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[PMID]:29505523
[Au] Autor:Kang X; Zeng Y; Liang J; Li J; Ren D; Chai L; Sun Z; Yu S; Wu X; Han W; Wang W
[Ad] Endereço:Department of Dermatology.
[Ti] Título:Aberrations and clinical significance of BRAF in malignant melanoma: A series of 60 cases in Chinese Uyghur.
[So] Source:Medicine (Baltimore);97(1):e9509, 2018 Jan.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Malignant melanoma (MM) is a highly malignant melanocytic tumor, it occurs mostly in the skin, the mucous membrane close to the skin, but also in the tunicae rhagoides and the pia mater. The Uyghur is the largest ethnic group living in the Xinjiang Uyghur Autonomous Region of China, accounting for 46% of the total population of 20 million. Large-scale studies on MMs in Asian countries are limited. This study aimed to investigate BRAF mRNA expression and mutations in Chinese Uyghur patients with MMs and to identify the clinical features associated with these parameters.Formalin-fixed, paraffin wax-embedded tumor sections from 60 MMs were analyzed for BRAF expression using reverse transcription polymerase chain reaction (RT-PCR). Exons 11 and 15 of BRAF were analyzed for the presence of mutations using PCR and DNA sequencing. Sixty MMs were followed by mobile phone for survival analysis.BRAF mRNA expression was higher in MMs than in pigmented moles and normal skin tissues. Fourteen of 60 MMs had BRAF mutations. The frequency of BRAF mutations was significantly higher in patients younger than 60 years (10/28, 4/32, P = .02). A significant difference was observed in the frequency of BRAF mutations among specimens of mucosal, acral, chronic sun-induced damage (CSD), and non-CSD MMs (2/10, 3/19, 8/25, 1/6, P = .002). No significant association was found among BRAF mutations, sex, ulceration, or lymph node metastasis. MMs lymph node metastasis (hazard ratio 2.54 [95% confidence interval 1.062 - 6.066], P = .01) affected survival.This study indicated that BRAF mutations and expression might serve as independent adverse prognostic factors in melanoma.
[Mh] Termos MeSH primário: Melanoma/genética
Proteínas Proto-Oncogênicas B-raf/genética
Neoplasias Cutâneas/genética
[Mh] Termos MeSH secundário: Idoso
Grupo com Ancestrais do Continente Asiático/genética
China/epidemiologia
Feminino
Seres Humanos
Masculino
Melanoma/metabolismo
Melanoma/mortalidade
Meia-Idade
Mutação
Proteínas Proto-Oncogênicas B-raf/metabolismo
Neoplasias Cutâneas/metabolismo
Neoplasias Cutâneas/mortalidade
Análise de Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.7.11.1 (BRAF protein, human); EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180306
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009509


  2 / 102889 MEDLINE  
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[PMID]:29363351
[Au] Autor:Faghfuri E; Nikfar S; Niaz K; Faramarzi MA; Abdollahi M
[Ad] Endereço:a Pharmaceutical Biotechnology, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.
[Ti] Título:Mitogen-activated protein kinase (MEK) inhibitors to treat melanoma alone or in combination with other kinase inhibitors.
[So] Source:Expert Opin Drug Metab Toxicol;14(3):317-330, 2018 Mar.
[Is] ISSN:1744-7607
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Malignant melanoma (MM) is an aggressive disease with a rapidly rising incidence due to neoplasm of melanocytes. Molecular targeted therapies have demonstrated lower toxicity and improved overall survival versus conventional therapies of MM. The revealing of mutations in the BRAF/MEK/ERK pathway has led to the development of BRAF inhibitors such as vemurafenib and dabrafenib for the treatment of cutaneous MM. Though, progression of resistance to these agents has prompted attempts to target downstream proteins in this pathway. Trametinib, a MEK1/2 inhibitor, was approved in 2013 for the treatment of BRAF V600E/K mutation-positive unresectable or metastatic cutaneous melanoma patients. Areas covered: The aim of the current review is to present an update on the role of MEK in progressive melanomas and summarize latest results of clinical studies with innovative MEK inhibitors and/or combined approaches with other kinase inhibitors such as BRAF inhibitors in the treatment of MM. Expert opinion: Two combined treatments (i.e. trametinib plus dabrafenib and vemurafenib plus cobimetinib) target two different kinases in the BRAF/MEK/ERK pathway. The simultaneous prohibition of both MEK and BRAF is associated with more durable response rate than BRAF monotherapy and can overcome acquired resistance.
