Medicine and Health Sciences Commons^™

Palina: A Phase Ii Safety Study Of Palbociclib In Combination With Letrozole Or Fulvestrant In African American Women With Hormone Receptor Positive Her2 Negative Advanced Breast Cancer, Filipa Lynce, Mervat Saleh, Ayesha Shajahan-Haq, Christopher Gallagher, Asma Dilawari, Olwen Hahn, Maysa Abu-Khalaf, Ling Cai, Paula Pohlmann, Mahsa Mohebtash, Lois Kamugisha, Claudine Isaacs

Department of Medical Oncology Faculty Papers

Palbociclib has been shown to be a highly effective therapy in hormone receptor positive metastatic breast cancer when used in combination with letrozole or fulvestrant. Grade 3/4 neutropenia is a common side effect although febrile neutropenia is relatively uncommon. Insufficient data exist to describe the hematological safety of palbociclib in African American women (AAW) known to have a high incidence of benign ethnic neutropenia (BEN). PALOMA 1, 2 and 3, the initial phase II/III studies that led to the U.S. Food and Drug Administration (FDA) approval of palbociclib in metastatic breast cancer, only included participants with baseline absolute neutrophil count …

A Systematic Review Of The Effects Of Handwriting Interventions On Adults With Parkinson’S Disease, J. Buchanan, W. Rybak, V. Stange, J. Wing, V. Yeh, L. Carvell

Student Papers, Posters & Projects

Occupational therapists working with this population have incorporated a variety of methods into their interventions in an attempt to facilitate greater ease and legibility in handwriting. These interventions include finemotor hand exercise programs, practice-based programs, and visual and auditory cueing (Bryant, Rintala, Lai, DeBakey & Protas, 2010). Improvement in handwriting skills can increase quality of life and independence, as well as decrease frustration, for those with PD (Collett et al., 2017). A systematic review of available research was completed in order to assess the efficacy of these interventions for both short and long-term outcomes. Eleven studies were identified as relevant …

Variability Of Extracorporeal Cardiopulmonary Resuscitation Utilization For Refractory Adult Out-Of-Hospital Cardiac Arrest: An International Survey Study., Patrick J. Coppler, Benjamin S. Abella, Clifton W. Callaway, Minjung Kathy Chae, Seung Pill Choi, Jonathan Elmer, Won Young Kim, Young-Min Kim, Michael Kurz, Joo Suk Oh, Joshua C. Reynolds, Jon C. Rittenberger, Kelly N. Sawyer, Chun Song Youn, Byung Kook Lee, David F. Gaieski

Department of Emergency Medicine Faculty Papers

Objective: A growing interest in extracorporeal cardiopulmonary resuscitation (ECPR) as a rescue strategy for refractory adult out-of-hospital cardiac arrest (OHCA) currently exists. This study aims to determine current standards of care and practice variation for ECPR patients in the USA and Korea.

Methods: In December 2015, we surveyed centers from the Korean Hypothermia Network (KORHN) Investigators and the US National Post-Arrest Research Consortium (NPARC) on current targeted temperature management and ECPR practices. This project analyzes the subsection of questions addressing ECPR practices. We summarized survey.

Results: Overall, 9 KORHN and 4 NPARC centers reported having ECPR programs and had complete …

Triad3a Induces The Degradation Of Early Necrosome To Limit Ripk1-Dependent Cytokine Production And Necroptosis., Norah A. Alturki, Scott Mccomb, Ardeshir Ariana, Dikchha Rijal, Robert G. Korneluk, Shao-Cong Sun, Emad S Alnemri, Subash Sad

Department of Biochemistry and Molecular Biology Faculty Papers

Understanding the molecular signaling in programmed cell death is vital to a practical understanding of inflammation and immune cell function. Here we identify a previously unrecognized mechanism that functions to downregulate the necrosome, a central signaling complex involved in inflammation and necroptosis. We show that RipK1 associates with RipK3 in an early necrosome, independent of RipK3 phosphorylation and MLKL-induced necroptotic death. We find that formation of the early necrosome activates K48-ubiquitin-dependent proteasomal degradation of RipK1, Caspase-8, and other necrosomal proteins. Our results reveal that the E3-ubiquitin ligase Triad3a promotes this negative feedback loop independently of typical RipK1 ubiquitin editing enzymes, …

