Skin and Connective Tissue Diseases Commons^™

Antihypertensive Medications And Risk Of Melanoma And Keratinocyte Carcinomas: A Systematic Review And Meta-Analysis, Olivia G Cohen, Matthew Taylor, Cassandra Mohr, Kevin T Nead, Candice L Hinkston, Sharon H Giordano, Sinead M Langan, David J Margolis, Mackenzie R Wehner

Student and Faculty Publications

Some antihypertensive medications are photosensitizing. The implications for skin cancer risk remain unclear because results from prior studies are inconsistent and as new evidence is published. We performed a systematic review and meta-analysis to evaluate the association between antihypertensives and common skin cancers (cutaneous squamous cell carcinoma, basal cell carcinoma, and melanoma) and to evaluate dose-response relationships. Forty-four articles met inclusion criteria, and 42 could be meta analyzed. Increased risks were seen for basal cell carcinoma with calcium channel blockers (relative risk [RR] = 1.17, 95% confidence interval [CI] = 1.11-1.22), diuretics (RR = 1.06, 95% CI = 1.03-1.10), and …

Risk Of Developing Hypertension In Atopic Dermatitis Patients Receiving Long-Term And Low-Dose Cyclosporine: A Nationwide Population-Based Cohort Study, Yu Ri Woo, Arum Choi, Seo Won Song, Suyeun Kim, Sang Wook Son, Sang Hyun Cho, Sukil Kim, Jung Eun Kim

Student and Faculty Publications

BACKGROUND: Cyclosporine (CS) is a first-line immunosuppressive agent used to manage moderate to severe atopic dermatitis (AD). To date, the risk of developing hypertension associated with the long-term use of low-dose CS in AD patients is understudied.

OBJECTIVE: To determine the cumulative dose-dependent effect of CS on the risk of developing hypertension in patients with AD.

METHODS: A nationwide population-based retrospective cohort with 1,844,009 AD patients was built from the Korean National Health Insurance System database from 2005 to 2009. A Cox proportional-hazard regression analysis was performed according to patients' CS treatment history adjusted for potential confounders.

RESULTS: Current use …

Health Economic Consequences Associated With Covid-19-Related Delay In Melanoma Diagnosis In Europe, Lara V Maul, Dagmar Jamiolkowski, Rebecca A Lapides, Alina M Mueller, Axel Hauschild, Claus Garbe, Paul Lorigan, Jeffrey E Gershenwald, Paolo Antonio Ascierto, Georgina V Long, Michael Wang-Evers, Richard A Scolyer, Babak Saravi, Matthias Augustin, Alexander A Navarini, Stefan Legge, István B Németh, Ágnes J Jánosi, Simone Mocellin, Anita Feller, Dieter Manstein, Alexander Zink, Julia-Tatjana Maul, Alessandra Buja, Kaustubh Adhikari, Elisabeth Roider

Student and Faculty Publications

IMPORTANCE: The COVID-19 pandemic resulted in delayed access to medical care. Restrictions to health care specialists, staff shortages, and fear of SARS-CoV-2 infection led to interruptions in routine care, such as early melanoma detection; however, premature mortality and economic burden associated with this postponement have not been studied yet.

OBJECTIVE: To determine the premature mortality and economic costs associated with suspended melanoma screenings during COVID-19 pandemic lockdowns by estimating the total burden of delayed melanoma diagnoses for Europe.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter economic evaluation used population-based data from patients aged at least 18 years with invasive primary cutaneous …

Clinical Efficacy Of 5-Fluorouracil And Bleomycin In Dermatology, Suyeon Kim, Yu Ri Woo, Sang Hyun Cho, Jeong Deuk Lee, Hei Sung Kim

Student and Faculty Publications

Bleomycin and 5-fluorouracil (5-FU) are widely used in various dermatological disorders. Both drugs are well-recognized as antineoplastic drugs and exert their effect by blocking the cell cycle. Topical and intralesional formulations are available and have been studied in both non-neoplastic and cancerous lesions. However, data comparing the effect of bleomycin and 5-FU in the dermatological disorders are limited. This review outlines the action mechanisms of both drugs and compares their clinical efficacies in a wide range of dermatologic diseases including hypertrophic scar, wart, skin cancer, vascular malformation, hemangioma, and vitiligo, and discusses the overall safety of the drugs. Intralesional bleomycin …

