RESUMO
BACKGROUND AND PURPOSE: MR imaging can reflect the pathologic progression of carcinoma ex pleomorphic adenoma (CXPA). This study aimed to identify the imaging findings related to extracapsular invasion of CXPA. Additionally, the pathologic background of these findings was investigated. MATERIALS AND METHODS: This retrospective study included 37 patients with histologically confirmed CXPA. Three radiologists independently evaluated whether the CXPA showed the following characteristic MR imaging findings: border, capsule, the corona sign on fat-saturated T2WI and contrast-enhanced fat-saturated T1WI, and the black ring sign. The corona sign appeared larger on fat-saturated and/or contrast-enhanced fat-saturated T1WI than on T1WI. The black ring sign was defined as an intratumoral nodule with a thick low-intensity rim on T2WI. Interreader agreement of the visual assessment was performed using κ analysis, and MR imaging and histopathologic findings were also correlated. Kaplan-Meier survival and the log-rank test were used to estimate the 3-year disease-free survival. RESULTS: MR imaging findings, especially peritumoral findings, showed a significant difference between invasive and noninvasive CXPA. The reliability was poor for the border and capsule. In contrast, it was good for the corona sign on fat-saturated and contrast-enhanced fat-saturated T1WI and the black ring sign. Pathologically, the corona sign reflected the invasiveness of the tumor and inflammatory cells, while the black ring sign reflected hyalinization or fibrosis. The corona sign also showed a significant difference in the 3-year disease-free survival. CONCLUSIONS: MR imaging findings, including the corona and black ring signs, reliably differentiated invasive and noninvasive CXPA. The corona sign can be used as a prognostic factor for CXPA.
Assuntos
Adenoma Pleomorfo , Carcinoma , Neoplasias das Glândulas Salivares , Humanos , Adenoma Pleomorfo/diagnóstico por imagem , Neoplasias das Glândulas Salivares/diagnóstico por imagem , Neoplasias das Glândulas Salivares/patologia , Estudos Retrospectivos , Reprodutibilidade dos Testes , Prognóstico , Imageamento por Ressonância Magnética , Carcinoma/diagnóstico por imagemRESUMO
BACKGROUND: MicroRNAs (miRNAs) have been shown to play major roles in carcinogenesis in a variety of cancers. The aim of this study was to determine the miRNA expression signature of oral squamous cell carcinoma (OSCC) and to investigate the functional roles of miR-26a and miR-26b in OSCC cells. METHODS: An OSCC miRNA signature was constructed by PCR-based array methods. Functional studies of differentially expressed miRNAs were performed to investigate cell proliferation, migration, and invasion in OSCC cells. In silico database and genome-wide gene expression analyses were performed to identify molecular targets and pathways mediated by miR-26a/b. RESULTS: miR-26a and miR-26b were significantly downregulated in OSCC. Restoration of both miR-26a and miR-26b in cancer cell lines revealed that these miRNAs significantly inhibited cancer cell migration and invasion. Our data demonstrated that the novel transmembrane TMEM184B gene was a direct target of miR-26a/b regulation. Silencing of TMEM184B inhibited cancer cell migration and invasion, and regulated the actin cytoskeleton-pathway related genes. CONCLUSIONS: Loss of tumour-suppressive miR-26a/b enhanced cancer cell migration and invasion in OSCC through direct regulation of TMEM184B. Our data describing pathways regulated by tumour-suppressive miR-26a/b provide new insights into the potential mechanisms of OSCC oncogenesis and metastasis.
Assuntos
Carcinoma de Células Escamosas/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Bucais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular , Feminino , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Transdução de SinaisRESUMO
BACKGROUND: Hypopharyngeal squamous cell carcinoma (HSCC) has a very poor prognosis because of its high rates of regional and distant metastasis. Identification of differentially expressed miRNAs and their regulated molecular targets in tumour cells might enhance our understanding of the molecular mechanisms of metastasis in human cancers. METHODS: A HSCC miRNA signature was constructed by array-based methods. Functional studies of microRNA-451a (miR-451a) and target genes were performed to investigate cell proliferation, migration and invasion by cancer cell lines. To identify miR-451a-regulated molecular targets, we adopted gene expression analysis and in silico database analysis. RESULTS: Our miRNA signature revealed that miR-451a was significantly downregulated in HSCC. Restoration of miR-451a in cancer cell lines revealed that this miRNA significantly inhibited cancer cell migration and invasion. Our data demonstrated that the gene coding for endothelial and smooth muscle cell-derived neuropilin-like molecule (ESDN/DCBLD2) was a direct target of miR-451a regulation. Silencing of ESDN inhibited cell migration and invasion by cancer cells. CONCLUSIONS: Loss of tumour suppressive miR-451a enhanced cancer cell migration and invasion in HSCC through direct regulation of ESDN. Our miRNA signature and functional analysis of targets regulated by tumour suppressive miR-451a provide new insights into the potential mechanisms of HSCC oncogenesis and metastasis.
Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias Hipofaríngeas/genética , MicroRNAs/genética , Idoso , Carcinoma de Células Escamosas/patologia , Processos de Crescimento Celular/genética , Linhagem Celular Tumoral , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Hipofaríngeas/patologia , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço , TransfecçãoRESUMO
Invariant natural killer T (iNKT) cells play important immunoregulatory functions in allergen-induced airway hyperresponsiveness and inflammation. To clarify the role of iNKT cells in allergic rhinitis (AR), we generated bone marrow-derived dendritic cells (BMDCs), which were pulsed by ovalbumin (OVA) and α-galactosylceramide (OVA/α-GalCer-BMDCs) and administered into the oral submucosa of OVA-sensitized mice before nasal challenge. Nasal symptoms, level of OVA-specific immunoglobulin (IgE), and T helper type 2 (Th2) cytokine production in cervical lymph nodes (CLNs) were significantly ameliorated in wild-type (WT) mice treated with OVA/α-GalCer-BMDCs, but not in WT mice treated with OVA-BMDCs. These anti-allergic effects were not observed in Jα18(-/-) recipients that lack iNKT cells, even after similar treatment with OVA/α-GalCer-BMDCs in an adoptive transfer study with CD4(+) T cells and B cells from OVA-sensitized WT mice. In WT recipients of OVA/α-GalCer-BMDCs, the number of interleukin (IL)-21-producing iNKT cells increased significantly and the Th1/Th2 balance shifted towards the Th1 dominant state. Treatment with anti-IL-21 and anti-interferon (IFN)-γ antibodies abrogated these anti-allergic effects in mice treated with α-GalCer/OVA-BMDCs. These results suggest that activation of iNKT cells in regional lymph nodes induces anti-allergic effects through production of IL-21 or IFN-γ, and that these effects are enhanced by simultaneous stimulation with antigen. Thus, iNKT cells might be a useful target in development of new treatment strategies for AR.
Assuntos
Células Dendríticas/imunologia , Interferon gama/imunologia , Interleucinas/imunologia , Linfonodos/imunologia , Células T Matadoras Naturais/imunologia , Animais , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Epitopos , Feminino , Galactosilceramidas/imunologia , Hipersensibilidade/imunologia , Imunoglobulina E/imunologia , Imunoterapia Adotiva/métodos , Interferon gama/biossíntese , Interleucinas/biossíntese , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Rinite/imunologia , Células Th1/imunologia , Células Th2/imunologiaRESUMO
BACKGROUND: Our recent studies of microRNA (miRNA) expression signatures demonstrated that microRNA-29s (miR-29s; miR-29a/b/c) were significantly downregulated in head and neck squamous cell carcinoma (HNSCC) and were putative tumour-suppressive miRNAs in human cancers. Our aim in this study was to investigate the functional significance of miR-29s in cancer cells and to identify novel miR-29s-mediated cancer pathways and responsible genes in HNSCC oncogenesis and metastasis. METHODS: Gain-of-function studies using mature miR-29s were performed to investigate cell proliferation, migration and invasion in two HNSCC cell lines (SAS and FaDu). To identify miR-29s-mediated molecular pathways and targets, we utilised gene expression analysis and in silico database analysis. Loss-of-function assays were performed to investigate the functional significance of miR-29s target genes. RESULTS: Restoration of miR-29s in SAS and FaDu cell lines revealed significant inhibition of cancer cell migration and invasion. Gene expression data and in silico analysis demonstrated that miR-29s modulated the focal adhesion pathway. Moreover, laminin γ2 (LAMC2) and α6 integrin (ITGA6) genes were candidate targets of the regulation of miR-29s. Luciferase reporter assays showed that miR-29s directly regulated LAMC2 and ITGA6. Silencing of LAMC2 and ITGA6 genes significantly inhibited cell migration and invasion in cancer cells. CONCLUSION: Downregulation of miR-29s was a frequent event in HNSCC. The miR-29s acted as tumour suppressors and directly targeted laminin-integrin signalling. Recognition of tumour-suppressive miRNA-mediated cancer pathways provides new insights into the potential mechanisms of HNSCC oncogenesis and metastasis and suggests novel therapeutic strategies for the disease.
Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Movimento Celular/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Integrinas/genética , Laminina/genética , MicroRNAs/fisiologia , Proliferação de Células , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica/genética , Genes Supressores de Tumor/fisiologia , Humanos , Invasividade Neoplásica , Transdução de Sinais/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço , Transfecção , Células Tumorais CultivadasRESUMO
BACKGROUND: Our recent studies of microRNA (miRNA) expression signature demonstrated that microRNA-874 (miR-874) was significantly downregulated in maxillary sinus squamous cell carcinoma (MSSCC), and a putative tumour-suppressive miRNA in human cancers. Our aim of this study was to investigate the functional significance of miR-874 in cancer cells and to identify novel miR-874-mediated cancer pathways and responsible genes in head and neck squamous cell carcinoma (HNSCC). METHODS: Gain-of-function studies using mature miR-874 were performed to investigate cell proliferation and cell cycle distribution in HNSCC cell lines (SAS and FaDu). To identify miR-874-mediated molecular pathways and targets, we utilised gene expression analysis and in silico database analysis. Loss-of-function assays were performed to investigate the functional significance of miR-874 target genes. RESULTS: Expression levels of miR-874 were significantly downregulated in HNSCC tissues (including oral, pharyngeal and laryngeal SCCs) compared with normal counterpart epithelia. Restoration of miR-874 in SAS and FaDu cell lines revealed significant inhibition of cell proliferation and induction of G2/M arrest and cell apoptosis. Our expression data and in silico analysis demonstrated that miR-874 modulated the cell cycle pathway. Moreover, histone deacetylase 1 (HDAC1) was a candidate target of miR-874 regulation. Luciferase reporter assays showed that miR-874 directly regulated HDAC1. Silencing of the HDAC1 gene significantly inhibited cell proliferation and induced G2/M arrest and cell apoptosis in SAS cells. CONCLUSIONS: Downregulation of miR-874 was a frequent event in HNSCC. miR-874 acted as a tumour suppressor and directly targeted HDAC1. Recognition of tumour-suppressive miRNA-mediated cancer pathways provides new insights into the potential mechanisms of HNSCC oncogenesis and suggests novel therapeutic strategies for the disease.
Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias de Cabeça e Pescoço/genética , Histona Desacetilase 1/genética , MicroRNAs/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose/genética , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Ciclo Celular/genética , Processos de Crescimento Celular/genética , Linhagem Celular Tumoral , Regulação para Baixo , Feminino , Genes Supressores de Tumor , Neoplasias de Cabeça e Pescoço/enzimologia , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Histona Desacetilase 1/biossíntese , Histona Desacetilase 1/metabolismo , Humanos , Masculino , Neoplasias do Seio Maxilar/enzimologia , Neoplasias do Seio Maxilar/genética , Neoplasias do Seio Maxilar/metabolismo , Neoplasias do Seio Maxilar/patologia , MicroRNAs/biossíntese , MicroRNAs/metabolismo , Pessoa de Meia-Idade , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço , TransfecçãoRESUMO
BACKGROUND: On the basis of the microRNA (miRNA) expression signature of maxillary sinus squamous cell carcinoma (MSSCC), we found that miR-874 was significantly reduced in cancer cells. We focused on the functional significance of miR-874 in cancer cells and identification of miR-874-regulated novel cancer networks in MSSCC. METHODS: We used PCR-based methods to investigate the downregulated miRNAs in clinical specimens of MSSCC. Our signature analyses identified 23 miRNAs that were significantly reduced in cancer cells, such as miR-874, miR-133a, miR-375, miR-204, and miR-1. We focused on miR-874 as the most downregulated novel miRNA in our analysis. RESULTS: We found potential tumour suppressive functions such as inhibition of cancer cell proliferation and invasion. A molecular target search of miR-874 revealed that PPP1CA was directly regulated by miR-874. Overexpression of PPP1CA was observed in MSSCC clinical specimens. Silencing of the PPP1CA gene significantly inhibited cancer cell proliferation and invasion. CONCLUSION: The downregulation of miR-874 was a frequent event in MSSCC, which suggests that miR-874 functions as a tumour suppressive miRNA, directly regulating PPP1CA that has a potential role of an oncogene. The identification of novel miR-874-regulated cancer pathways could provide new insights into potential molecular mechanisms of MSSCC oncogenesis.
