoxicity, neurite outgrowth and dendritic formation, neurotrophic factors and …

The Evolution Of Epilepsy Surgery Between 1991 And 2011 In Nine Major Epilepsy Centers Across The United States, Germany, And Australia., Lara Jehi, Daniel Friedman, Chad Carlson, Gregory Cascino, Sandra Dewar, Christian Elger, Jerome Engel, Robert Knowlton, Ruben Kuzniecky, Anne Mcintosh, Terence J O'Brien, Dennis Spencer, Michael R. Sperling, Gregory Worrell, Bill Bingaman, Jorge Gonzalez-Martinez, Werner Doyle, Jacqueline French

Department of Neurology Faculty Papers

OBJECTIVE: Epilepsy surgery is the most effective treatment for select patients with drug-resistant epilepsy. In this article, we aim to provide an accurate understanding of the current epidemiologic characteristics of this intervention, as this knowledge is critical for guiding educational, academic, and resource priorities.

METHODS: We profile the practice of epilepsy surgery between 1991 and 2011 in nine major epilepsy surgery centers in the United States, Germany, and Australia. Clinical, imaging, surgical, and histopathologic data were derived from the surgical databases at various centers.

RESULTS: Although five of the centers performed their highest number of surgeries for mesial temporal sclerosis …

Use Of High-Speed X Ray And Video To Analyze Distal Radius Fracture Pathomechanics., Christina Gutowski, Kurosh Darvish, Frederic E. Liss, Asif M. Ilyas, Christopher M. Jones

Department of Orthopaedic Surgery Faculty Papers

The purpose of this study is to investigate the failure sequence of the distal radius during a simulated fall onto an outstretched hand using cadaver forearms and high-speed X ray and video systems. This apparatus records the beginning and propagation of bony failure, ultimately resulting in distal radius or forearm fracture. The effects of 3 different wrist guard designs are investigated using this system. Serving as a proof-of-concept analysis, this study supports this imaging technique to be used in larger studies of orthopedic trauma and protective devices and specifically for distal radius fractures.

Targeting The Mrna-Binding Protein Hur Impairs Malignant Characteristics Of Pancreatic Ductal Adenocarcinoma Cells., Masaya Jimbo, Fernando F Blanco, Yu-Hung Huang, Aristeidis G Telonis, Brad A Screnci, Gabriela L Cosma, Vitali Alexeev, Gregory E Gonye, Charles Yeo, Janet A Sawicki, Jordan M Winter, Jonathan Brody, Md

Computational Medicine Center Faculty Papers

Post-transcriptional regulation is a powerful mediator of gene expression, and can rapidly alter the expression of numerous transcripts involved in tumorigenesis. We have previously shown that the mRNA-binding protein HuR (ELAVL1) is elevated in human pancreatic ductal adenocarcinoma (PDA) specimens compared to normal pancreatic tissues, and its cytoplasmic localization is associated with increased tumor stage. To gain a better insight into HuR's role in PDA biology and to assess it as a candidate therapeutic target, we altered HuR expression in PDA cell lines and characterized the resulting phenotype in preclinical models. HuR silencing by short hairpin and small interfering RNAs …

Fostering The Development Of Emotional Intelligence Among Health Science Students: Empowering Students To Impact Institutional Culture, Julia Ward, Phd, Rn, Mary Hanson-Zalot, Msn, Rn, Aocn, Collleen Dempsey, Ms, Rt(R)

College of Nursing Posters

Objectives:

Identify challenges of navigating institutional culture for students interacting in a variety of clinical settings

Discuss the importance of integrating concepts of emotional intelligence throughout curricular plans of study

Consider contemporary research findings in the health science literature regarding emotional intelligence among students.

Endoscopic Management Of Idiopathic Subglottic Stenosis In Twenty-Five Patients, Katherine Mckee-Cole, Md, Ethan C. Bassett, Md, Maurits Boon, Md, Joseph Spiegel, Md

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Introduction

While multiple causes exist for the development of subglottic stenosis, the mechanism responsible for idiopathic subglottic stenosis (ISS) remains unknown. Proposed etiologies include gastro-esophageal reflux (GERD) related exposure, telescoping of the first tracheal ring under the cricoid cartilage, a hormonal cause, and the possibility of an unidentified autoimmune process (1,3,6,8,12,18,19).

