Medical Specialties Commons^™

Mir-196b Target Screen Reveals Mechanisms Maintaining Leukemia Stemness With Therapeutic Potential., Sara E. Meyer, David E. Muench, Andrew M. Rogers, Tess J. Newkold, Emily Orr, Eric O'Brien, John P. Perentesis, John G. Doench, Ashish Lal, Patrick J. Morris, Craig J. Thomas, Judy Lieberman, Edwina Mcglinn, Bruce J. Aronow, Nathan Salomonis, H. Leighton Grimes

Department of Cancer Biology Faculty Papers

We have shown that antagomiR inhibition of miRNA miR-21 and miR-196b activity is sufficient to ablate MLL-AF9 leukemia stem cells (LSC) in vivo. Here, we used an shRNA screening approach to mimic miRNA activity on experimentally verified miR-196b targets to identify functionally important and therapeutically relevant pathways downstream of oncogenic miRNA in MLL-r AML. We found Cdkn1b (p27^Kip1) is a direct miR-196b target whose repression enhanced an embryonic stem cell–like signature associated with decreased leukemia latency and increased numbers of leukemia stem cells in vivo. Conversely, elevation of p27^Kip1 significantly reduced MLL-r leukemia self-renewal, promoted monocytic differentiation …

Accuracy Of Height Estimation Among Bystanders, Sara Carey, Michaeleena Carr, Komaira Ferdous, Gina Marie Moffa, Jennifer Axelband, Shaila Quazi

Jefferson Health - Northeast Papers (formerly Aria Health Papers)

Introduction: High-risk mechanisms in trauma usually dictate certain treatment and evaluation in protocolized care. A 10-15 feet (ft) fall is traditionally cited as an example of a high-risk mechanism, triggering trauma team activations and costly work-ups. The height and other details of mechanism are usually reported by lay bystanders or prehospital personnel. This small observational study was designed to evaluate how accurate or inaccurate height estimation may be among typical bystanders. Methods: This was a blinded, prospective study conducted on the grounds of a community hospital. Four panels with lines corresponding to varying heights from 1-25 ft were hung within …

Listeria Monocytogenes As A Vector For Cancer Immunotherapy: Current Understanding And Progress, John C. Flickinger, Ulrich Rodeck, Adam E. Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Listeria monocytogenes, a Gram-positive facultative anaerobic bacterium, is becoming a popular vector for cancer immunotherapy. Indeed, multiple vaccines have been developed utilizing modified Listeria as a tool for generating immune responses against a variety of cancers. Moreover, over a dozen clinical trials testing Listeria cancer vaccines are currently underway, which will help to understand the utility of Listeria vaccines in cancer immunotherapy. This review aims to summarize current views on how Listeria-based vaccines induce potent antitumor immunity and the current state of Listeria-based cancer vaccines in clinical trials. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.

Ferritin Level Prospectively Predicts Hepatocarcinogenesis In Patients With Chronic Hepatitis B Virus Infection, Zhenyuan Bian, Hie-Won Hann, Zhong Ye, Chun Yin, Yang Wang, Wan Fang, Shaogui Wan, Chun Wang, Kaishan Tao

Department of Medical Oncology Faculty Papers

Previous studies have detected a higher level of ferritin in patients with hepatocellular carcinoma (HCC), but a potential causal association between serum ferritin level and hepatocarcinogenesis remains to be clarified. Using a well-established prospective cohort and longitudinally collected serial blood samples, the association between baseline ferritin levels and HCC risk were evaluated in 1,152 patients infected with hepatitis B virus (HBV), a major risk factor for HCC. The association was assessed by Cox proportional hazards regression model using univariate and multivariate analyses and longitudinal analysis. It was demonstrated that HBV patients who developed HCC had a significantly higher baseline ferritin …

Outcomes Of Shoulder Arthroplasty Performed For Postinfectious Arthritis., Eric M. Padegimas, Thema A. Nicholson, Stephen Silva, Matthew L. Ramsey, Gerald R. Williams, Mark D. Lazarus, Surena Namdari

Rothman Institute Papers

Background: The purpose of this study was to evaluate the functional outcomes, infection rate, and complications associated with shoulder arthroplasty for sequelae of prior septic arthritis.

