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Metformin Clinical Trial In Hpv+ And Hpv- Head And Neck Squamous Cell Carcinoma: Impact On Cancer Cell Apoptosis And Immune Infiltrate., Joseph M. Curry, Jennifer Johnson, Mehri Mollaee, Patrick Tassone, Dev Amin, Alexander Knops, Diana Whitaker Menezes, My Mahoney, Andrew P. South, Ulrich Rodeck, Tingting Zhan, Larry A. Harshyne, Nancy Philp, Adam J. Luginbuhl, David Cognetti, Madalina Tuluc, Ubaldo E. Martinez-Outshoorn, MD 2018 Thomas Jefferson University

Metformin Clinical Trial In Hpv+ And Hpv- Head And Neck Squamous Cell Carcinoma: Impact On Cancer Cell Apoptosis And Immune Infiltrate., Joseph M. Curry, Jennifer Johnson, Mehri Mollaee, Patrick Tassone, Dev Amin, Alexander Knops, Diana Whitaker Menezes, My Mahoney, Andrew P. South, Ulrich Rodeck, Tingting Zhan, Larry A. Harshyne, Nancy Philp, Adam J. Luginbuhl, David Cognetti, Madalina Tuluc, Ubaldo E. Martinez-Outshoorn, Md

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Background: Metformin, an oral anti-hyperglycemic drug which inhibits mitochondrial complex I and oxidative phosphorylation has been reported to correlate with improved outcomes in head and neck squamous cell carcinoma (HNSCC) and other cancers. This effect is postulated to occur through disruption of tumor-driven metabolic and immune dysregulation in the tumor microenvironment (TME). We report new findings on the impact of metformin on the tumor and immune elements of the TME from a clinical trial of metformin in HNSCC. Methods: Human papilloma virus-(HPV-) tobacco+ mucosal HNSCC samples (n = 12) were compared to HPV+ oropharyngeal squamous cell carcinoma (OPSCC) samples (n ...


Biological Therapy In The Treatment Of Melanoma, Simona Roxana Georgescu, Mihaela Roxana Ioghen, Maria Isabela Sarbu, Alexandra-Florentina Ion, Ela Ghita, Cristina-Iulia Mitran, Madalina-Irina Mitran, Vasile Benea, Mircea Tampa 2018 Carol Davila University of Medicine and Pharmacy, Department of Dermatology and Venereology, Bucharest, Romania

Biological Therapy In The Treatment Of Melanoma, Simona Roxana Georgescu, Mihaela Roxana Ioghen, Maria Isabela Sarbu, Alexandra-Florentina Ion, Ela Ghita, Cristina-Iulia Mitran, Madalina-Irina Mitran, Vasile Benea, Mircea Tampa

Journal of Mind and Medical Sciences

Melanoma is one of the most aggressive tumors and its incidence is on the rise. The low rates of survival in metastatic melanoma has led to the development of new drugs for this type of patient, such as biological therapy which has shown remarkable results. This therapy is based on stimulation of the immune system to fight tumoral cells through: injection of cytokines with immunomodulatory properties (interleukin-2, alpha-interferon), vaccination with tumor antigens or immune cells that process tumor antigens, adoptive immunotherapy, inhibition of immune checkpoints (PD-1, CTLA-4), inhibition or stimulation of immune modulator molecules (OX-40, LAG-3), inhibition of signaling pathways ...


In Vitro Transport Of Methotrexate By Drosophila Multidrug Resistance-Associated Protein., Agnes Karasik, András Váradi, Flóra Szeri 2018 Hungarian Academy of Sciences

In Vitro Transport Of Methotrexate By Drosophila Multidrug Resistance-Associated Protein., Agnes Karasik, András Váradi, Flóra Szeri

Department of Dermatology and Cutaneous Biology Faculty Papers

Methotrexate (MTX) is a widely used chemotherapeutic agent, immune suppressant and antimalarial drug. It is a substrate of several human ABC proteins that confer multidrug resistance to cancer cells and determine compartmentalization of a wide range of physiological metabolites and endo or xenobiotics, by their primary active transport across biological membranes. The substrate specificity and tissue distribution of these promiscuous human ABC transporters show a high degree of redundancy, providing robustness to these key physiological and pharmacological processes, such as the elimination of toxins, e.g. methotrexate from the body. A similar network of proteins capable of transporting methotrexate has ...