[Mh] Termos MeSH primário: Melanoma/tratamento farmacológico
Inibidores de Proteínas Quinases/administração & dosagem
Neoplasias Cutâneas/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
Resistência a Medicamentos Antineoplásicos
Seres Humanos
Melanoma/genética
Melanoma/patologia
Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores
Terapia de Alvo Molecular
Mutação
Inibidores de Proteínas Quinases/farmacologia
Proteínas Proto-Oncogênicas B-raf/genética
Neoplasias Cutâneas/genética
Neoplasias Cutâneas/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Protein Kinase Inhibitors); EC 2.7.11.1 (BRAF protein, human); EC 2.7.11.1 (Proto-Oncogene Proteins B-raf); EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180125
[St] Status:MEDLINE
[do] DOI:10.1080/17425255.2018.1432593


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[PMID]:29400030
[Au] Autor:Clarós P; Clarós A; Sarr MC
[Ti] Título:[Dermatofibrosarcoma protuberans of the face: Long term patient of a follow up].
[So] Source:Rev Laryngol Otol Rhinol (Bord);136(3):113-5, 2015.
[Is] ISSN:0035-1334
[Cp] País de publicação:France
[La] Idioma:fre
[Ab] Resumo:We report the case of a patient 40 years old affected by a facial tumour diagnosed as a dermatofibrosarcoma protu­berans. He has been followed in our clinic for the last 22 years. He got a recurrency after 11 years and after an other surgery he his actually free of disease. The purpose of this article is to evaluate the tumoral recurrency and the long term follow up.
[Mh] Termos MeSH primário: Dermatofibrossarcoma/patologia
Neoplasias Cutâneas/patologia
[Mh] Termos MeSH secundário: Adulto
Dermatofibrossarcoma/cirurgia
Intervalo Livre de Doença
Seres Humanos
Masculino
Recidiva Local de Neoplasia/cirurgia
Neoplasias Cutâneas/cirurgia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180206
[St] Status:MEDLINE


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[PMID]:29181576
[Au] Autor:Araújo R; Santos JMO; Fernandes M; Dias F; Sousa H; Ribeiro J; Bastos MMSM; Oliveira PA; Carmo D; Casaca F; Silva S; Medeiros R; Gil da Costa RM
[Ad] Endereço:Molecular Oncology and Viral Pathology Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.
[Ti] Título:Expression profile of microRNA-146a along HPV-induced multistep carcinogenesis: a study in HPV16 transgenic mice.
[So] Source:J Cancer Res Clin Oncol;144(2):241-248, 2018 Feb.
[Is] ISSN:1432-1335
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Persistent human papillomavirus (HPV) infection is associated with the development of certain types of cancer and the dysregulation of microRNAs has been implicated in HPV-associated carcinogenesis. This is the case of microRNA-146a (miR-146a), which is thought to regulate tumor-associated inflammation. We sought to investigate the expression levels of miR-146a during HPV16-mediated carcinogenesis using skin samples from K14-HPV16 transgenic mice which develop the consecutive phases of the carcinogenesis process. METHODS: Female transgenic (HPV ) and wild-type (HPV ) mice were sacrificed at 24-26 weeks-old or 28-30 weeks-old. Chest and ear skin samples from HPV and HPV mice were histologically classified and used for microRNA extraction and quantification by qPCR. RESULTS: Chest skin samples from 24 to 26 weeks-old HPV mice presented diffuse epidermal hyperplasia and only 22.5% showed multifocal dysplasia, while at 28-30 weeks-old all (100.0%) HPV animals showed epidermal dysplasia. All HPV ear skin samples showed carcinoma in situ (CIS). MiR-146a expression levels were higher in HPV compared to HPV mice (p = 0.006). There was also an increase in miR-146a expression in dysplastic skin lesions compared with hyperplasic lesions (p = 0.011). Samples showing CIS had a significant decrease in miR-146a expression when compared to samples showing epidermal hyperplasia (p = 0.018) and epidermal dysplasia (p = 0.009). CONCLUSIONS: These results suggest that HPV16 induces the overexpression of miR-146a in the initial stages of carcinogenesis (hyperplasia and dysplasia), whereas decreases its expression at later stages (CIS). Taken together, these data implicate and suggest different roles of miR-146a in HPV-mediated carcinogenesis.
