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Melanocytic neoplasms originate from melanocytes and melanoma, the malignant form, is a common canine neoplasm and the most aggressive human skin cancer. Despite many similarities between these neoplasms in both species, only a limited number of studies have approached these entities in a comparative manner. Therefore, this review compares benign and malignant melanocytic neoplasms in dogs and humans, exclusively those arising in the haired skin, with regard to their clinicopathological, immunohistochemical and molecular aspects. Shared features include spontaneous occurrence, macroscopic features and microscopic findings when comparing human skin melanoma in the advanced/invasive stage and canine cutaneous melanoma, immunohistochemical markers and several histopathological prognostic factors. Differences include the apparent absence of active mutations in the BRAF gene in canine cutaneous melanoma and less aggressive clinical behaviour in dogs than in humans. Further studies are required to elucidate the aetiology and genetic development pathways of canine cutaneous melanocytic neoplasms. Evaluation of the applicability of histopathological prognostic parameters commonly used in humans for dogs are also needed. The similarities between the species and the recent findings regarding genetic mutations in canine cutaneous melanomas suggest the potential utility of dogs as a natural model for human melanomas that are not related to ultraviolet radiation.
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Doenças do Cão , Imuno-Histoquímica , Melanoma , Neoplasias Cutâneas , Cães , Neoplasias Cutâneas/veterinária , Neoplasias Cutâneas/patologia , Animais , Doenças do Cão/patologia , Melanoma/veterinária , Melanoma/patologia , Humanos , Biomarcadores Tumorais , Melanoma Maligno CutâneoAssuntos
Hiperpigmentação , Melanose , Adulto , Humanos , Feminino , Prevalência , Melanose/epidemiologia , FaceRESUMO
BACKGROUND: Clobetasol has demonstrated remarkable results in treating melasma within a short time frame; however, its use is limited because of the risk of local side effects. To date, there is no controlled trial on sequential clobetasol/hydroquinone for melasma. This study aimed to investigate the tolerability and efficacy of 0.05% clobetasol followed by 4% hydroquinone (CLOB-HQ) in comparison to the isolated use of 4% hydroquinone (HQ). METHODS: A double-blinded, randomized clinical trial involving 50 women with facial melasma was performed. They were directed to apply 0.05% clobetasol every night for 14 days, followed by 4% hydroquinone for 46 days (CLOB-HQ group), or the use of hydroquinone for 60 days (HQ group). Evaluations were carried out at inclusion, and after 14 and 60 days of treatment, measuring modified Melasma Area and Severity Index (mMASI), Melasma Quality of Life scale (MELASQoL), and colorimetry. The Global Aesthetic Improvement Scale (GAIS) was assessed by a blinded evaluator. RESULTS: There was no difference in the main outcomes at D14 and D60 (P > 0.1). For CLOB-HQ, the mean (CI 95%) reduction in mMASI was 13.2% (5.1-21.3%) and 43.1% (32.2-54.0%) at D14 and D60, and for HQ, they were 10.6% (5.9-27.5%) and 44.8% (33.2-52.3%). The MELASQoL, colorimetric luminosity, and GAIS showed a progressive improvement for both groups despite no difference between them. No severe side effects were identified. No cases of telangiectasias, atrophy, or perioral dermatitis were associated with the use of CLOB. CONCLUSION: The sequential CLOB-HQ regimen was safe and well tolerated, even though its efficacy was not different from HQ after 14 or 60 days of treatment. Based on these findings, the use of clobetasol 14 days before hydroquinone is not advisable for the treatment of melasma.
