Thomas Z. Rohan , Jenna L. Mandel , Henry Y. Yang , Lauren Banner , Daniel Joffe , Rachel Zachian , Jaanvi Mehta , Safiyyah Bhatti , Tingting Zhan , Neda Nikbakht
{"title":"Identifying Subsets of Cancer Patients with an Increased Risk of Developing Cutaneous Melanoma: A Surveillance, Epidemiology, and End Results–Based Analysis","authors":"Thomas Z. Rohan , Jenna L. Mandel , Henry Y. Yang , Lauren Banner , Daniel Joffe , Rachel Zachian , Jaanvi Mehta , Safiyyah Bhatti , Tingting Zhan , Neda Nikbakht","doi":"10.1016/j.xjidi.2024.100323","DOIUrl":"10.1016/j.xjidi.2024.100323","url":null,"abstract":"<div><div>Cancer survivors have an increased risk of developing second primary malignancies. We aimed to identify whether certain cancers lead to an increased risk of developing melanoma among cancer survivors. We evaluated the risk of developing cutaneous melanoma after the 20 most common cancers in the United States through the Surveillance, Epidemiology, and End Results database. We identified 9 primary cancers linked to increased risk of developing a subsequent cutaneous melanoma: cutaneous melanoma (standardized incidence ratio [SIR] = 9.65), leukemia (SIR = 1.76), non-Hodgkin lymphoma (SIR = 1.33), thyroid cancer (SIR = 1.32), brain and nervous system cancer (SIR = 1.31), myeloma (SIR = 1.23), breast cancer (SIR = 1.13), oral cavity/pharynx cancer (SIR= 1.12), and prostate cancer (SIR = 1.03). The risk of developing melanoma was highest 1–5 years after diagnosis of most primary cancers. Notably, individuals aged under 50 years with a prior melanoma had a 14-fold increased risk. Our findings highlight specific at-risk groups—such as those aged under 50 years with recent melanoma, individuals in their 60s diagnosed with leukemia, and those aged over 80 years with recent thyroid cancer—who may benefit from heightened clinical vigilance and tailored melanoma screening strategies.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 1","pages":"Article 100323"},"PeriodicalIF":0.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Corrigendum to ‘Proteomic Profiling of CCCA Reveals Role of Humoral Immune Response Pathway and Metabolic Dysregulation’ JID Innovations, Volume 4, Issue 3, May 2024, 100263","authors":"","doi":"10.1016/j.xjidi.2024.100312","DOIUrl":"10.1016/j.xjidi.2024.100312","url":null,"abstract":"","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 6","pages":"Article 100312"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142660973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jason C. Klein , Ruchika Mahapatra , Gary C. Hon , Richard C. Wang
{"title":"Identification of Associations with Dermatologic Diseases through a Focused GWAS of the UK Biobank","authors":"Jason C. Klein , Ruchika Mahapatra , Gary C. Hon , Richard C. Wang","doi":"10.1016/j.xjidi.2024.100322","DOIUrl":"10.1016/j.xjidi.2024.100322","url":null,"abstract":"<div><div>The UK Biobank includes genotype information for about 500,000 patients for over 7000 phenotypes. However, owing to multiple testing correction for approximately 200 billion tests, many clinically and statistically significant associations remain unappreciated. We perform a focused analysis of the UK Biobank for 13 dermatologic conditions, including malignant melanoma, melanoma in situ, squamous cell carcinoma, basal cell carcinoma, actinic keratosis, seborrheic keratosis, psoriasis, lichen planus, systemic lupus erythematosus, hyperhidrosis, pilonidal cyst, sebaceous cyst, and lipoma. We identify 447 sentinel variants, which are enriched for protein-coding variants and an elevated combined annotation-dependent depletion (CADD) score compared with background variants. Through gene ontology enrichment analysis, we identify known pathways involved in melanoma, actinic keratoses, and squamous cell carcinoma and uncover additional pathways. We also uncover 5 protein-coding variants, which, to our knowledge, have not been previously reported, including <em>LRP3</em> for lipomas, <em>PLCD1</em> for sebaceous cysts, <em>EIF3CL</em> for lichen planus, <em>TTK</em> for pilonidal cysts, and <em>MAPK15</em> for systemic lupus erythematosus.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 1","pages":"Article 100322"},"PeriodicalIF":0.0,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142658395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aygun Israyilova , Tsvetomira Zhivkova Peykova , Ben Kittleson , Paul Caleb Sprowl , Taha Osman Mohammed , Cassandra L. Quave
