RESUMEN
Androgenic alopecia (AGA) is the most prevalent type of progressive hair loss and has psychological repercussions. Nevertheless, the effectiveness of current pharmacological treatments remains limited, in part because the molecular basis of the disease has not been fully elucidated. Our group previously highlighted the important roles of aromatase and 5α-reductase (5α-R) in alopecia in young women with female pattern hair loss. Additionally, an association has been proposed between AGA and prostate cancer (PCa), suggesting that genes implicated in PCa would also be involved in AGA. A low-invasive, sensitive, and precise method was used to determine mRNA levels of aromatase, 5α-R isozymes, and 84 PCa-related genes in samples of plucked hair from young men with AGA and controls. Samples were obtained with a trichogram from the vertex scalp, and mRNA levels were quantified using real-time RT-PCR. The men with AGA had significantly higher 5α-R2 mRNA levels in comparison to controls; interestingly, some of them also showed markedly elevated mRNA levels of 5α-R1 or 5α-R3 or of both, which may explain the varied response to 5α-R inhibitor treatments. The men with AGA also showed significant changes versus controls in 6 out of the 84 genes implicated in PCa. This study contributes greater knowledge of the molecular bases of AGA, facilitating early selection of the most appropriate pharmacological therapy and opening the way to novel treatments.
Asunto(s)
Colestenona 5 alfa-Reductasa , Neoplasias de la Próstata , Masculino , Humanos , Colestenona 5 alfa-Reductasa/genética , Aromatasa/genética , Isoenzimas/uso terapéutico , ARN Mensajero/genética , Cabello , Alopecia/genética , Alopecia/tratamiento farmacológico , Neoplasias de la Próstata/genéticaRESUMEN
BACKGROUND: To our knowledge, there are no large multicenter studies concerning frontal fibrosing alopecia (FFA) that could give clues about its pathogenesis and best treatment. OBJECTIVE: We sought to describe the epidemiology, comorbidities, clinical presentation, diagnostic findings, and therapeutic choices in a large series of patients with FFA. METHODS: This retrospective multicenter study included patients given the diagnosis of FFA. Clinical severity was classified based on the recession of the frontotemporal hairline. RESULTS: In all, 355 patients (343 women [49 premenopausal] and 12 men) with a mean age of 61 years (range 23-86) were included. Early menopause was detected in 49 patients (14%), whereas 46 (13%) had undergone hysterectomy. Severe FFA was observed in 131 patients (37%). Independent factors associated with severe FFA after multivariate analysis were: eyelash loss, facial papules, and body hair involvement. Eyebrow loss as the initial clinical presentation was associated with mild forms. Antiandrogens such as finasteride and dutasteride were used in 111 patients (31%), with improvement in 52 (47%) and stabilization in 59 (53%). LIMITATIONS: The retrospective design is a limitation. CONCLUSIONS: Eyelash loss, facial papules, and body hair involvement were associated with severe FFA. Antiandrogens were the most useful treatment.
Asunto(s)
Alopecia/tratamiento farmacológico , Alopecia/patología , Azaesteroides/uso terapéutico , Finasterida/uso terapéutico , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Alopecia/epidemiología , Biopsia con Aguja , Estudios de Cohortes , Dutasterida , Femenino , Fibrosis/epidemiología , Fibrosis/patología , Frente , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Análisis Multivariante , Posmenopausia/fisiología , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Distribución por Sexo , España/epidemiología , Resultado del Tratamiento , Adulto JovenRESUMEN
Paintings often show women with a clearance of the frontal hairline. We previously remarked how this was a form of pseudoalopecia that was voluntarily caused by women who shaved the frontal part of their hair for fashionable and esthetic reasons. In this paper, we emphasize in a second set of paintings showing a true alopecia that was caused by traction of the hair due to a tight hairstyle and was culturally favored in the 17th century.