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Clobetasol , Quimioterapia Combinada , Hidroquinonas , Melanose , Qualidade de Vida , Índice de Gravidade de Doença , Humanos , Hidroquinonas/administração & dosagem , Hidroquinonas/efeitos adversos , Melanose/tratamento farmacológico , Melanose/diagnóstico , Feminino , Método Duplo-Cego , Adulto , Clobetasol/administração & dosagem , Clobetasol/efeitos adversos , Pessoa de Meia-Idade , Dermatoses Faciais/tratamento farmacológico , Esquema de Medicação , Administração Cutânea , Resultado do Tratamento , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/efeitos adversosRESUMO
BACKGROUND: This study presents a case series and scoping review of oral melanoacanthoma to examine its clinical, histopathological, and immunohistochemical characteristics. METHODS: Nine cases of oral melanoacanthoma were included in the case series. Clinical data were collected from biopsy charts. Hematoxylin-eosin and immunohistochemistry for TRP2, CD3, and CD20 were done. For the scoping review, MEDLINE/PubMed, Web of Science, EMBASE, and Scopus were searched. RESULTS: Case series: The mean age was 46.8 years (female-to-male ratio 2:1). Lesion's mean size was 11.0 mm (±9.3). Lesions were mainly macular (77.8%) with brown or black coloration (88.9%) and often affected multiple sites (44.4%). The evolution time ranged from 15 days to 96 months. Lesions commonly showed epithelial acanthosis (66.7%), spongiosis (55.6%), exocytosis (77.8%), melanin incontinence (88.9%), and inflammatory infiltrate in the lamina propria (77.8%), from which all showed lymphocytes. TRP2-positive melanocytes were identified in the basal and spinous layer of all cases, and in the superficial layer of three cases. CD3-positive cells predominate over the CD20-positive. Scoping review: 85 cases of oral melanoacanthoma were retrieved from 55 studies. Patients were primarily female (female-to-male ratio 2.2:1), black-skinned (64.1%), with a mean age of 36.13 (± 17.24). Lesions were flat (81.9%), often brown (62.4%). Buccal mucosa was the preferred site (32.9%), followed by multiple sites (28.2%). CONCLUSION: Oral melanoacanthoma mainly affects women across a wide age range, with lesions commonly appearing as brown/black macules, particularly on the buccal mucosa. TRP2-positive melanocytes and T-lymphocytes were consistently found and could participate in oral melanoacanthoma pathogenesis.
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Neoplasias Bucais , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biópsia , Imuno-Histoquímica , Melanócitos/patologia , Mucosa Bucal/patologia , Neoplasias Bucais/patologiaRESUMO
The human epidermal melanocyte (hEM) are melanin-producing cells that provide skin pigmentation and protection against ultraviolet radiation. Although purinergic signaling is involved in skin biology and pathology, the presence of NTPDase members, as well as the rate of nucleotides degradation by melanocytes were not described yet. Therefore, in this study, we analyzed the expression of ectonucleotidases in hEM derived from discarded foreskin of male patients. The expression of purinergic enzymes was confirmed by mRNA and flow cytometry. Among the ectonucleotidases, ectonucleoside triphosphate diphosphohydrolase1 (NTPDase1) and ecto-5´-nucleotidase were the ectoenzymes with higher expressions. The hydrolysis rate for ATP, ADP, and AMP was low in comparison to other primary cells already investigated. The amount of ATP in the culture medium was increased after a scratch wound and decreased to basal levels in 48 h, while the NTPDase1 and P2X7 expressions increased. Therefore, it is possible to suggest that after cell injury, the ATP released by hEM into the extracellular space will be hydrolyzed by ectonucleotidases as the NTPDase1 that will control the levels of nucleotides in the skin micro-environment.
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Nucleotídeos , Raios Ultravioleta , Humanos , Masculino , 5'-Nucleotidase/genética , 5'-Nucleotidase/metabolismo , Melanócitos/metabolismo , Pele/metabolismo , Trifosfato de Adenosina/metabolismoRESUMO
O melanoacantoma oral é uma lesão pigmentada benigna, rara, de coloração marrom- preta, que se distingue pelo aparecimento súbito e crescimento rápido. Sua etiologia ainda não foi bem determinada, mas é sugerido na literatura que possa estar associada a processos reacionais. O objetivo do presente estudo é apresentar uma série de casos de melanoacantoma oral, explorando suas características clínicas, histopatológicas e imunoistoquímicas. Neste estudo foram recuperados nove casos de melanoacantoma oral diagnosticadas em quatro serviços de Patologia Oral no Brasil, entre 1956 a 2022. Os dados clínicos foram coletados dos prontuários de biópsia e as lâminas de hematoxilina-eosina foram revisadas para análise histopatológica. A Imuno-histoquímica para TRP2, CD3 e CD20 foi realizada. A média de idade encontrada foi de 47,1 anos (± 19,0), com relação mulher/homem de 2:1. O tamanho médio da lesão foi de 11,0 mm (± 9,3). A apresentação clínica foi predominantemente de lesões maculares (77,8%), com coloração marrom ou preta (77,8%). Múltiplos locais foram acometidos em 3 casos, seguidos por lábio inferior e palato mole (2 cada). O tempo de evolução variou de 1 a 96 meses. As lesões comumente mostraram acantose epitelial (66,7%), espongiose (55,6%) e exocitose (77,8%). A melanina foi detectada na lâmina própria de 8 casos. Sete casos apresentaram infiltrado inflamatório na lâmina própria, dos quais todos apresentaram linfócitos. Os plasmócitos foram visualizadas em 4 casos, enquanto eosinófilos, neutrófilos e mastócitos foram raramente observados. As células CD3 positivas predominam sobre as células CD20 positivas em cinco dos sete casos que apresentaram inflamação. Melanócitos positivos para TRP2 foram identificados na camada basal e espinhosa de todos os casos e na camada superficial de três casos. Conclui-se que o melanoacantoma oral ocorre principalmente em pacientes do sexo feminino, podendo acometer uma ampla faixa etária. As lesões geralmente surgem como máculas marrons/pretas, sendo os lábios o local mais comum. LinfócitosT e melanócitos positivos para TRP2 foram consistentemente encontrados e devem participar da patogênese do melanoacantoma oral.