[Mh] Termos MeSH primário: Carcinogênese/genética
Papillomavirus Humano 16/genética
MicroRNAs/biossíntese
[Mh] Termos MeSH secundário: Animais
Carcinogênese/metabolismo
Carcinogênese/patologia
Feminino
Hiperplasia/virologia
Camundongos
Camundongos Transgênicos
MicroRNAs/genética
Infecções por Papillomavirus/genética
Infecções por Papillomavirus/metabolismo
Infecções por Papillomavirus/virologia
Pele/patologia
Pele/virologia
Neoplasias Cutâneas/genética
Neoplasias Cutâneas/metabolismo
Neoplasias Cutâneas/patologia
Neoplasias Cutâneas/virologia
Transcriptoma
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MicroRNAs); 0 (Mirn146 microRNA, mouse)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171129
[St] Status:MEDLINE
[do] DOI:10.1007/s00432-017-2549-5


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[PMID]:28466385
[Au] Autor:Atilla E; Atilla PA; Bozdag SC; Yuksel MK; Toprak SK; Topcuoglu P; Akay BN; Sanli H; Gurman G; Ozcan M
[Ad] Endereço:BMT Unit, Department of Hematology, Cebeci Hospital, School of Medicine, Ankara University, Dikimevi, 06590, Ankara, Turkey. erdenatilla@gmail.com.
[Ti] Título:Allogeneic hematopoietic stem cell transplantation for refractory mycosis fungoides (MF) and Sezary syndrome (SS).
[So] Source:Int J Hematol;106(3):426-430, 2017 Sep.
[Is] ISSN:1865-3774
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Cutaneous T cell lymphoma is a heterogeneous group of lymphoproliferative disorders with different clinical behavior and prognosis in which malignant T cells accumulate in the skin. In the relapsed/refractory stage, treatment strategy varies depending on clinical perspective. We retrospectively evaluated advanced stage relapse or refractory mycosis fungoides and Sezary syndrome patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at our hospital. The overall response rate was 25%, while the disease progressed and relapsed after transplant in 38% of patients. Allo-HSCT may be a reasonable treatment option in the relapsed/refractory stage.
[Mh] Termos MeSH primário: Aloenxertos
Transplante de Células-Tronco Hematopoéticas
Micose Fungoide/terapia
Síndrome de Sézary/terapia
Neoplasias Cutâneas/terapia
[Mh] Termos MeSH secundário: Feminino
Seres Humanos
Masculino
Meia-Idade
Recidiva Local de Neoplasia
Estudos Retrospectivos
Neoplasias Cutâneas/reabilitação
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1007/s12185-017-2245-x


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[PMID]:29489698
[Au] Autor:Zuradelli M; Masci G; Ferraro E; Losurdo A; De Sanctis R; Torrisi R; Santoro A
[Ti] Título:Never too old to fight breast cancer: A case report.
[So] Source:Medicine (Baltimore);97(9):e9981, 2018 Mar.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Breast cancer is the most common cancer affecting females worldwide and its lifetime risk increases with age. Human epidermal growth factor receptor gene-2 (HER-2) positive breast cancer represents about 20% of all breast cancers, 1 out of 10 is diagnosed in women over 70 years of age. It tends to be more aggressive and to spread more quickly than other subtypes, but the introduction in clinical practice of new anti-HER-2 agents combined with chemotherapy has significantly improved progression free and overall survival. Elderly patients are frequently undertreated because of concerns about their age, performance status, and comorbidities. Here, we report a case of an octogenarian patient treated with T-DM1 with brilliant results. PATIENT CONCERNS: An 87 years old woman affected with HER-2 positive breast cancer presented progression of disease with lymph node and skin metastases after 3 lines of chemoimmunotherapy. DIAGNOSES: Breast cancer in elderly patient, lymph node, and skin metastases. INTERVENTIONS: Chemoimmunotherapy (trastuzumab emtansine). OUTCOME: Objective response of the disease and significant clinical benefit. LESSONS: This case clearly suggests that age and comorbidities do not always represent an absolute contraindication to combined treatments.
