Ontology highlight
ABSTRACT:
PROVIDER: PRJNA837426 | ENA |
REPOSITORIES: ENA
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Project description:Background: First- and third-generation retinoids are the main treatment in acne. Even though efficacious, they lack full selectivity for RARγ expressed in the epidermis and infundibulum. Objectives: To characterize the in vitro metabolism and the pharmacology of the novel retinoid trifarotene. Methods: In vitro assays determined efficacy, potency and selectivity on RARs, as well as the activity on the expression of retinoid target genes in human keratinocytes and ex vivo cultured skin. In vivo studies investigated topical comedolytic, anti-inflammatory and depigmenting properties. The trifarotene-induced gene expression profile was investigated in non-lesional skin of acne patients and compared to ex vivo and in vivo models. Finally, the metabolic stability in human keratinocytes and hepatic microsomes was established. Results: Trifarotene is a selective RARγ agonist with >20-fold selectivity over RAR and RARβ. Trifarotene is active and stable in keratinocytes but rapidly metabolized by human hepatic microsomes, predicting improved safety. In vivo, trifarotene 0.01% applied topically is highly comedolytic and has antiinflammatory and antipigmenting properties. Gene expression studies indicated potent activation of known retinoid-modulated processes (epidermal differentiation, proliferation, stress response, RA metabolism) and novel pathways (proteolysis, transport/skin hydration, cell adhesion) in ex vivo and in vivo models, as well as in human skin after four weeks of topical application of trifarotene 0.005% cream. Conclusion: Based on its RARγ selectivity, rapid degradation in human hepatic microsomes and pharmacological properties including potent modulation of epidermal processes, topical treatment with trifarotene is expected to provide strong efficacy combined with a favourable safety profile in acne and ichthyotic disorders.
2018-04-28 | GSE107232 | GEO
Project description:The purpose of this study is to see if the investigators can prevent or reduce the severity of the Cetuximab-related acne rash. Two different topical agents will be applied to the skin. One topical agent is the dapsone gel and the other is a skin moisturizer. Dapsone gel is an FDA approved medication that you apply to the face. It is commonly used to treat acne. Skin moisturizers are recommended to patients who receive Cetuximab treatment. In addition to these topical agents they will be given a pill to take once a day. This pill has already been shown to help fight rashes from Cetuximab.
| 2150735 | ecrin-mdr-crc
Project description:The hypothesis of this study is that patients who suffered from acne vulgaris during adolescence are at greater risk of developing acneiform skin rash due to cetuximab.
| 2108857 | ecrin-mdr-crc
Project description:The pathogenesis of acne has been linked to multiple factors such as increased sebum production, inflammation, follicular hyperkeratinization, and the action of Propionibacterium acnes within the follicle. In an attempt to understand the specific genes involved in inflammatory acne, we performed gene expression profiling in acne patients. Skin biopsies were obtained from an inflammatory papule and from normal skin in six patients with acne. Biopsies were also taken from normal skin of six subjects without acne. Gene array expression profiling was conducted using Affymetrix HG-U133A 2.0 arrays comparing lesional to nonlesional skin in acne patients and comparing nonlesional skin from acne patients to skin from normal subjects. Within the acne patients, 211 genes are upregulated in lesional skin compared to nonlesional skin. A significant proportion of these genes are involved in pathways that regulate inflammation and extracellular matrix remodeling, and they include matrix metalloproteinases 1 and 3, IL-8, human beta-defensin 4, and granzyme B. These data indicate a prominent role of matrix metalloproteinases, inflammatory cytokines, and antimicrobial peptides in acne lesions. These studies are the first describing the comprehensive changes in gene expression in inflammatory acne lesions and are valuable in identifying potential therapeutic targets in inflammatory acne. Experiment Overall Design: total 18 chips. 6 for acne lesion samples, 6 for normal skin samples, 6 for non-acne patient normal skin samples
2008-06-14 | E-GEOD-6475 | biostudies-arrayexpress
Project description:<p>Acne vulgaris affects 17 million Americans, more than 80% of the people of age 12-24. The goal of this study is to investigate the relationship between acne pathogenesis and the skin microbiota residing in the microcomedones. This study will enroll approximately 100 healthy individuals and acne patients, both male and female with age 13 or older. Data obtained from this study will help better understand the disease pathogenesis and may lead to the development of new effective therapeutic strategies for treatment of acne.</p>
| phs000263 | dbGaP
