RESUMO
We report the case of a 70-year-old woman with vaginal melanoma and multiple metastases in the lung. After the third dose of nivolumab, decreased room-air resting arterial oxygen saturation with bilateral basal fine crackles on auscultation developed despite the absence of respiratory symptoms. Computed tomography showed ground-glass opacities with airspace consolidations scattered with a peculiar distribution, and most were observed around the existing metastatic tumors in the lung. From the 42nd day to the 56th day after the last administration of nivolumab, she received dexamethasone 1-2 mg/body for the prevention of adverse events after stereotactic radiation for brain metastasis. At 3 months after the last administration of nivolumab, a computed tomography scan revealed improvement of the pneumonia and a decreased size and number of metastatic lesions in the lung, although some lesions showed enlargement. Further examination is needed to clarify the relationship between the pattern of pneumonia after Nivo therapy and clinical effects.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Pneumonia em Organização Criptogênica/induzido quimicamente , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Vaginais/tratamento farmacológico , Idoso , Anticorpos Monoclonais/administração & dosagem , Antineoplásicos/administração & dosagem , Pneumonia em Organização Criptogênica/diagnóstico por imagem , Feminino , Humanos , Nivolumabe , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Characterization of the MAPK signaling pathway in melanoma has led to the development of MEK inhibitors for the treatment of NRAS-mutated melanoma. The success of molecular-targeted therapies underscores the need to identify mutations in target genes. Most of the current data on genetic mutations have been obtained from Caucasian melanoma patients, and screenings of Asian populations are limited. OBJECTIVE: The aim of the present study was to examine NRAS mutations in primary and metastatic lesions of Japanese melanoma patients. METHODS: Clinical melanoma specimens were collected from 127 Japanese patients, including primary (n = 67), metastatic (n = 25) and paired primary and metastatic lesions (n = 35). NRAS mutations in exons 1 and 2 were assessed by polymerase chain reaction and Sanger sequencing. RESULTS: The incidence of NRAS mutations was 7.1 %. NRAS (Q61) was the predominant genetic alteration (77.8 %). NRAS mutations were most frequently detected in acral melanomas (9.3 %), followed by melanomas without chronic sun-induced damage (7.0 %) and mucosal melanomas (4.8 %), and were not detected in melanomas with chronic sun-induced damage. In addition, NRAS mutations were more prevalent in the extremities than in other sites. The NRAS sequence in metastatic lesions did not match that of the primary tumor in one case. CONCLUSION: The frequency of NRAS mutations is lower in the Asian population than in Caucasian patients. The observed heterogeneity of melanoma suggests that genotyping of both primary and metastatic lesions is important to identify candidate patients for molecular-targeted therapies.
Assuntos
GTP Fosfo-Hidrolases/genética , Melanoma/genética , Proteínas de Membrana/genética , Mutação , Neoplasias Cutâneas/genética , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , Éxons , Feminino , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Neoplasias Cutâneas/patologia , População Branca/genéticaAssuntos
Herpesvirus Humano 3 , Interleucinas/genética , Psoríase/genética , Psoríase/virologia , Ciclosporina/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Heterozigoto , Humanos , Lactente , Interleucinas/deficiência , Masculino , Mutação , Psoríase/tratamento farmacológico , RecidivaAssuntos
Autoanticorpos/sangue , Colite Ulcerativa/imunologia , Eosinofilia/imunologia , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Infiltração de Neutrófilos , Pênfigo/imunologia , Pele/imunologia , Idoso , Autoantígenos/imunologia , Biomarcadores/sangue , Biópsia , Colite Ulcerativa/diagnóstico , Desmocolinas/imunologia , Ensaio de Imunoadsorção Enzimática , Eosinofilia/diagnóstico , Eosinofilia/tratamento farmacológico , Feminino , Glucocorticoides/administração & dosagem , Humanos , Infiltração de Neutrófilos/efeitos dos fármacos , Colágenos não Fibrilares/imunologia , Pênfigo/sangue , Pênfigo/diagnóstico , Pênfigo/tratamento farmacológico , Prednisolona/administração & dosagem , Testes Sorológicos , Pele/efeitos dos fármacos , Pele/patologia , Resultado do Tratamento , Colágeno Tipo XVIIRESUMO
BACKGROUND: Notch signaling controls a number of cellular processes, including cell fate decisions, proliferation, differentiation, and survival/apoptosis, in multiple tissues. In the epidermis, Notch1 functions as a molecular switch that controls the transition of cells from an undifferentiated state into a differentiated state. OBJECTIVE: To clarify the functions of Notch in the regenerated epidermis during wound healing. METHODS: Wounds on mouse skin were immunostained. To investigate the functions of Notch, Notch was inhibited in primary keratinocytes by treatment with a γ-secretase inhibitor and by small interfering RNA-mediated knockdown, and was activated by a recombinant adenovirus approach. RESULTS: Notch1 and Notch2 were down-regulated in the regenerated epidermis during wound healing. To clarify the significance of this down-regulation, we examined its effect on expression of the interleukin (IL)-1 family of proinflammatory cytokines because wounds are exposed to pathogens from the outside world. Among the IL-1 family, IL-36α expression was induced by Notch inhibition. This was consistent with the decreased IL-36α expression in Notch-overexpressing keratinocytes. Notch down-regulation in the regenerated epidermis may reinforce defense against stress from the outside world by inducing IL-36α expression. Next, we examined the effects of Notch down-regulation on keratinocyte growth and differentiation. Notch down-regulation did not alter keratinocyte proliferation. On the other hand, Notch1 down-regulation suppressed induction of spinous layer-specific keratins (keratin1 and keratin10) in keratinocytes, which was consistent with the decreased expression of these keratins in the regenerated epidermis. The reduced levels of these keratins would increase cellular flexibility. CONCLUSION: Notch down-regulation in the epidermis appears to contribute to tissue regeneration during wound healing.