ABSTRACT
Majocchi granuloma is an uncommon deep follicular inflammation caused by dermatophytes and affects immunocompetent and immunocompromised patients. The clinical findings overlap with other skin conditions such bacterial infections and inflammatory skin diseases, thereby delaying correct diagnosis. We describe 2 cases in immunocompetent patients
El granuloma de Majocchi es una inflamación folicular profunda poco común causada por dermatofitos que afecta a pacientes inmunocompetentes o inmunodeprimidos. Los hallazgos clínicos se mezclan con otras enfermedades cutáneas tales como infecciones bacterianas o dermatopatías inflamatorias, lo que retrasa el diagnóstico acertado. Se presentan 2 casos en pacientes inmunocompetentes
Subject(s)
Humans , Male , Young Adult , Adult , Trichophyton/pathogenicity , Granuloma/microbiology , Antifungal Agents/therapeutic use , Tinea/complications , Dermatomycoses/complicationsABSTRACT
Melanoma tumors usually retain wild-type p53; however, its tumor-suppressor activity is functionally disabled, most commonly through an inactivating interaction with mouse double-minute 2 homolog (Mdm2), indicating p53 release from this complex as a potential therapeutic approach. P53 and the tumor-promoter insulin-like growth factor type 1 receptor (IGF-1R) compete as substrates for the E3 ubiquitin ligase Mdm2, making their relative abundance intricately linked. Hence we investigated the effects of pharmacological Mdm2 release from the Mdm2/p53 complex on the expression and function of the IGF-1R. Nutlin-3 treatment increased IGF-1R/Mdm2 association with enhanced IGF-1R ubiquitination and a dual functional outcome: receptor downregulation and selective downstream signaling activation confined to the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. This Nutlin-3 functional selectivity translated into IGF-1-mediated bioactivities with biphasic effects on the proliferative and metastatic phenotype: an early increase and late decrease in the number of proliferative and migratory cells, while the invasiveness was completely inhibited following Nutlin-3 treatment through an impaired IGF-1-mediated matrix metalloproteinases type 2 activation mechanism. Taken together, these experiments reveal the biased agonistic properties of Nutlin-3 for the mitogen-activated protein kinase pathway, mediated by Mdm2 through IGF-1R ubiquitination and provide fundamental insights into destabilizing p53/Mdm2/IGF-1R circuitry that could be developed for therapeutic gain.
Subject(s)
Biomarkers, Tumor/metabolism , Insulin-Like Growth Factor I/metabolism , Melanoma/pathology , Proto-Oncogene Proteins c-mdm2/metabolism , Receptor, IGF Type 1/metabolism , Skin Neoplasms/pathology , Tumor Suppressor Protein p53/metabolism , Apoptosis , Biomarkers, Tumor/genetics , Cell Cycle , Cell Proliferation , Humans , Melanoma/genetics , Melanoma/metabolism , Neoplasm Invasiveness , Phenotype , Proto-Oncogene Proteins c-mdm2/genetics , Receptor, IGF Type 1/genetics , Signal Transduction , Skin Neoplasms/genetics , Skin Neoplasms/metabolism , Tumor Cells, Cultured , Tumor Suppressor Protein p53/geneticsABSTRACT
Majocchi granuloma is an uncommon deep follicular inflammation caused by dermatophytes and affects immunocompetent and immunocompromised patients. The clinical findings overlap with other skin conditions such bacterial infections and inflammatory skin diseases, thereby delaying correct diagnosis. We describe 2 cases in immunocompetent patients.