Methods: This is a retrospective cohort study of 17 patients who underwent shoulder arthroplasty for sequelae of septic arthritis. Patients were analyzed for patient-reported outcomes, complications, and reoperations.

Results: The 17 patients in this cohort were an average age of 65.4 ± 12.2 years old, were 58.8% male, and had an average body mass index of 27.9 ± 4.1 kg/m

Conclusions: Shoulder arthroplasty after septic arthritis had inconsistent functional outcomes and high complication rates …

Evaluation Of The Sharkcore, Benjamin L. Witt, Rachel E. Factor, Barbara E. Chadwick, Justin Caron, Ali A. Siddiqui, Douglas G. Adler

Division of Gastroenterology and Hepatology Faculty Papers

Background and Objectives:

EUS guided core biopsy was once rarely performed but is now entering mainstream practice. Neuroendocrine tumors often warrant core biopsy as sufficient tissue must be obtained to allow for special staining to ensure a correct diagnosis. Traditionally these lesions were sampled with FNA needles. We performed a retrospective pilot study to evaluate the clinical value and efficacy of the a new EUS core needle biopsy needle as compared to a standard EUS FNA needle in the evaluation of patients with known or suspected neuroendocrine tumors.

Methods:

A retrospective analysis of the first 10 patients (between January 2015 …

Plasma Soluble Human Elastin Fragments As An Intra-Aneurysmal Localized Biomarker For Ruptured Intracranial Aneurysm, Daichi Nakagawa, Mario Zanaty, Joseph Hudson, Nahom Teferi, Daizo Ishii, Lauren Allan, Pascal Jabbour, Santiago Ortega-Gutierrez, Edgar A. Samaniego, David M. Hasan

Department of Neurosurgery Faculty Papers

Background—Fragmentation of the tunica media is a hallmark of intracranial aneurysm formation, often leading to aneurysmal progression and subsequent rupture. The objective of this study is to determine the plasma level of elastin fragments in the lumen of ruptured versus unruptured human intracranial aneurysms. Methods and Results—One hundred consecutive patients with/without ruptured saccular intracranial aneurysms undergoing endovascular coiling or stent-assisted coiling were recruited. Blood samples were collected from the lumen of intracranial aneurysm using a microcatheter. The tip of the microcatheter was placed inside the aneurysm’s sac in close proximity to the inner wall of the dome. Plasma levels of …

A Narrative Review On Contrast-Enhanced Ultrasound In Aortic Endograft Endoleak Surveillance., Sriharsha Gummadi, John R. Eisenbrey, Andrej Lyshchik

Department of Radiology Faculty Papers

Endovascular repair of abdominal aortic aneurysms have been performed successfully since 1991. However, 20% to 50% of these patients may develop an endoleak or continued aneurysmal sac expansion or perfusion despite stent graft coverage. Current recommendations suggest lifelong surveillance with computed tomographic angiography (CTA) at least 1 month after intervention and yearly after that. In select patients with a stable aneurysm sac on computed tomography performed 1 year after treatment, future screening could be performed with ultrasonography. However, color Doppler ultrasound can fail to detect as many as 31% of endoleaks. Contrast-enhanced ultrasound (CEUS) provides an alternative approach to excluded …

Pretty Peachy., Li-Anne Lim, Basil K. Williams, Carol L. Shields

Wills Eye Hospital Papers

No abstract provided.

