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1.
Dermatol Reports ; 14(3): 9444, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36199902

RESUMO

Acne vulgaris is the most common inflammatory disease of the skin. IL-1b has been found in acne lesions and is a promising target for therapy, but the evidence is limited. Therefore, this study was conducted to investigate the immunohistochemical expression of IL-1b in papule biopsies of inflammatory acne and its association with disease severity. This study involved 20 patients with acne vulgaris (13 females, median age: 22 years). Samples were taken using punch biopsy. Immunohistochemical IL-1b expression was semi-quantitatively assessed as absent, mild, moderate or strong. Disease severity was evaluated according to the Global Acne Grading System (GAGS). There were 7 patients with mild disease and 11 patients with moderate disease. Median GAGS score was 20. Mild and moderate accounted for 65% and 30% for dermal IL-1b expression, 60% and 40% for epidermal expression, and 70% and 15% for perifollicular expression. Moderate-strong perifollicular expression had significant higher GAGS score than absent-mild expression (median: 22 versus 16). This study shows the elevated immunoreactivity of IL-1b in papule biopsies of inflammatory acne vulgaris. The levels of IL-1b expression also correlates with disease severity. IL-1b could be a good candidate for targeting treatment of acne vulgaris.

2.
BMC Infect Dis ; 17(1): 311, 2017 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-28446137

RESUMO

BACKGROUND: Cryptococcosis is an opportunistic infection caused by the encapsulated yeast Cryptococcus neoformans and most remarkably manifests in HIV-infected individuals, especially in the settings of very low CD4 count. Development of cryptococcosis in HIV-uninfected individuals is exceedingly rare and usually signifies a marked immunodeficiency. Cryptococcosis in association with myasthenia gravis or thymoma has been previously documented in only very few cases in the literature. CASE PRESENTATION: We reported a complicated case of severe cutaneous cryptococcosis in a 39-year-old Vietnamese male patient with myasthenia gravis on long-term immunosuppressive therapy. The patient presented with a five month history of recurrent and progressive skin lesions that later on progressed into cryptococcal meningitis. CONCLUSION: Through this case, we aimed to emphasize the importance of including cutaneous cryptococcosis in the differential diagnosis of cutaneous lesions in patients on chronic immunosuppressive therapy. The cutaneous manifestations of cryptococcosis can be the first clue for a disseminated disease, which makes early recognition crucial and life-saving.


Assuntos
Criptococose/complicações , Dermatomicoses/complicações , Meningite Criptocócica/diagnóstico , Miastenia Gravis/complicações , Adulto , Criptococose/patologia , Cryptococcus neoformans/isolamento & purificação , Cryptococcus neoformans/patogenicidade , Dermatomicoses/patologia , Diagnóstico Diferencial , Humanos , Imunossupressores/uso terapêutico , Masculino , Meningite Criptocócica/etiologia , Miastenia Gravis/tratamento farmacológico , Infecções Oportunistas/complicações
3.
Nat Commun ; 6: 8792, 2015 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-26635184

RESUMO

Bevacizumab exerts anti-angiogenic effects in cancer patients by inhibiting vascular endothelial growth factor (VEGF). However, its use is still limited due to the development of resistance to the treatment. Such resistance can be regulated by various factors, although the underlying mechanisms remain incompletely understood. Here we show that bone marrow-derived fibrocyte-like cells, defined as alpha-1 type I collagen-positive and CXCR4-positive cells, contribute to the acquired resistance to bevacizumab. In mouse models of malignant pleural mesothelioma and lung cancer, fibrocyte-like cells mediate the resistance to bevacizumab as the main producer of fibroblast growth factor 2. In clinical specimens of lung cancer, the number of fibrocyte-like cells is significantly increased in bevacizumab-treated tumours, and correlates with the number of treatment cycles, as well as CD31-positive vessels. Our results identify fibrocyte-like cells as a promising cell biomarker and a potential therapeutic target to overcome resistance to anti-VEGF therapy.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Bevacizumab/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Fibroblastos/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Fator 2 de Crescimento de Fibroblastos/metabolismo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Patológica , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
4.
Clin Exp Metastasis ; 29(3): 207-16, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22170031

RESUMO

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) show dramatic antitumor activity in a subset of patients with non-small cell lung cancer who have an active mutation in the epidermal growth factor receptor (EGFR) gene. On the other hand, some lung cancer patients with wild type EGFR also respond to EGFR-TKIs, suggesting that EGFR-TKIs have an effect on host cells as well as tumor cells. However, the effect of EGFR-TKIs on host microenvironments is largely unknown. A multiple organ metastasis model was previously established in natural killer cell-depleted severe combined immunodeficient mice using human lung cancer cells. This model was used to investigate the therapeutic efficacy of erlotinib, an EGFR-TKI, on multiple organ metastases induced by human small cell lung cancer cells (SBC-5 cells) that did not express EGFR. Although erlotinib did not have any effect on the proliferation of SBC-5 cells in vitro, it significantly suppressed bone and lung metastases in vivo, but not liver metastases. An immunohistochemical analysis revealed that, erlotinib significantly suppressed the number of osteoclasts in bone metastases, whereas no difference was seen in microvessel density. Moreover, erlotinib inhibited EGF-induced receptor activator of nuclear factor kappa-B expression in an osteoblastic cell line (MC3T3-E1 cells). These results strongly suggested that erlotinib prevented bone metastases by affecting host microenvironments irrespective of its direct effect on tumor cells.


