JID innovations : skin science from molecules to population health最新文献_第7页

Factors Associated with Adoption of Immune Checkpoint Inhibitor Treatment for Advanced Melanoma: A SEER-Medicare Cohort Study 采用免疫检查点抑制剂治疗晚期黑色素瘤的相关因素： SEER-医保队列研究

JID innovations : skin science from molecules to population health Pub Date : 2024-05-21 DOI: 10.1016/j.xjidi.2024.100289

Cassandra Mohr , Kaiping Liao , Candice L. Hinkston , Mackenzie R. Wehner , Meng Li

{"title":"Factors Associated with Adoption of Immune Checkpoint Inhibitor Treatment for Advanced Melanoma: A SEER-Medicare Cohort Study","authors":"Cassandra Mohr , Kaiping Liao , Candice L. Hinkston , Mackenzie R. Wehner , Meng Li","doi":"10.1016/j.xjidi.2024.100289","DOIUrl":"10.1016/j.xjidi.2024.100289","url":null,"abstract":"<div><p>We aimed to explore the differences in immune checkpoint inhibitor (ICI) immunotherapy utilization for advanced melanoma by examining patient and neighborhood characteristics. We performed a retrospective cohort study using a deidentified, random sample of SEER-Medicare beneficiaries aged ≥65 years with stage III or stage IV melanoma (2011–2017). Our primary outcome was initiation of ICI immunotherapy (ipilimumab, pembrolizumab, nivolumab, or atezolizumab) after stage III or stage IV melanoma diagnosis. We analyzed ICI usage with multivariable logistic regression. After analyzing the entire 2011–2017 cohort, we conducted a secondary analysis in which we separately analyzed the 2011–2014 and 2015–2017 cohorts to assess possible differences over time. We included 3531 beneficiaries, with mean follow-up of 2.1 (SD = 2.0) years. Higher likelihood of ICI usage was associated with male sex (OR = 1.21, 95% confidence interval = 1.04–1.42) and higher density of medical oncologists (OR = 1.02, 95% confidence interval = 1.01–1.04). Lower likelihood of ICI usage was associated with older age group and Charlson comorbidity score (score ≥2; OR = 0.72, 95% confidence interval = 0.60–0.86). These associations were diminished in more recent years (no association with sex, medical oncologist density, Charlson comorbidity score, and association with only the oldest age group in years 2015–2017). We found significant sex- and age-related differences in initiation among SEER-Medicare beneficiaries with stage III or stage IV melanoma, which appear to be improving over time.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 4","pages":"Article 100289"},"PeriodicalIF":0.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000365/pdfft?md5=9afd44e58671efdf3c0ed9288dd00f3c&pid=1-s2.0-S2667026724000365-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141134453","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}

引用次数: 0

MicroRNA Signatures Associated with Basal Cell Carcinoma Subtypes 与基底细胞癌亚型相关的微RNA特征

JID innovations : skin science from molecules to population health Pub Date : 2024-05-03 DOI: 10.1016/j.xjidi.2024.100286

Suzanne Fastner , Hafeez Rahman , Jose Gutierrez , Nathan Shen , Scott R. Florell , Abigail Florell , Chris J. Stubben , Kenneth M. Boucher , Dekker C. Deacon , Robert L. Judson-Torres , Douglas Grossman

{"title":"MicroRNA Signatures Associated with Basal Cell Carcinoma Subtypes","authors":"Suzanne Fastner , Hafeez Rahman , Jose Gutierrez , Nathan Shen , Scott R. Florell , Abigail Florell , Chris J. Stubben , Kenneth M. Boucher , Dekker C. Deacon , Robert L. Judson-Torres , Douglas Grossman","doi":"10.1016/j.xjidi.2024.100286","DOIUrl":"10.1016/j.xjidi.2024.100286","url":null,"abstract":"<div><p>Basal cell carcinoma (BCC) is classified histologically into subtypes that determine treatment decisions. MicroRNAs (miRs) are short noncoding RNAs that may serve as diagnostic biomarkers. We investigated if particular miRs could distinguish BCC subtypes. We sequenced miRs from 55 archival BCC and 9 control skin specimens and then validated these miRs by qRT-PCR assay on a second BCC cohort (18 superficial, 16 nodular, 15 infiltrative) and control skin (n = 12). Expression values for individual miRs were normalized to miR-16-5p, which was the least variant among the control skin and BCC samples. We found that (i) miR-383-5p and miR-145-5p are downregulated in all BCC subtypes compared with control skin, (ii) miR-181c-5p is downregulated in superficial compared with invasive (nodular/infiltrative) BCC, and (iii) miR-22-5p and miR-708-5p are upregulated in infiltrative compared with superficial/nodular BCC and miR-30c-5p is downregulated in infiltrative compared with nodular BCC. Receiver operating characteristic analysis demonstrated excellent capacity of these miRs to discriminate between BCC and control skin (area under the curve, 0.94–0.98), whereas the capacity to discriminate between superficial and invasive subtypes was less robust (area under the curve, 0.7–0.8). Future prospective studies may determine the utility of these miRs as diagnostic biomarkers to guide biopsy and treatment of BCC.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 4","pages":"Article 100286"},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266702672400033X/pdfft?md5=5b73694006f30288640b9ea9f57e5331&pid=1-s2.0-S266702672400033X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141035605","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}