Oral melanoacanthoma is a rare, benign, black-brown pigmented lesion, characterized by its sudden appearance and rapid growth. The pathogenesis of oral melanoacanthoma remains uncertain, but most authors suggest a reactive process The aim of the present study is to present a case series of oral melanoacanthoma, exploring its clinical, histopathological, and immunohistochemical features. Nine cases of oral melanoacanthoma were retrieved. Clinical data were collected from biopsy charts. Hematoxylin-eosin slides were reviewed for histopathological analysis. Immunohistochemistry for TRP2, CD3, and CD20 was done. The mean age was 47.1 years (± 19.0), with a female to male ratio of 2:1. Lesion mean size was 11.0 mm (± 9.3). Clinical presentation was mostly of macular lesions (77.8%), with brown or black coloration (77.8%). Multiple sites were affected in 3 cases, followed by lower lip and soft palate (2 each). The evolution time ranged from 1 to 96 months. Lesions commonly showed epithelial acanthosis (66.7%), spongiosis (55.6%), and exocytosis (77.8%). Melanin was detected in the lamina propria of 8 cases. Seven cases showed inflammatory infiltrate in the lamina propria, from which all showed lymphocytes. Plasma cells were visualized in 4 cases, while eosinophils, neutrophils, and mast cells were rarely seen. CD3-positive cells predominate over the CD20-positive cells in five of the seven cases that presented inflammation. TRP2 positive melanocytes were identified in the basal and spinous layer of all cases, and in the superficial layer of three cases. Oral melanoacanthoma occurs mainly in female patients, and a wide age range may be affected. Lesions usually arise as brown/black macules, and the lips are the most common site. T-lymphocytes and TRP2-positive melanocytes were consistently found and should participate in the pathogenesis of oral melanoacanthoma.
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Transtornos da Pigmentação , Estudo Clínico , Melanócitos , Mucosa BucalRESUMO
Hair graying, a prototypical sign of human aging, is a progressive loss of pigmentation from growing hair shafts caused by disease and as a side effect of medications. Cerebrolysin is a neuropeptide preparation that mimics the effect of endogenous neurotrophic factors. Cerebrolysin has been widely used in neurologic conditions, such as cerebral stroke, Alzheimer's disease, and dementia, among others. Cerebrolysin treatment has achieved to regain or maintain the cognitive ability of affected patients; however, up to date, there are no reports about the reactivation of hair pigmentation. We describe a previously not described effect occurring on patients receiving Cerebrolysin treatment for neurologic diseases and whether this effect is associated in reactivation of melanocytes and melanin expression. Here, we report five patients (mean age, 70.6 years), who also had age-related hair graying and scalp hair repigmentation during Cerebrolysin treatment. Macroscopic analysis revealed hair repigmentation consisted in diffuse darkening of the scalp hair. Impregnation and immunostaining analysis were performed on scalp biopsies taken before and after Cerebrolysin treatment; the results showed greater melanin and melanocyte marker MART-1/Melan-A staining following Cerebrolysin treatment. We present, to our knowledge, the first report on hair repigmentation is a previously not described effect occurring following Cerebrolysin treatment.