[Mh] Termos MeSH primário: Antineoplásicos Imunológicos/uso terapêutico
Neoplasias da Mama/tratamento farmacológico
Maitansina/análogos & derivados
Trastuzumab/uso terapêutico
[Mh] Termos MeSH secundário: Idoso de 80 Anos ou mais
Neoplasias da Mama/química
Neoplasias da Mama/patologia
Feminino
Seres Humanos
Linfonodos/patologia
Metástase Linfática
Maitansina/uso terapêutico
Receptor ErbB-2/análise
Neoplasias Cutâneas/tratamento farmacológico
Neoplasias Cutâneas/secundário
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Immunological); 14083FR882 (Maytansine); EC 2.7.10.1 (ERBB2 protein, human); EC 2.7.10.1 (Receptor, ErbB-2); P188ANX8CK (Trastuzumab); SE2KH7T06F (ado-trastuzumab emtansine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180301
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009981


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[PMID]:28922786
[Au] Autor:Suciu S; Eggermont AMM; Lorigan P; Kirkwood JM; Markovic SN; Garbe C; Cameron D; Kotapati S; Chen TT; Wheatley K; Ives N; de Schaetzen G; Efendi A; Buyse M
[Ad] Endereço:European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium; Gustave Roussy Cancer Campus Grand Paris, Villejuif, France; The Christie NHS Foundation Trust, Manchester, UK; University of Pittsburgh Cancer Institute and School of Medicine, Pittsburgh, PA; Mayo Clinic Ro
[Ti] Título:Relapse-Free Survival as a Surrogate for Overall Survival in the Evaluation of Stage II-III Melanoma Adjuvant Therapy.
[So] Source:J Natl Cancer Inst;110(1), 2018 Jan 01.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: We assessed whether relapse-free survival (RFS; time until recurrence/death) is a valid surrogate for overall survival (OS) among resected stage II-III melanoma patients through a meta-analysis of randomized controlled trials. Methods: Individual patient data (IPD) on RFS and OS were collected from 5826 patients enrolled in 11 randomized adjuvant trials comparing interferon (IFN) to observation. In addition, IPD from two studies comparing IFN and vaccination in 989 patients were included. A two-level modeling approach was used for assessing Spearman's patient-level correlation (rho) of RFS and OS and the trial-level coefficient of determination (R²) of the treatment effects on RFS and on OS. The results were validated externally in 13 adjuvant studies without available IPD. We then tested the results on the European Organisation for Research and Treatment of Cancer (EORTC) 18071 double-blind trial comparing ipilimumab 10 mg/kg with placebo, which showed a statistically significant impact of the checkpoint inhibitor on RFS and OS. All statistical tests were two-sided. Results: With a median follow-up of seven years, 12 of 13 trials showed a consistency between the IFN vs No IFN differences regarding RFS (hazard ratio [HR]RFS = 0.88) and OS (HROS = 0.91), but the small trial, Eastern Cooperative Oncology Group 2696, was an outlier (HRRFS = 0.72 vs HROS = 1.11). Therefore, even if rho was high, R² was low and could not reliably be estimated. Based on the 12 trials, rho remained high (0.89), and the hazard ratios for RFS and OS were strongly correlated (R² = 0.91). The surrogate threshold effect for RFS was estimated to be 0.77. For the EORTC 18071 trial, the hazard ratio for RFS was 0.75, predicting an effect of ipilimumab on OS. This was subsequently confirmed (HROS = 0.72, 95.1% confidence interval = 0.58 to 0.88, P = .001). Conclusions: In high-risk stage II-III melanoma, RFS appeared to be a valid surrogate end point for OS for adjuvant randomized studies assessing interferon or a checkpoint inhibitor. In future similar adjuvant studies, a hazard ratio for RFS of 0.77 or less would predict a treatment impact on OS.