Listeria Monocytogenes As A Vector For Cancer Immunotherapy: Current Understanding And Progress, John C. Flickinger, Ulrich Rodeck, Adam E. Snook 2018 Thomas Jefferson University

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.


How Do Health Care Providers Identify And Address Lifestyle Factors With Community Dwelling Adults Who Have Chronic Wounds?, Linda Norton 2018 The University of Western Ontario

How Do Health Care Providers Identify And Address Lifestyle Factors With Community Dwelling Adults Who Have Chronic Wounds?, Linda Norton

Electronic Thesis and Dissertation Repository

Wound prevention and management best practice guidelines and literature contain recommendations that treatment plans need to consider the client’s lifestyle but offer little guidance about the specific lifestyle factors to be considered, nor how to address these. A post positivist constructivist grounded theory study was used to explore this gap Participants were health care providers with at least 5 years of experience working with community dwelling adults with chronic wounds. Data were transcripts of two semi structured individual interviews, a reflective journal, relevant documents identified by participants and transcripts of focus groups.

A common understanding of lifestyle factors was ...


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 2018 Queen Mary University of London

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 ...


Trametinib Prevents Mesothelial-Mesenchymal Transition And Ameliorates Abdominal Adhesion Formation, Edward J. Macarak, Christine Lotto, Deepika Koganti, Xiaoling Jin, Pete J. Wermuth, Anna-Karin Olsson, Matthew Montgomery, Joel Rosenbloom 2018 Thomas Jefferson University

Trametinib Prevents Mesothelial-Mesenchymal Transition And Ameliorates Abdominal Adhesion Formation, Edward J. Macarak, Christine Lotto, Deepika Koganti, Xiaoling Jin, Pete J. Wermuth, Anna-Karin Olsson, Matthew Montgomery, Joel Rosenbloom

Department of Dermatology and Cutaneous Biology Faculty Papers

Background

Intra-abdominal adhesions are a major cause of morbidity after abdominal or gynecologic surgery. However, knowledge about the pathogenic mechanism(s) is limited, and there are no effective treatments. Here, we investigated a mouse model of bowel adhesion formation and the effect(s) of an Federal Drug Administration-approved drug (trametinib) in preventing adhesion formation.

Materials and methods

C57BL/6 mice were used to develop a consistent model of intra-abdominal adhesion formation by gentle cecal abrasion with mortality rates ofEDA) which arises from alternative splicing of the fibronectin messenger RNA resulting in different protein isoforms. Trichrome staining assessed collagen deposition. Quantitative ...


Cadaveric Simulation For Improving Surgical Training In Dermatology., Ezra Hazan, Richard Torbeck, Deirdre Connolly, Jordan V. Wang, Thomas Griffin, Matthew Keller, Joshua Trufant 2018 Thomas Jefferson University

Cadaveric Simulation For Improving Surgical Training In Dermatology., Ezra Hazan, Richard Torbeck, Deirdre Connolly, Jordan V. Wang, Thomas Griffin, Matthew Keller, Joshua Trufant

Department of Dermatology and Cutaneous Biology Faculty Papers

Simulation models are rapidly changing medical education, especially the training of dermatology residents. Various models are available, including cadaveric simulations. Our study evaluates the impact of a cadaveric simulation on the training of dermatology residents. Over a period of three years, cadaveric simulation was shown to increase the surgical knowledge of residents. Residents were more confident in their knowledge of surgical anatomy and also surgical skills. Cadaveric simulation may offer a positive impact on resident training in dermatology.