Assuntos
Carcinoma de Células Escamosas/genética , Seio Maxilar , MicroRNAs/metabolismo , Idoso , Idoso de 80 Anos ou mais , Proliferação de Células , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteína Fosfatase 1/genéticaRESUMO
OBJECTIVES: The purpose of our study was to describe the MR appearance of Kimura disease and to interpret the differences in appearance from malignant parotid gland tumours. METHODS: MR studies of seven patients with Kimura disease were reviewed. The MR studies included T(1) weighted, T(2) weighted, short tau inversion-recovery, diffusion-weighted (DW) and dynamic contrast-enhanced imaging. RESULTS: Typical Kimura disease featured subcutaneous lesions, continuously infiltrated parotid lesions from the subcutaneous lesions with or without intraparotid lymphadenopathies, and reactive cervical lymphadenopathies. The subcutaneous lesions showed gradual upward enhancement on dynamic contrast-enhanced MR images. Reactive lymph nodes showed early enhancement on contrast-enhanced MR images and marked high intensity and low apparent diffusion coefficient values on DW images. CONCLUSION: An indication for making the diagnosis of Kimura disease should be the subcutaneous tissue of the head and neck showing gradual upward enhancement on dynamic contrast-enhanced MRI and a lack of high intensity on DW images, associated with reactive lymph nodes.
Assuntos
Hiperplasia Angiolinfoide com Eosinofilia/diagnóstico , Imagem de Difusão por Ressonância Magnética , Neoplasias de Cabeça e Pescoço/diagnóstico , Linfoma/diagnóstico , Adolescente , Adulto , Idoso , Hiperplasia Angiolinfoide com Eosinofilia/patologia , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Linfonodos/patologia , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Parotídeas/diagnóstico , Neoplasias Parotídeas/patologia , Adulto JovemRESUMO
BACKGROUND: Hypopharyngeal squamous cell carcinoma (HSCC) is an aggressive malignancy with one of the worst prognoses among all head and neck cancers. Greater understanding of the pertinent molecular oncogenic pathways could help improve diagnosis, therapy, and prevention of this disease. The aim of this study was to identify tumour-suppressive microRNAs (miRNAs), based on miRNA expression signatures from clinical HSCC specimens, and to predict their biological target genes. METHODS: Expression levels of 365 human mature miRNAs from 10 HSCC clinical samples were screened using stem-loop real-time quantitative PCR. Downregulated miRNAs were used in cell proliferation assays to identify a tumour-suppressive miRNA. Genome-wide gene expression analyses were then performed to identify the target genes of the tumour-suppressive miRNA. RESULTS: Expression analysis identified 11 upregulated and 31 downregulated miRNAs. Gain-of-function analysis of the downregulated miRNAs revealed that miR-489 inhibited cell growth in all head and neck cancer cell lines examined. The gene PTPN11 coding for a cytoplasmic protein tyrosine phosphatase containing two Src Homology 2 domains was identified as a miR-489-targeted gene. Knockdown of PTPN11 resulted in the inhibition of cell proliferation in head and neck SCC cells. CONCLUSION: Identification of the tumour-suppressive miRNA miR-489 and its target, PTPN11, might provide new insights into the underlying molecular mechanisms of HSCC.
Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Hipofaríngeas/genética , MicroRNAs/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Idoso , Linhagem Celular Tumoral , Regulação para Baixo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Interferente Pequeno , Reação em Cadeia da Polimerase Via Transcriptase Reversa , TransfecçãoRESUMO
We describe a rare case of SFT existing along the mandibular division of the trigeminal nerve and extending down into the infratemporal fossa through the foramen ovale. The tumor showed heterogeneous hypointensity on T2-weighted images and marked enhancement on CT and MR images.
