Medicine and Health Sciences Commons^™

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 …

Segment And Fit Thresholding: A New Method For Image Analysis Applied To Microarray And Immunofluorescence Data., Elliot Ensink, Jessica Sinha, Arkadeep Sinha, Huiyuan Tang, Heather M. Calderone, Galen Hostetter, Jordan M. Winter, David Cherba, Randall E. Brand, Peter J. Allen, Lorenzo F. Sempere, Brian B. Haab

Department of Surgery Faculty Papers

Experiments involving the high-throughput quantification of image data require algorithms for automation. A challenge in the development of such algorithms is to properly interpret signals over a broad range of image characteristics, without the need for manual adjustment of parameters. Here we present a new approach for locating signals in image data, called Segment and Fit Thresholding (SFT). The method assesses statistical characteristics of small segments of the image and determines the best-fit trends between the statistics. Based on the relationships, SFT identifies segments belonging to background regions; analyzes the background to determine optimal thresholds; and analyzes all segments to …

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 …

Autophosphorylation Of The Smk1 Mapk Is Spatially And Temporally Regulated By Ssp2 During Meiotic Development In Yeast., Chong Wai Tio, Gregory Omerza, Sham Sunder, Edward Winter

Department of Biochemistry and Molecular Biology Faculty Papers

Smk1 is a meiosis-specific MAPK that controls spore wall morphogenesis in Saccharomyces cerevisiae. Although Smk1 is activated by phosphorylation of the threonine (T) and tyrosine (Y) in its activation loop, it is not phosphorylated by a dual-specificity MAPK kinase. Instead, the T is phosphorylated by the cyclin-dependent kinase (CDK)-activating kinase, Cak1. The Y is autophosphorylated in an intramolecular reaction that requires a meiosis-specific protein named Ssp2. The meiosis-specific CDK-like kinase, Ime2, was previously shown to positively regulate Smk1. Here we show that Ime2 activity is required to induce the translation of SSP2 mRNA at anaphase II. Ssp2 protein is then …

Nurses Alumni Association Bulletin, Fall 2015, Susan Albrecht Curcio, Aileen Ishuin Macmillan, Ruth Huff Iuliano

Nursing Alumni Bulletins

2014 – 2015 Meeting Dates Calendar

2015 Annual Luncheon & Meeting Notice

Officers, Committee Chairs, Satellite and Volunteers

2015 President’s Message

Treasurer’s Financial Report

Resume of Minutes

Alumni Office News

Committee Reports

• Social
• Relief Trust Fund
• Satellite–Harrisburg Satellite Area
• Scholarship
• Nominating
• Bulletin
• By Laws

Jefferson Alumni Relations

125th Anniversary

Annual Giving Contributors

Janet C. Hindson Award

• Janet C. Hindson 2015 Award winner

News About Our Graduates

History of the Cap

Pearls of Wisdom

Happy Birthday – To Be 80 or More

Annual Luncheon

• 50th Anniversary Class List for 1965 – 2015 Luncheon
• 2015 Luncheon Attendees
• 50th Anniversary Class List for …

Jefferson Digital Commons Quarterly Report: July-September 2015,, Daniel G. Kipnis, Msi, Kelsey Duinkerken, Msi, James Copeland, Libt

Jefferson Digital Commons Reports

This quarterly report includes:

• Redesign update
• Enhanced reporting statistics
• New assets including:
• 20 yearbooks!
• Book chapters
• New batch of OT capstone presentations
• Assorted Grand Rounds
• New journal issues including The Medicine Forum and JHN
• New newsletters and much more
• What people are saying about the JDC

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.