[Mh] Termos MeSH primário: Anticorpos Monoclonais/uso terapêutico
Antineoplásicos/uso terapêutico
Interferon-alfa/uso terapêutico
Melanoma/tratamento farmacológico
Melanoma/mortalidade
Neoplasias Cutâneas/tratamento farmacológico
Neoplasias Cutâneas/mortalidade
[Mh] Termos MeSH secundário: Quimioterapia Adjuvante
Intervalo Livre de Doença
Seres Humanos
Ipilimumab
Melanoma/patologia
Melanoma/cirurgia
Estadiamento de Neoplasias
Ensaios Clínicos Controlados Aleatórios como Assunto
Neoplasias Cutâneas/patologia
Neoplasias Cutâneas/cirurgia
Taxa de Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Antineoplastic Agents); 0 (Interferon-alpha); 0 (Ipilimumab)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx133


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[PMID]:29429158
[Au] Autor:Sun M; Liu JG; Weng QY; Yu L; Wang J
[Ad] Endereço:Department of Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
[Ti] Título:[Pleomorphic and dedifferentiated leiomyosarcoma: a clinicopathologic analysis].
[So] Source:Zhonghua Bing Li Xue Za Zhi;47(2):87-93, 2018 Feb 08.
[Is] ISSN:0529-5807
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To investigate the clinicopathologic features, differential diagnosis and biological behavior of pleomorphic leiomyosarcoma (PLMS) and dedifferentiated leiomyosarcoma (DLMS). Forty-nine cases were collected from November 2007 to December 2016, including eight that diagnosed at Fudan University Shanghai Cancer Center, and 41 consultation cases. The clinical findings and pathologic features were reviewed. Immunophenotype was obtained in 33 cases and follow-up information was available in 38 cases. There were 22 males and 27 females with ages ranging from 24 to 83 years (mean 52.5 years). Fifteen cases occurred in extremities, 14 in deep body cavity, 11 in the trunk, 4 in the head and neck, 2 in the bladder, and 1 each in the inguinal region, perineum and femoral vein, respectively. Tumor sizes ranged from 3 to 30 cm (mean 9.1 cm). The tumors were composed of at least small foci of typical leiomyosarcoma (LMS) and areas of high-grade pleomorphic/undifferentiated sarcoma. The typical LMS component showed the characteristic morphology of smooth muscle differentiation and was low to intermediate grade in most cases. Pleomorphic areas were mainly composed of atypical spindle and polygonal cells admixed with variable large, bizarre atypical cells and multinuclear giant cells, mostly mimicking undifferentiated pleomorphic sarcoma. The pleomorphic and leiomyosarcomatous areas were usually intermixed, but the demarcation may be distinct or gradual in some cases. The classical LMS component was positive for at least one myogenic marker: α-SMA in 97.0%(32/33), desmin in 72.7%(24/33), H-caldesmon in 90.9% (20/22), MSA in 14/16, and calponin in 15/15 of cases. The pleomorphic sarcoma component was reactive for at least one myogenic marker in 87.9% (29/33) of cases, usually showing focal and less intense immunoreactivity than classical LMS component: α-SMA was positive in 81.8%(27/33), desmin in 48.5%(16/33), H-caldesmon in 72.7% (16/22), MSA in 12/16, and calponin in 11/15 of cases. Based on staining for muscle markers in the pleomorphic component, 29 cases were designated as PLMS, 4 as DLMS. Ki-67 index ranged from 15% to 70% (mean 40%). Follow-up data was available in 38 cases (77.6%), of which 11 patients (28.9%) died of disease, 12 patients were alive with unresectable or recurrent disease, 14 patients were alive with no evidence of disease and another one died of unrelated cause. The median disease-free and overall survival was 6 and 10 months respectively. Twelve patients exhibited local recurrence and 11 developed metastases. The median interval to progression was 8 months. The identification of areas of typical LMS is crucial for accurate diagnosis of PLMS and DLMS. Both PLMS and DLMS show more aggressive behavior and poorer prognosis than ordinary LMS.
[Mh] Termos MeSH primário: Leiomiossarcoma/patologia
Neoplasias Cutâneas/patologia
[Mh] Termos MeSH secundário: Actinas/análise
Adulto
Idoso
Idoso de 80 Anos ou mais
Biomarcadores Tumorais/análise
Proteínas de Ligação ao Cálcio/análise
Proteínas de Ligação a Calmodulina/análise
Diferenciação Celular
China
Desmina/análise
Diagnóstico Diferencial
Extremidades
Feminino
Histiocitoma Fibroso Maligno/química
Histiocitoma Fibroso Maligno/patologia
Seres Humanos
Imuno-Histoquímica
Imunofenotipagem
Leiomiossarcoma/química
Masculino
Proteínas dos Microfilamentos/análise
Meia-Idade
Recidiva Local de Neoplasia
Neoplasias Cutâneas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ACTA2 protein, human); 0 (Actins); 0 (Biomarkers, Tumor); 0 (Calcium-Binding Proteins); 0 (Calmodulin-Binding Proteins); 0 (Desmin); 0 (Microfilament Proteins); 0 (calponin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180213
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0529-5807.2018.02.002


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[PMID]:29348270
[Au] Autor:Liu XK; Li J
[Ad] Endereço:Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
[Ti] Título:Hyperpigmentation in the skin folds.