Metformin: A Potential Treatment For Acne, Hidradenitis Suppurativa And Rosacea, Minah Cho, Yu Ri Woo, Sang Hyun Cho, Jeong Deuk Lee, Hei Sung Kim

Student and Faculty Publications

Metformin is a widely used drug for treatment of diabetes mellitus, due to its safety and efficacy. In addition to its role as an antidiabetic drug, numerous beneficial effects of metformin have enabled its use in various diseases. Considering the anti-androgenic, anti-angiogenic, anti-fibrotic and antioxidant properties of metformin, it may have the potential to improve chronic inflammatory skin diseases. However, further evidence is needed to confirm the efficacy of metformin in dermatological conditions, This review focuses on exploring the therapeutic targets of metformin in acne vulgaris, hidradenitis suppurativa and rosacea, by studying their pathogeneses.

Ccdc50 Promotes Tumor Growth Through Regulation Of Lysosome Homeostasis, Penghui Jia, Tian Tian, Zibo Li, Yicheng Wang, Yuxin Lin, Weijie Zeng, Yu Ye, Miao He, Xiangrong Ni, Ji'an Pan, Xiaonan Dong, Jian Huang, Chun-Mei Li, Deyin Guo, Panpan Hou

Student and Faculty Publications

The maintenance of lysosome homeostasis is crucial for cell growth. Lysosome-dependent degradation and metabolism sustain tumor cell survival. Here, we demonstrate that CCDC50 serves as a lysophagy receptor, promoting tumor progression and invasion by controlling lysosomal integrity and renewal. CCDC50 monitors lysosomal damage, recognizes galectin-3 and K63-linked polyubiquitination on damaged lysosomes, and specifically targets them for autophagy-dependent degradation. CCDC50 deficiency causes the accumulation of ruptured lysosomes, impaired autophagic flux, and superfluous reactive oxygen species, consequently leading to cell death and tumor suppression. CCDC50 expression is associated with malignancy, progression to metastasis, and poor overall survival in human melanoma. Targeting CCDC50 …

Gut Microbiome In Patients With Early-Stage And Late-Stage Melanoma, Russell G Witt, Samuel H Cass, Tiffaney Tran, Ashish Damania, Emelie E Nelson, Elizabeth Sirmans, Elizabeth M Burton, Manoj Chelvanambi, Sarah Johnson, Hussein A Tawbi, Jeffrey E Gershenwald, Michael A Davies, Christine Spencer, Aditya Mishra, Matthew C Wong, Nadim J Ajami, Christine B Peterson, Carrie R Daniel, Jennifer A Wargo, Jennifer L Mcquade, Kelly C Nelson

Student and Faculty Publications

IMPORTANCE: The gut microbiome modulates the immune system and responses to immunotherapy in patients with late-stage melanoma. It is unknown whether fecal microbiota profiles differ between healthy individuals and patients with melanoma or if microbiota profiles differ among patients with different stages of melanoma. Defining gut microbiota profiles in individuals without melanoma and those with early-stage and late-stage melanoma may reveal features associated with disease progression.

OBJECTIVE: To characterize and compare gut microbiota profiles between healthy volunteers and patients with melanoma and between patients with early-stage and late-stage melanoma.

DESIGN, SETTING, AND PARTICIPANTS: This single-site case-control study took place at …

Garetosmab In Fibrodysplasia Ossificans Progressiva: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial, Maja Di Rocco, Eduardo Forleo-Neto, Robert J Pignolo, Richard Keen, Philippe Orcel, Thomas Funck-Brentano, Christian Roux, Sami Kolta, Annalisa Madeo, Judith S Bubbear, Jacek Tabarkiewicz, Małgorzata Szczepanek, Javier Bachiller-Corral, Angela M Cheung, Kathryn M Dahir, Esmée Botman, Pieter G Raijmakers, Mona Al Mukaddam, Lianne Tile, Cynthia Portal-Celhay, Neena Sarkar, Peijie Hou, Bret J Musser, Anita Boyapati, Kusha Mohammadi, Scott J Mellis, Andrew J Rankin, Aris N Economides, Dinko Gonzalez Trotter, Gary A Herman, Sarah J O'Meara, Richard Delgizzi, David M Weinreich, George D Yancopoulos, E Marelise W Eekhoff, Frederick S Kaplan