{"title":"From Plant to Patient: A Historical Perspective and Review of Selected Medicinal Plants in Dermatology","authors":"Aygun Israyilova , Tsvetomira Zhivkova Peykova , Ben Kittleson , Paul Caleb Sprowl , Taha Osman Mohammed , Cassandra L. Quave","doi":"10.1016/j.xjidi.2024.100321","DOIUrl":"10.1016/j.xjidi.2024.100321","url":null,"abstract":"<div><div>Skin conditions are a common health concern faced by patients of all ages. For thousands of years, plants have been used to treat various skin conditions, including acne, vitiligo, and psoriasis, to name a few. Today, with increasing patient preference for natural therapies, modern medicine is now more than ever incorporating age-old knowledge of herbal remedies useful in treating skin conditions into modern-day treatments. This review covers various plant-derived therapeutics (polyphenon E [sincatechins], psoralen, salicylic acid, anthralin, podophyllotoxin, and Filsuvez [birch triterpenes, oleogel-S10]) that have demonstrated scientific evidence of clinical efficacy for dermatologic disorders. The discovery, composition, history of use, and current uses in dermatology are summarized for each botanical ingredient.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 1","pages":"Article 100321"},"PeriodicalIF":0.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142704288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alessandra S.P. Cereghetti , Patrick Turko , Phil Cheng , Stephan Benke , Ala’a Al Hrout , Andreas Dzung , Reinhard Dummer , Michael O. Hottiger , Richard Chahwan , Lorenza P. Ferretti , Mitchell P. Levesque
{"title":"DNA Methyltransferase Inhibition Upregulates the Costimulatory Molecule ICAM-1 and the Immunogenic Phenotype of Melanoma Cells","authors":"Alessandra S.P. Cereghetti , Patrick Turko , Phil Cheng , Stephan Benke , Ala’a Al Hrout , Andreas Dzung , Reinhard Dummer , Michael O. Hottiger , Richard Chahwan , Lorenza P. Ferretti , Mitchell P. Levesque","doi":"10.1016/j.xjidi.2024.100319","DOIUrl":"10.1016/j.xjidi.2024.100319","url":null,"abstract":"<div><div>In cutaneous melanoma, epigenetic dysregulation is implicated in drug resistance and tumor immune escape. However, the epigenetic mechanisms that influence immune escape remain poorly understood. To elucidate how epigenetic dysregulation alters the expression of surface proteins that may be involved in drug targeting and immune escape, we performed a 3-dimensional surfaceome screen in primary melanoma cultures and identified the DNA-methyltransferase inhibitor decitabine as significantly upregulating the costimulatory molecule ICAM-1. By analyzing The Cancer Genome Atlas melanoma dataset, we further propose ICAM-1 upregulation on melanoma cells as a biomarker of a proinflammatory and antitumorigenic signature. Specifically, we showed that DNA-methyltransferase inhibitor administration upregulated the expression of the antigen-presenting machinery, HLA class I/II, as well as the secretion of the proinflammatory chemokines CXCL9 and CXCL10. Our in silico analysis on The Cancer Genome Atlas and ex vivo experiments on human primary melanoma samples revealed that increased ICAM-1 expression positively correlated with increased immunogenicity of human melanoma cells and correlated with increased immune cell infiltration. These findings suggest a therapeutic approach to modulate the immunogenic phenotype of melanoma cells, hence supporting the exploration of DNA-methyltransferase inhibitor as a potential inducer of infiltration in immunologically cold tumors.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 2","pages":"Article 100319"},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christina Cho , Nazgol-Sadat Haddadi , Michal Kidacki , Gavitt A. Woodard , Saeed Shakiba , Ümmügülsüm Yıldız-Altay , Jillian M. Richmond , Matthew D. Vesely
{"title":"Spatial Transcriptomics in Inflammatory Skin Diseases Using GeoMx Digital Spatial Profiling: A Practical Guide for Applications in Dermatology","authors":"Christina Cho , Nazgol-Sadat Haddadi , Michal Kidacki , Gavitt A. Woodard , Saeed Shakiba , Ümmügülsüm Yıldız-Altay , Jillian M. Richmond , Matthew D. Vesely","doi":"10.1016/j.xjidi.2024.100317","DOIUrl":"10.1016/j.xjidi.2024.100317","url":null,"abstract":"<div><div>The spatial organization of the skin is critical for its function. In particular, the skin immune microenvironment is arranged spatially and temporally, such that imbalances in the immune milieu are indicative of disease. Spatial transcriptomic platforms are helping to provide additional insights into aberrant inflammation in tissues that are not captured by tissue processing required for single-cell