Competency-Based Assessment For The Training Of Phd Students And Early-Career Scientists., Michael F. Verderame, Victoria H. Freedman, Lisa M. Kozlowski, Wayne T. Mccormack

College of Life Sciences Faculty Papers

The training of PhD students and early-career scientists is largely an apprenticeship in which the trainee associates with an expert to become an independent scientist. But when is a PhD student ready to graduate, a postdoctoral scholar ready for an independent position, or an early-career scientist ready for advanced responsibilities? Research training by apprenticeship does not uniformly include a framework to assess if the trainee is equipped with the complex knowledge, skills and attitudes required to be a successful scientist in the 21st century. To address this problem, we propose competency-based assessment throughout the continuum of training to evaluate more …

The Mitochondrial Protease Htra2 Restricts The Nlrp3 And Aim2 Inflammasomes., Ian Gaël Rodrigue-Gervais, Karine Doiron, Claudia Champagne, Lindsey Mayes, Gabriel André Leiva-Torres, Paulin Vanié, Todd Douglas, Silvia M. Vidal, Emad S. Alnemri, Maya Saleh

Department of Biochemistry and Molecular Biology Faculty Papers

Activation of the inflammasome pathway is crucial for effective intracellular host defense. The mitochondrial network plays an important role in inflammasome regulation but the mechanisms linking mitochondrial homeostasis to attenuation of inflammasome activation are not fully understood. Here, we report that the Parkinson's disease-associated mitochondrial serine protease HtrA2 restricts the activation of ASC-dependent NLRP3 and AIM2 inflammasomes, in a protease activity-dependent manner. Consistently, disruption of the protease activity of HtrA2 results in exacerbated NLRP3 and AIM2 inflammasome responses in macrophages ex vivo and systemically in vivo. Mechanistically, we show that the HtrA2 protease activity regulates autophagy and controls the magnitude …

New Targets For Resolution Of Airway Remodeling In Obstructive Lung Diseases., Ajay P. Nayak, Deepak A. Deshpande, Raymond B. Penn

Center for Translational Medicine Faculty Papers

Airway remodeling (AR) is a progressive pathological feature of the obstructive lung diseases, including asthma and chronic obstructive pulmonary disease (COPD). The pathology manifests itself in the form of significant, progressive, and (to date) seemingly irreversible changes to distinct respiratory structural compartments. Consequently, AR correlates with disease severity and the gradual decline in pulmonary function associated with asthma and COPD. Although current asthma/COPD drugs manage airway contraction and inflammation, none of these effectively prevent or reverse features of AR. In this review, we provide a brief overview of the features and putative mechanisms affecting AR. We further discuss recently proposed …

First Results On Survival From A Large Phase 3 Clinical Trial Of An Autologous Dendritic Cell Vaccine In Newly Diagnosed Glioblastoma., Linda M. Liau, Keyoumars Ashkan, David D. Tran, Jian L. Campian, John E. Trusheim, Charles S. Cobbs, Jason A. Heth, Michael Salacz, Sarah Taylor, Stacy D. D'Andre, Fabio M. Iwamoto, Edward J. Dropcho, Yaron A. Moshel, Kevin A. Walter, Clement P. Pillainayagam, Robert Aiken, Rekha Chaudhary, Samuel A. Goldlust, Daniela A. Bota, Paul Duic, Jai Grewal, Heinrich Elinzano, Steven A. Toms, Kevin O. Lillehei, Tom Mikkelsen, Tobias Walbert, Steven R. Abram, Andrew J. Brenner, Steven Brem, Matthew G. Ewend, Simon Khagi, Jana Portnow, Lyndon J. Kim, William G. Loudon, Reid C. Thompson, David E Avigan, Karen L. Fink, Francois J. Geoffroy, Scott Lindhorst, Jose Lutzky, Andrew E. Sloan, Gabriele Schackert, Dietmar Krex, Hans-Jorg Meisel, Julian Wu, Raphael P Davis, Christopher Duma, Arnold B. Etame, David Mathieu, Santosh Kesari, David Piccioni, Manfred Westphal, David S. Baskin, Pamela Z. New, Michel Lacroix, Sven-Axel May, Timothy J. Pluard, Victor Tse, Richard M. Green, John L. Villano, Michael Pearlman, Kevin Petrecca, Michael Schulder, Lynne P Taylor, Anthony E. Maida, Robert M. Prins, Timothy F. Cloughesy, Paul Mulholland, Marnix L. Bosch

