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Dermatology Commons

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2018

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Full-Text Articles in Dermatology

Agep Overlap Induced By Hydroxychloroquine: A Case Report And Literature Review., Christopher Mercogliano, Muhammad Khan, Catherine Lin, Elan Mohanty, Ryan Zimmerman Dec 2018

Agep Overlap Induced By Hydroxychloroquine: A Case Report And Literature Review., Christopher Mercogliano, Muhammad Khan, Catherine Lin, Elan Mohanty, Ryan Zimmerman

Reading Hospital Internal Medicine Residency

Acute Generalized Exanthematous Pustulosis (AGEP) is a rare drug reaction manifesting as pustular lesions with surrounding erythema following exposure. The disease is often self-limited and treatment is supportive. It may present in an atypical variant with vesicles that desquamate into erosions, which classifies the disease as an AGEP/SJS Overlap. This overlap syndrome can carry a substantial mortality rate and necessitate elevation in the level of care. Hydroxychloroquine has been implicated in cases of AGEP, and we present a case of AGEP/SJS overlap attributed to this common medication. Given the prevalence of drug eruptions, it is critical for the physicians to …


Impact Of Copper And Iron Binding Properties On The Anticancer Activity Of 8-Hydroxyquinoline Derived Mannich Bases., Veronika F.S. Pape, Nóra V. May, G. Tamás Gál, István Szatmári, Flóra Szeri, Ferenc Fülöp, Gergely Szakács, Éva A. Enyedy Dec 2018

Impact Of Copper And Iron Binding Properties On The Anticancer Activity Of 8-Hydroxyquinoline Derived Mannich Bases., Veronika F.S. Pape, Nóra V. May, G. Tamás Gál, István Szatmári, Flóra Szeri, Ferenc Fülöp, Gergely Szakács, Éva A. Enyedy

Department of Dermatology and Cutaneous Biology Faculty Papers

The anticancer activity of 8-hydroxyquinolines relies on complex formation with redox active copper and iron ions. Here we employ UV-visible spectrophotometry and EPR spectroscopy to compare proton dissociation and complex formation processes of the reference compound 8-hydroxyquinoline (Q-1) and three related Mannich bases to reveal possible correlations with biological activity. The studied derivatives harbor a CH2-N moiety at position 7 linked to morpholine (Q-2), piperidine (Q-3), and chlorine and fluorobenzylamino (Q-4) substituents. Solid phase structures of Q-3, Q-4·HCl·H2O, [(Cu(HQ-2)2)2]·(CH3OH)2·Cl4·(H2O)2, [Cu(Q-3)2]·Cl2 and [Cu(HQ-4)2(CH3OH)]·ZnCl4·CH3OH were characterized by single-crystal X-ray diffraction analysis. In addition, the redox properties of the copper and iron complexes …


Total Body Skin Exams: Sensitivity, Specificity, And Number Needed To Screen, Shayan Waseh, Michael Bui, Audra Hugo, Alexander Sherban, Elizabeth Jones, Md Dec 2018

Total Body Skin Exams: Sensitivity, Specificity, And Number Needed To Screen, Shayan Waseh, Michael Bui, Audra Hugo, Alexander Sherban, Elizabeth Jones, Md

Phase 1

Introduction: Skin cancer, the most common form of cancer worldwide, has one of the highest cure rates among cancers if diagnosed and treated early in its course. The Total Body Skin Exam (TBSE) is the primary modality used to screen for skin cancers. Currently, few studies have characterized the effectiveness of the TBSE in contemporary populations.

Objective: Characterizing the number-needed-to-screen (NNS) to diagnose a case of skin cancer through TBSEs will make it possible to better understand its effectiveness as a screening modality and its utility in an increasingly population health-based healthcare system.