引用次数: 0

NOD/Scid IL2Rγnull Mice Reconstituted with PBMCs from Patients with Atopic Dermatitis or Psoriasis Vulgaris Reflect the Respective Phenotype 用特应性皮炎或寻常型银屑病患者的外周血单核细胞重组的 NOD/Scid IL2Rγ 空鼠反映了各自的表型。

JID innovations : skin science from molecules to population health Pub Date : 2024-05-01 DOI: 10.1016/j.xjidi.2024.100268

Marietta Schindler , Paula Schuster-Winkelmann , Veronika Weß , Sophia Czell , Franziska Rueff , Andreas Wollenberg , Matthias Siebeck , Roswitha Gropp

{"title":"NOD/Scid IL2Rγnull Mice Reconstituted with PBMCs from Patients with Atopic Dermatitis or Psoriasis Vulgaris Reflect the Respective Phenotype","authors":"Marietta Schindler , Paula Schuster-Winkelmann , Veronika Weß , Sophia Czell , Franziska Rueff , Andreas Wollenberg , Matthias Siebeck , Roswitha Gropp","doi":"10.1016/j.xjidi.2024.100268","DOIUrl":"10.1016/j.xjidi.2024.100268","url":null,"abstract":"<div><p>NSG (NOD/Scid IL2Rγ<sup>null</sup>) mice reconstituted with PBMCs donated by patients with ulcerative colitis or Crohn’s disease highly reflect the respective pathological phenotype. To determine whether these findings could be applicable to atopic dermatitis (AD) and psoriasis vulgaris (PV), PBMCs isolated from patients with AD and PV were first subjected to immunological profiling. Subsequently, NSG mice were reconstituted with these PBMCs. Hierarchical clustering and network analysis revealed a distinct profile of patients with AD and PV with activated CD4+ T cells (CD69, CD25) occupying a central position in the AD network and CD4+ CD134+ cells acting as the main hub in the PV network. After dermal application of DMSO, both NSG mice reconstituted with PBMCs from donors with AD (ie, NSG-AD mice) and NSG mice reconstituted with PBMCs from donors with PV (ie, NSG-PV mice) exhibited increased clinical, skin, and histological scores. Immunohistochemical analysis, frequencies of splenic human leukocytes, and cytokine expression levels indicated that CD4+ CD69+ cells, M1 and TSLP receptor–expressing monocytes, switched B cells, and monocyte chemoattractant protein 3 were the driving factors of inflammation in NSG-AD mice. In contrast, inflammation in NSG-PV mice was characterized by an increase in fibroblasts in the epidermis, frequencies of CD1a-expressing monocytes, and IL-17 levels. Therefore, the pathological phenotypes of NSG-AD mice and NSG-PV mice differ and partially reflect the respective human diseases.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 3","pages":"Article 100268"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000146/pdfft?md5=00fd321e7bee9d649d4f7311c571778b&pid=1-s2.0-S2667026724000146-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139875284","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}

引用次数: 0

Identification of Keratinocyte Cytoprotectants against Toxicity by the Multikinase Inhibitor Sorafenib Using Drug Repositioning 利用药物重定位技术鉴定角质形成细胞细胞保护剂，以对抗多激酶抑制剂索拉非尼的毒性

JID innovations : skin science from molecules to population health Pub Date : 2024-05-01 DOI: 10.1016/j.xjidi.2024.100271

Yayoi Kamata , Rui Kato , Mitsutoshi Tominaga , Sumika Toyama , Eriko Komiya , Jun Utsumi , Takahide Kaneko , Yasushi Suga , Kenji Takamori