Early Investigations And Recent Advances In Intraperitoneal Immunotherapy For Peritoneal Metastasis., Anusha Thadi, Marian Khalili, William F. Morano, Scott D. Richard, Steven C. Katz, Wilbur B. Bowne

Department of Obstetrics and Gynecology Faculty Papers

Peritoneal metastasis (PM) is an advanced stage malignancy largely refractory to modern therapy. Intraperitoneal (IP) immunotherapy offers a novel approach for the control of regional disease of the peritoneal cavity by breaking immune tolerance. These strategies include heightening T-cell response and vaccine induction of anti-cancer memory against tumor-associated antigens. Early investigations with chimeric antigen receptor T cells (CAR-T cells), vaccine-based therapies, dendritic cells (DCs) in combination with pro-inflammatory cytokines and natural killer cells (NKs), adoptive cell transfer, and immune checkpoint inhibitors represent significant advances in the treatment of PM. IP delivery of CAR-T cells has shown demonstrable suppression of tumors …

Procarbazine, Ccnu And Vincristine (Pcv) Versus Temozolomide Chemotherapy For Patients With Low-Grade Glioma: A Systematic Review., Karim Hafazalla, Arjun Sahgal, Blessing Jaja, James R Perry, Sunit Das

Student Papers, Posters & Projects

Low-grade gliomas (LGG) encompass a heterogeneous group of tumors that are clinically, histologically and molecularly diverse. Treatment decisions for patients with LGG are directed toward improving upon the natural history while limiting treatment-associated toxiceffects. Recent evidence has documented a utility for adjuvant chemotherapy with procarbazine, CCNU (lomustine), and vincristine (PCV) or temozolomide (TMZ). We sought to determine the comparative utility of PCV and TMZ for patients with LGG, particularly in context of molecular subtype. A literature search of PubMed was conducted to identify studies reporting patient response to PCV, TMZ, or a combination of chemotherapy and radiation therapy (RT). Eligibility …

Antiphosphatidylserine Antibody As A Cause Of Multiple Dural Venous Sinus Thromboses And St-Elevation Myocardial Infarction, Chelsea K. Varner, Caillin W. Marquardt, Peter V. Pickens

Student Papers, Posters & Projects

Objective: Rare disease Background: Antiphospholipid syndrome (APS) is an autoimmune disease characterized by antibodies directed against phos-pholipids on plasma membranes. Through unclear mechanisms, APS confers hypercoagulability. APS may cause recurrent thromboses in the arterial and venous vasculature. We report a case of primary APS resulting in cerebral venous thrombosis and ST-elevation myocardial infarction (STEMI) for which only antiphosphatidylserine (aPS) IgM antibody was positive after extensive investigation. Case Report: A 48-year-old male was admitted after a witnessed generalized seizure with subsequent confusion. Imaging demonstrated thrombosis of multiple central nervous system (CNS) sinuses, including the superior sagittal sinus and bilateral transverse sinuses. …

Hypoglycemic, Hypolipidemic And Antioxidant Effects Of Iridoid Glycosides Extracted From: Corni Fructus: Possible Involvement Of The Pi3k-Akt/Pkb Signaling Pathway, Jiefang Kang, Chen Guo, Rodolfo Thome, Ning Yang, Yuan Zhang, Xing Li, Xiaoyan Cao

Department of Neurology Faculty Papers

Iridoid glycosides (CIG) are the major component of Corni fructus. In this work, we researched the antioxidative, hypoglycemic and lowering blood lipids effects of CIG on diabetic mice induced by a high-fat diet (HFD) and streptozotocin (STZ). Furthermore, to investigate the molecular mechanism of action, the phosphorylation and protein expression of phosphoinositide 3-kinase (PI3K) and its downstream proteins, such as insulin receptor (INSR), protein kinase B (Akt/PKB) and glucose transporter 4 (GLUT4) have been detected. The results showed that CIG significantly improved oral glucose tolerance in diabetic mice. Biochemical indices also revealed that CIG had a positive effect on lipid …

Evaluation Of Hybrid Arc And Volumetric-Modulated Arc Therapy Treatment Plans For Fractionated Stereotactic Intracranial Radiotherapy., Jun Li, David To, Vickie Gunn, Wenyin Shi, Yan Yu, Haisong Lui

Department of Radiation Oncology Faculty Papers

PURPOSE: The study was aimed to compare hybrid arc and volumetric-modulated arc therapy treatment plans for fractionated stereotactic radiotherapy of brain tumors.