Epidermodysplasia Verruciformis: Inborn Errors Of Immunity To Human Beta-Papillomaviruses, Sarah J. de Jong, Elias Imahorn, Peter Itin, Jouni Uitto, Gerard Orth, Emmanuelle Jouanguy, Jean-Laurent Casanova, Bettina Burger 2018 The Rockefeller University

Epidermodysplasia Verruciformis: Inborn Errors Of Immunity To Human Beta-Papillomaviruses, Sarah J. De Jong, Elias Imahorn, Peter Itin, Jouni Uitto, Gerard Orth, Emmanuelle Jouanguy, Jean-Laurent Casanova, Bettina Burger

Department of Dermatology and Cutaneous Biology Faculty Papers

Epidermodysplasia verruciformis (EV) is an autosomal recessive skin disorder with a phenotype conditional on human beta-papillomavirus (beta-HPV) infection. Such infections are common and asymptomatic in the general population, but in individuals with EV, they lead to the development of plane wart-like and red or brownish papules or pityriasis versicolor-like skin lesions, from childhood onwards. Most patients develop non-melanoma skin cancer (NMSC), mostly on areas of UV-exposed skin, from the twenties or thirties onwards. At least half of the cases of typical EV are caused by biallelic loss-of-function mutations of TMC6/EVER1 or TMC8/EVER2. The cellular and molecular basis of ...


Fas Ligand Promotes An Inducible Tlr-Dependent Model Of Cutaneous Lupus-Like Inflammation, Purvi Mande, Bahar Zirak, Wei-Che Ko, Keyon Taravati, Karen L. Bride, Tia Bumpus Brodeur, April C. Deng, Karen A. Dresser, Zhaozhao Jiang, Rachel Ettinger, Katherine A. Fitzgerald, Michael D. Rosenblum, John E. Harris, Ann Marshak-Rothstein 2018 University of Massachusetts Medical School

Fas Ligand Promotes An Inducible Tlr-Dependent Model Of Cutaneous Lupus-Like Inflammation, Purvi Mande, Bahar Zirak, Wei-Che Ko, Keyon Taravati, Karen L. Bride, Tia Bumpus Brodeur, April C. Deng, Karen A. Dresser, Zhaozhao Jiang, Rachel Ettinger, Katherine A. Fitzgerald, Michael D. Rosenblum, John E. Harris, Ann Marshak-Rothstein

University of Massachusetts Medical School Faculty Publications

Toll-like receptors TLR7 and TLR9 are both implicated in the activation of autoreactive B cells and other cell types associated with systemic lupus erythematosus (SLE) pathogenesis. However, Tlr9-/- autoimmune-prone strains paradoxically develop more severe disease. We have now leveraged the negative regulatory role of TLR9 to develop an inducible rapid-onset murine model of systemic autoimmunity that depends on T cell detection of a membrane-bound OVA fusion protein expressed by MHC class II+ cells, expression of TLR7, expression of the type I IFN receptor, and loss of expression of TLR9. These mice are distinguished by a high frequency of OVA-specific Tbet ...


Patient Acceptance Of Remote Scribing Powered By Google Glass In Outpatient Dermatology: Cross-Sectional Study, Sandra Odenheimer, Deepika Goyal, Veena Jones, Ruth Rosenblum, Lam Ho, Albert Chan 2018 Palo Alto Medical Foundation

Patient Acceptance Of Remote Scribing Powered By Google Glass In Outpatient Dermatology: Cross-Sectional Study, Sandra Odenheimer, Deepika Goyal, Veena Jones, Ruth Rosenblum, Lam Ho, Albert Chan

Faculty Publications

Background: The ubiquitous use of electronic health records (EHRs) during medical office visits using a computer monitor and keyboard can be distracting and can disrupt patient-health care provider (HCP) nonverbal eye contact cues, which are integral to effective communication. Provider use of a remote medical scribe with face-mounted technology (FMT), such as Google Glass, may preserve patient-HCP communication dynamics in health care settings by allowing providers to maintain direct eye contact with their patients while still having access to the patient’s relevant EHR information. The medical scribe is able to chart patient encounters in real-time working in an offsite ...