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Cor de Cabelo , Melaninas , Humanos , Idoso , Antígeno MART-1 , CabeloRESUMO
RESUMEN Introducción: la melanosis neurocutánea es un trastorno congénito no hereditario que se caracteriza por la asociación de nevus pigmentados múltiples o de gran tamaño y una excesiva proliferación de melanocitos en el sistema nervioso central. La incidencia es similar en ambos sexos, y se observa historia familiar de melanoma en un único caso. Presentación del caso: se trata de un neonato masculino que nace en Hospital General de Luanda en Angola, con mancha melánica gigante que se extiende desde el cuello, cara, tórax, abdomen, espalda y miembros superiores, requiere una vigilancia de las lesiones dérmicas y un control de las crisis convulsivas. Discusión: se realizaron revisiones de la literatura médica disponible sobre el tema, consultando el programa de genética Oxford, y se tomaron fotos de las características clínicas sobresalientes. Por lo general los síntomas neurológicos son de temprana aparición en la etapa neonatal o de lactante con presencia de convulsiones de difícil control, al crear un pronóstico reservado. Conclusiones: se considera importante el seguimiento del neurodesarrollo de forma multidisciplinario para intervención oportuna si fuera necesario.
ABSTRACT Introduction: neurocutaneous melanosis is a non-hereditary congenital disorder characterized by the association of multiple or large pigmented nevi and an excessive proliferation of melanocytes in the central nervous system. The incidence is similar in both sexes, and a family history of melanoma is observed in a single case. Case presentation: this is a male neonate born at the General Hospital of Luanda in Angola, with a giant melanic spot that extends from the neck, face, chest, abdomen, back and upper limbs, requires surveillance of dermal lesions and control of seizures. Discussion: reviews of the available medical literature on the subject were conducted, consulting the Oxford genetics program, and photos of outstanding clinical features were taken. Usually the neurological symptoms are of early onset in the neonatal or infant stage with the presence of seizures that are difficult to control, creating a reserved prognosis. Conclusions: it is considered important to monitor neurodevelopment in a multidisciplinary way for timely intervention if necessary.
RESUMO Introdução: a melanose neurocutânea é uma doença congênita não hereditária caracterizada pela associação de nevi pigmentado múltiplo ou grande e uma proliferação excessiva de melanócitos no sistema nervoso central. A incidência é semelhante em ambos os sexos, e um histórico familiar de melanoma é observado em um único caso. Apresentação do caso: trata-se de um recém-nascido no Hospital Geral de Luanda, em Angola, com um ponto melanico gigante que se estende do pescoço, rosto, tórax, abdômen, costas e membros superiores, requer vigilância de lesões dérmicas e controle de convulsões. Discussão: foram realizadas revisões da literatura médica disponível sobre o tema, consultando o programa de genética de Oxford e fotos de características clínicas de destaque. Geralmente os sintomas neurológicos são de início precoce no estágio neonatal ou infantil com a presença de convulsões de difícil controle, criando um prognóstico reservado. Conclusões: é considerado importante monitorar o neurodesenvolvimento de forma multidisciplinar para intervenção oportuna, se necessário.
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Melasma is a multifactorial dyschromia that results from exposure to external factors (such as solar radiation) and hormonal factors (such as sex hormones and pregnancy), as well as skin inflammation (such as contact dermatitis and esthetic procedures), in genetically predisposed individuals. Beyond hyperfunctional melanocytes, skin with melasma exhibits a series of structural and functional alterations in the epidermis, basement membrane, and upper dermis that interact to elicit and sustain a focal hypermelanogenic phenotype. Evolution in the knowledge of the genetic basis of melasma and the cutaneous response to solar radiation, as well as the roles of endocrine factors, antioxidant system, endothelium proliferation, fibroblast senescence, mast cell degranulation, autophagy deficits of the melanocyte, and the paracrine regulation of melanogenesis, will lead to the development of new treatments and preventive strategies. This review presents current knowledge on these aspects of the pathogenesis of melasma and discusses the effects of specific treatments and future research on these issues.
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BACKGROUND: Vitiligo is a common disease with a high burden, and its recalcitrant type is unresponsive to current medical treatments. Autologous non-cultured and trypsinized melanocyte grafting, which is a simple and experience-based procedure, has been suggested for the treatment of vitiligo. OBJECTIVE: To assess autologous non-cultured and trypsinised melanocyte grafting in recalcitrant vitiligo. METHODS: This clinical trial was done on 28 patients (20 females and 8 males). After demarcation and preparation of both donor and recipient sites, both sites were shaved by a curette. The materials harvested from the donor site were trypsinized and centrifuged. The resulting suspension was mixed with hyaluronic acid gel and was spread over the shaved recipient area. RESULTS: Twenty-eight patients with a total of 108 lesions and a mean age of 25.93 ± 7.11 years were included in the present study. Generalized vitiligo (57.1%) was the most common clinical type and the face and neck regions (38%) were the most frequent treated sites. Good to excellent repigmentation was seen in the face and neck, trunk, upper extremity, and genitals in 31 (57.4%), 11 (20.4%), 9 (16.7%) and 3 (5.5%) patients, respectively. Face and neck showed significantly better results (p < 0.05). STUDY LIMITATIONS: Low sample size and single-center study. CONCLUSION: Autologous non-cultured and trypsinized melanocyte grafting is a safe method with satisfactory outcomes in recalcitrant vitiligo. Appropriate training of physicians and proper use of specialists' experiences can be effective in increasing the improvement rate.