Assuntos
Neoplasias dos Nervos Cranianos/diagnóstico por imagem , Imageamento por Ressonância Magnética , Tumores Fibrosos Solitários/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Nervo Trigêmeo/diagnóstico por imagem , Neoplasias dos Nervos Cranianos/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Tumores Fibrosos Solitários/patologia , Nervo Trigêmeo/patologiaRESUMO
BACKGROUND: In recent years, many countries have experienced an increase in the prevalence of allergic rhinitis. No effective approach is currently available to prevent the onset of symptoms in allergic individuals. Pranlukast, a leukotriene receptor antagonist with a good safety and efficacy record for the management of allergic inflammation, may be appropriate for early intervention in the management of pollinosis. OBJECTIVE: To investigate the efficacy of pranlukast as an early intervention in the control of cedar pollinosis. METHODS: In a double-blind comparative study, pranlukast (n = 102) or placebo (n = 91) was administered to cedar pollinosis patients immediately before the start of the dispersion season and continued for 4 weeks. Subsequently, pranlukast was administered to all patients for 2 weeks until the end of the cedar pollen dispersion season (mid-March). All patients were carefully monitored for severity of nasal symptoms, symptom scores, medication scores, symptom-medication scores, and quality of life (QOL). RESULTS: Compared with placebo, therapy with pranlukast before and during the dispersion of cedar pollen in these patients significantly improved nasal symptoms (paroxysmal sneezing, rhinorrhea, and nasal congestion), symptom scores, and symptom-medication scores. The drug also significantly reduced deterioration of QOL, and improved nasal symptoms and QOL throughout the dispersion period. CONCLUSION: Administering pranlukast immediately before the beginning of cedar pollen dispersion is effective in reducing symptoms of allergic rhinitis throughout the dispersion period.
Assuntos
Cromonas/uso terapêutico , Cryptomeria/imunologia , Antagonistas de Leucotrienos/uso terapêutico , Pólen/imunologia , Rinite Alérgica Sazonal/tratamento farmacológico , Adulto , Cromonas/administração & dosagem , Cromonas/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Antagonistas de Leucotrienos/administração & dosagem , Antagonistas de Leucotrienos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Rinite Alérgica Sazonal/imunologiaRESUMO
The purpose of our study was to describe the MR appearance of Kuttner's tumours and to interpret their differences in appearance from other submandibular gland tumours. MR studies of 7 Kuttner's, 8 malignant and 12 benign submandibular gland tumours were reviewed. MR sequences obtained included T(1) weighted, short inversion time inversion recovery (STIR), T(2) weighted, diffusion-weighted (DW) and dynamic contrast-enhanced MR (dynamic MR) images. In all cases of Kuttner's tumour, the affected submandibular glands were swollen with slightly higher intensity on T(2) weighted, STIR and DW images, but the tumour margin could not be defined. Conversely, the margins of the other tumours could be detected. On T(2) weighted, STIR and DW images, the mean signal intensity ratios and the mean apparent diffusion coefficient (ADC) values for Kuttner's tumours and malignant tumours were significantly lower than those of benign tumours, but there were no significant differences between those of Kuttner's tumours and those of malignant tumours. All benign tumours showed late enhancement, with peak enhancement later than 120 s on dynamic MR images. Kuttner's tumours and malignant tumours showed variable enhancement patterns. In conclusion, signal intensity ratios for T(2) weighted and STIR images, ADC values and patterns of enhancement may help distinguish Kuttner's tumours from benign submandibular gland tumours, but not from malignant tumours. Although the intensities, ADC values and enhanced patterns of Kuttner's tumours were similar to those of malignant tumours, there were some morphological differences.