Methods: A retrospective chart review of 3155 …


The Genomic Landscape Of Cutaneous Scc Reveals Drivers And A Novel Azathioprine Associated Mutational Signature., Gareth J. Inman, Jun Wang, Ai Nagano, Ludmil B. Alexandrov, Karin J. Purdie, Richard G. Taylor, Victoria Sherwood, Jason Thomson, Sarah Hogan, Lindsay C. Spender, Andrew P. South, Michael Stratton, Claude Chelala, Catherine A. Harwood, Charlotte M. Proby, Irene M. Leigh Dec 2018

The Genomic Landscape Of Cutaneous Scc Reveals Drivers And A Novel Azathioprine Associated Mutational Signature., Gareth J. Inman, Jun Wang, Ai Nagano, Ludmil B. Alexandrov, Karin J. Purdie, Richard G. Taylor, Victoria Sherwood, Jason Thomson, Sarah Hogan, Lindsay C. Spender, Andrew P. South, Michael Stratton, Claude Chelala, Catherine A. Harwood, Charlotte M. Proby, Irene M. Leigh

Department of Dermatology and Cutaneous Biology Faculty Papers

Cutaneous squamous cell carcinoma (cSCC) has a high tumour mutational burden (50 mutations per megabase DNA pair). Here, we combine whole-exome analyses from 40 primary cSCC tumours, comprising 20 well-differentiated and 20 moderately/poorly differentiated tumours, with accompanying clinical data from a longitudinal study of immunosuppressed and immunocompetent patients and integrate this analysis with independent gene expression studies. We identify commonly mutated genes, copy number changes and altered pathways and processes. Comparisons with tumour differentiation status suggest events which may drive disease progression. Mutational signature analysis reveals the presence of a novel signature (signature 32), whose incidence correlates with chronic exposure …


The Dermatologist And Color, Andrzej Grzybowski, Lawrence Charles Parish Dec 2018

The Dermatologist And Color, Andrzej Grzybowski, Lawrence Charles Parish

Department of Dermatology and Cutaneous Biology Faculty Papers

The idea for an issue on color and the skin was initiated by the 2017 exhibit “Breathing Color” that had been created by the new Design Museum in London, England. While variations in color may play a significant role in diagnosing a skin disease, little attention has been directed towards the influence that color may be used to identify a dermatologic disease and even monitor a therapeutic agent. The reader need only to recall how early dermatology atlases were hand colored to provide a more realistic picture of a disease.


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 Oct 2018

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 …


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

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 been …


The Human Cib1-Ever1-Ever2 Complex Governs Keratinocyte-Intrinsic Immunity To Β-Papillomaviruses., Sarah Jill De Jong, Amandine Créquer, Irina Matos, David Hum, Vignesh Gunasekharan, Lazaro Lorenzo, Fabienne Jabot-Hanin, Elias Imahorn, Andres A. Arias, Hassan Vahidnezhad, Leila Youssefian, Janet G. Markle, Etienne Patin, Aurelia D'Amico, Claire Q.F. Wang, Florian Full, Armin Ensser, Tina M. Leisner, Leslie V. Parise, Matthieu Bouaziz, Nataly Portilla Maya, Xavier Rueda Cadena, Bayaki Saka, Amir Hossein Saeidian, Nessa Aghazadeh, Sirous Zeinali, Peter Itin, James G. Krueger, Lou Laimins, Laurent Abel, Elaine Fuchs, Jouni Uitto, Jose Luis Franco, Bettina Burger, Gérard Orth, Emmanuelle Jouanguy, Jean-Laurent Casanova Sep 2018

The Human Cib1-Ever1-Ever2 Complex Governs Keratinocyte-Intrinsic Immunity To Β-Papillomaviruses., Sarah Jill De Jong, Amandine Créquer, Irina Matos, David Hum, Vignesh Gunasekharan, Lazaro Lorenzo, Fabienne Jabot-Hanin, Elias Imahorn, Andres A. Arias, Hassan Vahidnezhad, Leila Youssefian, Janet G. Markle, Etienne Patin, Aurelia D'Amico, Claire Q.F. Wang, Florian Full, Armin Ensser, Tina M. Leisner, Leslie V. Parise, Matthieu Bouaziz, Nataly Portilla Maya, Xavier Rueda Cadena, Bayaki Saka, Amir Hossein Saeidian, Nessa Aghazadeh, Sirous Zeinali, Peter Itin, James G. Krueger, Lou Laimins, Laurent Abel, Elaine Fuchs, Jouni Uitto, Jose Luis Franco, Bettina Burger, Gérard Orth, Emmanuelle Jouanguy, Jean-Laurent Casanova