RNA sequencing. In this paper, we discuss a technical and user experience overview of NanoString's GeoMx Digital Spatial Profiler to perform in-depth spatial analysis of the transcriptome in inflammatory skin diseases. Our objective is to provide potential pitfalls and methods to optimize RNA capture that are not readily available in the manufacturer’s guidelines. We use concrete examples from our experiments to demonstrate these strategies in inflammatory skin diseases, including psoriasis, lichen planus, and discoid lupus erythematosus. Overall, we hope to illustrate the potential of digital spatial profiling to dissect skin disease pathogenesis in a spatially resolved manner and provide a framework for other skin biology investigators using digital spatial profiling.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 1","pages":"Article 100317"},"PeriodicalIF":0.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142593706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dominique du Crest , Philipp Wustrow , Oliver Worsley , Barbara Geusens , Omar Badri , Monisha Madhumita , Art Papier , Alexander Zink , Merete Hædersdal , Lilit Garibyan
{"title":"Skin & Digital: The 2023 Startups/Innovators","authors":"Dominique du Crest , Philipp Wustrow , Oliver Worsley , Barbara Geusens , Omar Badri , Monisha Madhumita , Art Papier , Alexander Zink , Merete Hædersdal , Lilit Garibyan","doi":"10.1016/j.xjidi.2024.100316","DOIUrl":"10.1016/j.xjidi.2024.100316","url":null,"abstract":"","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 1","pages":"Article 100316"},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sireesh Kumar Teertam , Vijayasaradhi Setaluri , Jose M. Ayuso
{"title":"Advances in Microengineered Platforms for Skin Research","authors":"Sireesh Kumar Teertam , Vijayasaradhi Setaluri , Jose M. Ayuso","doi":"10.1016/j.xjidi.2024.100315","DOIUrl":"10.1016/j.xjidi.2024.100315","url":null,"abstract":"<div><div>The skin plays a critical role in human physiology, acting both as a barrier to environmental insults and as a window to environmental stimuli. Disruption of this homeostasis leads to numerous skin disorders. Human and animal skin differ significantly, limiting the translational potential of animal-based investigations to advance therapeutics to human skin diseases. Hence, there is a critical need for physiologically relevant human skin models to explore novel treatment strategies. Recent advances in microfluidic technologies now allow design and generation of organ-on-chip devices that mimic critical features of tissue architecture. Skin-on-a-chip and microfluidic platforms hold promise as useful models for diverse dermatology applications. Compared with traditional in vitro models, microfluidic platforms offer improved control of fluid flow, which in turn allows precise manipulation of cell and molecular distribution. These properties enable the generation of multilayered in vitro models that mimic human skin structure while simultaneously offering superior control over nutrient and drug distribution. Researchers have used microfluidic platforms for a variety of applications in skin research, including epidermal–dermal cellular crosstalk, cell migration, mechanobiology, microbiome–immune response interactions, vascular biology, and wound healing. In this review, we comprehensively review state-of-the-art microfluidic models for skin research. We discuss the challenges and promise of current skin-on-a-chip technologies and provide a roadmap for future research in this active field.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 1","pages":"Article 100315"},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142554849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mackenzie L. Sennett , George W. Agak , Diane M. Thiboutot , Amanda M. Nelson
{"title":"Transcriptomic Analyses Predict Enhanced Metabolic Activity and Therapeutic Potential of mTOR Inhibitors in Acne-Prone Skin","authors":"Mackenzie L. Sennett , George W. Agak , Diane M. Thiboutot , Amanda M. Nelson","doi":"10.1016/j.xjidi.2024.100306","DOIUrl":"10.1016/j.xjidi.2024.100306","url":null,"abstract":"<div><p>Current acne therapies center on preventing new lesions in patients with acne. These therapies were historically found to be beneficial yet were chosen without knowledge of the specific changes in the skin that favor lesion development. A major challenge in developing new treatments is the incomplete understanding of nonlesional (NL), acne-prone skin’s molecular characteristics. To address this, we compared RNA-sequencing data from NL skin of 49 patients with acne (denoted as NL acne [NLA]) with those from 19 healthy controls with no acne history. We found 77 differentially expressed genes in NLA (log fold change > 1; <em>P</em> < .05), including genes associated with innate immunity and epidermal barrier function. Notably, <em>K</em><em>RT</em><em>6C</em>, <em>K</em><em>RT</em><em>16</em>, <em>S100A8</em>, <em>S100A9</em>, and lactotransferrin were upregulated<em>,</em> and <em>LCE4A, LCE6A,</em> and <em>CTSE</em> were downregulated<em>.