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Alopecia/etiología , Alopecia/historia , Estética/historia , Remoción del Cabello/efectos adversos , Cabello , Medicina en las Artes , Pinturas , Alopecia/patología , Cultura , Femenino , Historia del Siglo XV , Historia del Siglo XVI , Historia del Siglo XVII , Humanos , Clase SocialRESUMEN
Metastatic disease is the primary cause of death in cutaneous malignant melanoma (CMM) patients. To understand the mechanisms of CMM metastasis and identify potential predictive markers, we analyzed gene-expression profiles of 34 vertical growth phase melanoma cases using cDNA microarrays. All patients had a minimum follow-up of 36 months. Twenty-one cases developed nodal metastatic disease and 13 did not. Comparison of gene expression profiling of metastatic and nonmetastatic melanoma cases identified 243 genes with a >2-fold differential expression ratio and a false discovery rate of <0.2 (206 up-regulated and 37 down-regulated). This set of genes included molecules involved in cell cycle and apoptosis regulation, epithelial-mesenchymal transition (EMT), signal transduction, nucleic acid binding and transcription, protein synthesis and degradation, metabolism, and a specific group of melanoma- and neural-related proteins. Validation of these expression data in an independent series of melanomas using tissue microarrays confirmed that the expression of a set of proteins included in the EMT group (N-cadherin, osteopontin, and SPARC/osteonectin) were significantly associated with metastasis development. Our results suggest that EMT-related genes contribute to the promotion of the metastatic phenotype in primary CMM by supporting specific adhesive, invasive, and migratory properties. These data give a better understanding of the biology of this aggressive tumor and may provide new prognostic and patient stratification markers in addition to potential therapeutic targets.
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Melanoma/patología , Melanoma/secundario , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/secundario , Adulto , Anciano , Anciano de 80 o más Años , Células Epiteliales/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Melanoma/genética , Melanoma/metabolismo , Mesodermo/patología , Persona de Mediana Edad , Neoplasias Cutáneas/genéticaRESUMEN
Malignant melanoma (MM) prognosis has been related to tumour thickness and clinical stage and metastasis risk has been associated with presence of tumour cells in peripheral blood. The aim of this study was to determine the relationship between presence of tyrosinase in peripheral blood of MM patients and their clinical prognosis. Blood samples from 58 MM patients (stage I-IV) were analysed, using RT-PCR assay to detect tyrosinase mRNA. The results showed that positive RT-PCR assay for tyrosinase were significantly associated with clinical status and tumour thickness. After a median follow-up of 24 months, RT-PCR results were found to be significant correlated with recurrence (p<0.05) and clinical stage III (p<0.05). Separate analysis of stage III tumours to determine the prognostic value of tyrosinase presence in peripheral blood showed an overall 24-month survival rate of 70% in the RT-PCR negative group versus 10% in the positive group (p<0.02). These results suggest that detection of circulating melanoma cells may be especially relevant in stage III patients, in whom RT-PCR positivity defines a subpopulation at high risk of recurrence.
Asunto(s)
Melanoma/diagnóstico , Monofenol Monooxigenasa/genética , ARN Neoplásico/sangre , Neoplasias Cutáneas/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monofenol Monooxigenasa/sangre , Estadificación de Neoplasias , Células Neoplásicas Circulantes/química , Pronóstico , ARN Mensajero/análisis , ARN Mensajero/sangre , ARN Neoplásico/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND: The role of genes involved in the control of progression from the G1 to the S phase of the cell cycle in melanoma tumors in not fully known. The aim of our study was to analyse mutations in TP53, CDKN1A, CDKN2A, and CDKN2B genes in melanoma tumors and melanoma cell lines METHODS: We analysed 39 primary and metastatic melanomas and 9 melanoma cell lines by single-stranded conformational polymorphism (SSCP). RESULTS: The single-stranded technique showed heterozygous defects in the TP53 gene in 8 of 39 (20.5%) melanoma tumors: three new single point mutations in intronic sequences (introns 1 and 2) and exon 10, and three new single nucleotide polymorphisms located in introns 1 and 2 (C to T transition at position 11701 in intron 1; C insertion at position 11818 in intron 2; and C insertion at position 11875 in intron 2). One melanoma tumor exhibited two heterozygous alterations in the CDKN2A exon 1 one of which was novel (stop codon, and missense mutation). No defects were found in the remaining genes. CONCLUSION: These results suggest that these genes are involved in melanoma tumorigenesis, although they may be not the major targets. Other suppressor genes that may be informative of the mechanism of tumorigenesis in skin melanomas should be studied.