{"title":"Identification of Keratinocyte Cytoprotectants against Toxicity by the Multikinase Inhibitor Sorafenib Using Drug Repositioning","authors":"Yayoi Kamata , Rui Kato , Mitsutoshi Tominaga , Sumika Toyama , Eriko Komiya , Jun Utsumi , Takahide Kaneko , Yasushi Suga , Kenji Takamori","doi":"10.1016/j.xjidi.2024.100271","DOIUrl":"10.1016/j.xjidi.2024.100271","url":null,"abstract":"<div><p>Hand–foot skin reaction is the most common adverse event of multikinase inhibitors, such as sorafenib. Although hand–foot skin reaction is not life threatening, severe cases impair quality of life because of pain and reduced activities of daily living. However, the pathological mechanisms of hand–foot skin reaction have not yet been elucidated in detail, and there is currently no effective treatment. We aimed to identify keratinocyte cytoprotectants against sorafenib toxicity. The screening of cytoprotectants against sorafenib toxicity was performed using cultured normal human epidermal keratinocytes or a reconstructed human epidermis model and off-patent approved drugs in the Prestwick Chemical library. Among 1273 drugs in the chemical library, 8 dose-dependently increased cell viability by >200% in the presence of sorafenib. In the presence of sorafenib, the number of proliferating cell nuclear antigen–positive cells was significantly higher in clofazimine-, cyclosporin A–, and itraconazole-treated reconstructed human epidermis models than in sorafenib-treated models, and candidate drugs suppressed sorafenib-induced apoptosis in normal human epidermal keratinocytes. In addition, clofazimine, itraconazole, and pyrvinium pamoate significantly recovered the phosphorylation of extracellular signal–regulated kinase 1/2 in the presence of sorafenib. Collectively, hit drugs promoted cell viability and normalized keratinocyte proliferation in the presence of sorafenib. These candidate drugs have potential as treatments for multikinase inhibitor–induced hand–foot skin reaction.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 3","pages":"Article 100271"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000183/pdfft?md5=6ac09b2f5c88dad96300d97f7d0fd131&pid=1-s2.0-S2667026724000183-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140470031","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}

引用次数: 0

In Silico Elucidation of Key Drivers of Staphyloccocus aureus–Staphyloccocus epidermidis–Induced Skin Damage in Atopic Dermatitis Lesions 在特应性皮炎皮损中，金黄色葡萄球菌-表皮茵诱发皮肤损伤的关键驱动因素的硅学阐释

JID innovations : skin science from molecules to population health Pub Date : 2024-05-01 DOI: 10.1016/j.xjidi.2024.100269

Jamie Lee , Ahmad A. Mannan , Takuya Miyano , Alan D. Irvine , Reiko J. Tanaka

{"title":"In Silico Elucidation of Key Drivers of Staphyloccocus aureus–Staphyloccocus epidermidis–Induced Skin Damage in Atopic Dermatitis Lesions","authors":"Jamie Lee , Ahmad A. Mannan , Takuya Miyano , Alan D. Irvine , Reiko J. Tanaka","doi":"10.1016/j.xjidi.2024.100269","DOIUrl":"10.1016/j.xjidi.2024.100269","url":null,"abstract":"<div><p><em>Staphylococcus aureus</em> (SA) colonizes and can damage skin in atopic dermatitis lesions, despite being commonly found with <em>Staphylococcus epidermidis</em> (SE), a commensal that can inhibit SA’s virulence and kill SA. In this study, we developed an <em>in silico</em> model, termed a virtual skin site, describing the dynamic interplay between SA, SE, and the skin barrier in atopic dermatitis lesions to investigate the mechanisms driving skin damage by SA and SE. We generated 10<sup>6</sup> virtual skin sites by varying model parameters to represent different skin physiologies and bacterial properties. <em>In silico</em> analysis revealed that virtual skin sites with no skin damage in the model were characterized by parameters representing stronger SA and SE growth attenuation than those with skin damage. This inspired an <em>in silico</em> treatment strategy combining SA-killing with an enhanced SA–SE growth attenuation, which was found through simulations to recover many more damaged virtual skin sites to a non-damaged state, compared with SA-killing alone. This study demonstrates that <em>in silico</em> modelling can help elucidate the key factors driving skin damage caused by SA–SE colonization in atopic dermatitis lesions and help propose strategies to control it, which we envision will contribute to the design of promising treatments for clinical studies.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 3","pages":"Article 100269"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266702672400016X/pdfft?md5=178aabaf5651f027521d8120342ea113&pid=1-s2.0-S266702672400016X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140467524","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}

引用次数: 0

Inflammatory Memory in Chronic Skin Disease 慢性皮肤病的炎症记忆。

JID innovations : skin science from molecules to population health Pub Date : 2024-05-01 DOI: 10.1016/j.xjidi.2024.100277