Student and Faculty Publications

Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by heterotopic ossification (HO) in connective tissues and painful flare-ups. In the phase 2 LUMINA-1 trial, adult patients with FOP were randomized to garetosmab, an activin A-blocking antibody (n = 20) or placebo (n = 24) in period 1 (28 weeks), followed by an open-label period 2 (28 weeks; n = 43). The primary end points were safety and for period 1, the activity and size of HO lesions. All patients experienced at least one treatment-emergent adverse event during period 1, notably epistaxis, madarosis and skin abscesses. Five deaths …

Atopic Dermatitis And The Risk Of Myocardial Infarction And All-Cause Mortality: A Nationwide Population-Based Cohort Study, Yu Ri Woo, Minah Cho, Kyung Do Han, Sang Hyun Cho, Ji Hyun Lee

Student and Faculty Publications

PURPOSE: Atopic dermatitis (AD) is a chronic inflammatory skin disorder associated with various comorbidities. However, inconsistent results on the risk of myocardial infarction (MI) and mortality have been reported in patients with AD. This study was aimed to evaluate the risk of MI and all-cause mortality in patients with AD.

METHODS: This nationwide population-based retrospective cohort study enrolled 56,205 adults ≥ 20 years of age with AD and 3,825,609 controls without AD from the Korean National Health Service (NHIS) database from 2009 to 2016.

RESULTS: The risk of MI (adjusted hazard ratio [aHR], 1.111, 95% confidence interval [CI], 1.050-1.176) was …

Perspectives In Melanoma: Meeting Report From The Melanoma Bridge (December 1st–3rd, 2022-Naples, Italy), Paolo A Ascierto, Sanjiv S Agarwala, Allison Betof Warner, Marc S Ernstoff, Bernard A Fox, Thomas F Gajewski, Jérôme Galon, Claus Garbe, Brian R Gastman, Jeffrey E Gershenwald, Pawel Kalinski, Michelle Krogsgaard, Rom S Leidner, Roger S Lo, Alexander M Menzies, Olivier Michielin, Poulikos I Poulikakos, Jeffrey S Weber, Corrado Caracò, Iman Osman, Igor Puzanov, Magdalena Thurin

Student and Faculty Publications

Outcomes for patients with melanoma have improved over the past decade with the clinical development and approval of immunotherapies targeting immune checkpoint receptors such as programmed death-1 (PD-1), programmed death ligand 1 (PD-L1) or cytotoxic T lymphocyte antigen-4 (CTLA-4). Combinations of these checkpoint therapies with other agents are now being explored to improve outcomes and enhance benefit-risk profiles of treatment. Alternative inhibitory receptors have been identified that may be targeted for anti-tumor immune therapy, such as lymphocyte-activation gene-3 (LAG-3), as have several potential target oncogenes for molecularly targeted therapy, such as tyrosine kinase inhibitors. Unfortunately, many patients still progress and …

Presence Of Circulating Tumor Cells Predates Imaging Detection Of Relapse In Patients With Stage Iii Melanoma, Anthony Lucci, Sridevi Addanki, Yi-Ju Chiang, Salyna Meas, Vanessa N Sarli, Joshua R Upshaw, Mayank Manchem, Sapna P Patel, Jennifer A Wargo, Jeffrey E Gershenwald, Merrick I Ross

Student and Faculty Publications

Stage III melanoma includes nodal metastasis or in-transit disease. Five-year survival rates vary between 32% and 93%. The identification of high-risk patients is important for clinical decision making. We demonstrated previously that ≥1 circulating tumor cells (CTCs) at baseline was associated with recurrence. In this study, we investigated how frequently CTCs were identified prior to radiologically detected recurrence. Stage III patients (n = 325) had imaging at baseline and q 3 months. Baseline and q 6-12 months blood draws (7.5 mL) were performed to identify CTCs up to 3.5 years from diagnosis. CTC assessment was performed using the immunomagnetic …

Factors Affecting Treatment Adherence Among Leprosy Patients: Perceptions Of Healthcare Providers, Veincent Christian F Pepito, Arianna Maever Loreche, Rae Erica D Samontina, Sarah Jane A Abdon, David Norman L Fuentes, Ofelia P Saniel

Student and Faculty Publications

BACKGROUND: Treatment adherence is a vital aspect in the management of chronic diseases like leprosy; however, most studies on treatment adherence focus on patients. This study aims to examine the perceptions of healthcare providers on factors that can promote or prevent patients from adhering to treatment.