As ISS represents a rare disease of yet unknown etiology, the optimal management remains to be defined. The treatment options range from endoscopic management, which is less invasive but tends to show recurrence to open tracheal resection with anastomosis for those patients in whom endoscopic techniques are ineffective or …

Novel Targeted Sirna-Loaded Hybrid Nanoparticles: Preparation, Characterization And In Vitro Evaluation., Nneka Dim, Maryna Perepelyuk, Olukayode Gomes, Chellappagounder Thangavel, Yi Liu, Robert Den, Ashakumary Lakshmikuttyamma, Sunday A Shoyele

Department of Radiation Oncology Faculty Papers

BACKGROUND: siRNAs have a high potential for silencing critical molecular pathways that are pathogenic. Nevertheless, their clinical application has been limited by a lack of effective and safe nanotechnology-based delivery system that allows a controlled and safe transfection to cytosol of targeted cells without the associated adverse effects. Our group recently reported a very effective and safe hybrid nanoparticle delivery system composing human IgG and poloxamer-188 for siRNA delivery to cancer cells. However, these nanoparticles need to be optimized in terms of particle size, loading capacity and encapsulation efficiency. In the present study, we explored the effects of certain production …

Off-Target V(D)J Recombination Drives Lymphomagenesis And Is Escalated By Loss Of The Rag2 C Terminus., Martina Mijušković, Yi-Fan Chou, Vered Gigi, Cory R Lindsay, Olga Shestova, Susanna M Lewis, David B Roth

Cardeza Foundation for Hematologic Research

Genome-wide analysis of thymic lymphomas from Tp53(-/-) mice with wild-type or C-terminally truncated Rag2 revealed numerous off-target, RAG-mediated DNA rearrangements. A significantly higher fraction of these errors mutated known and suspected oncogenes/tumor suppressor genes than did sporadic rearrangements (p < 0.0001). This tractable mouse model recapitulates recent findings in human pre-B ALL and allows comparison of wild-type and mutant RAG2. Recurrent, RAG-mediated deletions affected Notch1, Pten, Ikzf1, Jak1, Phlda1, Trat1, and Agpat9. Rag2 truncation substantially increased the frequency of off-target V(D)J recombination. The data suggest that interactions between Rag2 and a specific chromatin modification, H3K4me3, support V(D)J recombination fidelity. Oncogenic effects of off-target rearrangements created by this highly regulated recombinase may need to be considered in design of site-specific nucleases engineered for genome modification.

Disc In Flames: Roles Of Tnf-Α And Il-1Β In Intervertebral Disc Degeneration., Z I Johnson, Z R Schoepflin, H Choi, I M Shapiro, M V Risbud

Department of Orthopaedic Surgery Faculty Papers

The intervertebral disc is an important mechanical structure that allows range of motion of the spinal column. Degeneration of the intervertebral disc--incited by aging, traumatic insult, genetic predisposition, or other factors--is often defined by functional and structural changes in the tissue, including excessive breakdown of the extracellular matrix, increased disc cell senescence and death, as well as compromised biomechanical function of the tissue. Intervertebral disc degeneration is strongly correlated with low back pain, which is a highly prevalent and costly condition, significantly contributing to loss in productivity and health care costs. Disc degeneration is a chronic, progressive condition, and current …

Lysyl Hydroxylase 3 Localizes To Epidermal Basement Membrane And Is Reduced In Patients With Recessive Dystrophic Epidermolysis Bullosa., Stephen A Watt, Jasbani H S Dayal, Sheila Wright, Megan Riddle, Celine Pourreyron, James R Mcmillan, Roy M Kimble, Marco Prisco, Ulrike Gartner, Emma Warbrick, W H Irwin Mclean, Irene M Leigh, John A Mcgrath, Julio C Salas-Alanis, Jakub Tolar, Andrew P South

Department of Dermatology and Cutaneous Biology Faculty Papers

Recessive dystrophic epidermolysis bullosa (RDEB) is caused by mutations in COL7A1 resulting in reduced or absent type VII collagen, aberrant anchoring fibril formation and subsequent dermal-epidermal fragility. Here, we identify a significant decrease in PLOD3 expression and its encoded protein, the collagen modifying enzyme lysyl hydroxylase 3 (LH3), in RDEB. We show abundant LH3 localising to the basement membrane in normal skin which is severely depleted in RDEB patient skin. We demonstrate expression is in-part regulated by endogenous type VII collagen and that, in agreement with previous studies, even small reductions in LH3 expression lead to significantly less secreted LH3 …

Frontal Gray Matter Abnormalities Predict Seizure Outcome In Refractory Temporal Lobe Epilepsy Patients, Gaelle Eve Doucet, Xiaosong He, Michael R Sperling, Ashwini Sharan Md, Joseph I. Tracy

Department of Neurology Faculty Papers

This article has been peer reviewed. It was published in: NeuroImage: Clinical. Volume 9, 2015, Pages 458-466.