METHODS: Treatment plans of 22 patients were studied. Hybrid arc and volumetric-modulated arc therapy plans were generated using Brainlab iPlanDose and Varian Eclipse treatment planning systems, respectively, with 6 MV photon beams on a Varian TrueBeam STx linear accelerator (Palo Alto, CA). Prescription dose was 54 Gy. The fractionation was 1.8 Gy per fraction and 30 fractions in total, or 2 Gy per fraction and 27 fractions in total. Planning target volume ranged from 2.4 to 28.6 cm …

Monocarboxylate Transporter 4 (Mct4) Knockout Mice Have Attenuated 4nqo Induced Carcinogenesis; A Role For Mct4 In Driving Oral Squamous Cell Cancer., Sara Bisetto, Diana Whitaker Menezes, Nicole A. Wilski, Madalina Tuluc, Joseph Curry, Tingting Zhan, Christopher M. Snyder, Ubaldo E. Martinez-Outshoorn, Nancy J. Philp

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common human cancer and affects approximately 50,000 new patients every year in the US. The major risk factors for HNSCC are tobacco and alcohol consumption as well as oncogenic HPV infections. Despite advances in therapy, the overall survival rate for all-comers is only 50%. Understanding the biology of HNSCC is crucial to identifying new biomarkers, implementing early diagnostic approaches and developing novel therapies. As in several other cancers, HNSCC expresses elevated levels of MCT4, a member of the SLC16 family of monocarboxylate transporters. MCT4 is a H⁺-linked …

Metformin As A Therapeutic Target In Endometrial Cancers., Teresa Lee, Ubaldo E. Martinez-Outshoorn, Russell J. Schilder, Christine H. Kim, Scott D. Richard, Norman G. Rosenblum, Jennifer Johnson

Department of Medical Oncology Faculty Papers

Endometrial cancer is the most common gynecologic malignancy in developed countries. Its increasing incidence is thought to be related in part to the rise of metabolic syndrome, which has been shown to be a risk factor for the development of hyperestrogenic and hyperinsulinemic states. This has consequently lead to an increase in other hormone-responsive cancers as well e.g., breast and ovarian cancer. The correlation between obesity, hyperglycemia, and endometrial cancer has highlighted the important role of metabolism in cancer establishment and persistence. Tumor-mediated reprogramming of the microenvironment and macroenvironment can range from induction of cytokines and growth factors to stimulation …

Chronically Implanted Intracranial Electrodes: Tissue Reaction And Electrical Changes., Andrew Campbell, Chengyuan Wu

Department of Neurosurgery Faculty Papers

The brain-electrode interface is arguably one of the most important areas of study in neuroscience today. A stronger foundation in this topic will allow us to probe the architecture of the brain in unprecedented functional detail and augment our ability to intervene in disease states. Over many years, significant progress has been made in this field, but some obstacles have remained elusive-notably preventing glial encapsulation and electrode degradation. In this review, we discuss the tissue response to electrode implantation on acute and chronic timescales, the electrical changes that occur in electrode systems over time, and strategies that are being investigated …

Lafora Disease Masquerading As Hepatic Dysfunction, Faisal Inayat, Waqas Ullah, Hanan T. Lodhi, Zarak H. Khan, Ghulam Ilyas, Nouman Safdar Ali, Hafez Mohammad A. Abdullah

Abington Jefferson Health Papers

Lafora disease is fatal intractable progressive myoclonic epilepsy. It is frequently characterized by epileptic seizures, difficulty walking, muscle spasms, and dementia in late childhood or adolescence. We chronicle here an unusual case of an asymptomatic young male soccer player who presented with elevated liver enzymes. Neurological examination was unremarkable. The diagnostic workup for hepatitis, infectious etiologies, autoimmune disorders, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, and other related diseases was inconclusive. He subsequently underwent an uneventful percutaneous liver biopsy. Based on the pathognomonic histopathological findings, Lafora disease was considered the likely etiology. The present study is a unique illustration of this …