Department of Dermatology and Cutaneous Biology Faculty Papers

Patients with epidermodysplasia verruciformis (EV) and biallelic null mutations of TMC6 (encoding EVER1) or TMC8 (EVER2) are selectively prone to disseminated skin lesions due to keratinocyte-tropic human β-papillomaviruses (β-HPVs), which lack E5 and E8. We describe EV patients homozygous for null mutations of the CIB1 gene encoding calcium- and integrin-binding protein-1 (CIB1). CIB1 is strongly expressed in the skin and cultured keratinocytes of controls but not in those of patients. CIB1 forms a complex with EVER1 and EVER2, and CIB1 proteins are not expressed in EVER1- or EVER2-deficient cells. The known functions of EVER1 and EVER2 in human keratinocytes are …


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

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.


Applying The Phenotype Approach For Rosacea To Practice And Research, J Tan, M Berg, R L Gallo, James Q. Del Rosso Sep 2018

Applying The Phenotype Approach For Rosacea To Practice And Research, J Tan, M Berg, R L Gallo, James Q. Del Rosso

College of Osteopathic Medicine (TUN) Publications and Research

BACKGROUND: Rosacea diagnosis and classification have evolved since the 2002 National Rosacea Society expert panel subtype approach. Several working groups are now aligned to a more patient-centric phenotype approach, based on an individual's presenting signs and symptoms. However, subtyping is still commonplace across the field and an integrated strategy is required to ensure widespread progression to the phenotype approach.

OBJECTIVES: To provide practical recommendations that facilitate adoption of a phenotype approach across the rosacea field.

METHODS: A review of the literature and consolidation of rosacea expert experience.

RESULTS: We identify challenges to implementing a phenotype approach in rosacea and offer …


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 Aug 2018

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 …


Dietary Recommendations For Adults With Psoriasis Or Psoriatic Arthritis From The Medical Board Of The National Psoriasis Foundation: A Systematic Review, Adam Ford, Michael Siegel, Jerry Bagel, Kelly M. Cordoro, Amit Garg, Alice Gottlieb, April W. Armstrong Aug 2018

Dietary Recommendations For Adults With Psoriasis Or Psoriatic Arthritis From The Medical Board Of The National Psoriasis Foundation: A Systematic Review, Adam Ford, Michael Siegel, Jerry Bagel, Kelly M. Cordoro, Amit Garg, Alice Gottlieb, April W. Armstrong

NYMC Faculty Publications

Importance: Psoriasis is a chronic, inflammatory skin disease and has significant associated morbidity and effect on quality of life. It is important to determine whether dietary interventions help reduce disease severity in patients with psoriatic diseases. Objective: To make evidence-based dietary recommendations for adults with psoriasis and/or psoriatic arthritis from the Medical Board of the National Psoriasis Foundation. Evidence Review: We used literature from prior systematic reviews as well as additional primary literature from the MEDLINE database from January 1, 2014, to August 31, 2017, that evaluated the impact of diet on psoriasis. We included observational and interventional studies of …


Psoriasiform Sarcoidosis Presenting In Pregnancy And Treatment Considerations, Christian A. Albornoz, Jordan Wang, Matthew Keller Jul 2018

Psoriasiform Sarcoidosis Presenting In Pregnancy And Treatment Considerations, Christian A. Albornoz, Jordan Wang, Matthew Keller

Department of Dermatology and Cutaneous Biology Faculty Papers

Cutaneous sarcoidosis is a common presentation for patients with sarcoidosis. Rarely, patients can present with psoriasiform lesions mimicking chronic plaque psoriasis. Here, we present a case of psoriasiform sarcoidosis in a pregnant patient. Pregnancy represents a unique challenge to systemic treatments if topical management fails. Tumor necrosis factor alpha inhibitors warrant special consideration during pregnancy.