Joseph A. Daccache , Shruti Naik

引用次数: 0

Systematic Review of Intralesional Therapies for Cutaneous Warts 皮肤疣局部治疗方法的系统性综述

JID innovations : skin science from molecules to population health Pub Date : 2024-05-01 DOI: 10.1016/j.xjidi.2024.100264

Sarah A. Mullen , Emma L. Myers , Rebecca L. Brenner , Kim T. Nguyen , Tara A. Harper , Darby Welsh , Storm Keffer , Jenna Mueller , Melodi Javid Whitley

{"title":"Systematic Review of Intralesional Therapies for Cutaneous Warts","authors":"Sarah A. Mullen , Emma L. Myers , Rebecca L. Brenner , Kim T. Nguyen , Tara A. Harper , Darby Welsh , Storm Keffer , Jenna Mueller , Melodi Javid Whitley","doi":"10.1016/j.xjidi.2024.100264","DOIUrl":"10.1016/j.xjidi.2024.100264","url":null,"abstract":"<div><p>Intralesional therapies are used for recalcitrant warts, but no Food and Drug Administration–approved treatment exists nor is there consensus regarding the most efficacious therapy. Therefore, this systematic review aims to summarize efficacy and adverse events reported in 62 randomized controlled trials (RCTs) of intralesional therapies for cutaneous warts. The most studied intralesional therapies included measles, mumps, rubella (MMR) vaccine (n = 24 studies), purified protein derivative (PPD) (n = 19 studies), vitamin D3 (n = 15 studies), and Candida antigen (n = 14 studies). Most studies included adult and pediatric patients or adults alone, with only 4 studies on pediatric patients alone. MMR vaccine was the most studied treatment (n = 853 patients). MMR had a complete response rate of 27–90%. The next most common treatment, PPD, had a complete response rate of 45–87%. Other treatments included Candida antigen and vitamin D3, with complete response rates of 25–84% and 40–96%, respectively. The most frequent side effects were injection-site reactions and flu-like symptoms. This systematic review represents a useful summary of intralesional therapy RCTs for clinician reference. This study also highlights the lack of large multi-institutional RCTs, despite many patients being treated for this widespread problem.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 3","pages":"Article 100264"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000109/pdfft?md5=cf21b5dcafa5a1711fe7695ee5532160&pid=1-s2.0-S2667026724000109-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139632661","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}

引用次数: 0

An Optimized and Advanced Algorithm for the Quantification of Immunohistochemical Biomarkers in Keratinocytes 用于量化角朊细胞免疫组化生物标记物的先进优化算法

JID innovations : skin science from molecules to population health Pub Date : 2024-05-01 DOI: 10.1016/j.xjidi.2024.100270

Lindsey G. Siegfried , Sophie M. Bilik , Jamie L. Burgess , Paola Catanuto , Ivan Jozic , Irena Pastar , Rivka C. Stone , Marjana Tomic-Canic

{"title":"An Optimized and Advanced Algorithm for the Quantification of Immunohistochemical Biomarkers in Keratinocytes","authors":"Lindsey G. Siegfried , Sophie M. Bilik , Jamie L. Burgess , Paola Catanuto , Ivan Jozic , Irena Pastar , Rivka C. Stone , Marjana Tomic-Canic","doi":"10.1016/j.xjidi.2024.100270","DOIUrl":"10.1016/j.xjidi.2024.100270","url":null,"abstract":"<div><p>Advancements in pathology have given rise to software applications intended to minimize human error and improve efficacy of image analysis. Still, the subjectivity of image quantification performed manually and the limitations of the most ubiquitous tissue stain analysis software requiring parameters tuned by the observer, reveal the need for a highly accurate, automated nuclear quantification software specific to immunohistochemistry, with improved precision and efficiency compared with the methods currently in use. We present a method for the quantification of immunohistochemical biomarkers in keratinocyte nuclei proposed to overcome these limitations, contributing sensitive shape-focused segmentation, accurate nuclear detection, and automated device-independent color assessment, without observer-dependent analysis parameters.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 3","pages":"Article 100270"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000171/pdfft?md5=d3e1293c9de3ee42e7a6f4a0308b4765&pid=1-s2.0-S2667026724000171-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139965668","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}

引用次数: 0

Skin Barrier– and Immune Response–Related Biomarkers of Solar UVR Exposure Comparing Indoor and Outdoor Workers 室内和室外工人暴露于太阳紫外线辐射的皮肤屏障和免疫反应相关生物标志物