</em> Gene set enrichment analysis revealed that metabolic pathways were enriched in NLA skin, whereas keratinization was negatively enriched. To identify compounds that could shift the gene expression signature of NLA skin toward healthy control skin, we performed connectivity mapping with the Library of Integrated Network-Based Signatures. We identified 187 compounds, particularly mTOR inhibitors, that could potentially normalize the gene expression profile of acne-prone skin to that of healthy skin. Our findings indicate that NLA skin has distinct differences in epidermal differentiation, cellular metabolism, and innate immunity that may promote lesion formation and suggest that mTOR inhibitors could restore NLA skin toward a healthier state, potentially reversing the predisposition to lesion development.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 6","pages":"Article 100306"},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000535/pdfft?md5=d23043e7c7fe4614bbbea701eaadc7a9&pid=1-s2.0-S2667026724000535-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142173030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Caroline J. Stone , Geeta Ahuja , Lais Lopes Almeida Gomes , Joy Poroye , Daniella Forman Faden , Lillian Xie , Rui Feng , Barbara White , Victoria P. Werth
{"title":"Long-Term Safety and Efficacy of Lenabasum, a Cannabinoid Receptor Type 2 Agonist, in Patients with Dermatomyositis with Refractory Skin Disease: Follow-Up Data from a 3-Year Open-Label Extension Study","authors":"Caroline J. Stone , Geeta Ahuja , Lais Lopes Almeida Gomes , Joy Poroye , Daniella Forman Faden , Lillian Xie , Rui Feng , Barbara White , Victoria P. Werth","doi":"10.1016/j.xjidi.2024.100311","DOIUrl":"10.1016/j.xjidi.2024.100311","url":null,"abstract":"<div><h3>Background</h3><div>Dermatomyositis (DM) is a rare autoimmune condition involving skin manifestations often resistant to standard treatments such as immunosuppressants and antimalarials. Biopsies show elevated inflammatory cells such as CD4+ T cells, dendritic cells, and cytokines. Lenabasum, a selective cannabinoid receptor 2 agonist, has demonstrated significant benefits in treating autoimmune skin diseases. Objectives: This study utilizes data from the open-label extension (OLE) phase of the lenabasum phase 2 trial and additional post-OLE follow-up data. Key aims include evaluating the drug’s long-term effectiveness and assessing disease manifestation recurrence. Methods: The phase 2 lenabasum trial enrolled patients with treatment-resistant, skin-predominant DM. The OLE consisted of a 3-year period during which 20 patients were on the drug for the entire duration, with assessments every 8 weeks to evaluate drug safety and efficacy. Subsequently, a follow-up retrospective chart review was performed on patients who completed the OLE as well as on control subjects with DM who did not participate in the lenabasum trial. Results: By week 68, patients exhibited reductions in Cutaneous Dermatomyositis Disease Area and Severity Index activity score (−21.8), Patient Skin Activity Visual Analog Scale (−3.0), and Skindex-29 (−28.0) from OLE baseline. After OLE, 58.3% maintained stable disease, significantly higher than controls (<em>P</em> = .035), with 41.7% not experiencing flares compared with 91.6% of controls. In addition, 50% of patients reported sustained pruritus improvement. Conclusions: Data from OLE and subsequent follow-up periods demonstrate lenabasum’s efficacy in maintaining disease stability, reducing flares, and improving DM symptoms, suggesting that it is a promising option for patients with treatment-resistant skin-predominant DM. Trial Registration: This study was registered at <span><span>clinicaltrials.gov</span><svg><path></path></svg></span>, with <span><span>NCT02466243</span><svg><path></path></svg></span>. Study registration was first submitted on June 2, 2015.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"5 1","pages":"Article 100311"},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}