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 …

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 …

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 …

Akt Kinase C-Terminal Modifications Control Activation Loop Dephosphorylation And Enhance Insulin Response., Tung O. Chan, Jin Zhang, Brian C. Tiegs, Brian Blumhof, Linda Yan, Nikhil Keny, Morgan Penny, Xue Li, John M. Pascal, Roger S. Armen, Ulrich Rodeck, Raymond B. Penn

Center for Translational Medicine Faculty Papers

The Akt protein kinase, also known as protein kinase B, plays key roles in insulin receptor signalling and regulates cell growth, survival and metabolism. Recently, we described a mechanism to enhance Akt phosphorylation that restricts access of cellular phosphatases to the Akt activation loop (Thr(308) in Akt1 or protein kinase B isoform alpha) in an ATP-dependent manner. In the present paper, we describe a distinct mechanism to control Thr(308) dephosphorylation and thus Akt deactivation that depends on intramolecular interactions of Akt C-terminal sequences with its kinase domain. Modifications of amino acids surrounding the Akt1 C-terminal mTORC2 (mammalian target of rapamycin …

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 …

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 …

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 …

Human Polyclonal Antibodies Produced Through Dna Vaccination Of Transchromosomal Cattle Provide Mice With Post-Exposure Protection Against Lethal Zaire And Sudan Ebolaviruses., Callie E Bounds, Steven A Kwilas, Ana I Kuehne, Jennifer M Brannan, Russell R Bakken, John M Dye, Jay W Hooper, Lesley C Dupuy, Barry Ellefsen, Drew Hannaman, Hua Wu, Jin-An Jiao, Eddie J Sullivan, Connie S Schmaljohn, Matthias J. Schnell

Department of Medicine Faculty Papers

DNA vaccination of transchromosomal bovines (TcBs) with DNA vaccines expressing the codon-optimized (co) glycoprotein (GP) genes of Ebola virus (EBOV) and Sudan virus (SUDV) produce fully human polyclonal antibodies (pAbs) that recognize both viruses and demonstrate robust neutralizing activity. Each TcB was vaccinated by intramuscular electroporation (IM-EP) a total of four times and at each administration received 10 mg of the EBOV-GPco DNA vaccine and 10 mg of the SUDV-GPco DNA vaccine at two sites on the left and right sides, respectively. After two vaccinations, robust antibody responses (titers > 1000) were detected by ELISA against whole irradiated EBOV or SUDV …

Accelerating Curriculum Design: "A Love It, Don't Leave It" Approach To Creative Process And Idealized Design, Mary Bouchaud, Phd, Rn, Angela Gerolamo, Phd, Aprn, Bcps, Beth Ann Swan, Phd, Crnp, Faan, Kathleen Black, Phd, Rnc, Karen Alexander, Msn, Rn, Ccrn, Jennifer L. Bellot, Phd, Mhsa, Cne, Denise Brown, Msn, Rnc, Susan Egger, Phd, Rn, Rachel Scherzer, Msn, Rn, Ccrn, Kathy Shaffer, Edd, Rn, Cne, Catherine Levonian, Phd, Rn, Dori Sullivan, Phd, Rn, Ne-Bc, Cphq, Faan

College of Nursing Posters

Purpose and Background:

The Institute of Medicine’s (IOM) report (2010) on the “Future of Nursing” emphasized the need for nurses to lead health care change. One of the key messages in this report is a call to action for nursing schools to re-envision nursing education that focuses on a population-based perspective and emerging roles for nurses across the care continuum. With an evolving focus on primary and community-based care rather than acute care, and recognition of the importance of coordinating care and managing transitions across providers and settings of care, registered nurses now and in the future will need to …

The Use Of Narrative Pedagogy And Unfolding Case “Ivan” To Promote Interprofessional Collaboration And Education Among Nursing And Radiology Students, Mary Bouchaud, Phd, Rn, Elizabeth Speakman, Edd, Rn, Anef, Fnap

College of Nursing Posters

Purpose:

Nursing students are unfamiliar with roles and responsibilities of their healthcare colleagues and how partnering with them can impact patient health outcomes. Many are unaware of how an interprofessional healthcare team contributes to preventing and resolving healthcare issues affecting care transition from tertiary settings back to the community. Case “Ivan” is a real lived experience that was shared to prepare nursing and allied health students for interprofessional, patient-centered care practice.