Assuntos
Sialadenite/patologia , Neoplasias da Glândula Submandibular/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Esclerose/patologiaRESUMO
We set out to retrospectively review the clinical and imaging features of patients with post-radiation sarcoma, especially in the head and neck region. We reviewed the records of 4194 patients with carcinoma of the head and neck region who had a history of radiation. They had undergone CT and/or MRI. Medical records were reviewed for the primary diagnosis, radiation history and latency period to the development of sarcoma. The patients included four men and two women with a mean age of 64.5 years. The mean latency period for the development of sarcoma was 11.5 years. Primary diagnoses were maxillary carcinoma, nasopharyngeal carcinoma, adenoid cystic carcinoma of the oral floor, tonsilar carcinoma, soft palate carcinoma and tongue carcinoma. Histopathological examinations revealed osteosarcoma, spindle cell sarcoma, chondrosarcoma, malignant peripheral nerve sheath tumour, spindle cell carcinoma and malignant fibrous histiocytoma, respectively. Common findings were a heterogeneous and well-enhanced soft tissue mass and bone destruction. There is at present little or no prospect for the effective prevention of radiation-induced sarcoma of the head and neck. This emphasizes the importance of the earliest possible diagnosis for such patients. The imaging findings are not diagnosis specific, but strict follow-up within the radiation field by CT and MRI and an appreciation of the expected latency period may help to provide the diagnosis. When radiotherapy is performed for head and neck neoplasms, periodic follow-up observations may be necessary for many years.
Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias Induzidas por Radiação/diagnóstico , Sarcoma/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/radioterapia , Evolução Fatal , Feminino , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Incidência , Japão , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sarcoma/etiologia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The underlying relationship between viral infections and allergic diseases of the upper respiratory tract has not been well clarified. METHODS: In order to clarify the relationship between viral infection and nasal hypersensitivity, mice were sensitized with ovalbumin (OVA) and then infected intranasally with respiratory syncytial virus (RSV), after which their nasal sensitivity to histamine or antigen was examined. RESULTS: Non-sensitized mice showed transient mild nasal hypersensitivity following nasal administration of histamine after intranasal RSV inoculation. In mice sensitized with OVA, RSV infection significantly exaggerated their nasal hypersensitivity to histamine and OVA. Treatment of these mice with a neurokinin (NK)-1/NK-2 receptor antagonist, but not with anti-IL-5 antibodies, reduced their hypersensitivity. The infiltration of nasal mucosa with eosinophils was temporarily associated with accelerated rate of RSV elimination in these animals. CONCLUSION: RSV infection induced transient nasal hypersensitivity. Several mechanisms, including impairment of nasal epithelial cells are thought to mediate this effect. In allergen-sensitized mice, RSV inoculation strongly enhanced nasal hypersensitivity.
Assuntos
Nariz/imunologia , Hipersensibilidade Respiratória/virologia , Infecções por Vírus Respiratório Sincicial/imunologia , Administração Intranasal , Animais , Anticorpos/imunologia , Eosinófilos/imunologia , Histamina/administração & dosagem , Histamina/imunologia , Interleucina-5/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mucosa Nasal/imunologia , Antagonistas dos Receptores de Neurocinina-1 , Ovalbumina/imunologia , Receptores da Neurocinina-1/imunologia , Receptores da Neurocinina-2/antagonistas & inibidores , Receptores da Neurocinina-2/imunologia , Hipersensibilidade Respiratória/imunologia , Replicação Viral/imunologiaRESUMO
Oxidative stress is a characteristic of chronic inflammatory diseases. The reactive oxygen intermediate hydrogen peroxide (H(2)O(2)) is an important signaling molecule that modulates gene expression. We have demonstrated that H(2)O(2) significantly enhanced cytokine production in BEAS-2B cells, with a maximal effect at 4h. This did not result from enhanced NF-kappaB activation, but through decreased activity of histone deacetylase (HDAC)2. This results in increased inflammatory gene expression following acetylation of specific histone residues. Decreased HDAC2 activity was associated with tyrosine nitration status. Peroxynitrite and SIN-1, a peroxynitrite generator, were also able to reduce HDAC2 activity via tyrosine nitration. Our data suggest that oxidative stress contributes to worsening inflammation via reduction of HDAC2 activity through HDAC2 nitration. This novel mechanism of inflammation may be important in increasing the severity and chronicity of inflammatory diseases.