Examining Relationships Between Age At Diagnosis And Health-Related Quality Of Life Outcomes In Prostate Cancer Survivors., Christine J. Kurian, Amy Leader, Melissa S.Y. Thong, Scott W. Keith, Charnita Zeigler-Johnson

Department of Medical Oncology Faculty Papers

BACKGROUND: Patient reports of health related quality of life can provide important information about the long-term impact of prostate cancer. Because patient symptoms and function can differ by age of the survivor, the aim of our study was to examine patient-reported quality of life and prostate symptoms by age at diagnosis among a registry of Dutch prostate cancer survivors.

METHODS: A population of 617 individuals from the Patient Reported Outcomes Following Initial Treatment and Long-Term Evaluation of Survivorship (PROFILES) database was surveyed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) and prostate symptom …

Consecutive Case Series Of Melanoma Sentinel Node Biopsy For Lymphoseek Compared To Sulfur Colloids, Caitlin Silvestri, Adrienne Christopher, Md, Charles Intenzo, Md, John C. Kairys, Md, Sung Kim, Md, Alliric Willis, Md, Adam C. Berger, Md

Department of Surgery Faculty Papers

Introduction: Sentinel lymph node biopsy (SLNB) is an important adjunct in the staging of patients with melanoma. Preoperative lymphoscintigraphy (LS) with radiolabeled isotopes is essential to localize sentinel nodes for removal. Our study compared the effectiveness of Lymphoseek to standard sulfur colloids (SC) in patients with melanoma undergoing SLNB.

Methods: We queried our IRB-approved melanoma database to identify 370 consecutive patients who underwent SLNB from 2012-2016 with at least one year of follow up. There were 185 patients in each group. Data points included characteristics of the primary melanoma lymphoscintigraphy, and SLNB. Student’s t-test and Chi-Square were used to analyze …

Lacrimal Gland Tumors In Turkey: Types, Frequency, And Outcomes., Yağmur Seda Yeşiltaş, Ahmet Kaan Gündüz, Esra Erden, Carol L. Shields

Wills Eye Hospital Papers

AIM: To evaluate the clinical, radiological, and treatment features of lacrimal gland tumors.

METHODS: Retrospective review of 99 eyes of 92 patients with lacrimal gland tumors diagnosed and managed in a single institution between January 1999 and March 2017. Clinical and radiological features, histopathology, treatment methods, and prognosis were evaluated.

RESULTS: The mean patient age was 40.3 (range: 7-80)y. The diagnosis was made histopathologically in 91 (91.9%) tumors and on a clinical and radiological basis in 8 (8.1%) tumors. Final diagnoses included idiopathic orbital inflammation (pseudotumor) in 46 (46.5%) lesions, pleomorphic adenoma in 14 (14.1%), adenoid cystic carcinoma in 12 …

Development And Validation Of A Prostate Cancer Genomic Signature That Predicts Early Adt Treatment Response Following Radical Prostatectomy., R. Jeffrey Karnes, Vidit Sharma, Voleak Choeurng, Hussam Al-Deen Ashab, Nicholas Erho, Mohammed Alshalalfa, Bruce Trock, Ashley Ross, Kasra Yousefi, Harrison Tsai, Shuang G. Zhao, Jeffrey J. Tosoian, Zaid Haddad, Mandeep Takhar, S. Laura Chang, Daniel E. Spratt, Firas Abdollah, Robert B. Jenkins, Eric A. Klein, Paul L. Nguyen, Adam P. Dicker, Robert B. Den, Elai Davicioni, Felix Y. Feng, Tamara L. Lotan, Edward M. Schaeffer

Department of Radiation Oncology Faculty Papers

Purpose: Currently, no genomic signature exists to distinguish men most likely to progress on adjuvant androgen deprivation therapy (ADT) after radical prostatectomy for high-risk prostate cancer. Here we develop and validate a gene expression signature to predict response to postoperative ADT.