Department of Medical Oncology Faculty Papers

BACKGROUND: Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax

METHODS: After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS).

RESULTS: For the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months from surgery. Because of the cross-over trial design, nearly …

The Genetic Basis Of Hyaline Fibromatosis Syndrome In Patients From A Consanguineous Background: A Case Series., Leila Youssefian, Hassan Vahidnezhad, Andrew Touati, Vahid Ziaee, Amir Hossein Saeidian, Sara Pajouhanfar, Sirous Zeinali, Jouni Uitto

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Hyaline fibromatosis syndrome (HFS) is a rare heritable multi-systemic disorder with significant dermatologic manifestations. It is caused by mutations in ANTXR2, which encodes a transmembrane receptor involved in collagen VI regulation in the extracellular matrix. Over 40 mutations in the ANTXR2 gene have been associated with cases of HFS. Variable severity of the disorder in different patients has been proposed to be related to the specific mutations in these patients and their location within the gene.

CASE PRESENTATION: In this report, we describe four cases of HFS from consanguineous backgrounds. Genetic analysis identified a novel homozygous frameshift deletion c.969del …

A Curious Researcher's Guide On Successfully Publishing Scientific Manuscripts., Xiao Chi Zhang, Alexander H Tran, Dimitrios Papanagnou

Department of Emergency Medicine Faculty Papers

Publishing a manuscript in an academic journal represents more than just 'promotional currency.' It provides the opportunity to provoke debate, share your experiences, and challenge the status quo on provider practices. Writing a manuscript relies on collaboration and shared responsibility from a research team, which can often challenge mentors as they supervise and guide its development. While there are numerous online resources and peer-reviewed journal articles on 'How to write a scientific article,' we aim to tackle an even larger and overarching theme that transcends specific journal categories, writing styles, and citation formatting. In order to guide new researchers in …

Integrating A Behavioral Activation Approach Within Occupation-Based Intervention To Reduce Depression In Older Adults With Low Vision, Tracey Vause-Earland, Phd, Otr/L, Catherine Verrier Piersol, Phd, Otr/L, Faota

Department of Occupational Therapy Posters and Presentations

No abstract provided.

A Rare Case Of Diffuse Alveolar Hemorrhage Secondary To Dabigatran Successfully Treated With Extracorporeal Membrane Oxygenation, C. Hutchinson, F. M. West, H. Hirose

Department of Medicine Posters

Introduction

Dabigatran, a direct thrombin inhibitor, is used for stroke risk reduction in non-valvular atrial fibrillation and for treatment and prevention of venous thromboembolism. Minor side effects include indigestion and stomach pain. Major life threatening bleeding occurs in up to 2% of patients and is largely attributed to gastrointestinal hemorrhage. Here, we describe a case of a dabigatran related diffuse alveolar hemorrhage (DAH) treated successfully with extracorporeal membrane oxygenation.

Internet And Social Media Access Among Youth Experiencing Homelessness: Mixed-Methods Study., Lauren A. Houdek Vonholtz, Rosemary Frasso, Jesse M. Golinkoff, Alicia J. Lozano, Alexandra Hanlon, Nadia Dowshen

College of Population Health Faculty Papers

BACKGROUND: Youth experiencing homelessness are at a risk for a variety of adverse outcomes. Given the widespread use of the internet and social media, these new technologies may be used to address their needs and for outreach purposes. However, little is known about how this group uses these resources.

