ABSTRACT
El melanoma subungueal es un tumor poco común, con peor pronóstico comparado con los de otras localizaciones. Corresponde al 1-23% de los melanomas, según la población. El objetivo de este estudio fue describir las características clínicas e histopatológicas del melanoma subungueal en la población mexicana. Se incluyeron 57 pacientes con melanoma subungueal (19% de los 303 melanomas totales), con una mediana de edad de 71 años. La localización predominante fueron los miembros inferiores (52,6% de los melanomas subungueales) y el primer dedo (75,4% de los casos). El subtipo histológico más frecuente fue el acral lentiginoso (50,9%). La mediana de Breslow fue de 3mm. El estadio IA fue el más frecuente (28,1%). Se encontró una tasa de recurrencia del 19,3% y de metástasis del 8,8%. Las características clínico-patológicas fueron semejantes a lo descrito en la literatura. Es importante realizar un diagnóstico y tratamiento tempranos de cara a mejorar su pronóstico.(AU)
Although subungual melanoma is uncommon, it is associated with worse outcomes than melanomas in other locations and accounts for 1% to 23% of all melanomas, depending on the population. The aim of this study was to describe the clinical and histopathologic features of subungual melanoma in a Mexican population. We identified 303 patients with melanoma, and of these, 19% (57 patients with a median age of 71 years) had subungual melanoma. The main sites affected were the lower limbs (52.6%) and the toe (75.4%). The most common histologic subtype was acral lentiginous melanoma (50.9%). Median Breslow thickness was 3 mm, and stage IA tumors were the most common (in 28.1% of patients). Recurrence and metastasis occurred in 19.3% and 8.8% of patients, respectively. The clinical and histopathologic features identified are similar to those described in the literature. Early diagnosis and treatment are crucial for improving prognosis.(AU)
Subject(s)
Humans , Male , Female , Aged , Skin Diseases/drug therapy , Melanoma/classification , Skin Neoplasms , Nail Diseases/drug therapy , Nail Diseases/diagnostic imaging , Longitudinal Studies , Epidemiology, Descriptive , Retrospective Studies , Mexico , Cohort Studies , DermatologyABSTRACT
El melanoma subungueal es un tumor poco común, con peor pronóstico comparado con los de otras localizaciones. Corresponde al 1-23% de los melanomas, según la población. El objetivo de este estudio fue describir las características clínicas e histopatológicas del melanoma subungueal en la población mexicana. Se incluyeron 57 pacientes con melanoma subungueal (19% de los 303 melanomas totales), con una mediana de edad de 71 años. La localización predominante fueron los miembros inferiores (52,6% de los melanomas subungueales) y el primer dedo (75,4% de los casos). El subtipo histológico más frecuente fue el acral lentiginoso (50,9%). La mediana de Breslow fue de 3mm. El estadio IA fue el más frecuente (28,1%). Se encontró una tasa de recurrencia del 19,3% y de metástasis del 8,8%. Las características clínico-patológicas fueron semejantes a lo descrito en la literatura. Es importante realizar un diagnóstico y tratamiento tempranos de cara a mejorar su pronóstico.(AU)
Although subungual melanoma is uncommon, it is associated with worse outcomes than melanomas in other locations and accounts for 1% to 23% of all melanomas, depending on the population. The aim of this study was to describe the clinical and histopathologic features of subungual melanoma in a Mexican population. We identified 303 patients with melanoma, and of these, 19% (57 patients with a median age of 71 years) had subungual melanoma. The main sites affected were the lower limbs (52.6%) and the toe (75.4%). The most common histologic subtype was acral lentiginous melanoma (50.9%). Median Breslow thickness was 3 mm, and stage IA tumors were the most common (in 28.1% of patients). Recurrence and metastasis occurred in 19.3% and 8.8% of patients, respectively. The clinical and histopathologic features identified are similar to those described in the literature. Early diagnosis and treatment are crucial for improving prognosis.(AU)
Subject(s)
Humans , Male , Female , Aged , Skin Diseases/drug therapy , Melanoma/classification , Skin Neoplasms , Nail Diseases/drug therapy , Nail Diseases/diagnostic imaging , Longitudinal Studies , Epidemiology, Descriptive , Retrospective Studies , Mexico , Cohort Studies , DermatologyABSTRACT
Although subungual melanoma is uncommon, it is associated with worse outcomes than melanomas in other locations and accounts for 1% to 23% of all melanomas, depending on the population. The aim of this study was to describe the clinical and histopathologic features of subungual melanoma in a Mexican population. We identified 303 patients with melanoma, and of these, 19% (57 patients with a median age of 71 years) had subungual melanoma. The main sites affected were the lower limbs (52.6%) and the toe (75.4%). The most common histologic subtype was acral lentiginous melanoma (50.9%). Median Breslow thickness was 3 mm, and stage IA tumors were the most common (in 28.1% of patients). Recurrence and metastasis occurred in 19.3% and 8.8% of patients, respectively. The clinical and histopathologic features identified are similar to those described in the literature. Early diagnosis and treatment are crucial for improving prognosis.
