Assuntos
Abatacepte , Toxidermias , Micose Fungoide , Humanos , Abatacepte/efeitos adversos , Micose Fungoide/patologia , Micose Fungoide/tratamento farmacológico , Toxidermias/etiologia , Toxidermias/patologia , Feminino , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/tratamento farmacológico , Antirreumáticos/efeitos adversos , Pessoa de Meia-Idade , Masculino , Artrite Reumatoide/tratamento farmacológico , IdosoRESUMO
Bosutinib, widely used as a primary treatment for chronic myeloid leukemia (CML), is known to frequently cause cutaneous drug eruptions. Fixed Drug Eruption (FDE) is common, typically presenting as recurrent lesions that heal with residual hyperpigmentation. Diagnosing FDE, especially Non-Pigmenting Fixed Drug Eruption (NPFDE), is often challenging. A correlation exists between the dosage of certain medications, such as levetiracetam, and the emergence of drug eruptions. This report details a unique case of dose-dependent NPFDE caused by bosutinib. In managing cutaneous drug eruptions, particularly when the causative drug is crucial for treatment, a strategy of tapering the dosage should be considered.
Assuntos
Toxidermias , Quinolinas , Humanos , Toxidermias/diagnóstico , Toxidermias/etiologia , Toxidermias/patologia , Compostos de Anilina/efeitos adversos , Nitrilas/efeitos adversosRESUMO
We report a case of pyoderma gangrenosum (PG) caused by secukinumab, which was successfully treated with risankizumab. We also reviewed reported cases of PG caused by interleukin (IL)-17 inhibitors. The clinical course of this case indicates that IL-23 may play an important role in the pathogenesis of PG and therefore IL-23-targeting therapies may be a treatment option for PG.
Assuntos
Pioderma Gangrenoso , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Humanos , Interleucina-23 , Pioderma Gangrenoso/tratamento farmacológicoRESUMO
Angiosarcoma is a rare malignant tumor derived from endothelial cells, and its prognosis is poor because advanced angiosarcoma is often resistant to taxane therapy. Endoglin (CD105) acts as a coreceptor for TGF-ß signaling and is overexpressed in tumor-associated endothelial cells and enhances tumor angiogenesis. Numerous clinical trials are testing the effectiveness of anti-endoglin antibodies in various types of malignancies. Here, we investigated the role of endoglin in the pathogenesis of angiosarcoma and whether endoglin inhibition results in antitumor activity. Endoglin was overexpressed in angiosarcoma, and its inhibition was effective in promoting apoptosis and the suppression of migration, invasion, tube formation, and Warburg effect in angiosarcoma cells. Knockdown of endoglin activated caspase 3/7 that is essential for apoptosis, reduced survivin levels, and decreased paxillin and vascular endothelial cadherin phosphorylation and matrix metalloproteinase 2 and matrix metalloproteinase 9 activities in angiosarcoma cells. Although endoglin is a coreceptor that regulates TGF-ß signaling, the antitumor effect of endoglin in angiosarcoma was not based on Smad signaling regulation but on non-Smad TGF-ß signaling. Taken together, these results indicated that endoglin could be a novel therapeutic target for angiosarcoma.