OBJECTIVE: This study investigated how homeless adolescents use these technologies for general and health-related purposes, whether the scope of their use changes with housing status, and their interest in a website dedicated to youth experiencing homelessness.

METHODS: A convenience sample of youth aged 18 to 21 years was recruited from a …

Antimicrobial Peptide Ll-37 And Recombinant Human Mannose-Binding Lectin Express Distinct Age- And Pathogen-Specific Antimicrobial Activity In Human Newborn Cord Blood In Vitro, Annette Scheid, Ning Li, Carleen Jeffers, Francesco Borriello, Sweta Joshi, Al Ozonoff, Matthew Pettengill, Ofer Levy

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: There is a need to prevent and treat infection in newborns. One approach is administration of antimicrobial proteins and peptides (APPs) such as LL-37, a membrane-active cathelicidin antimicrobial peptide, and mannose-binding lectin (MBL), a pattern-recognition protein that binds to microbial surface polysaccharides resulting in opsonization and complement activation. Low plasma/serum levels of LL-37 and of MBL have been correlated with infection and exogenous administration of these agents may enhance host defense. Methods: The antimicrobial activity of LL-37 (15 µg/ml) or rMBL (0.5, 2 and 10 µg/ml) was tested in hirudin-anticoagulated preterm and term human cord blood (N = 12-14) …

Iron Isomaltoside Is Superior To Iron Sucrose In Increasing Hemoglobin In Gynecological Patients With Iron Deficiency Anemia., Richard Derman, Eloy Roman, Gioi N. Smith-Nguyen, Maureen M. Achebe, Lars L. Thomsen, Michael Auerbach

Global Health Articles

No abstract provided.

Placement Of Lumen-Apposing Metal Stents To Drain Pseudocysts And Walled-Off Pancreatic Necrosis Can Be Safely Performed On An Outpatient Basis: A Multicenter Study, Douglas G. Adler, Janak Shah, Jose Nieto, Kenneth Binmoeller, Yasser Bhat, Linda Jo Taylor, Ali A. Siddiqui

Division of Gastroenterology and Hepatology Faculty Papers

Backgrounds and Objectives: No study on the use of lumen-apposing fully covered self-expanding metal stent (LAMS) to drain pancreatic fluid collections (PFCs) has evaluated outcomes of patients in the outpatient setting. The objective of this multicenter study was to evaluate the clinical outcomes, success rate, and adverse events of the LAMS for endoscopic ultrasound (EUS)-guided transmural drainage of patients with symptomatic PFCs on an inpatient versus an outpatient basis.

Methods: This was a multicenter, retrospective study conducted at 4 tertiary care centers. Results: We identified eighty patients with PFCs in whom EUS-guided transmural drainage using the LAMS was performed. The …

The Effect Of Diabetes Self-Management Education On Hba1c And Quality Of Life In African-Americans: A Systematic Review And Meta-Analysis., Amy T. Cunningham, Denine R. Crittendon, Neva White, Geoffrey D. Mills, Victor Diaz, Marianna Lanoue

Department of Family & Community Medicine Faculty Papers

BACKGROUND: Type 2 diabetes presents a major morbidity and mortality burden in the United States. Diabetes self-management education (DSME) is an intervention associated with improved hemoglobin A1c(HbA1c) and quality of life(QOL), and is recommended for all individuals with type 2 diabetes. African-Americans have disproportionate type 2 diabetes morbidity and mortality, yet no prior meta-analyses have examined DSME outcomes exclusively in this population. This systematic review and meta-analysis examined the impact of DSME on HbA1c and QOL in African-Americans compared to usual care.

