RESUMO
BACKGROUND: Cell adhesion molecules are essential to lymphocyte migration in neoplastic and inflammatory skin diseases. Our aim was to investigate possible differences in cell adhesion molecule expression between mycosis fungoides (MF) and inflammatory skin diseases (drug reactions and allergic contact dermatitis). METHODS: We selected 33 biopsies from patients with MF and 10 biopsies of patients with inflammatory skin diseases from Department of Pathology-Universidade Federal de São Paulo (UNIFESP) from January 1997 to December 2013. Expression of α4ß1 integrin and αEß7 integrin was assessed by immunohistochemistry in intraepidermal lymphocytes by counting 4 microscopic epidermal fields (×400) and comparing those between the 2 groups. RESULTS: We observed increased expression of integrin αEß7 in intraepidermal lymphocytes in advanced stages of MF (T3 and T4). αEß7 expression was detected in intraepidermal dendritic cells of MF and inflammatory diseases samples. The expression of E-cadherin in epidermal cells in MF outlined Pautrier microabscesses, whereas in inflammatory diseases, spongiosis reduced its expression in keratinocytes. CONCLUSIONS: The findings presented here support the idea that the lymphocyte migratory mechanism observed in neoplasms is similar to that of inflammatory processes of the skin.
Assuntos
Biomarcadores Tumorais/análise , Moléculas de Adesão Celular/análise , Dermatite/patologia , Integrinas/metabolismo , Micose Fungoide/patologia , Neoplasias Cutâneas/patologia , Idoso , Biomarcadores Tumorais/genética , Biópsia por Agulha , Brasil , Estudos Transversais , Dermatite/genética , Progressão da Doença , Feminino , Hospitais Universitários , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Micose Fungoide/genética , Prognóstico , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Neoplasias Cutâneas/genéticaRESUMO
BACKGROUND: Diseases caused by melanized fungi include mycetoma, chromoblastomycosis and phaeohyphomycosis. This broad clinical spectrum depends on the dynamic interactions between etiologic agent and host. The immune status of the host influences on the development of the disease, as, an exemple. phaeohyphomicosis is more frequently observed in immunocompromised patients. OBJECTIVES: Examine the histological inflammatory response induced by Fonsecaea pedrosoi in several different strains of mice (BALB/c, C57BL/6, Nude and SCID, and reconstituted Nude). METHODS: Fonsecaea pedrosoi was cultivated on agar gel and a fragment of this gel was implanted subcutaneously in the abdominal region of female adult mice. After infection has been obtained, tissue fragment was studied histopathologically. RESULTS: There were significant changes across the strains, with the nodular lesion more persistent in Nude and SCID mice, whereas in immunocompetent mice the lesion progressed to ulceration and healing. The histopathological analysis showed a significant acute inflammatory reaction which consisted mainly of neutrophils in the initial phase that was subsequently followed by a tuberculoid type granuloma in immunocompetent mice. STUDY LIMITATIONS: There is no a suitable animal model for chromoblastomycosis. CONCLUSIONS: The neutrophilic infiltration had an important role in the containment of infection to prevent fungal spreading, including in immunodeficient mice. The fungal elimination was dependent on T lymphocytes. The re-exposure of C57BL/6 mice to Fonsecaea pedrosoi caused a delay in resolving the infection, and appearance of muriform cells, which may indicate that re-exposure to fungi, might lead to chronicity of infection.