METHODS: We conducted three focus group discussions (FGDs) with healthcare providers who have at least one year experience in managing leprosy in three large leprosy case-holding hospitals in Metro Manila, Philippines. We audio-recorded, transcribed, translated the FGD proceedings, and analyzed the transcripts thematically to identify patient-intrinsic and patient-extrinsic enablers and barriers to treatment adherence …

Non-Melanoma Skin Cancer Detection In The Age Of Advanced Technology: A Review, Haleigh Stafford, Jane Buell, Elizabeth Chiang, Uma Ramesh, Michael Migden, Priyadharsini Nagarajan, Moran Amit, Dan Yaniv

Student and Faculty Publications

Skin cancer is the most common cancer diagnosis in the United States, with approximately one in five Americans expected to be diagnosed within their lifetime. Non-melanoma skin cancer is the most prevalent type of skin cancer, and as cases rise globally, physicians need reliable tools for early detection. Artificial intelligence has gained substantial interest as a decision support tool in medicine, particularly in image analysis, where deep learning has proven to be an effective tool. Because specialties such as dermatology rely primarily on visual diagnoses, deep learning could have many diagnostic applications, including the diagnosis of skin cancer. Furthermore, with …

Survival Outcomes Of Patients With Mycosis Fungoides Involving The External Ear And Ear Canal, Alex J Wilkinson, Marc-Elie Nader, Dianna Roberts, Madeleine Duvic, Jillian R Gunther, Bouthaina S Dabaja, Paul W Gidley

Student and Faculty Publications

OBJECTIVES/HYPOTHESIS: Mycosis Fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma. Disease involvement of specific locations may be more significant than simply the symptoms associated with that site; it is possible that involvement of certain sites could be associated with poor prognosis. We aimed to evaluate the outcomes of patients with MF with documented involvement of the EAC and external ear.

STUDY DESIGN: Retrospective analysis.

METHODS: We retrospectively reviewed 40 patients with MF that were treated by otologists between 2012 and 2021.

RESULTS: We report the largest series of patients with MF involving the external ear and EAC. …

Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing

Dissertations & Theses (Open Access)

Systemic sclerosis (SSc; scleroderma) is a chronic systemic autoimmune and connective tissue disorder characterized by vasculopathy, autoimmune phenomena, and widespread fibrosis. Skin thickening and tightening is the cardinal feature of SSc and is responsible, in part, for the considerable morbidity of this disease. There are currently no targeted treatments for skin manifestations in SSc, primarily due to our fragmented understanding of its pathophysiologic mechanisms. In PART I, we report a previously unappreciated link between aberrant expression of the developmental gene sine oculis homeobox homolog 1 (SIX1) in skin-associated adipocytes in SSc skin and the early loss of dermal white adipose …

Itch And Janus Kinase Inhibitors, Yujin Han, Yu Ri Woo, Sang Hyun Cho, Jeong Deuk Lee, Hei Sung Kim

Student and Faculty Publications

Itch is a common skin symptom, with complex aetiology and pathogenesis. It is mediated by 2 pathways, the histaminergic and non-histaminergic pathways. Chronic itch is understood to be processed by the latter and is difficult to treat with traditional pruritus therapies. The Janus kinase and signal transducer and activator of transcription pathway is a signalling mechanism that regulates gene expression through various cytokines. Janus kinase inhibitors, which have been tested and used for several autoimmune diseases, have also been shown to be effective for itch through clinical trials and case reports. Janus kinase inhibitors could be a good choice for …

Immune Checkpoint Inhibitors In Advanced Cutaneous Squamous Cell Carcinoma: A Systemic Review And Meta-Analysis, Haoran Zhang, Ai Zhong, Junjie Chen

Student and Faculty Publications

BACKGROUND: To evaluate the immune checkpoint inhibitors (CPI) for the treatment of patients with advanced cutaneous squamous cell carcinoma (CSCC).