METHODS: Randomized controlled trials, cluster-randomized trials, and quasi-experimental interventions were included. 352 citations were retrieved; 279 abstracts were …

Ice-Man Down: Using Simulation To Practice The Safe Extrication Of Collapsed Hockey Players In A Confined Space., Meryl Abrams, Dimitrios Papanagnou, Carlos Rodriguez, Joshua Rudner, Hyunjoo Lee, Simran Buttar, Ronald V Hall, Xiao Chi Zhang

Department of Emergency Medicine Faculty Papers

Sporting event emergencies are common among both spectators and players, with unique sets of challenges associated with patient extrication in unfamiliar and chaotic environments. It is critical for sports physicians and trainers to deliberately train and prepare for emergent situations with limited resources during athletic events. One of the most difficult, yet commonly encountered challenges is determining when and how to safely remove an injured player's helmet and sporting equipment, particularly if a spinal injury is highly suspected. We created a high-fidelity simulation case to practice the safe extrication of a hockey player who collapses on the bench in the …

Mindfulness Meditation Targets Transdiagnostic Symptoms Implicated In Stress-Related Disorders: Understanding Relationships Between Changes In Mindfulness, Sleep Quality, And Physical Symptoms., Jeffrey M. Greeson, Haley Zarrin, Moria J. Smoski, Jeffrey G. Brantley, Thomas R. Lynch, Daniel M. Webber, Martica H. Hall, Edward C. Suarez, Ruth Q. Wolever

Student Papers, Posters & Projects

Mindfulness-Based Stress Reduction (MBSR) is an 8-week meditation program known to improve anxiety, depression, and psychological well-being. Other health-related effects, such as sleep quality, are less well established, as are the psychological processes associated with therapeutic change. This prospective, observational study (

Extragenital Blaschkoid Lichen Sclerosus Et Atrophicus In A Child, Christian A. Albornoz, Jordan Wang, Sherry Yang

Department of Dermatology and Cutaneous Biology Faculty Papers

Lichen sclerosus et atrophicus is a chronic inflammatory skin disease that typically affects prepubertal girls and peri- or post-menopausal women in genital and perineal areas. In some cases, it can also manifest as extragenital lesions. Extragenital Blaschkoid lesions have infrequently been reported. Here, we report a case of extragenital Blaschkoid lichen sclerosus et atrophicus in a child.

Regional Microglia Are Transcriptionally Distinct But Similarly Exacerbate Neurodegeneration In A Culture Model Of Parkinson's Disease., Eric Wildon Kostuk, Jingli Cai, Lorraine Iacovitti

Department of Neuroscience Faculty Papers

BACKGROUND: Parkinson's disease (PD) is characterized by selective degeneration of dopaminergic (DA) neurons of the substantia nigra pars compacta (SN) while neighboring ventral tegmental area (VTA) DA neurons are relatively spared. Mechanisms underlying the selective protection of the VTA and susceptibility of the SN are still mostly unknown. Here, we demonstrate the importance of balance between astrocytes and microglia in the susceptibility of SN DA neurons to the PD mimetic toxin 1-methyl-4-phenylpyridinium (MPP

METHODS: Previously established methods were used to isolate astrocytes and microglia from the cortex (CTX), SN, and VTA, as well as embryonic midbrain DA neurons from the …

Dna Checkpoint And Repair Factors Are Nuclear Sensors For Intracellular Organelle Stresses-Inflammations And Cancers Can Have High Genomic Risks., Huihong Zeng, Gayani K Nanayakkara, Ying Shao, Hangfei Fu, Yu Sun, Ramon Cueto, William Y Yang, Qian Yang, Haitao Sheng, Na Wu, Luqiao Wang, Wuping Yang, Hongping Chen, Lijian Shao, Jianxin Sun, Xuebin Qin, Joon Y. Park, Konstantinos Drosatos, Eric T. Choi, Qingxian Zhu, Hong Wang, Xiaofeng Yang

Department of Medicine Faculty Papers

Under inflammatory conditions, inflammatory cells release reactive oxygen species (ROS) and reactive nitrogen species (RNS) which cause DNA damage. If not appropriately repaired, DNA damage leads to gene mutations and genomic instability. DNA damage checkpoint factors (DDCF) and DNA damage repair factors (DDRF) play a vital role in maintaining genomic integrity. However, how DDCFs and DDRFs are modulated under physiological and pathological conditions are not fully known. We took an experimental database analysis to determine the expression of 26 DNA DD