Assuntos
Ascomicetos , Dermatomicoses/imunologia , Imunocompetência , Inflamação/imunologia , Inflamação/microbiologia , Animais , Contagem de Células Sanguíneas , Cromoblastomicose/imunologia , Cromoblastomicose/patologia , Doença Crônica , Dermatomicoses/patologia , Modelos Animais de Doenças , Feminino , Inflamação/patologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , Camundongos SCID , Neutrófilos , Especificidade da Espécie , Fatores de TempoRESUMO
Abstract: Background: Diseases caused by melanized fungi include mycetoma, chromoblastomycosis and phaeohyphomycosis. This broad clinical spectrum depends on the dynamic interactions between etiologic agent and host. The immune status of the host influences on the development of the disease, as, an exemple. phaeohyphomicosis is more frequently observed in immunocompromised patients. Objectives: Examine the histological inflammatory response induced by Fonsecaea pedrosoi in several different strains of mice (BALB/c, C57BL/6, Nude and SCID, and reconstituted Nude). Methods: Fonsecaea pedrosoi was cultivated on agar gel and a fragment of this gel was implanted subcutaneously in the abdominal region of female adult mice. After infection has been obtained, tissue fragment was studied histopathologically. Results: There were significant changes across the strains, with the nodular lesion more persistent in Nude and SCID mice, whereas in immunocompetent mice the lesion progressed to ulceration and healing. The histopathological analysis showed a significant acute inflammatory reaction which consisted mainly of neutrophils in the initial phase that was subsequently followed by a tuberculoid type granuloma in immunocompetent mice. Study limitations: There is no a suitable animal model for chromoblastomycosis. Conclusions: The neutrophilic infiltration had an important role in the containment of infection to prevent fungal spreading, including in immunodeficient mice. The fungal elimination was dependent on T lymphocytes. The re-exposure of C57BL/6 mice to Fonsecaea pedrosoi caused a delay in resolving the infection, and appearance of muriform cells, which may indicate that re-exposure to fungi, might lead to chronicity of infection.
Assuntos
Animais , Feminino , Ascomicetos , Dermatomicoses/imunologia , Imunocompetência , Inflamação/imunologia , Inflamação/microbiologia , Especificidade da Espécie , Fatores de Tempo , Contagem de Células Sanguíneas , Doença Crônica , Cromoblastomicose/imunologia , Cromoblastomicose/patologia , Camundongos SCID , Dermatomicoses/patologia , Modelos Animais de Doenças , Inflamação/patologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , NeutrófilosAssuntos
Humanos , Feminino , Idoso , Leucemia Plasmocitária , Macroglobulinemia de Waldenstrom , Citometria de FluxoRESUMO
Taphonomic processes affecting bone post mortem are important in forensic, archaeological and palaeontological investigations. In this study, the application of tissue microarray (TMA) analysis to a sample of femoral bone specimens from 20 exhumed individuals of known period of burial and age at death is described. TMA allows multiplexing of subsamples, permitting standardized comparative analysis of adjacent sections in 3-D and of representative cross-sections of a large number of specimens. Standard hematoxylin and eosin, periodic acid-Schiff and silver methenamine, and picrosirius red staining, and CD31 and CD34 immunohistochemistry were applied to TMA sections. Osteocyte and osteocyte lacuna counts, percent bone matrix loss, and fungal spheroid element counts could be measured and collagen fibre bundles observed in all specimens. Decalcification with 7% nitric acid proceeded more rapidly than with 0.5 M EDTA and may offer better preservation of histological and cellular structure. No endothelial cells could be detected using CD31 and CD34 immunohistochemistry. Correlation between osteocytes per lacuna and age at death may reflect reported age-related responses to microdamage. Methodological limitations and caveats, and results of the TMA analysis of post mortem diagenesis in bone are discussed, and implications for DNA survival and recovery considered.
Assuntos
Osso e Ossos/química , Osso e Ossos/metabolismo , Antropologia Forense/métodos , Análise Serial de Tecidos , Adulto , Idoso , Matriz Óssea/metabolismo , Calcificação Fisiológica , Células Endoteliais/metabolismo , Humanos , Pessoa de Meia-Idade , Osteócitos/metabolismoRESUMO
HSP70 connects multiple signaling pathways that work synergistically to protect tumor cells from death by proteotoxic stress and represents a possible target to establish a new approach for multiple myeloma treatment. Therefore, bioluminescent cell lines RPMI8226-LUC-PURO and U266-LUC-PURO were treated with HSP70 (VER155008) and/or proteasome (bortezomib) inhibitors and immunodeficient mice were used for subcutaneous xenograft models to evaluate tumor growth reduction and tumor growth inhibition after treatment. Bioluminescence imaging was used to follow tumor response. Treatment with bortezomib showed â¼60% of late apoptosis in RPMI8226-LUC-PURO (without additional benefit of VER155008 in this cell line). However, U266-LUC-PURO showed â¼60% of cell death after treatment with VER155008 (alone or with bortezomib). RPMI8226-LUC-PURO xenograft presented tumor reduction by bioluminescence imaging after treatment with bortezomib, VER155008 or drug combination compared to controls. Treatment with bortezomib, alone or combined with VER155008, showed inhibition of tumor growth assessed by bioluminescence imaging after one week in both RPMI8226-LUC-PURO and U266-LUC-PURO cell lines when compared to controls. In conclusion, our study shows that the combination of proteasome and HSP70 inhibitors induced cell death in tumor cells in vitro (late apoptosis induction) and in vivo (inhibition of tumor growth) with special benefit in U266-LUC-PURO, bearing 17p deletion.