Lipoid Proteinosis: Unfamiliar Skin Findings Delay Diagnosis, S Larkin, Elizabeth K. Blixit 2018 Mayo Clinic School of Medicine, Rochester

Lipoid Proteinosis: Unfamiliar Skin Findings Delay Diagnosis, S Larkin, Elizabeth K. Blixit

Articles

Lipoid proteinosis (LP) is a rare, inherited condition that progresses gradually with multisystemic manifestations. Histopathologic characteristics can be understated, delaying the diagnosis if a high degree of suspicion is not present.


Patient Acceptance Of Remote Scribing Powered By Google Glass In Outpatient Dermatology: Cross-Sectional Study, Sandra Odenheimer, Deepika Goyal, Veena Goel Jones, Ruth K. Rosenblum, Lam Ho, Albert S. Chan 2018 Palo Alto Medical Foundation

Patient Acceptance Of Remote Scribing Powered By Google Glass In Outpatient Dermatology: Cross-Sectional Study, Sandra Odenheimer, Deepika Goyal, Veena Goel Jones, Ruth K. Rosenblum, Lam Ho, Albert S. Chan

Deepika Goyal

Background: The ubiquitous use of electronic health records (EHRs) during medical office visits using a computer monitor and keyboard can be distracting and can disrupt patient-health care provider (HCP) nonverbal eye contact cues, which are integral to effective communication. Provider use of a remote medical scribe with face-mounted technology (FMT), such as Google Glass, may preserve patient-HCP communication dynamics in health care settings by allowing providers to maintain direct eye contact with their patients while still having access to the patient’s relevant EHR information. The medical scribe is able to chart patient encounters in real-time working in an offsite ...


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 2018 Thomas Jefferson University; Tehran University of Medical Sciences

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 ...


Patient Perceptions Of Google Glass In The Outpatient Dermatology Setting, Sandra Odenheimer 2018 California State University, Northern California Consortium Doctor of Nursing Practice

Patient Perceptions Of Google Glass In The Outpatient Dermatology Setting, Sandra Odenheimer

Doctoral Projects

Background: The ubiquitous use of electronic health record (EHRs) during medical office visits using a computer monitor and keyboard can be distracting and disrupt patient-healthcare provider (HCP) non-verbal eye contact cues, which are integral to effective communication. Provider use of a remote medical scribe with face-mounted eyeglass technology, such as Google Glass (GG), may preserve patient-HCP communication in the healthcare setting by allowing providers to access other parts of the patient’s EHR (e.g. laboratory results, current medications, immunization records) all while maintaining direct eye contact with their patients. The medical scribe is able to chart patient encounters in ...


Dystrophic Calcifications Point The Way-Unusual And Early Diagnostic Clue Of Conradi-Hünermann-Happle Syndrome, Kenneth Yu, Alexander T. Reid, Stephanie J T Chen, Rajiv M. Patel, Steven M. Donn, Johann E. Gudjonsson, Lori Lowe 2018 University of Iowa

Dystrophic Calcifications Point The Way-Unusual And Early Diagnostic Clue Of Conradi-Hünermann-Happle Syndrome, Kenneth Yu, Alexander T. Reid, Stephanie J T Chen, Rajiv M. Patel, Steven M. Donn, Johann E. Gudjonsson, Lori Lowe

Stead Family Department of Pediatrics Publications

No abstract provided.


Invasive Trichosporonosis Treated With Voriconazole, Vaibhav Garg, Elizabeth Jones, Ben J. Friedman, Jason B. Lee, Sherry Yang 2018 Penn State University

Invasive Trichosporonosis Treated With Voriconazole, Vaibhav Garg, Elizabeth Jones, Ben J. Friedman, Jason B. Lee, Sherry Yang

Department of Dermatology and Cutaneous Biology Faculty Papers

Introduction

Trichosporon is a genus of yeast-like fungi. It is perhaps most widely known as the cause of white piedra, a benign superficial mycosis seen in immunocompetent individuals in tropical and subtropical regions. However, the incidence of invasive trichosporonosis has increased in immunocompromised patients, most notably those with hematologic malignancies. The following case illustrates characteristic features of trichosporonosis fungemia.