MATERIALS AND METHODS: A meta-analysis was conducted, and the efficacy and safety of CPI were assessed.

RESULTS: A total of 13 studies with 980 patients were included. The pooled objective response rate (ORR) and disease control rate were 47.2% and 64.4%, separately. In addition, patients with primary tumor located in head and neck (odds ratio [OR]: 0.374, 95% confidence interval [CI]: 0.219-0.640, p < 0.001) and positive expression of programmed death ligand 1 (OR: 0.364, 95% CI: 0.158-0.842, P = 0.018) had superior ORR during CPI treatment. The incidence of progression free survival at 6 and 12 months was 59.3% and 52.8%, and 80.6% and 76.4% for overall survival. As for safety, the overall incidence of adverse events with all grades and 3-4 grade was 76.9% and 20.2%.

CONCLUSIONS: Our systematic review confirmed the satisfying efficacy and acceptable toxicity of CPI for advanced CSCC.

Prognostic Model For Predicting Overall And Cancer-Specific Survival Among Patients With Superficial Spreading Melanoma: A Seer Based Study, Qiang Ji, Jun Tang, Shulian Li, Junjie Chen

Student and Faculty Publications

Skin malignant melanoma is one of the most aggressive skin tumors. Superficial spreading melanoma (SSM) is the most common histological type, which can originate from different body skin sites, and some patients can still accumulate regional lymph nodes and even have distant metastasis in some cases. This study used the relevant data from the monitoring, epidemiology and results database of the National Cancer Institute database to study the overall survival (OS) and cancer-specific survival (CSS) of SSM patients and established an SSM nomogram to evaluate the prognosis of patients. A total of 13,922 patients were collected from the monitoring, epidemiology …

Allergic Sensitization Pattern In The Korean Dermatologic Patients, Yujin Han, Yu Ri Woo, Hei Sung Kim, Jeong Deuk Lee, Sookhee Choi, Jeesuk Yu, Sang Hyun Cho

Student and Faculty Publications

BACKGROUND: Avoiding causative allergens is important for controlling the clinical course of allergic diseases. Allergen sensitization is influenced by many factors including the environment and lifestyle. The socioeconomic development, climate, and lifestyle changes have increased the prevalence of allergic diseases worldwide. However, there is little information about changes in the trend of the common allergens over time.

OBJECTIVE: This study was aimed at identifying the trends of the common allergens in Korea over a 10-year period based on the results of the multiple allergosorbent test chemiluminescent assay (MAST-CLA).

METHODS: We retrospectively reviewed the medical records of 5,760 patients aged ≥18 …

Tilsotolimod Exploits The Tlr9 Pathway To Promote Antigen Presentation And Type 1 Ifn Signaling In Solid Tumors: A Multicenter International Phase I/Ii Trial (Illuminate-101), Hani Babiker, Erkut Borazanci, Vivek Subbiah, Sanjiv Agarwala, Alain Algazi, Jacob Schachter, Michael Lotem, Corinne Maurice-Dror, Daniel Hendler, Shah Rahimian, Hans Minderman, Cara Haymaker, Daruka Mahadevan, Chantale Bernatchez, Ravi Murthy, Rolf Hultsch, Nadia Kaplan, Gregory Woodhead, Charles Hennemeyer, Srinivas Chunduru, Peter M Anderson, Adi Diab, Igor Puzanov

Student and Faculty Publications

PURPOSE: Tilsotolimod is an investigational synthetic Toll-like receptor 9 (TLR9) agonist that has demonstrated antitumor activity in preclinical models. The ILLUMINATE-101 phase I study explored the safety, dose, efficacy, and immune effects of intratumoral (it) tilsotolimod monotherapy in multiple solid tumors.