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Vitiligo , Adolescente , Adulto , Feminino , Humanos , Irã (Geográfico) , Masculino , Melanócitos/patologia , Transplante Autólogo , Resultado do Tratamento , Vitiligo/patologia , Vitiligo/terapia , Adulto JovemRESUMO
BACKGROUND: French maritime pine bark (Pinus pinaster) extract (PBE), the registered trade name of which is Pycnogenol® , has been studied for its depigmenting action due to its antioxidant, anti-inflammatory, and anti-melanogenic activity. However, the mechanisms through which PBE are still not fully clear. OBJECTIVE: Evaluate the impact of PBE on four in vitro parameters closely associated with cutaneous pigmentation, including melanin synthesis, tyrosinase activity, endothelin-1 (ED1), and production of peroxisome proliferator-activated receptor α, δ, and γ (PPAR α, δ, and γ), by studying the modulation of action of ultraviolet radiation A (UVA)/ultraviolet radiation B (UVB), infrared-A (IR-A), visible light (VL), and association of UVA/UVB, IR-A, and VL (ASS). METHODS: Human melanocytes were incubated in a dry extract solution of PBE, exposed to UVA/UVB, IR-A, VL, and ASS for subsequent quantification of melanin, ED1, and PPAR α, δ, and γ. The effects of PBE on inhibition of tyrosinase activity were also performed by monophenolase activity assay. RESULTS: UVA/UVB, IR-A, VL, and ASS radiation caused significant increases in the synthesis of melanin, ED1, and PPAR α, δ, and γ when compared to baseline control. However, PBE significantly reduced the production of melanin, ED1, and PPAR α, δ, and γ, as well as reducing about 66.5% of the tyrosinase activity. CONCLUSIONS: PBE reduces in vitro melanin production by downregulating tyrosinase and reducing pigmentation-related mediators, such as ED1 and PPAR α, δ, and γ, therefore contributing to the inhibition of pathways associated with skin hyperpigmentation.
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Melaninas , Monofenol Mono-Oxigenase , Endotelina-1/metabolismo , Endotelina-1/farmacologia , Humanos , Melanócitos/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/farmacologia , Casca de Planta/metabolismo , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Raios UltravioletaRESUMO
Abstract Background Vitiligo is a common disease with a high burden, and its recalcitrant type is unresponsive to current medical treatments. Autologous non-cultured and trypsinized melanocyte grafting, which is a simple and experience-based procedure, has been suggested for the treatment of vitiligo. Objective To assess autologous non-cultured and trypsinised melanocyte grafting in recalcitrant vitiligo. Methods This clinical trial was done on 28 patients (20 females and 8 males). After demarcation and preparation of both donor and recipient sites, both sites were shaved by a curette. The materials harvested from the donor site were trypsinized and centrifuged. The resulting suspension was mixed with hyaluronic acid gel and was spread over the shaved recipient area. Results Twenty-eight patients with a total of 108 lesions and a mean age of 25.93 ± 7.11 years were included in the present study. Generalized vitiligo (57.1%) was the most common clinical type and the face and neck regions (38%) were the most frequent treated sites. Good to excellent repigmentation was seen in the face and neck, trunk, upper extremity, and genitals in 31 (57.4%), 11 (20.4%), 9 (16.7%) and 3 (5.5%) patients, respectively. Face and neck showed significantly better results (p < 0.05). Study limitations Low sample size and single-center study. Conclusion Autologous non-cultured and trypsinized melanocyte grafting is a safe method with satisfactory outcomes in recalcitrant vitiligo. Appropriate training of physicians and proper use of specialists' experiences can be effective in increasing the improvement rate.