The published version is available at DOI: 10.1016/j.nicl.2015.09.006

Copyright © 2015 The Authors.

Current State Of The Art Of Regional Hyperthermia Treatment Planning: A Review., H P Kok, P Wust, Paul R. Stauffer, F Bardati, G C Van Rhoon, J Crezee

Department of Radiation Oncology Faculty Papers

Locoregional hyperthermia, i.e. increasing the tumor temperature to 40-45 °C using an external heating device, is a very effective radio and chemosensitizer, which significantly improves clinical outcome. There is a clear thermal dose-effect relation, but the pursued optimal thermal dose of 43 °C for 1 h can often not be realized due to treatment limiting hot spots in normal tissue. Modern heating devices have a large number of independent antennas, which provides flexible power steering to optimize tumor heating and minimize hot spots, but manual selection of optimal settings is difficult. Treatment planning is a very valuable tool to improve …

Computerized Adaptive Tests Detect Change Following Orthopaedic Surgery In Youth With Cerebral Palsy., M J Mulcahey, Mary D Slavin, Pengsheng Ni, Lawrence C Vogel, Scott H Kozin, Stephen M Haley, Alan M Jette

Department of Occupational Therapy Faculty Papers

BACKGROUND: The Cerebral Palsy Computerized Adaptive Test (CP-CAT) is a parent-reported outcomes instrument for measuring lower and upper-extremity function, activity, and global health across impairment levels and a broad age range of children with cerebral palsy (CP). This study was performed to examine whether the Lower Extremity/Mobility (LE) CP-CAT detects change in mobility following orthopaedic surgery in children with CP.

METHODS: This multicenter, longitudinal study involved administration of the LE CP-CAT, the Pediatric Outcomes Data Collection Instrument (PODCI) Transfer/Mobility and Sports/Physical Functioning domains, and the Timed "Up & Go" test (TUG) before and after elective orthopaedic surgery in a convenience …

The Fate Of Spacers In The Treatment Of Periprosthetic Joint Infection., Miguel M Gomez, Timothy L Tan, Jorge Manrique, Gregory K Deirmengian, Javad Parvizi Md

Rothman Institute Papers

BACKGROUND: Two-stage exchange arthroplasty remains the preferred method to treat periprosthetic joint infection. The aim of this study was to investigate the clinical course of periprosthetic joint infection following resection arthroplasty and insertion of a spacer.

METHODS: Our institutional database was used to identify 504 cases of periprosthetic joint infection (326 knees and 178 hips) treated with resection arthroplasty and spacer insertion as part of a two-stage exchange arthroplasty. A review of the patient charts was performed to extract information relevant to the objectives of this study that included the details of the clinical course following resection arthroplasty.

RESULTS: The …

Thromboembolism After Intramedullary Nailing For Metastatic Bone Lesions., Brandon Shallop, Alexandria Starks, Simon Greenbaum, David S Geller, Alan Lee, John Ready, Geno J Merli, Mitchell Maltenfort, Phd, John A Abraham

Rothman Institute Papers

BACKGROUND: The risk of venous thromboembolism (VTE) in patients undergoing intramedullary nailing for skeletal metastatic disease is currently undefined. The purpose of our study was to determine the risk of thromboembolic events, to define the risk factors for VTE, and to define the rate of wound complications in this population.

METHODS: A retrospective review of surgical databases at three National Cancer Institute (NCI)-designated cancer centers identified 287 patients with a total of 336 impending or pathologic long-bone fractures that were stabilized with intramedullary nailing between February 2001 and April 2013. Statistical analysis was performed utilizing multivariable logistic regression and Fisher …

Gm1 Ganglioside In Parkinson's Disease: Pilot Study Of Effects On Dopamine Transporter Binding., Jay S. Schneider, Franca Cambi, Stephen M. Gollomp, Hiroto Kuwabara, James R. Brašić, Benjamin E. Leiby, Stephanie Sendek, Dean F. Wong

Department of Pharmacology and Experimental Therapeutics Faculty Papers

OBJECTIVE: GM1 ganglioside has been suggested as a treatment for Parkinson's disease (PD), potentially having symptomatic and disease modifying effects. The current pilot imaging study was performed to examine effects of GM1 on dopamine transporter binding, as a surrogate measure of disease progression, studied longitudinally.