Project description:The pathogenesis of acne has been linked to multiple factors such as increased sebum production, inflammation, follicular hyperkeratinization, and the action of Propionibacterium acnes within the follicle. In an attempt to understand the specific genes involved in inflammatory acne, we performed gene expression profiling in acne patients. Skin biopsies were obtained from an inflammatory papule and from normal skin in six patients with acne. Biopsies were also taken from normal skin of six subjects without acne. Gene array expression profiling was conducted using Affymetrix HG-U133A 2.0 arrays comparing lesional to nonlesional skin in acne patients and comparing nonlesional skin from acne patients to skin from normal subjects. Within the acne patients, 211 genes are upregulated in lesional skin compared to nonlesional skin. A significant proportion of these genes are involved in pathways that regulate inflammation and extracellular matrix remodeling, and they include matrix metalloproteinases 1 and 3, IL-8, human beta-defensin 4, and granzyme B. These data indicate a prominent role of matrix metalloproteinases, inflammatory cytokines, and antimicrobial peptides in acne lesions. These studies are the first describing the comprehensive changes in gene expression in inflammatory acne lesions and are valuable in identifying potential therapeutic targets in inflammatory acne. Keywords: acne lesion, normal skin
2006-12-12 | GSE6475 | GEO
Project description:Mild vs. severe psoriasis vulgaris is often distinguished by the Psoriasis Area and Severity Index. It is widely assumed that severe psoriasis involves higher levels of skin inflammation, but comparative molecular profiles of mild vs. severe disease have not been previously performed. In this study, we used gene arrays to phenotype North American patients with mild psoriasis vs. severe psoriasis.
2017-02-19 | GSE78097 | GEO
Project description:Background: Possible outcomes of acne lesions are atrophic scars which may cause serious physical and psychological distress. Current treatments of post-acne scarring remain difficult and often require invasive procedures. Pathophysiological studies on acne scaring investigated only the first week of papule life. Objectives: Study the pathophysiology of atrophic acne scar formation to identify molecular and cellular pathways that can lead to new therapies for the prevention of acne scarring. Methods: Large-scale gene expression profiling of uninvolved acne skin and acne papules of 48 hours and 3 weeks of age, respectively, of both, scar-prone (SP) and non-scar-prone (NSP) patients was performed. Immunohistochemistry techniques were applied to confirm transcriptomics results on the protein and cellular level. Results: Gene expression and immunohistochemistry analyses showed a very similar immune response in 48 hours-old papules in SP and NSP populations characterized by elevated numbers of T cells, neutrophils and macrophages. However, only in SP patients the immune response persisted in 3 week-old papules, and was characterized by an important infiltrate of B cells. Transient down-modulation of genes related to lipid metabolism was observed in 48 hours-old papules in NSP patients, followed by normalization of gene expression levels after 3 weeks. In contrast, in SP patients a drastic reduction of lipid metabolizing enzymes was observed in 3 week-old papules, suggesting irreversible modifications. The affected lipid metabolism genes were found preferentially expressed in human sebaceous glands, pointing to a destruction of sebaceous gland structures after 3 weeks of inflammatory remodelling in SP acne patients.
2018-04-30 | GSE108110 | GEO
Project description:Recent studies have demonstrated that ablative fractional laser (AFL) can inhibit the hedgehog pathway, enhance immune infiltration, and clear basal cell carcinomas (BCCs) in murine models. In this study, we applied RNA sequencing to further characterize the impact of AFL on the transcriptome of murine skin containing early-stage microscopic BCCs, contrasting it with the effects of the FDA approved hedgehog inhibitor vismodegib. Our results showed that BCC induction in murine skin was primarily linked to gene upregulation. Both AFL and vismodegib treatments were able to reverse this upregulation with vismodegib demonstrating superior performance by reversing the most genes (AFL: 59/277; vismodegib 180/277). Surprisingly, Ingenuity Pathway Analysis revealed that both treatments also caused considerable immune cell infiltration. Based on gene set enrichment analysis and cell type deconvolution, AFL treatment resulted in the largest immune cell recruitment, which for both treatments primarily consisted of infiltrating neutrophils, macrophages, and monocytes. In conclusion, the distinct effects observed in BCC skin following AFL and vismodegib treatment highlight key differences between the two interventions. Future applications of AFL or vismodegib treatments could leverage their individual effects, for example by combining AFL’s effects on the immune system with other topical treatments.
2024-11-28 | GSE254404 | GEO