Subject(s)
Melanoma , Nail Diseases , Skin Neoplasms , Humans , Aged , Melanoma/pathology , Cohort Studies , Skin Neoplasms/pathology , Nail Diseases/diagnosis , PrognosisABSTRACT
Although subungual melanoma is uncommon, it is associated with worse outcomes than melanomas in other locations and accounts for 1% to 23% of all melanomas, depending on the population. The aim of this study was to describe the clinical and histopathologic features of subungual melanoma in a Mexican population. We identified 303 patients with melanoma, and of these, 19% (57 patients with a median age of 71 years) had subungual melanoma. The main sites affected were the lower limbs (52.6%) and the toe (75.4%). The most common histologic subtype was acral lentiginous melanoma (50.9%). Median Breslow thickness was 3 mm, and stage IA tumors were the most common (in 28.1% of patients). Recurrence and metastasis occurred in 19.3% and 8.8% of patients, respectively. The clinical and histopathologic features identified are similar to those described in the literature. Early diagnosis and treatment are crucial for improving prognosis.
Subject(s)
Melanoma , Nail Diseases , Skin Neoplasms , Humans , Aged , Melanoma/pathology , Cohort Studies , Skin Neoplasms/pathology , Nail Diseases/diagnosis , PrognosisABSTRACT
Scanning ion-conductance microscopy allowed us to document an external Ca2+ dependent ATP driven volume increase (ATPVI) in capacitated human sperm heads. We examined the involvement of purinergic receptors (PRs) P2X2R and P2X4R in ATPVI using their co-agonists progesterone and Ivermectin (Iver), and Cu2+, which co-activates P2X2Rs and inhibits P2X4Rs. Iver enhanced ATPVI and Cu2+ and 5BDBD inhibited it, indicating P2X4Rs contributed to this response. Moreover, Cu2+ and 5BDBD inhibited the ATP-induced acrosome reaction (AR) which was enhanced by Iver. ATP increased the concentration of intracellular Ca2+ ([Ca2+]i) in >45% of individual sperm, most of which underwent AR monitored using FM4-64. Our findings suggest that human sperm P2X4R activation by ATP increases [Ca2+]i mainly due to Ca2+ influx which leads to a sperm head volume increase, likely involving acrosomal swelling, and resulting in AR.
Subject(s)
Semen , Spermatozoa , Humans , Male , Spermatozoa/physiology , Acrosome Reaction/physiology , Adenosine Triphosphate , Calcium , Acrosome/physiologyABSTRACT
Sperm motility is essential for fertilization. The asymmetry of flagellar beat in spermatozoa is finely regulated by intracellular calcium concentration ([Ca2+]i). Recently, we demonstrated that the application of high concentrations (10-20 µM) of the Ca2+ ionophore A23187 promotes sperm immobilization after 10 min, and its removal thereafter allows motility recovery, hyperactivation, and fertilization. In addition, the same ionophore treatment overcomes infertility observed in sperm from Catsper1-/-, Slo3-/-, and Adcy10-/-, but not PMCA4-/-, which strongly suggest that regulation of [Ca2+]i is mandatory for sperm motility and hyperactivation. In this study, we found that prior to inducing sperm immobilization, high A23187 concentrations (10 µM) increase flagellar beat. While 5-10 µM A23187 substantially elevates [Ca2+]i and rapidly immobilizes sperm in a few minutes, smaller concentrations (0.5 and 1 µM) provoke smaller [Ca2+]i increases and sperm hyperactivation, confirming that [Ca2+]i increases act as a motility switch. Until now, the [Ca2+]i thresholds that switch motility on and off were not fully understood. To study the relationship between [Ca2+]i and flagellar beating, we developed an automatic tool that allows the simultaneous measurement of these two parameters. Individual spermatozoa were treated with A23187, which is then washed to evaluate [Ca2+]i and flagellar beat recovery using the implemented method. We observe that [Ca2+]i must decrease below a threshold concentration range to facilitate subsequent flagellar beat recovery and sperm motility.
Subject(s)
Calcium/physiology , Sperm Motility/physiology , Sperm Tail/physiology , Animals , Calcimycin/pharmacology , Calcium/metabolism , Cells, Immobilized , In Vitro Techniques , Ionophores/pharmacology , Male , Mice , Microscopy, Fluorescence , Spermatozoa/drug effects , Spermatozoa/metabolismABSTRACT
Celecoxib (Cx), an anti-inflammatory drug designed to inhibit COX2, can affect some ion channels. T-type (CaV3) channels have been implicated in sperm physiology. Here we report and characterize the Cx induced inhibition of T-type channels in mouse spermatogenic cells. Unexpectedly, Cx can also induce the acrosome reaction (AR), an intracellular Ca(2+) ([Ca(2+)]i) increase and a sperm depolarization. This [Ca(2+)]i increase possibly results from the ability Cx has to alkalinize intracellular pH (pHi), which is known to activate the sperm specific Ca(2+) channel CatSper. As the Cx induced [Ca(2+)]i increase is sensitive to mibefradil, a CatSper blocker, this channel may mediate the Cx-induced Ca(2+) entry leading to the AR. Our observations demonstrate that Cx can compromise fertilization.