METHODS: Positron emission tomography (PET) imaging data were obtained from a subset of subjects enrolled in a delayed start clinical trial of GM1 in PD [1]: 15 Early-start (ES) subjects, 14 Delayed-start (DS) subjects, and 11 Comparison (standard-of-care) subjects. Treatment subjects were studied over a 2.5 year period while Comparison subjects were studied over 2 …

A Prospective Highlight On Exosomal Nanoshuttles And Cancer Immunotherapy And Vaccination., Mohammad Rafi, Yadollah Omidi

Department of Neurology Faculty Papers

INTRODUCTION: Exosomes (EXOs) and ectosomes (ECTOs) are nanoscale membranous extracellular vesicles (EVs) derived from different cells mediating various cellular communications. EXOs are liberated based on the exocytosis of multivesicular bodies, while ECTOs are ubiquitously released from the plasma membranes.

METHODS: Here, in this paper, we go over the extracellular vesicular machineries and concisely highlight their clinical importance in solid tumors and their possible applications in cancer immunotherapy/vaccination.

RESULTS: In various types of cancers, these vesicles play central roles delivering cancer cell messages to the target cells, as a result both of them seem to provide a novel useful means for …

Dissecting Tumor Metabolic Heterogeneity: Telomerase And Large Cell Size Metabolically Define A Sub-Population Of Stem-Like, Mitochondrial-Rich, Cancer Cells., Rebecca Lamb, Bela Ozsvari, Gloria Bonuccelli, Duncan L Smith, Richard Pestell, Ubaldo E. Martinez-Outshoorn, Md, Robert B Clarke, Federica Sotgia, Michael P Lisanti

Kimmel Cancer Center Faculty Papers

Tumor cell metabolic heterogeneity is thought to contribute to tumor recurrence, distant metastasis and chemo-resistance in cancer patients, driving poor clinical outcome. To better understand tumor metabolic heterogeneity, here we used the MCF7 breast cancer line as a model system to metabolically fractionate a cancer cell population. First, MCF7 cells were stably transfected with an hTERT-promoter construct driving GFP expression, as a surrogate marker of telomerase transcriptional activity. To enrich for immortal stem-like cancer cells, MCF7 cells expressing the highest levels of GFP (top 5%) were then isolated by FACS analysis. Notably, hTERT-GFP(+) MCF7 cells were significantly more efficient at …

Chimeric Cells Of Maternal Origin Do Not Appear To Be Pathogenic In The Juvenile Idiopathic Inflammatory Myopathies Or Muscular Dystrophy., Carol M Artlett, Sihem Sassi-Gaha, Ronald C Ramos, Frederick W Miller, Lisa G Rider

Department of Medicine Faculty Papers

INTRODUCTION: Microchimeric cells have been studied for over a decade, with conflicting reports on their presence and role in autoimmune and other inflammatory diseases. To determine whether microchimeric cells were pathogenic or mediating tissue repair in inflammatory myopathies, we phenotyped and quantified microchimeric cells in juvenile idiopathic inflammatory myopathies (JIIM), muscular dystrophy (MD), and noninflammatory control muscle tissues.

METHOD: Fluorescence immunophenotyping for infiltrating cells with sequential fluorescence in situ hybridization was performed on muscle biopsies from ten patients with JIIM, nine with MD and ten controls.

RESULTS: Microchimeric cells were significantly increased in MD muscle (0.079 ± 0.024 microchimeric cells/mm(2) …

Role Of The Hospitalist And Maternal Fetal Medicine Physician In Obstetrical Inpatient Care., Lisa D. Levine, Jay Schulkin, Brian M. Mercer, Daniel O'Keeffe, Vincenzo Berghella, Thomas J. Garite

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: The objective of this study was to evaluate the role of hospitalists and Maternal Fetal Medicine (MFM) subspecialists in obstetrical inpatient care.

STUDY DESIGN: This electronic survey study was offered to members of the American College of Obstetrics & Gynecology (ACOG; n = 1,039) and the Society for Maternal-Fetal Medicine (SMFM; n = 1,813).

RESULTS: Overall, 607 (21%) respondents completed the survey. Overall, 35% reported that hospitalists provided care in at least one of their hospitals. Compared with ACOG respondents, a higher frequency of SMFM respondents reported comfort with hospitalists providing care for all women on labor and delivery …