Experimental Design: A training set consisting of 284 radical prostatectomy patients was established after 1:1 propensity score matching metastasis between adjuvant-ADT (a-ADT)-treated and no ADT–treated groups. An ADT Response Signature (ADT-RS) was identified from neuroendocrine and AR signaling–related genes. Two independent cohorts were used to form three separate data sets for validation (set I, n = 232; set II, …

The Role Of Human Papillomaviruses And Polyomaviruses In Braf-Inhibitor Induced Cutaneous Squamous Cell Carcinoma And Benign Squamoproliferative Lesions, Karin J. Purdie, Charlotte M. Proby, Hasan Rizvi, Heather Griffin, John Doorbar, Mary Sommerlad, Mariet C. Feltkamp, Els Van Der Meijden, Gareth J. Inman, Andrew P. South, Irene M. Leigh, Catherine A. Harwood

Department of Dermatology and Cutaneous Biology Faculty Papers

Background: Human papillomavirus (HPV) has long been proposed as a cofactor in the pathogenesis of cutaneous squamous cell carcinoma (cSCC). More recently, the striking clinico-pathological features of cSCCs that complicate treatment of metastatic melanoma with inhibitors targeting BRAF mutations (BRAFi) has prompted speculation concerning a pathogenic role for oncogenic viruses. Here, we investigate HPV and human polyomaviruses (HPyV) and correlate with clinical, histologic, and genetic features in BRAFi-associated cSCC. Materials and Methods: Patients receiving BRAFi treatment were recruited at Barts Health NHS Trust. HPV DNA was detected in microdissected frozen samples using reverse line probe technology and degenerate and nested …

Carnosol Modulates Th17 Cell Differentiation And Microglial Switch In Experimental Autoimmune Encephalomyelitis, Xing Li, Li Zhao, Juan-Juan Han, Fei Zhang, Shuai Liu, Lin Zhu, Zhe-Zhi Wang, Guang-Xian Zhang, Yuan Zhang

Department of Neurology Faculty Papers

Medicinal plants as a rich pool for developing novel small molecule therapeutic medicine have been used for thousands of years. Carnosol as a bioactive diterpene compound originated from Rosmarinus officinalis (Rosemary) and Salvia officinalis, herbs extensively applied in traditional medicine for the treatment of multiple autoimmune diseases (1). In this study, we investigated the therapeutic effects and molecule mechanism of carnosol in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Carnosol treatment significantly alleviated clinical development in the myelin oligodendrocyte glycoprotein (MOG35–55) peptide-induced EAE model, markedly decreased inflammatory cell infiltration into the central nervous system and reduced …

The Conceptual Relevance Of Assessment Measures In Patients With Mild/Mild-Moderate Alzheimer's Disease, Ann Hartry, Natalie V.J. Aldhouse, Tamara Al-Zubeidi, Myrlene Sanon, Richard G. Stefanacci, Sarah L. Knight

College of Population Health Faculty Papers

Introduction: This study aims to evaluate the conceptual relevance of four measures of disease activity in patients with mild/mild-moderate Alzheimer's disease (AD): (1) the Alzheimer's Disease Assessment Scale–Cognitive Subscale; (2) the Alzheimer's Disease Cooperative Study–Activities of Daily Living Inventory; (3) the Neuropsychiatry Inventory; and (4) the Dependence Scale. Methods: A conceptual model depicting patient experience of mild AD was developed via literature review; concepts were compared with the items of the four measures. Relevance of the concepts included in the four measures was evaluated by patients with mild AD in a survey and follow-up interviews. Results: The four measures assessed …

Modeling The Dynamics Of Human Liver Failure Post Liver Resection, Babita Verma, Pushpavanam Subramaniam, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Liver resection is an important clinical intervention to treat liver disease. Following liver resection, patients exhibit a wide range of outcomes including normal recovery, suppressed recovery, or liver failure, depending on the regenerative capacity of the remnant liver. The objective of this work is to study the distinct patient outcomes post hepatectomy and determine the processes that are accountable for liver failure. Our model based approach shows that cell death is one of the important processes but not the sole controlling process responsible for liver failure. Additionally, our simulations showed wide variation in the timescale of liver failure that is …