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 Jul 2018

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 polymerase chain reaction …


Drug-Induced Dermatomyositis After Lacosamide: A Case Report., Rebecca G. Gaffney, Meera Tarazi, Victoria P. Werth Jul 2018

Drug-Induced Dermatomyositis After Lacosamide: A Case Report., Rebecca G. Gaffney, Meera Tarazi, Victoria P. Werth

Student Papers, Posters & Projects

Here we describe a caseof a woman who had DM after treatment withlacosamide. To our knowledge, drug-induced DMfrom lacosamide has not been reported previously.


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

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 Jun 2018

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 disease in …


Lipoid Proteinosis: Unfamiliar Skin Findings Delay Diagnosis, S Larkin, Elizabeth K. Blixit Jun 2018

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 Jones, Ruth Rosenblum, Lam Ho, Albert Chan Jun 2018

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 location, …


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 May 2018

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 …


Extragenital Blaschkoid Lichen Sclerosus Et Atrophicus In A Child, Christian A. Albornoz, Jordan Wang, Sherry Yang May 2018

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.


A Preexisting Rare Pik3ca E545k Subpopulation Confers Clinical Resistance To Mek Plus Cdk4/6 Inhibition In Nras Melanoma And Is Dependent On S6k1 Signaling, Gabriele Romano, Pei-Ling Chen, Ping Song, Jennifer L. Mcquade, Roger J. Liang, Mingguang Liu, Whijae Roh, Dzifa Y. Duose, Fernando C.L. Carapeto, Jun Li, Jessica L.F. Teh, Andrew A. Aplin, Merry Chen, Jianhua Zhang, Alexander J. Lazar, Michael A. Davies, P. Andrew Futreal, Rodabe N. Amaria, David Y. Zhang, Jennifer A. Wargo, Lawrence N. Kwong May 2018

A Preexisting Rare Pik3ca E545k Subpopulation Confers Clinical Resistance To Mek Plus Cdk4/6 Inhibition In Nras Melanoma And Is Dependent On S6k1 Signaling, Gabriele Romano, Pei-Ling Chen, Ping Song, Jennifer L. Mcquade, Roger J. Liang, Mingguang Liu, Whijae Roh, Dzifa Y. Duose, Fernando C.L. Carapeto, Jun Li, Jessica L.F. Teh, Andrew A. Aplin, Merry Chen, Jianhua Zhang, Alexander J. Lazar, Michael A. Davies, P. Andrew Futreal, Rodabe N. Amaria, David Y. Zhang, Jennifer A. Wargo, Lawrence N. Kwong

Department of Cancer Biology Faculty Papers

Combined MEK and CDK4/6 inhibition (MEKi + CDK4i) has shown promising clinical outcomes in patients with NRAS- mutant melanoma. Here, we interrogated longitudinal biopsies from a patient who initially responded to MEKi + CDK4i therapy but subsequently developed resistance. Whole-exome sequencing and functional validation identified an acquired PIK3CA E545K mutation as conferring drug resistance. We demonstrate that PIK3CA E545K preexisted in a rare subpopulation that was missed by both clinical and research testing, but was revealed upon multiregion sampling due to PIK3CA E545K being nonuniformly distributed. This resistant population rapidly expanded after the initiation of MEKi + CDK4i therapy and …


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

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.


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

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 Apr 2018

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 selectively kill …


Optimizing Visiting Clerkships In Dermatology: A Dual Perspective Approach., Jordan V. Wang, Kathleen P. Mcguinn, Matthew Keller Apr 2018

Optimizing Visiting Clerkships In Dermatology: A Dual Perspective Approach., Jordan V. Wang, Kathleen P. Mcguinn, Matthew Keller

Department of Dermatology and Cutaneous Biology Faculty Papers

Matching into a dermatology residency program has become increasingly more challenging for medical students. As students continue to explore various methods to help them standout to programs, recent medical literature has continued to show evidence of the important role that visiting clerkships play. Visiting clerkships offer several benefits to both students and programs. In order to optimize visiting clerkships, the perspectives of both students and programs are each examined with recommendations provided to help maximize its benefits.