Periostin Antisense Oligonucleotide Suppresses Bleomycin-Induced Formation Of A Lung Premetastatic Niche For Melanoma, Takashi Semba, Eiji Sugihara, Nagisa Kamoshita, Sayaka Ueno, Keitaro Fukuda, Masafumi Yoshino, Kazumasa Takao, Kazunori Yoshikawa, Kenji Izuhara, Yoshimi Arima, Makoto Suzuki, Hideyuki Saya 2018 Keio University

Periostin Antisense Oligonucleotide Suppresses Bleomycin-Induced Formation Of A Lung Premetastatic Niche For Melanoma, Takashi Semba, Eiji Sugihara, Nagisa Kamoshita, Sayaka Ueno, Keitaro Fukuda, Masafumi Yoshino, Kazumasa Takao, Kazunori Yoshikawa, Kenji Izuhara, Yoshimi Arima, Makoto Suzuki, Hideyuki Saya

Open Access Articles

Metastasis is the leading cause of cancer death. A tumor-supportive microenvironment, or premetastatic niche, at potential secondary tumor sites plays an important role in metastasis, especially in tumor cell colonization. Although a fibrotic milieu is known to promote tumorigenesis and metastasis, the underlying molecular contributors to this effect have remained unclear. Here we show that periostin, a component of the extracellular matrix that functions in tissue remodeling, has a key role in formation of a fibrotic environment that promotes tumor metastatic colonization. We found that periostin was widely expressed in fibrotic lesions of mice with bleomycin-induced lung fibrosis, and that ...


Herpes Zoster Patient Education: A Coloring Book Approach, Sophia Charuhas 2018 Liberty University

Herpes Zoster Patient Education: A Coloring Book Approach, Sophia Charuhas

Senior Honors Theses

Shingles, the disease caused by the herpes zoster virus, is a widespread and widely misunderstood illness in the United States. It is preventable, but many at-risk patients do not know what measures they may take to prevent it. Clear communication from physician to patient is crucial for patient understanding of diseases. Many patient education materials on herpes zoster currently available are often unused. It is therefore beneficial to public health to disseminate new mediums of medical communication, and one way of accomplishing this is through adult coloring books. The pathophysiology of herpes zoster virus is here explored and the idea ...


Preclinical Comparison Of Proteasome And Ubiquitin E1 Enzyme Inhibitors In Cutaneous Squamous Cell Carcinoma: The Identification Of Mechanisms Of Differential Sensitivity, Angela McHugh, Kenneth Fernandes, Andrew P. South, Jemima E. Mellerio, Julio C. Salas-Alanis, Charlotte M. Proby, Irene M. Leigh, Mark K. Saville 2018 University of Dundee

Preclinical Comparison Of Proteasome And Ubiquitin E1 Enzyme Inhibitors In Cutaneous Squamous Cell Carcinoma: The Identification Of Mechanisms Of Differential Sensitivity, Angela Mchugh, Kenneth Fernandes, Andrew P. South, Jemima E. Mellerio, Julio C. Salas-Alanis, Charlotte M. Proby, Irene M. Leigh, Mark K. Saville

Department of Dermatology and Cutaneous Biology Faculty Papers

Proteasome inhibitors have distinct properties and the biochemical consequences of suppressing ubiquitin E1 enzymes and the proteasome differ. We compared the effects of the proteasome inhibitors bortezomib, ixazomib and carfilzomib and the ubiquitin E1 enzyme inhibitor MLN7243/TAK-243 on cell viability and cell death in normal keratinocytes and cutaneous squamous cell carcinoma (cSCC) cell lines. The effects of both a pulse of treatment and more extended incubation were investigated. This is relevant to directly-delivered therapy (topical treatment/intratumoral injection) where the time of exposure can be controlled and a short exposure may better reflect systemically-delivered inhibitor pharmacokinetics. These agents can ...


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