Poster presented at:

NLN Education Summit, 2015:Bridging Practice and Education, Las Vegas, Nevada, September 30, 2015-October 2, 2015.

Jefferson Center For Interprofessional Education (Jcipe), Christine A. Arenson, Md, Elizabeth T. Speakman, Edd, Rn, Anef, Fnap, Lauren Collins, Md, Shoshana Sicks, Med, Sarah Ballas, Ba, Abigail Sherburne, Bs, Catherine Mills

JCIPE Posters

Mission Statement

To promote excellence in healthcare through interprofessional education and scholarship.

Vision Statement

JCIPE will define the future of interprofessional care by creating a culture of collaborative educational practice, setting the standards for patient-centered care and team-based training, and becoming a national/international leader in developing an evidence-base to support interprofessional education.

Exercise And Hospitalized Leukemia Patients, Anne Delengowski, Rn, Msn, Aocn, Justine O'Connor, Rn, Msn, Ocn, Megan Stinsman, Rn, Bsn, Ocn, Kate Mchenry, Rn, Bsn, Ocn, Kaitlin Mostak, Rn, Bsn, Joann Silcox, Rn, Msn, Colleen Sweeney, Rn, Christine Muldoon, Rn, Bsn, Ocn, Lauren Gilbride, Rn, Bsn

Department of Nursing papers and presentations

Objective:

The purpose of this study was to determine if patients in a structured, monitored walking program experienced less symptom distress than patients receiving the usual standard of care during induction chemotherapy.

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 …

Isoform-Specific Dynamic Translocation Of Pkc By Α1-Adrenoceptor Stimulation In Live Cells., Jin O-Uchi, Jaime Sorenson, Bong Sook Jhun, Jyotsna Mishra, Stephen Hurst, Kaleef Williams, Shey-Shing Sheu, Coeli M.B. Lopes

Center for Translational Medicine Faculty Papers

Protein kinase C (PKC) plays key roles in the regulation of signal transduction and cellular function in various cell types. At least ten PKC isoforms have been identified and intracellular localization and trafficking of these individual isoforms are important for regulation of enzyme activity and substrate specificity. PKC can be activated downstream of Gq-protein coupled receptor (GqPCR) signaling and translocate to various cellular compartments including plasma membrane (PM). Recent reports suggested that different types of GqPCRs would activate different PKC isoforms (classic, novel and atypical PKCs) with different trafficking patterns. However, the knowledge of isoform-specific activation of PKC by each …

New Create Day Presentations In The Jdc, Daniel G. Kipnis, Msi

Jefferson Digital Commons News

Collaborative Research and Evidence Among Therapists and Educators (CREATE) Day is a clinical education program presented by occupational therapy graduate students in partial fulfillment of the Master of Science degree in Occupational Therapy at Thomas Jefferson University.

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.

Mir-497 Decreases Cisplatin Resistance In Ovarian Cancer Cells By Targeting Mtor/P70s6k1., Shaohua Xu, Guang-Bo Fu, Zhen Tao, Jun Ouyang, Fanfei Kong, Bing-Hua Jiang, Xiaoping Wan, Ke Chen

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The mechanism of cisplatin resistance in ovarian cancer is not clearly understood. In the present investigation, we found that the expression levels of miR-497 were reduced in chemotherapy-resistant ovarian cancer cells and tumor tissues due to hypermethylation of miR-497 promoter. Low miR-497 expression levels were associated with chemo-resistant phonotype of ovarian cancer. By analyzing the expression levels of miR-497, mTOR and p70S6K1 in a clinical gene-expression array dataset, we found that mTOR and p70S6K1, two proteins correlated to chemotherapy-resistance in multiple types of human cancers, were inversely correlated with miR-497 levels in ovarian cancer tissues. By using an orthotopic ovarian …