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Background: Melanoma is a malignant neoplasm that arises from melanocytes and malanoblasts. It is also more frequently reported in dogs than in other species. They may arise from melanocytes in the skin, on the surfaces of the mucous membranes, and eyes. The aim of this study was to describe the epidemiological aspects, risk factors and clinicopathological findings of melanoma in dogs in the backlands, northeastern Brazil. Materials, Methods & Results: A retrospective study was carried out in all biopsy samples and necropsy examinations of dogs, from January 2003 to December 2021, at the Animal Pathology Laboratory of the Federal University of Campina Grande, Patos, Paraiba, northeastern Brazil. Epidemiological data, clinical signs, and gross lesions were reviewed from the diagnostic laboratory reports. Samples of the skin, lymph nodes, central nervous system and organs of the thoracic and abdominal cavities were fixed in 10% buffered formalin, processed routinely for histopathology, embedded in paraffin wax, cut into 4 µm sections, and stained with hematoxylin and eosin (HE). Histological sections were also submitted to immunohistochemistry with the primary antibody anti-Melan A. Of the 4717 records found, 1158 (24.5%) were diagnosed with neoplasms, of which 48 (4.14%) cases were of melanoma. Of this total, 28 (58.3%) dogs were elderly, 19 (39.6%) were adults, and 1 (2.1%) was young. Mixed breed animals were the most affected (42.6%), followed by the pinscher breed (19.1%). According to the anatomical region, the most affected site was the skin (38/53=71.7%), followed by the oral cavity (12/53=22.65%) and the eyes (3/53=5.7%). Grossly, the skin lesions were characterized by exophytic and usually blackened, sometimes irregular and firm, nodules. At cut, they had a smooth, compact and blackened surface. Lesions in the oral cavity were characterized by blackened, irregular and infiltrating nodules or masses. The ocular lesions were always unilateral and were characterized by an enlarged and diffusely blackened eyeball, with areas of ulceration and subversion of tissue architecture. In 5 animals there was more than one anatomical site affected, totaling 53 lesions. In 9 (17%) cases, metastases were identified, 8 in regional lymph nodes and 1 in the lung. Histopathology showed a densely non-encapsulated, poorly delimited, expansive and infiltrative neoplasm, composed of neoplastic cells arranged in islands or nests and supported by fibrovascular stroma, containing a variable amount of brownish pigment (melanin). Immunohistochemistry showed strong immunostaining of the neoplastic cells in brown by the anti-Melan A antibody. Discussion: The diagnosis of melanoma was established based on epidemiological, clinical, anatomopathological, and immunohistochemical findings. Gender is not a predisposing factor, and although there was no statistically significant relationship, males were more affected. Senescence is a conditioning risk factor. Elderly animals were more affected (P < 0.0001) than adult ones, with OR = 4.38; and young ones (P = 0.0051), with OR = 12.65. Some breeds, especially those with marked skin pigmentation, were more affected, however the most affected ones in this survey were pinscher and poodle. Cutaneous melanoma accounted for almost 72% of cases, contesting recent studies where oral cavity melanoma was more frequent. Therefore, it is believed that the climatic conditions of the backlands sub-region, in northeastern Brazil, associated with the individual characteristics of the dogs, are involved in the development of these neoplasms, since the climate is predominantly dry, with high temperatures throughout the year, with maximums that can reach 40ºC, favoring the exposure to high incidence of ultraviolet radiation.
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Animais , Cães , Melanócitos/patologia , Melanoma/veterinária , Melanoma/epidemiologia , Dermatopatias/veterináriaRESUMO
Skin melanocytes harbor a complex photosensitive system comprised of opsins, which were shown, in recent years, to display light- and thermo-independent functions. Based on this premise, we investigated whether melanopsin, OPN4, displays such a role in normal melanocytes. In this study, we found that murine Opn4KO melanocytes displayed a faster proliferation rate compared to Opn4WT melanocytes. Cell cycle population analysis demonstrated that OPN4KO melanocytes exhibited a faster cell cycle progression with reduced G0-G1, and highly increased S and slightly increased G2/M cell populations compared to the Opn4WT counterparts. Expression of specific cell cycle-related genes in Opn4KO melanocytes exhibited alterations that corroborate a faster cell cycle progression. We also found significant modification in gene and protein expression levels of important regulators of melanocyte physiology. PER1 protein level was higher while BMAL1 and REV-ERBα decreased in Opn4KO melanocytes compared to Opn4WT cells. Interestingly, the gene expression of microphthalmia-associated transcription factor (MITF) was upregulated in Opn4KO melanocytes, which is in line with a higher proliferative capability. Taken altogether, we demonstrated that OPN4 regulates cell proliferation, cell cycle, and affects the expression of several important factors of the melanocyte physiology; thus, arguing for a putative tumor suppression role in melanocytes.