[So] Source:BMJ;360:j5729, 2018 01 18.
[Is] ISSN:1756-1833
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Acantose Nigricans/etiologia
Neoplasias Cutâneas/complicações
[Mh] Termos MeSH secundário: Acantose Nigricans/patologia
Virilha/patologia
Seres Humanos
Masculino
Meia-Idade
Neoplasias Cutâneas/patologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180120
[St] Status:MEDLINE
[do] DOI:10.1136/bmj.j5729


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[PMID]:29295999
[Au] Autor:Han S; Ren Y; He W; Liu H; Zhi Z; Zhu X; Yang T; Rong Y; Ma B; Purwin TJ; Ouyang Z; Li C; Wang X; Wang X; Yang H; Zheng Y; Aplin AE; Liu J; Shao Y
[Ad] Endereço:Frontier Institute of Science and Technology, and Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.
[Ti] Título:ERK-mediated phosphorylation regulates SOX10 sumoylation and targets expression in mutant BRAF melanoma.
[So] Source:Nat Commun;9(1):28, 2018 01 02.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In human mutant BRAF melanoma cells, the stemness transcription factor FOXD3 is rapidly induced by inhibition of ERK1/2 signaling and mediates adaptive resistance to RAF inhibitors. However, the mechanism underlying ERK signaling control of FOXD3 expression remains unknown. Here we show that SOX10 is both necessary and sufficient for RAF inhibitor-induced expression of FOXD3 in mutant BRAF melanoma cells. SOX10 activates the transcription of FOXD3 by binding to a regulatory element in FOXD3 promoter. Phosphorylation of SOX10 by ERK inhibits its transcription activity toward multiple target genes by interfering with the sumoylation of SOX10 at K55, which is essential for its transcription activity. Finally, depletion of SOX10 sensitizes mutant BRAF melanoma cells to RAF inhibitors in vitro and in vivo. Thus, our work discovers a novel phosphorylation-dependent regulatory mechanism of SOX10 transcription activity and completes an ERK1/2/SOX10/FOXD3/ERBB3 axis that mediates adaptive resistance to RAF inhibitors in mutant BRAF melanoma cells.
[Mh] Termos MeSH primário: Regulação Neoplásica da Expressão Gênica/genética
Melanoma/genética
Mutação
Proteínas Proto-Oncogênicas B-raf/genética
Fatores de Transcrição SOXE/genética
Neoplasias Cutâneas/genética
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Inibidores Enzimáticos/farmacologia
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Feminino
Fatores de Transcrição Forkhead/genética
Fatores de Transcrição Forkhead/metabolismo
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Seres Humanos
Indóis/farmacologia
Melanoma/tratamento farmacológico
Melanoma/metabolismo
Camundongos Endogâmicos BALB C
Camundongos Nus
Fosforilação
Proteínas Proto-Oncogênicas B-raf/metabolismo
Interferência de RNA
Receptor ErbB-3/genética
Receptor ErbB-3/metabolismo
Fatores de Transcrição SOXE/metabolismo
Neoplasias Cutâneas/tratamento farmacológico
Neoplasias Cutâneas/metabolismo
Sulfonamidas/farmacologia
Sumoilação
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (FOXD3 protein, human); 0 (Forkhead Transcription Factors); 0 (Indoles); 0 (SOX10 protein, human); 0 (SOXE Transcription Factors); 0 (Sulfonamides); 207SMY3FQT (vemurafenib); EC 2.7.10.1 (ERBB3 protein, human); EC 2.7.10.1 (Receptor, ErbB-3); EC 2.7.11.1 (Proto-Oncogene Proteins B-raf); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180104
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02354-x



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