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1.
J Dtsch Dermatol Ges ; 20(7): 980-1002, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35775593

RESUMO

Sjögren's syndrome (SjS) is an autoimmune disease characterized by the triad of sicca symptoms, fatigue and pain. This diagnosis is usually made in women at the average age of 60 years. Diagnosis is made when sicca symptoms persist for more than three months, after the exclusion of possible differential diagnoses, and using the ACR/EULAR 2016 classification criteria for SjS. Many organs can be affected in the course of this disease. Xerosis cutis and pruritus are the most common skin manifestations, followed by leukocytoclastic vasculitis and subacute cutaneous lupus erythematosus. In addition, SjS patients often have myoarthralgia and neuropsychiatric symptoms. In the long term, attention must be paid to the increased risk of cardiovascular disease and lymphoma. Due to the multiorgan involvement in SjS patients, interdisciplinary care is required.


Assuntos
Lúpus Eritematoso Cutâneo , Linfoma , Síndrome de Sjogren , Diagnóstico Diferencial , Feminino , Humanos , Lúpus Eritematoso Cutâneo/diagnóstico , Pessoa de Meia-Idade , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/terapia
2.
J Dtsch Dermatol Ges ; 20(4): 483-504, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35446494

RESUMO

The magnitude of the topic of melanocytic nevi (MN) is directly related to its relevance in everyday clinical work. The different MN have different prognostic significance in regard to comorbidity and possible risk of transformation. In addition to the criteria of the ABCDE rule, relevant criteria in the assessment of an MN are the time of occurrence, the growth tendency, the distribution and the comparison with other MN of the respective individual. The present CME article provides an overview of the knowledge that has been gained with regard to the development and genetic background of MN and any risk of degeneration that may exist. In addition, certain clinical and/or dermatoscopic features may provide the clinician with a decision-making aid in the management of different MNs.


Assuntos
Melanoma , Nevo Pigmentado , Neoplasias Cutâneas , Humanos , Nevo Pigmentado/diagnóstico , Prognóstico , Neoplasias Cutâneas/diagnóstico
3.
J Dtsch Dermatol Ges ; 20(7): 980-1003, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35881105
9.
EMBO Mol Med ; 14(12): e15200, 2022 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-36341492

RESUMO

Leukemic cutaneous T-cell lymphomas (L-CTCL) are lymphoproliferative disorders of skin-homing mature T-cells causing severe symptoms and high mortality through chronic inflammation, tissue destruction, and serious infections. Despite numerous genomic sequencing efforts, recurrent driver mutations have not been identified, but chromosomal losses and gains are frequent and dominant. We integrated genomic landscape analyses with innovative pharmacologic interference studies to identify key vulnerable nodes in L-CTCL. We detected copy number gains of loci containing the STAT3/5 oncogenes in 74% (n = 17/23) of L-CTCL, which correlated with the increased clonal T-cell count in the blood. Dual inhibition of STAT3/5 using small-molecule degraders and multi-kinase blockers abolished L-CTCL cell growth in vitro and ex vivo, whereby PAK kinase inhibition was specifically selective for L-CTCL patient cells carrying STAT3/5 gains. Importantly, the PAK inhibitor FRAx597 demonstrated encouraging anti-leukemic activity in vivo by inhibiting tumor growth and disease dissemination in intradermally xenografted mice. We conclude that STAT3/5 and PAK kinase interaction represents a new therapeutic node to be further explored in L-CTCL.


Assuntos
Linfoma Cutâneo de Células T , Quinases Ativadas por p21 , Animais , Camundongos , Genômica , Xenoenxertos , Linfoma Cutâneo de Células T/tratamento farmacológico
10.
J Immunother Cancer ; 9(5)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33986126

RESUMO

BACKGROUND: Checkpoint inhibitors revolutionized the treatment of metastatic melanoma patients. Although tumor burden and lactate dehydrogenase (LDH) are associated with overall survival (OS), the impact of tumor growth kinetics remains elusive and in part contradictory. The aims of this study were to develop a novel simple and rapid method that estimates pretreatment metastatic growth rate (MGR) and to investigate its prognostic impact in melanoma patients treated with antiprogrammed death receptor-1 (PD-1) antibodies. METHODS: MGR was assessed in three independent cohorts of a total of 337 unselected consecutive metastasized stage IIIB-IV melanoma patients (discovery cohort: n=53, confirmation cohort: n=126, independent multicenter validation cohort: n=158). MGR was computed during the pretreatment period before initiation of therapy with anti-PD-1 antibodies nivolumab or pembrolizumab by measuring the increase of the longest diameter of the largest target lesion. Tumor doubling time served as quality control. Kaplan-Meier analysis and univariable as well as multivariable Cox regression were used to examine the prognostic impact of MGR. RESULTS: Pretreatment MGR >3.9 mm/month was associated with impaired OS in the discovery cohort (HR 6.19, 95% CI 2.92 to 13.10, p<0.0001), in the confirmation cohort (HR 3.62, 95% CI 2.19 to 5.98, p<0.0001) and in the independent validation cohort (HR 2.57, 95% CI 1.56 to 4.25, p=0.00023). Prior lines of systemic treatment did not influence the significance of MGR. Importantly, the prognostic impact of MGR was independent of total tumor burden, diameter of the largest metastasis, number of prior lines of systemic treatment, LDH, as well as liver and brain metastasis (discovery and confirmation cohorts: both p<0.0001). Superiority of MGR compared with these variables was confirmed in the independent multicenter validation cohort (HR 2.92, 95% CI 1.62 to 5.26, p=0.00036). CONCLUSIONS: High pretreatment MGR is an independent strong prognostic biomarker associated with unfavorable survival of melanoma patients receiving anti-PD-1 antibodies. Further investigations are warranted to assess the predictive impact of MGR in distinct systemic therapeutic regimens.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Proliferação de Células , Inibidores de Checkpoint Imunológico/uso terapêutico , Melanoma/tratamento farmacológico , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Cutâneas/tratamento farmacológico , Tomografia Computadorizada por Raios X , Anticorpos Monoclonais Humanizados/efeitos adversos , Europa (Continente) , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Masculino , Melanoma/diagnóstico por imagem , Melanoma/imunologia , Melanoma/secundário , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nivolumabe/efeitos adversos , Valor Preditivo dos Testes , Receptor de Morte Celular Programada 1/imunologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Fatores de Tempo , Resultado do Tratamento
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