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Ciclo Celular/genética , Melanócitos/metabolismo , Opsinas de Bastonetes/deficiência , Animais , Biomarcadores , Proteínas CLOCK/genética , Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/genética , Proliferação de Células , Células Cultivadas , Citometria de Fluxo , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Inativação de Genes , Melanócitos/efeitos dos fármacos , Camundongos , Pele/citologia , Pele/metabolismoRESUMO
BACKGROUND: The aim was to analyze the frequency, clinical and demographic features of solitary and multiple/diffuse oral pigmented lesions submitted to histopathological examination, and to summarize the features that guide the clinical differential diagnosis. METHODS: Clinical and demographic data were retrieved from biopsy records and descriptive statistics were performed. RESULTS: Nine hundred and five (0.51%) oral pigmented lesions were retrieved among 177 356 specimens, being 95.9% solitary and 4.1% multiple/diffuse lesions. Regardless the overlapping clinical presentation, age, site, association with amalgam restoration, and a nodular appearance may help in the clinical differential diagnosis of solitary oral pigmentations. Patient's habits, site, and systemic signs and symptoms are helpful in the clinical differential diagnosis of multiple/diffuse lesions. CONCLUSIONS: Oral pigmented lesions are a rare diagnosis in oral pathology and solitary lesions are more commonly submitted to biopsy. Some key features help in the differential diagnosis, though biopsy can be warranted in doubtful cases.
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Mucosa Bucal , Úlceras Orais , Biópsia , Diagnóstico Diferencial , HumanosRESUMO
ABSTRACT: Gingival hyperpigmentation is produced by excessive melanin deposit, generating a dark gum coloring. Although it does not constitute a health issue, in some cases it usually represents an aesthetic problem that can affect psychologically, for which there are currently several treatment alternatives such as: surgery with scalpel, laser therapy, abrasion, cryosurgery, electrosurgery, among others. The aim of this literature review was to analyze the available information about gingival melanosis and the therapeutics that can be applied to improve the appearance of patients with this condition. Articles in English and Spanish, published during the period 2000-2020 in the PubMed, Medline, Scielo, Cochrane and Lilacs databases, were reviewed. It was concluded that the selection of the technique will depend on each particular case, however, the laser is the most relevant.
RESUMEN: La hiperpigmentación gingival se produce por el depósito excesivo de melanina, generando una coloración oscura de la encía. Aunque no constituye un inconveniente para la salud, en algunos casos suele representar un problema estético que puede afectar psicológicamente, por lo cual, en la actualidad existen diversas alternativas de tratamiento como: cirugía con bisturí, terapia láser, abrasión, criocirugía, electrocirugía, entre otros. El objetivo de esta revisión de la literatura fue analizar la información disponible acerca de la melanosis gingival y la terapéutica que puede ser aplicada para mejorar el aspecto de los pacientes con esta condición. Se revisaron artículos en inglés y español, publicados durante el período 2000-2020 en las bases de datos PubMed, Medline, Scielo, Cochrane y Lilacs. Se concluyó que la elección de la técnica dependerá de cada caso en particular, sin embargo, el láser es el más destacado.
Assuntos
Hiperpigmentação/classificação , Melanose/diagnóstico , Doenças da GengivaRESUMO
Melanoma is the most aggressive skin cancer, and in metastatic advanced states, it is completely refractory to chemotherapy. Therefore, it is relevant to understand the molecular bases that rule their aggressiveness. Connexins (Cxs) are proteins that under normal physiological conditions participate in intercellular communication, via the exchange of signaling molecules between the cytoplasm and extracellular milieu and the exchange of ions/second messengers between the cytoplasm of contacting cells. These proteins have shown important roles in cancer progression, chemo- and radiotherapy resistance, and metastasis. Accordingly, Cx26 and Cx43 seem to play important roles in melanoma progression and metastasis. On the other hand, Cx46 is typically expressed in the eye lens, where it seems to be associated with oxidative stress protection in fiber lens cells. However, in the last decade, Cx46 expression has been associated with breast and brain cancers, due to its role in potentiation of both extracellular vesicle release and cancer stem cell-like properties. In this review, we analyzed a potential role of Cx46 as a new biomarker and therapeutic target in melanoma.