Layout And Flow Of Dermatology Clinics: Principles From Operations Management., Jordan V. Wang Apr 2018

Layout And Flow Of Dermatology Clinics: Principles From Operations Management., Jordan V. Wang

Department of Dermatology and Cutaneous Biology Faculty Papers

Dermatology is a medical specialty that experiences high patient demand and long patient wait times. Dermatology clinics should look for ways to improve efficiency through the incorporation of principles from operations management. Addressing the layout and flow of a clinic can lead to operational efficiency. An ideal layout may lead to increased patient volume, satisfaction, and retention.


Optimizing Vaccine Immunotherapy For Prostate Cancer, G. Hattier, E. K. Bongiorno, C. Portocarrero, Trevor R. Baybutt, Adam E. Snook, U. Rodeck Apr 2018

Optimizing Vaccine Immunotherapy For Prostate Cancer, G. Hattier, E. K. Bongiorno, C. Portocarrero, Trevor R. Baybutt, Adam E. Snook, U. Rodeck

Sigma Xi Student Research Day

Introduction: Treatment options for metastatic prostate cancer are limited and cures are rare. In other cancers immunotherapy has shown remarkable efficacy in certain patient subsets particularly when combined with other treatment modalities. Our previous work showed that combining radiation and vaccine therapy slows the growth of syngeneic prostate cancer in mice more effectively than single modality treatment arms. Here we tested the hypothesis that addition of immune checkpoint inhibitors targeting the PD1/PD-L1 axis further improves efficacy of the dual radiation/vaccine treatment.

Methods: Mice were injected with tumor cells expressing human prostate specific antigen (TPSA-23). The mice were divided into six …


Gel Manicures And Ultraviolet A Light: A Call For Patient Education., Jordan V. Wang, Dorota Z. Korta, Christopher B. Zachary Mar 2018

Gel Manicures And Ultraviolet A Light: A Call For Patient Education., Jordan V. Wang, Dorota Z. Korta, Christopher B. Zachary

Department of Dermatology and Cutaneous Biology Faculty Papers

Gel manicures have become a popular beauty trend in recent years. The specially formulated nail polish must undergo curing under light-based units. The majority of these curing lamps emit high-intensity ultraviolet A, which can cause skin damage and increase the risk for skin cancers. Incorporating relevant information in patient education endeavors can help them practice avoidance, apply broad-spectrum sunscreen prior, or use nitrile exam gloves in order to prevent photoaging and skin cancer resulting from these procedures.


Randomized Phase Ii Trial Of Autologous Dendritic Cell Vaccines Versus Autologous Tumor Cell Vaccines In Metastatic Melanoma: 5-Year Follow Up And Additional Analyses., Robert O. Dillman, Andrew N Cornforth, Gabriel I Nistor, Edward F Mcclay, Thomas T Amatruda, Carol Depriest Mar 2018

Randomized Phase Ii Trial Of Autologous Dendritic Cell Vaccines Versus Autologous Tumor Cell Vaccines In Metastatic Melanoma: 5-Year Follow Up And Additional Analyses., Robert O. Dillman, Andrew N Cornforth, Gabriel I Nistor, Edward F Mcclay, Thomas T Amatruda, Carol Depriest

Articles, Abstracts, and Reports

BACKGROUND: Despite improved survival following checkpoint inhibitors, there is still a potential role for anti-cancer therapeutic vaccines. Because of biological heterogeneity and neoantigens resulting from each patient's mutanome, autologous tumor may be the best source of tumor-associated antigens (TAA) for vaccines. Ex vivo loading of autologous dendritic cells with TAA may be associated with superior clinical outcome compared to injecting irradiated autologous tumor cells. We conducted a randomized phase II trial to compare autologous tumor cell vaccines (TCV) and autologous dendritic cell vaccines (DCV) loaded with autologous TAA.

METHODS: Short-term autologous tumor cell lines were established from metastatic tumor. Vaccines …