Assuntos
Carcinoma de Células Pequenas/patologia , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/patologia , Metástase Neoplásica/prevenção & controle , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Animais , Neoplasias Ósseas/prevenção & controle , Neoplasias Ósseas/secundário , Carcinoma de Células Pequenas/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fator de Crescimento Epidérmico/antagonistas & inibidores , Receptores ErbB/análise , Cloridrato de Erlotinib , Humanos , Neoplasias Pulmonares/química , Masculino , Camundongos , Neovascularização Patológica/prevenção & controle , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoclastos/efeitos dos fármacos , Ligante RANK/análise
5.
Mol Cancer Ther ; 10(7): 1218-28, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21551260

RESUMO

While epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors improve the prognosis of patients with EGFR mutant lung cancer, the prognosis of patients with nonmutant EGFR lung cancer, especially those with metastases, is still extremely poor. We have assessed the therapeutic efficacy of E7080, an orally available inhibitor of multiple tyrosine kinases including VEGF receptor 2 (VEGFR-2) and VEGFR-3, in experimental multiple organ metastasis of lung cancer cell lines without EGFR mutations. E7080 markedly inhibited the in vitro proliferation of VEGF-stimulated microvascular endothelial cells. Intravenous inoculation into natural killer cell-depleted severe combined immunodeficient mice of the small cell lung cancer cell lines H1048 (producing low amounts of VEGF) and SBC-5 (producing intermediate amounts of VEGF) resulted in hematogenous metastases into multiple organs, including the liver, lungs, kidneys, and bones, whereas intravenous inoculation of PC14PE6, a non-small cell lung cancer cell line producing high amounts of VEGF, resulted in lung metastases followed by massive pleural effusion. Daily treatment with E7080 started after the establishment of micrometastases significantly reduced the number of large (>2 mm) metastatic nodules and the amount of pleural effusion, and prolonged mouse survival. Histologically, E7080 treatment reduced the numbers of endothelial and lymph endothelial cells and proliferating tumor cells and increased the number of apoptotic cells in metastatic nodules. These results suggest that E7080 has antiangiogenic and antilymphangiogenic activity and may be of potential therapeutic value in patients with nonmutant EGFR lung cancer and multiple organ metastases.


Assuntos
Antineoplásicos/farmacologia , Células Endoteliais/efeitos dos fármacos , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação/genética , Compostos de Fenilureia/farmacologia , Quinolinas/farmacologia , Animais , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Camundongos SCID , Compostos de Fenilureia/uso terapêutico , Fosforilação/efeitos dos fármacos , Quinolinas/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/genética , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Análise de Sobrevida , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/genética , Fatores de Crescimento do Endotélio Vascular/genética , Fatores de Crescimento do Endotélio Vascular/metabolismo
6.
Clin Cancer Res ; 15(23): 7229-37, 2009 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-19934291

RESUMO

PURPOSE: Malignant pleural mesothelioma (MPM) is a biologically heterogeneous malignant disease with a poor prognosis. We reported previously that the anti-vascular endothelial growth factor (VEGF) antibody, bevacizumab, effectively inhibited the progression of VEGF-high-producing (but not VEGF-low-producing) MPM cells in orthotopic implantation models, indicating the need for novel therapeutic strategies to improve the poor prognosis of this disease. Therefore, we focused on the multi-tyrosine kinase inhibitor E7080 and assessed its therapeutic efficacy against MPM cells with different proangiogenic cytokine production profiles. EXPERIMENTAL DESIGN: The efficacy of E7080 was assayed in orthotopic implantation of severe combined immunodeficient mouse models with three human MPM cell lines (MSTO-211H, NCI-H290, and Y-MESO-14). RESULTS: With regard to proangiogenic cytokine production profiles, MSTO-211H and Y-MESO-14 cells were MPM cells producing high levels of fibroblast growth factor-2 and VEGF, respectively. NCI-H290 cells produced low levels of fibroblast growth factor-2 and VEGF compared with the other two cell lines. E7080 potently suppressed the phosphorylation of VEGF receptor-2 and FGF receptor 1 and, thus, inhibited proliferation of endothelial cells, but not that of the MPM cell lines, in vitro. Orthotopically inoculated MSTO-211H cells produced only thoracic tumors, whereas NCI-H290 and Y-MESO-14 cells also developed pleural effusions. Treatment with E7080 potently inhibited the progression of these three MPM cell lines and markedly prolonged mouse survival, which was associated with decreased numbers of tumor-associated vessels and proliferating MPM cells in the tumor. CONCLUSIONS: These results strongly suggest broad-spectrum activity of E7080 against MPM with different proangiogenic cytokine production profiles in humans.


Assuntos
Citocinas/biossíntese , Mesotelioma/tratamento farmacológico , Mesotelioma/patologia , Neovascularização Patológica , Compostos de Fenilureia/farmacologia , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/patologia , Quinolinas/farmacologia , Animais , Linhagem Celular Tumoral , Fator 2 de Crescimento de Fibroblastos/metabolismo , Humanos , Masculino , Camundongos , Camundongos SCID , Transplante de Neoplasias , Fosforilação , Fator de Crescimento Derivado de Plaquetas/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
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