Assuntos
Endoglina/fisiologia , Hemangiossarcoma/etiologia , Fator de Crescimento Transformador beta/fisiologia , Linhagem Celular Tumoral , Endoglina/antagonistas & inibidores , Hemangiossarcoma/tratamento farmacológico , Hemangiossarcoma/patologia , Humanos , Metaloproteinases da Matriz/fisiologia , Receptores de Fatores de Crescimento Transformadores beta/análise , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologiaRESUMO
BACKGROUND: Previous studies have indicated that MFG-E8 enhances tumor cell survival, invasion and angiogenesis. However, the role of MFG-E8 in angiosarcoma (AS) has not been clarified. OBJECTIVE: Objective was to elucidate the mechanism of the regulation by MFG-E8 in AS and the association between MFG-E8 and clinicopathological features of AS. METHODS: The effects of the depletion of MFG-E8 by siRNA on tube formation, migration and proliferation in murine AS cells were examined. The effect of administration of anti-MFG-E8 antibody (Ab) on tumor growth of AS in mice was examined. The associations of MFG-E8 expression and clinicopathological features of human AS were assessed. RESULTS: The expressions of MFG-E8 in murine and human AS cells were significantly higher than those in melanoma cells, macrophages and endothelial cells. Depletion of MFG-E8 in murine AS cells by siRNA significantly inhibited the formation of capillary-like structures and migration, but not proliferation. Administration of anti-MFG-E8 Ab significantly inhibited tumor growth and decreased the number of tumor-associated macrophages (TAMs) in AS tumors. Tumor size and the number of TAMs in human AS with high expression of MFG-E8 were significantly increased compared to those of AS with low expression of MFG-E8. Progression-free survival and overall survival time of the patients of AS with high expression of MFG-E8 were significantly shorter than those of AS with low expression of MFG-E8. CONCLUSIONS: AS-derived MFG-E8 might enhance tumor growth via angiogenesis and the induction of TAMs in autocrine/paracrine manner, and administration of anti-MFG-E8 Ab could be a therapeutic potential for AS.
Assuntos
Antígenos de Superfície/metabolismo , Hemangiossarcoma/patologia , Proteínas do Leite/metabolismo , Neovascularização Patológica/patologia , Neoplasias Cutâneas/patologia , Idoso , Animais , Anticorpos/administração & dosagem , Antígenos de Superfície/genética , Biópsia , Linhagem Celular Tumoral/transplante , Modelos Animais de Doenças , Feminino , Técnicas de Silenciamento de Genes , Hemangiossarcoma/irrigação sanguínea , Hemangiossarcoma/tratamento farmacológico , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Proteínas do Leite/antagonistas & inibidores , Proteínas do Leite/genética , Neovascularização Patológica/tratamento farmacológico , Pericitos , Células RAW 264.7 , RNA Interferente Pequeno/metabolismo , Pele/irrigação sanguínea , Pele/patologia , Neoplasias Cutâneas/irrigação sanguínea , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
BACKGROUND: Angiosarcoma is a rare malignant tumor with a poor prognosis. It is known that hypoxic condition activates tumor progression in several cancers. Additionally, hypoxic tumor microenvironment accelerates immune escape. However, the presence and significance of hypoxia in angiosarcoma has not been adequately investigated. OBJECTIVE: To study the role of hypoxia in the progression of angiosarcoma. METHODS: The protein level of hypoxia inducible factor-1α (HIF-1α) in angiosarcoma was examined using immunohistochemistry and immunoblotting. To study the effect of hypoxia on tumor progression, cell proliferation, migration, invasion, and tube formation assays were performed in angiosarcoma cells. The influence of tumor cell supernatant in hypoxia from angiosarcoma cells on immune escape and angiogenesis was analysed to investigate the modulatory effect of hypoxia on tumor microenvironment of angiosarcoma. The molecular mechanism related to these results was investigated using immunoblotting and real time RT-PCR. RESULTS: HIF-1α protein was over-expressed in angiosarcoma tissues and cell lines under hypoxic conditions, and there was heterogeneity of oxygen supply in angiosarcoma. Hypoxia enhanced the proliferation, migration, and invasion abilities and inhibited tube formation in angiosarcoma cells. Tumor cell supernatant in hypoxia from angiosarcoma cells activated the monocyte invasion ability, facilitated its differentiation into M2-like macrophages, and suppressed cell-adhesion. These in vitro results were compatible to the pathological findings of angiosarcoma patients. CONCLUSION: Hypoxia plays a major role in progression of angiosarcoma cells by enhancing cell proliferation, migration, and invasion and by modulating the tumor microenvironment.