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Inhibidor p15 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Genes p53/genética , Melanoma/genética , Neoplasias Cutáneas/genética , Secuencia de Bases , Ciclo Celular , Línea Celular Tumoral , Codón de Terminación , Inhibidor p15 de las Quinasas Dependientes de la Ciclina/biosíntesis , Inhibidor p16 de la Quinasa Dependiente de Ciclina/biosíntesis , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/biosíntesis , Análisis Mutacional de ADN , Fase G1 , Heterocigoto , Humanos , Intrones , Melanoma/patología , Datos de Secuencia Molecular , Mutación Missense , Mutación Puntual , Polimorfismo de Nucleótido Simple , Polimorfismo Conformacional Retorcido-Simple , Fase S , Neoplasias Cutáneas/patología , Proteína p53 Supresora de Tumor/biosíntesisRESUMEN
The aim of this study was to evaluate the correlation between the detection of circulating melanoma cells and prognostic criteria for malignant melanoma such as clinical stage, tumor thickness and histological type of the primary tumor. Using a reverse transcriptase-polymerase chain reaction (RT-PCR) technique, melanoma cells were identified by detecting tyrosinase mRNA in peripheral blood from 58 patients with malignant melanoma classified according to the American Joint Committee on Cancer guidelines. The results of the RT-PCR assay for tyrosinase were related to two prognostic markers typically used to evaluate these tumors: clinical stage and thickness. Positive PCR results were more frequent in primary tumors measuring > 4 mm (83%) than in thinner tumors (1.1-4.0 mm, 74%; < or = 1.0 mm, 23%) (P = 0.005). No statistical correlation was found between the PCR results and histological appearance of the primary tumor. Although further studies are necessary, our results suggest the possible application of the PCR assay for tyrosinase mRNA in clinical evaluation of the prognosis of malignant melanoma.
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Melanoma/sangre , Células Neoplásicas Circulantes/patología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Neoplasias Cutáneas/sangre , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Melanoma/enzimología , Melanoma/secundario , Persona de Mediana Edad , Monofenol Monooxigenasa/genética , Monofenol Monooxigenasa/metabolismo , Estadificación de Neoplasias , ARN Mensajero/sangre , ARN Neoplásico/análisis , Factores Sexuales , Neoplasias Cutáneas/enzimología , Neoplasias Cutáneas/patologíaAsunto(s)
Miasis/diagnóstico , Dermatosis del Cuero Cabelludo/parasitología , Adulto , Fiebre/etiología , Humanos , Mordeduras y Picaduras de Insectos/complicaciones , Masculino , Miasis/complicaciones , Miasis/cirugía , Dermatosis del Cuero Cabelludo/complicaciones , Dermatosis del Cuero Cabelludo/cirugía , Trastornos del Inicio y del Mantenimiento del Sueño/etiología , Infecciones Estreptocócicas/complicaciones , Acúfeno/etiologíaRESUMEN
El desarrollo de la Dermatología en la Facultad de Medicina de Granada se produjo en el contexto general de la Historia de la Dermatología española. Destacan dos figuras, D. Benito Hernando y Espinosa, por su contribución al estudio de la lepra y la creación de los pilares de la escuela granadina y D. José Pareja Garrido, primer catedrático numerario de la Dermatología española que, procedente de la cirugía general, dio los primeros tintes quirúrgicos a la especialidad. En este artículo describimos los antecedentes y aportamos algunos datos biográficos, con sus principales aportaciones, de estas dos figuras de la Dermatología Granadina (AU)
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Humanos , Historia del Siglo XIX , Historia del Siglo XX , Dermatología/historia , Facultades de Medicina/historia , España , Lepra/historiaRESUMEN
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