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OBJECTIVE: The aim of this work was to demonstrate a possible relationship between anti-latency-associated peptide human latent transforming growth factor beta 1 (latent TGF-ß1) expression in megakaryocytes and microvascular density in bone marrow biopsies from patients with essential thrombocythemia and primary myelofibrosis. METHODS: Microvascular density was evaluated by immunohistochemical analysis and the expression of latent TGF-ß1 in samples (100 megakaryocytes per bone marrow sample) from 18 essential thrombocythemia and 38 primary myelofibrosis (19 prefibrotic and 19 fibrotic) patients. Six bone marrow donor biopsies were used as controls. Fibrosis in the bone marrow biopsies was evaluated according to the European Consensus. RESULTS: The average fibrosis grade differed between essential thrombocythemia and primary myelofibrosis groups when compared to the control group. Latent TGF-ß1 expression differed significantly between the fibrotic primary myelofibrosis (PMF) group and the control group (p-value<0.01). A high degree of neo-angiogenesis (demonstrated by analysis of CD34 expression) was detected in patients with myelofibrosis. There were correlations between latent TGF-ß1 expression and microvascular density (r=0.45; p-value<0.0009) and between degree of microvascular density and fibrosis grade (r=0.80; p-value<0.0001). Remarkable differences for neo-angiogenesis were not observed between patients with essential thrombocythemia and controls. CONCLUSION: Angiogenesis participates in the pathogenesis of primary myelofibrosis, in both the prefibrotic and fibrotic stages, while latent TGF-ß is differentially expressed only in the prefibrotic stage.
RESUMO
Objective: The aim of this work was to demonstrate a possible relationship between anti-latency-associated peptide human latent transforming growth factor beta 1 (latent TGF-β1) expression in megakaryocytes and microvascular density in bone marrow biopsies from patients with essential thrombocythemia and primary myelofibrosis. Methods: Microvascular density was evaluated by immunohistochemical analysis and the expression of latent TGF-β1 in samples (100 megakaryocytes per bone marrow sample) from 18 essential thrombocythemia and 38 primary myelofibrosis (19 prefibrotic and 19 fibrotic) patients. Six bone marrow donor biopsies were used as controls. Fibrosis in the bone marrow biopsies was evaluated according to the European Consensus. Results: The average fibrosis grade differed between essential thrombocythemia and primary myelofibrosis groups when compared to the control group. Latent TGF-β1 expression differed significantly between the fibrotic primary myelofibrosis (PMF) group and the control group (p-value < 0.01). A high degree of neo-angiogenesis (demonstrated by analysis of CD34 expression) was detected in patients with myelofibrosis. There were correlations between latent TGF-β1 expression and microvascular density (r = 0.45; p-value < 0.0009) and between degree of microvascular density and fibrosis grade (r = 0.80; p-value < 0.0001). Remarkable differences for neo-angiogenesis were not observed between patients with essential thrombocythemia and controls. Conclusion: Angiogenesis participates in the pathogenesis of primary myelofibrosis, in both the prefibrotic and fibrotic stages, while latent TGF-β is differentially expressed only in the prefibrotic stage...
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Humanos , Indutores da Angiogênese , Fibrose , Mielofibrose Primária , Fator de Crescimento Transformador beta1RESUMO
Transformation of myelodysplastic syndrome (MDS) into acute myelogenous leukemia occurs in approximately 30 % of cases, while progression into acute lymphoblastic leukemia (ALL) is rare. We report on a 67-year-old man with the diagnosis of MDS, subtype refractory anemia with ring sideroblasts (RARS), karyotype 20q- , JAK-2 negative and grade III fibrosis on the bone marrow biopsy, who evolved into ALL 33 months after the diagnosis of MDS. RARS is one of the subtypes of MDS with most indolent course. Deletion of the long arm of chromosome 20 (20q-) is considered as good prognosis by the International Prognostic Scoring System, an important scoring system for predicting survival and evolution of MDS. Primary MDS with bone marrow fibrosis may represent a distinct clinicopathological and is supposed to have an unfavorable prognosis. The combined analysis of these features makes this rare report still more challenging and illustrates that biology of MDS is yet to be discovered.