JID innovations : skin science from molecules to population health Pub Date : 2024-05-01 DOI: 10.1016/j.xjidi.2024.100280

Florentine L. de Boer , Henk F. van der Molen , Jen-Hung Wang , Ellen Raun , Jorge Pereda , Edwin En-Te Hwu , Ivone Jakasa , Sandrine Dubrac , Thomas Rustemeyer , Sanja Kezic

{"title":"Skin Barrier– and Immune Response–Related Biomarkers of Solar UVR Exposure Comparing Indoor and Outdoor Workers","authors":"Florentine L. de Boer , Henk F. van der Molen , Jen-Hung Wang , Ellen Raun , Jorge Pereda , Edwin En-Te Hwu , Ivone Jakasa , Sandrine Dubrac , Thomas Rustemeyer , Sanja Kezic","doi":"10.1016/j.xjidi.2024.100280","DOIUrl":"10.1016/j.xjidi.2024.100280","url":null,"abstract":"<div><p>Outdoor workers have increased risk of developing keratinocyte cancer due to accumulated skin damage resulting from chronic and excessive exposure to UVR. This study aims to identify potential noninvasive biomarkers to assess chronic UVR exposure. We analyzed stratum corneum biomarkers collected from 2 skin locations and 2 occupational groups with contrasting solar UVR exposure: the forehead and retroauricular skin among outdoor workers and indoor workers. Using a linear mixed model adjusting for age and skin phototype, we compared biomarkers between both skin sites in indoor and outdoor workers. We measured markers of the immune response and skin barrier, including cytokines, GFs, 15-hydroxyeicosatetraenoic acid, cis- and <em>trans</em>-urocanic acid, and corneocyte topography, indicated by circular nano objects. Differences between the 2 skin sites were found for cis-urocanic acid, total urocanic acid, IL-1α, IL-1RA, IL-1RA/IL-1α, IL-18, 15-hydroxyeicosatetraenoic acid, CCL4, and circular nano objects. The levels of cis-urocanic acid and CCL4 also differed between indoor and outdoor workers. These findings underscore changes in both immune response and skin barrier induced by UVR. They indicate the potential utility of stratum corneum biomarkers in detecting both chronic UVR exposure in occupational setting and aiding in the development of preventive measures.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 3","pages":"Article 100280"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000274/pdfft?md5=d28d1a7220a0b9d9874db0551d5797ff&pid=1-s2.0-S2667026724000274-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140794024","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}

引用次数: 0

Molecular Analysis of Murine KitK641E Melanoma Progression 小鼠 KitK641E 黑色素瘤进展的分子分析

JID innovations : skin science from molecules to population health Pub Date : 2024-05-01 DOI: 10.1016/j.xjidi.2024.100266

Emily Everdell , Zhenyu Ji , Ching-Ni Njauw , Hensin Tsao

{"title":"Molecular Analysis of Murine KitK641E Melanoma Progression","authors":"Emily Everdell , Zhenyu Ji , Ching-Ni Njauw , Hensin Tsao","doi":"10.1016/j.xjidi.2024.100266","DOIUrl":"10.1016/j.xjidi.2024.100266","url":null,"abstract":"<div><p>Acral and mucosal melanomas are often driven by sequence variants in the KIT receptor tyrosine kinase, with nearly 40% harboring alterations in the <em>KIT</em> locus. Despite advances in the knowledge of <em>KIT</em>-mutated melanomas, little is known about the molecular reprogramming that occurs during KIT-mediated melanoma progression owing to the rarity of acral and mucosal melanomas and the lack of comprehensive biological tools and models. To this end, we used a murine model that allows us to ascertain the molecular underpinnings of the stages of cancer progression—transformation, tumorigenesis, immune engagement, and tumor escalation. We found dramatic increases in biosynthetic demands associated with the transformation stage, including DNA and RNA metabolism, leading to replication stress. Tumorigenesis was closely linked to neuronal and axonal development, likely necessary for invasion into the host. Immune engagement highlighted early immune excitation and rejection pathways, possibly triggered by abrupt neoantigen exposure. Finally, tumor escalation pathways proved consistent with immune evasion, with immune-related pathways becoming significantly downregulated. To our knowledge, it is previously unreported that these critical milestones needed for KIT-driven melanoma tumor formation have been studied at the molecular level using isogenically matched and phenotypically defined cells.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 3","pages":"Article 100266"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000122/pdfft?md5=5b2a6d12bc9524b3679788530b36ea31&pid=1-s2.0-S2667026724000122-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140518492","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}

引用次数: 0