Gamification Of Hospital Utilization: Incorporating Cost-Consciousness In Daily Practices., Peter J Tomaselli, Dimitrios Papanagnou, Md, Jonathan E Karademos, Elizabeth Teixeira, Xiao Chi Zhang

Department of Emergency Medicine Faculty Papers

Healthcare costs in the United States have skyrocketed over the past decade, contributing to an estimated $750 billion in wasteful spending annually. Despite the demand to improve residency education on value-based, cost-conscious healthcare, there is no consensus on how to best teach this practice. Traditional lectures have failed to demonstrate enduring change in clinical practice patterns, provider attitudes, and reductions in hospital expenditures. We sought to evaluate whether gamification is an effective pedagogical tool to teach cost-consciousness to emergency medicine (EM) residents by creating a 60-minute interactive session based on the popular gameshow, the Price is Right. Costs and associated …

Endorepellin Remodels The Endothelial Transcriptome Toward A Pro-Autophagic And Pro-Mitophagic Gene Signature., Thomas Neill, Eva Andreuzzi, Zi-Xuan Wang, Stephen C. Peiper, Maurizo Mongiat, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Regulation of autophagy by proteolytically cleaved fragments of heparan sulfate proteoglycans is a novel and current research focus in tumor biology. Endorepellin is the C-terminal angiostatic fragment of the heparan sulfate proteoglycan perlecan and induces autophagy in endothelial cells. To further investigate this property, we used NanoString, a digital PCR platform for measuring pre-defined transcripts in biological samples to analyze a custom subset of 95 autophagy-related genes in human umbilical vein endothelial cells treated with ultrapure human recombinant endorepellin. We discovered an endorepellin-evoked pro-autophagic and pro-mitophagic gene expression signatures, which included two coordinately up-regulated mitochondrial-associated genes encoding the E3 ubiquitin …

Left Ventricular Pseudoaneurysm: An Overview Of Diagnosis And Management., Faisal Inayat, Ali Raza Ghani, Iqra Riaz, Nouman Safdar Ali, Usman Sarwar, Raphael Bonita, Hafeez Ul Hassan Virk

Abington Jefferson Health Papers

Left ventricular pseudoaneurysm is a rare but life-threatening disorder that is frequently reported secondary to myocardial infarction or cardiac surgery. In this article, we chronicle the case of a patient with no prior risk factors who presented with a 2-week history of nonexertional atypical left chest pain. Apical 2-chamber transthoracic echocardiography revealed an unexpected outpouching of basal inferoseptal wall of the left ventricle, which had a narrow neck and relatively wide apex. The patient was diagnosed with left ventricular pseudoaneurysm and medical therapy was initiated. He refused to undergo the surgical intervention and subsequently, he was discharged from the hospital …

Syntaphilin Ubiquitination Regulates Mitochondrial Dynamics And Tumor Cell Movements., Jae Ho Seo, Ekta Agarwal, Kelly G. Bryant, M. Cecilia Caino, Eui Tae Kim, Andrew V. Kossenkov, Hsin-Yao Tang, Lucia R. Languino, Dmitry I. Gabrilovich, Andrew R. Cohen, David W. Speicher, Dario C. Altieri

Department of Cancer Biology Faculty Papers

Syntaphilin (SNPH) inhibits the movement of mitochondria in tumor cells, preventing their accumulation at the cortical cytoskeleton and limiting the bioenergetics of cell motility and invasion. Although this may suppress metastasis, the regulation of the SNPH pathway is not well understood. Using a global proteomics screen, we show that SNPH associates with multiple regulators of ubiquitin-dependent responses and is ubiquitinated by the E3 ligase CHIP (or STUB1) on Lys111 and Lys153 in the microtubule-binding domain. SNPH ubiquitination did not result in protein degradation, but instead anchored SNPH on tubulin to inhibit mitochondrial motility and cycles of organelle fusion and fission, …