Assuntos
Hipóxia Celular , Hemangiossarcoma/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Cutâneas/patologia , Microambiente Tumoral , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Humanos , Invasividade Neoplásica , Cultura Primária de Células , Pele/citologia , Pele/patologiaRESUMO
Cutaneous angiosarcoma (CAS) is a malignant sarcoma with poor prognosis. Programmed cell death-1 (PD-1)/programmed cell death-1 ligand-1 (PD-L1) expression reflects antitumor immunity, and is associated with patient prognosis in various cancers. The purpose of this study is to investigate the relationship between PD-1/PD-L1 expression and CAS prognosis. CAS cases (n = 106) were immunohistochemically studied for PD-L1 and PD-1 expression, and the correlation with patient prognosis was analyzed. PD-L1 expression was assessed by flow cytometry on three CAS cell lines with or without IFNγ stimulation. A total of 30.2% of patients' samples were positive for PD-L1, and 17.9% showed a high infiltration of PD-1-positive cells. Univariate analysis showed a significant relationship between a high infiltration of PD-1-positive cells with tumor site PD-L1 expression and favorable survival in stage 1 patients (p = 0.014, log-rank test). Multivariable Cox-proportional hazard regression analysis also showed that patients with a high infiltration of PD-1-positive cells with tumor site PD-L1 expression were more likely to have favorable survival, after adjustment with possible confounders (hazard ratio (HR) = 0.38, p = 0.021, 95% confidence interval (CI) 0.16-0.86). Immunofluorescence staining of CAS samples revealed that PD-L1-positive cells were adjacent to PD-1-positive cells and/or tumor stroma with high IFNγ expression. In vitro stimulation with IFNγ increased PD-L1 expression in two out of three established CAS cell lines. Our results suggest that PD-1/PD-L1 expression is related to CAS progression, and the treatment with anti-PD-1 antibodies could be a new therapeutic option for CAS.
Assuntos
Antifúngicos/efeitos adversos , Dermatite Alérgica de Contato/etiologia , Dermatoses do Pé/induzido quimicamente , Doenças da Unha/induzido quimicamente , Triazóis/efeitos adversos , Administração Tópica , Idoso , Humanos , Masculino , Onicomicose/tratamento farmacológico , Testes do EmplastroAssuntos
Infecções por Actinomycetales/microbiologia , Bacteriemia/microbiologia , Eritema Multiforme/microbiologia , Infecções por Actinomycetales/tratamento farmacológico , Idoso , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Diagnóstico Diferencial , Quimioterapia Combinada , Eritema Multiforme/tratamento farmacológico , Glucocorticoides/uso terapêutico , Humanos , Masculino , Meropeném/uso terapêutico , Prednisolona/uso terapêuticoRESUMO
BACKGROUND: The prognosis of angiosarcoma is poor and a novel treatment option for the disease is desired. The aim of this study was to investigate the prognostic significance of Forkhead box M1 (FOXM1), a transcription factor that regulates cell-cycle progression and various crucial processes in tumor progression, and its potential as a new therapeutic target. METHODS: We investigated 125 angiosarcoma clinical samples (94 primary lesions and 31 metastatic lesions in 94 patients) and a human angiosarcoma cell line (HAMON) using immunohistochemical staining and molecular biological approaches. FOXM1 expression in angiosarcoma samples was also compared with that in Kaposi's sarcomas (n = 13), epithelioid hemangioendotheliomas (n = 13) and benign hemangiomas (n = 10). RESULTS: Patients with FOXM1-overexpressing angiosarcoma had significantly shorter survival (both for disease-specific survival [DSS] and event-free survival [EFS]) than other patients (5-year DSS, 23.5% vs. 47.1%, P = 0.013; and 5-year EFS, 5.5% vs. 28.7%, P = 0.004). FOXM1 overexpression was also an independent prognostic factor for both DSS and EFS in Cox multivariate analyses (hazard ratio [HR] 2.84, 95% confidence interval [CI] 1.10-5.81, P = 0.039; and HR 4.16, 95%CI 2.03-8.67, P = 0.0001, respectively). FOXM1 inhibition using both small interfering RNA and a specific inhibitor (thiostrepton) suppressed cell proliferation of the angiosarcoma cell line. Furthermore, FOXM1 inhibition improved the chemosensitivity to docetaxel in vitro. CONCLUSIONS: FOXM1 inhibition may be a potential therapeutic option for angiosarcoma.