Implementation Of An Evidence-Based Intervention To Improve The Wellbeing Of People With Dementia And Their Carers: Study Protocol For 'Care Of People With Dementia In Their Environments (Cope)' In The Australian Context., Lindy Clemson, Kate Laver, Yun-Hee Jeon, Tracy A. Comans, Justin Scanlan, Miia Rahja, Jennifer Culph, Lee-Fay Low, Sally Day, Monica Cations, Maria Crotty, Susan Kurrle, Catherine V. Piersol, Laura N Gitlin

Department of Occupational Therapy Faculty Papers

BACKGROUND: There are effective non-pharmacological treatment programs that reduce functional disability and changed behaviours in people with dementia. However, these programs (such as the Care of People with dementia in their Environments (COPE) program) are not widely available. The primary aim of this study is to determine the strategies and processes that enable the COPE program to be implemented into existing dementia care services in Australia.

METHODS: This study uses a mixed methods approach to test an implementation strategy. The COPE intervention (up to ten consultations with an occupational therapist and up to two consultations with a nurse) will be …

Recurrent Hotspot Mutations In Hras Q61 And Pi3k-Akt Pathway Genes As Drivers Of Breast Adenomyoepitheliomas., Felipe C. Geyer, Anqi Li, Anastasios D. Papanastasiou, Alison Smith, Pier Selenica, Kathleen A. Burke, Marcia Edelweiss, Huei-Chi Wen, Salvatore Piscuoglio, Anne M. Schultheis, Luciano G. Martelotto, Fresia Pareja, Rahul Kumar, Alissa Brandes, Dan Fan, Thais Basili, Arnaud Da Cruz Paula, John R. Lozada, Pedro Blecua, Simone Muenst, Achim A. Jungbluth, Maria P. Foschini, Hannah Y. Wen, Edi Brogi, Juan P. Palazzo, Brian P. Rubin, Charlotte K.Y. Ng, Larry Norton, Zsuzsanna Varga, Ian O. Ellis, Emad A. Rakha, Sarat Chandarlapaty, Britta Weigelt, Jorge S. Reis-Filho

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Adenomyoepithelioma of the breast is a rare tumor characterized by epithelial-myoepithelial differentiation, whose genetic underpinning is largely unknown. Here we show through whole-exome and targeted massively parallel sequencing analysis that whilst estrogen receptor (ER)-positive adenomyoepitheliomas display PIK3CA or AKT1 activating mutations, ER-negative adenomyoepitheliomas harbor highly recurrent codon Q61 HRAS hotspot mutations, which co-occur with PIK3CA or PIK3R1 mutations. In two- and three-dimensional cell culture models, forced expression of HRAS

Ophthalmic Manifestations Of Heimler Syndrome Due To Pex6 Mutations., Nutsuchar Wangtiraumnuay, Waleed Abed Alnabi, Mai Tsukikawa, Avrey Thau, Jenina Capasso, Reuven Sharony, Chris F. Inglehearn, Alex V. Levin

Wills Eye Hospital Papers

BACKGROUND/AIMS: Pigmentary retinal dystrophy and macular dystrophy have been previously reported in Heimler syndrome due to mutations in PEX1. Here we reported the ocular manifestations in Heimler syndrome due to mutations in PEX6.

MATERIALS AND METHODS: Medical records were reviewed to identify patient demographics, ophthalmic and systemic findings, and results of diagnostic testing including whole genome sequencing.

RESULTS: Patient 1 is 12-year-old boy with a novel mutation c.275T>G (p.Val92Gly) and known mutation c.1802G>A (p.Arg601Gln) in PEX6. Patient 2 is a 7-year-old girl with the same known c.1802G>A (p.Arg601Gln) mutation and another novel missense mutation c.296G>T (p.Arg99Leu). …

Synchronous Gastric And Duodenal Metastases From Head And Neck Squamous Cell Carcinoma: A Unique Presentation Of Upper Gastrointestinal Bleeding., Nicholas P. Tarangelo, Charles Andrew Kistler, Zachary Daitch, Wei Jiang, Daniel M. Quirk