Assuntos
Comunicação Celular , Conexinas/metabolismo , Melanoma/metabolismo , Proteínas de Neoplasias/metabolismo , Conexinas/genética , Humanos , Cristalino/metabolismo , Cristalino/patologia , Melanoma/genética , Melanoma/patologia , Proteínas de Neoplasias/genéticaRESUMO
The research purpose to perform a retrospective study of pigmented lesions in the oral mucosa and to discuss important aspects of their differential diagnosis and management in dental practice. Methods: This is a descriptive retrospective study of pigmented lesions in the oral cavity that were recorded and diagnosed at a referral service over a period of 28 years. Results: There were 172 cases of pigmented lesions among a total of 13,743 records, corresponding to a prevalence of 1.25% at this service. Females accounted for 61.6% of cases. The most affected age range was 31-40 years (23.8%). The most common anatomical location involved was the cheek mucosa (20.19%), followed by the lower lip (19.2%) and alveolar ridge (15.2%). Amalgam tattoo and melanotic macule (33.1%) were the most common pigmented lesions, followed by melanocytic nevus (21.6%). The lack of some information on the biopsy request forms was the main limitation of the study. Conclusion: Oral pigmented lesions were uncommon at the service analyzed, probably because not all of them were sent for histopathological analysis. However, a correct diagnosis is important so that patients receive adequate treatment(AU)
O objetivo da pesquisa é realizar um estudo retrospectivo de lesões pigmentadas na mucosa bucal e discutir aspectos importantes de seu diagnóstico e tratamento diferenciado na prática odontológica. Métodos: Trata-se de um estudo retrospectivo descritivo de lesões pigmentadas na cavidade oral que foram registradas e diagnosticadas na clínica de Estomatologia e laboratório de Patologia Oral por um período de 28 anos. Resultados: Ocorreram 172 casos de lesões pigmentadas em um total de 13.743 registros, correspondendo a uma prevalência de 1,25% neste serviço. O sexo feminino foi responsável por 61,6% dos casos. A faixa etária mais afetada foi de 31 a 40 anos (23,8%). A localização anatômica mais comum envolvida foi a mucosa da bochecha (20,19%), seguida pelo lábio inferior (19,2%) e crista alveolar (15,2%). Tatuagem de amálgama e mácula melanótica (33,1%) foram as lesões pigmentadas mais comuns, seguidas por nevo melanocítico (21,6%). A falta de algumas informações nos formulários de solicitação de biópsia foi a principal limitação do estudo. Conclusão: Lesões orais pigmentadas eram incomuns no serviço analisado, provavelmente porque nem todas foram encaminhadas para análise histopatológica. No entanto, um diagnóstico correto é importante para que os pacientes recebam tratamento adequado(AU)
Assuntos
Humanos , Feminino , Adulto , Melanócitos , Mucosa Bucal , Mucosa Bucal/lesões , Boca/lesõesRESUMO
BACKGROUND: Normal skin pigmentation pattern is an extremely important component of the appearance of a person, as it can be a significant factor in the social context of any person. A condition known as vitiligo is caused by the death of melanocytes leading to pigmentation loss in the skin. This affects all races across the globe and sometimes leads to social avoidance as in some communities, it is stigmatized. Although there are different pathobiological processes suspected because of the different underlying causes of vitiligo, autoimmunity and oxidative stress are suspected to be the most probable ones. OBJECTIVE: In this review, we present an overview of the underlying mechanisms causing and developing the disease. Also, some of the most successful treatments along with the clinical applications of Mesenchymal Stem Cells (MSCs) as a comprehensive approach for treating this condition will be covered. RESULTS: Autoreactive CD8+ T-cells are the primary suspect considered to be responsible for the destruction of melanocytes. Therefore, topical use of autoimmune inhibitors including those derived from MSCs, thanks to their immune-modulatory properties, have been reported to be successful in the promotion of repigmentation. MSCs can suppress the proliferation of CD8+T via the NKG2D pathway while inducing T-cell apoptosis. The use of pharmacological agents for reducing cellular oxidative stress with the help of topical application of antioxidants and growth factors also have been in use. Intravenous administration of MSCs has been shown to regulate the level of reactive oxidative species (ROS) in a mice model. Growth factors derived from platelet-rich-plasma (PRP) or from MSCs caused rapid tissue regeneration. CONCLUSIONS: Finally, MSC therapy also has been shown to stimulate the mobilization of healthy melanocytes, leading to successful repigmentation of skin lesions in vitiligo patients.