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1.
JPRAS Open ; 15: 81-85, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32158803

RESUMO

Pyoderma gangrenosum (PG) is a rare and painful idiopathic skin condition that has one or more areas of chronic ulceration with well demarcated and undermined borders. Bone osteolysis (the pathological destruction of bone tissue) secondary to PG is a rare phenomenon with limited cases reported in children only. This is the first case report of scalp PG with cranial osteolysis in an 80-year-old adult, with an initial presentation mimicking skin carcinoma. This case highlights the importance of a multidisciplinary team (MDT) meeting discussion, diagnosis of PG by exclusion and the successful treatment of this patient's PG eroding to the bone.

2.
Br J Cancer ; 105(1): 118-23, 2011 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-21654685

RESUMO

BACKGROUND: Cutaneous melanoma is an aggressive disease. S100beta is an established biomarker of disease progression; however, the mechanism of its regulation in melanoma is undefined. METHODS: Expression of HOXC11 and SRC-1 was examined by immunohistochemistry and immunofluorescence. Molecular and cellular techniques were used to investigate regulation of S100beta, including, western blot, qPCR, ChIP and migration assays. RESULTS: Expression levels of the transcription factor HOXC11 and its coactivator SRC-1 were significantly elevated in malignant melanoma in comparison with benign nevi (P<0.001 and P=0.017, respectively, n=80), and expression of HOXC11 and SRC-1 in the malignant tissue associated with each other (P<0.001). HOXC11 recruitment to the promoter of S100beta was observed in the primary melanoma cell line SKMel28. S100beta expression was found to be dependant on both HOXC11 and SRC-1. Treatment with the Src/Abl inhibitor, dasatinib, reduced HOXC11-SRC-1 interaction and prevented recruitment of HOXC11 to the S100beta promoter. Dasatinib inhibited both mRNA and protein levels of S100beta and reduced migration of the metastatic cell line MeWo. CONCLUSION: We have defined a signalling mechanism regulating S100beta in melanoma, which can be modulated by dasatinib. Profiling patients for expression of key markers of this network has the potential to increase the efficacy of dasatinib treatment.


Assuntos
Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Fatores de Crescimento Neural/genética , Coativador 1 de Receptor Nuclear/metabolismo , Pirimidinas/farmacologia , Proteínas S100/genética , Tiazóis/farmacologia , Western Blotting , Proliferação de Células/efeitos dos fármacos , Imunoprecipitação da Cromatina , Dasatinibe , Imunofluorescência , Proteínas de Homeodomínio/antagonistas & inibidores , Proteínas de Homeodomínio/genética , Humanos , Técnicas Imunoenzimáticas , Imunoprecipitação , Melanoma/genética , Fatores de Crescimento Neural/metabolismo , Coativador 1 de Receptor Nuclear/genética , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Subunidade beta da Proteína Ligante de Cálcio S100 , Proteínas S100/metabolismo , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Células Tumorais Cultivadas
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