Department of Medicine Faculty Papers

Metastatic disease to the stomach or duodenum is an infrequent diagnosis, and head and neck squamous cell carcinoma (HNSCC) is one of the least common primary malignancies that lead to gastric or duodenal metastases. We report the case of a 65-year-old man with human immunodeficiency virus infection and previously diagnosed HNSCC who presented with melena. The patient had a percutaneous endoscopic gastrostomy tube placed 3 months prior to his presentation. Laboratory testing was significant for normocytic anemia and a digital rectal examination was positive for melena. Esophagogastroduodenoscopy revealed numerous cratered nodules with contact bleeding in the stomach as well as …

Abrogation Of Transforming Growth Factor-Β-Induced Tissue Fibrosis In Tbricacol1a2cre Transgenic Mice By The Second Generation Tyrosine Kinase Inhibitor Ski-606 (Bosutinib)., Peter J. Wermuth, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

Transforming growth factor-β (TGF-β) plays a crucial role in the pathogenesis of Systemic Sclerosis (SSc) and other fibrotic disorders. TGF-β-mediated c-Abl and Src kinase activation induces strong profibrotic cascade signaling. The purpose of this study was to test in vivo the antifibrotic activity of Bosutinib (SKI-606), a second generation c-Abl and Src kinase inhibitor, on TGF-β induced cutaneous and pulmonary fibrosis. For this purpose, we employed the TBRIcaCol1a2Cre transgenic mice expressing an inducible constitutively active TGF-β receptor 1 constitutively activated by Col1a promoter-mediated Cre recombinase. The mice were treated parenterally with 2.5, 5.0 or 10.0 mg/kg/day of Bosutinib for 42 …

The Comparison Of Spectral Domain Optical Coherence Tomography (Sd-Oct) To Histopathology In A Patient With Diffuse Macular Drusen, Harold Salmons, Ralph Eagle, Md

Department of Pathology Honors Program Student Research Symposium

Background: Spectral Domain Optical Coherence Tomography (SD-OCT) has become a gold standard technique in ophthalmologic practice, and has revolutionized the diagnosis and treatment of retinal disease. As SD-OCT uses low interference interferometry and mathematical algorithms to produce detailed theoretical cross-sectional images of the retina, it is crucial to examine correlations between SD-OCT images and their corresponding histopathologic slides.

Methods: In the present study, careful correlative light microscopy was performed on the eye that was enucleated from an elderly patient who had a uveal melanoma and early agerelated macular degeneration evident clinically as soft drusen. SD-OCT was performed prior to enucleation …

The Use Of Liquid Biopsy In The Fight Against Cancer, Chamaka Kalutota, Emanual Rubin, Md

Department of Pathology Honors Program Student Research Symposium

In recent years, liquid biopsy has emerged as a potential alternative/adjunct to standard tissue biopsy in the diagnosis of malignancies. Current use of this technique, which tracks distinctive molecules released from neoplastic cells including circulating tumor cells (CTCs), exosomes, circulating tumor DNA (ctDNA), cell-free DNA (cfDNA) and miRNA, has generally been limited to determining therapies in lung cancer based on detectable mutations (EFGR, EML4-ALK). However, recent studies have demonstrated the possibility for using these molecules as more efficient prognostic and diagnostic biomarkers in breast, colon, rectum, lung, liver, and pancreatic cancer. Due to the need for standardization in sampled material …

Genome Editing Technology, Crispr Cas-9, Provides A Potential Future For Xenotransplantation: Can Pigs Become Our New Organ Donors?, Shelby Smith, Bs, Emanual Rubin, Md

Department of Pathology Honors Program Student Research Symposium

Organ shortage has been a significant issue in United States for many decades. There were over 116,000 people on the transplant waiting list as of August 2017, with a new person added every 10 minutes. Animals have been considered as potential organ donors for humans, with the pig being the most ideal candidate because of its excellent breeding profile, low maintenance costs, large litters, rapid growth and organ similarity. A notable challenge that comes with porcine organs are endogenous retroviruses that establish themselves in the DNA of offspring in utero, thereby allowing for no time to prevent infection and integration. …