PATIENTS AND METHODS: Patients with a diagnosis of refractory cancer not amenable to curative therapies received tilsotolimod in doses escalating from 8 to 32 mg into a single lesion at weeks 1, 2, 3, 5, 8, and 11. Additional patients with advanced malignant melanoma were enrolled into an expansion cohort at the 8 mg dose. Objectives included characterizing the …

Assessment Of Disease Severity And Quality Of Life In Patients With Atopic Dermatitis From South Korea, Sang Wook Son, Ji Hyun Lee, Jiyoung Ahn, Sung Eun Chang, Eung Ho Choi, Tae Young Han, Yong Hyun Jang, Hye One Kim, Moon-Bum Kim, You Chan Kim, Hyun Chang Ko, Joo Yeon Ko, Sang Eun Lee, Yang Won Lee, Bark-Lynn Lew, Chan Ho Na, Chang Ook Park, Chun Wook Park, Kui Young Park, Kun Park, Young Lip Park, Joo Young Roh, Young-Joon Seo, Min Kyung Shin, Sujin Lee, Sang Hyun Cho

Student and Faculty Publications

BACKGROUND: Data illustrating the impact of atopic dermatitis (AD) on lives of adults with AD in South Korea are limited.

OBJECTIVE: To assess the AD disease severity and its impact on quality of life (QoL) in patients with AD from South Korea.

METHODS: Patients with AD utilizing the specialist dermatology services of major hospitals in South Korea were assessed for disease severity using Eczema Area and Severity Index (EASI) score, for QoL using Dermatology Life Quality Index (DLQI) (for QoL), and for comorbidities and treatment experience via retrospective review of 12-month medical records. Clinical and sociodemographic characteristics were also measured. …

Lineage-Coupled Clonal Capture Identifies Clonal Evolution Mechanisms And Vulnerabilities Of Brafv600e Inhibition Resistance In Melanoma, Ze-Yan Zhang, Yingwen Ding, Ravesanker Ezhilarasan, Tenzin Lhakhang, Qianghu Wang, Jie Yang, Aram S Modrek, Hua Zhang, Aristotelis Tsirigos, Andrew Futreal, Giulio F Draetta, Roel G W Verhaak, Erik P Sulman

Student and Faculty Publications

Targeted cancer therapies have revolutionized treatment but their efficacies are limited by the development of resistance driven by clonal evolution within tumors. We developed "CAPTURE", a single-cell barcoding approach to comprehensively trace clonal dynamics and capture live lineage-coupled resistant cells for in-depth multi-omics analysis and functional exploration. We demonstrate that heterogeneous clones, either preexisting or emerging from drug-tolerant persister cells, dominated resistance to vemurafenib in BRAF

Clinical And Pathological Characteristics And Outcomes Among Patients With Subcutaneous Panniculitis-Like T-Cell Lymphoma And Related Adipotropic Lymphoproliferative Disorders, Joan Guitart, Aaron R Mangold, Maria Estela Martinez-Escala, Christina J Walker, Nneka I Comfere, Mellissa Pulitzer, Kerri E Rieger, Carlos A Torres-Cabala, Laura B Pincus, Erica S Kumar, Erica Bo Kyung Wang, Katherine E Park, Maria L Espinosa, Madeleine Duvic, Youn H Kim, Steven Horwitz

Student and Faculty Publications

IMPORTANCE: There is a knowledge gap about subcutaneous panniculitis-like T-cell lymphoma (SPTCL) owing to its rarity and diagnostic difficulty, resulting in an absence of well-documented large case series published to date.

OBJECTIVE: To generate consensus knowledge by a joint multi-institutional review of SPTCL and related conditions.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective clinical and pathological review included cases initially diagnosed as SPTCL at 6 large US academic centers. All cases were reviewed by a group of pathologists, dermatologists, and oncologists with expertise in cutaneous lymphomas. Through a process of group consensus applying defined clinical and pathological diagnostic criteria, the cohort …

Efficacy And Safety Of Topical Hypericin Photodynamic Therapy For Early-Stage Cutaneous T-Cell Lymphoma (Mycosis Fungoides): The Flash Phase 3 Randomized Clinical Trial, Ellen J Kim, Aaron R Mangold, Jennifer A Desimone, Henry K Wong, Lucia Seminario-Vidal, Joan Guitart, James Appel, Larisa Geskin, Edward Lain, Neil J Korman, Nathalie Zeitouni, Neda Nikbakht, Kenneth Dawes, Oleg Akilov, Joi Carter, Michi Shinohara, Timothy M Kuzel, Warren Piette, Neal Bhatia, Amy Musiek, David Pariser, Youn H Kim, Dirk Elston, Erin Boh, Madeleine Duvic, Auris Huen, Theresa Pacheco, Jeffrey P Zwerner, Seung Tae Lee, Michael Girardi, Christiane Querfeld, Kimberly Bohjanen, Elise Olsen, Gary S Wood, Adam Rumage, Oreola Donini, Andrea Haulenbeek, Christopher J Schaber, Richard Straube, Christopher Pullion, Alain H Rook, Brian Poligone

Student and Faculty Publications

IMPORTANCE: Given that mycosis fungoides-cutaneous T-cell lymphoma (MF/CTCL) is chronic, there is a need for additional therapies with minimal short- and long-term adverse effects. Topical synthetic hypericin ointment, 0.25%, activated with visible light is a novel, nonmutagenic photodynamic therapy (PDT).

OBJECTIVES: To determine the efficacy and safety of topical synthetic hypericin ointment, 0.25%, activated with visible light as a nonmutagenic PDT in early-stage MF/CTCL.

DESIGN, SETTINGS, AND PARTICIPANTS: This was a multicenter, placebo-controlled, double-blinded, phase 3 randomized clinical trial (FLASH study) conducted from December 2015 to November 2020 at 39 academic and community-based US medical centers. Participants were adults (≥18 …

Integrative Cancer Immunogenomic Analysis Of Serial Melanoma Biopsies Reveals Correlates Of Response And Resistance To Sequential Ctla-4 And Pd-1 Blockade Treatment, Whijae Roh

Dissertations & Theses (Open Access)

Melanoma is the most malignant form of skin cancer. The five-year survival rate for metastatic melanoma is 19.9%. Although targeted therapy of BRAF and MEK inhibitors were developed for melanoma, resistance to therapy is inevitable. Immune checkpoint blockade, which reverses the suppression of the immune system, on the other hand, has shown a durable response in 20-30% of patients with metastatic melanoma. However, more predictive and robust biomarkers of response to this therapy are still needed, and resistance mechanisms remain incompletely understood. To address this, we examined a cohort of metastatic melanoma patients treated with sequential checkpoint blockade against cytotoxic …

Characterization Of Differentiation And Prognostic Biomarkers On Cd8+ Tumor-Infiltrating Lymphocytes In Metastatic Melanoma, Richard C. Wu

Dissertations & Theses (Open Access)

CD8⁺ cytotoxic T lymphocytes (CTL) frequently infiltrate tumors, yet most melanoma patients fail to undergo tumor regression. We studied the differentiation of the CD8⁺ tumor-infiltrating lymphocytes (TIL) from 44 metastatic melanoma patients using known T-cell differentiation markers. We also compared CD8⁺ TIL against the T cells from matched melanoma patients’ peripheral blood. We discovered a novel subset of CD8⁺ TIL co-expressing early-differentiation markers, CD27, CD28, and a late/senescent CTL differentiation marker, CD57. This CD8⁺CD57⁺ TIL expressed a cytolytic enzyme, granzyme B (GB), yet did not express another cytolytic pore-forming molecule, perforin (Perf). In …

Plasmacytoid Dendritic Cells Sense Skin Injury And Promote Wound Healing Through Type I Interferons, Josh D. Gregorio

Dissertations & Theses (Open Access)

Plasmacytoid dendritic cells (pDCs) are a rare population of circulating cells, which selectively express intracellular Toll-like receptors (TLR)-7 and TLR-9 and have the capacity to produce large amounts of type I IFNs (IFN-a/b) in response to viruses or host derived nucleic acid containing complexes. pDCs are normally absent in skin but accumulate in the skin of psoriasis patients where their chronic activation to produce IFN-a/b drives the disease formation. Whether pDCs and their activation to produce IFN-a/b play a functional role in healthy skin is unknown. Here we show that pDCs are rapidly and transiently recruited into healthy human and …