Assuntos
Histona Desacetilases/metabolismo , Interleucina-8/biossíntese , Nitratos/metabolismo , Estresse Oxidativo/fisiologia , Proteínas Repressoras/metabolismo , Tirosina/metabolismo , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Citocinas/biossíntese , DNA/metabolismo , Relação Dose-Resposta a Droga , Regulação Enzimológica da Expressão Gênica/fisiologia , Técnicas Genéticas , Histona Desacetilase 2 , Histona Desacetilases/genética , Histonas/metabolismo , Humanos , Peróxido de Hidrogênio/farmacologia , Interleucina-1/farmacologia , Interleucina-8/genética , NF-kappa B/metabolismo , Ácido Peroxinitroso/farmacologia , Testes de Precipitina , Regiões Promotoras Genéticas , Proteínas Repressoras/genética , Fatores de TempoRESUMO
19-nor-1alpha,25-Dihydroxyvitamin D(3) was synthesized by the Suzuki-Miyaura coupling of the A-ring intermediate 3, which was efficiently prepared from readily available 5-(tert-butyldimethylsilyl)oxycyclohex-2-enone (5), with the boronate compound of the C,D-ring portion. The method could be applied to a solid-phase synthesis to prepare the des-C,D derivatives of 19-nor-1alpha,25-dihydroxyvitamin D(3). [reaction: see text]
Assuntos
Calcitriol/análogos & derivados , Calcitriol/síntese química , Calcitriol/química , SoluçõesRESUMO
Exhaled nitric oxide (ENO), a marker of inflammation in airway diseases is decreased in cystic fibrosis (CF) patients, perhaps because nitric oxide (NO) is metabolized to oxidative end-products. A stable product, 3-nitrotyrosine, may indicate local formation of reactive nitrogen species. Whether NO metabolites in exhaled breath condensate may be increased in CF patients was investigated. The fractional concentration of ENO (Feno), nitrotyrosine and oxides of nitrogen in exhaled breath condensate from 36 stable CF patients were compared to 14 normal subjects using an enzyme immunoassay and fluorescence assay. Nitrotyrosine levels in breath condensate were increased significantly in stable CF patients, compared with normal subjects (25.3 +/- 1.5 versus 6.3 +/- 0.8 ng x mL(-1), p<0.0001). There was an inverse correlation between the levels of nitrotyrosine and the severity of lung disease. Feno levels were significantly lower in CF patients than in normal subjects (4.4 +/- 0.3 versus 5.6 +/- 0.4 (parts per billion), p<0.05). No correlation was found between nitrotyrosine and Feno levels in CF. There was no significant difference in the levels of nitrite and nitrate between CF patients and normals. The elevation in nitrotyrosine may reflect increased formation of reactive nitrogen species such as peroxynitrite or direct nitration by granulocyte peroxidases, indicating increased oxidative stress in airways of cystic fibrosis patients.
Assuntos
Testes Respiratórios , Fibrose Cística/diagnóstico , Tirosina/análogos & derivados , Tirosina/análise , Adulto , Feminino , Humanos , Medidas de Volume Pulmonar , Masculino , Estresse Oxidativo , Espécies Reativas de Nitrogênio/análise , Valores de ReferênciaRESUMO
[reaction: see text] The A-ring precursor of 19-nor-1alpha,25-dihydroxyvitamin D(3) (1) and its (13)C- or (2)H-labeled derivative were efficiently synthesized from readily available, optically active 5-(tert-butyldimethylsilyloxy)-2-cyclohexenone (2) through a five-step reaction in 68% overall yield.
Assuntos
Calcitriol , Cicloexanonas/química , Silanos/química , Calcitriol/análogos & derivados , Calcitriol/síntese química , Calcitriol/química , Isótopos de Carbono/química , Catálise , Ciclização , Deutério/química , Marcação por Isótopo , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Cigarette smoking reduces the level of exhaled nitric oxide (NO) in healthy subjects, although the mechanism is unclear. NO is a highly reactive molecule which can be oxidised or complexed with other biomolecules, depending on the microenvironment. The stable oxidation end products of NO metabolism are nitrite and nitrate. This study investigated the effect of smoking on NO metabolites in exhaled breath condensate. METHODS: Fifteen healthy current smokers were recruited together with 14 healthy non-smokers. Measurement of exhaled NO, lung function, and collection of exhaled breath condensate were performed. Nitrite, nitrite + nitrate, S-nitrosothiols, and nitrotyrosine levels were measured. The effect of inhaling two cigarettes in smokers was also evaluated. The mean level of exhaled NO in smokers was significantly lower than in non-smokers (4.3 (0.3) ppb v 5.5 (0.5) ppb, p<0.05). RESULTS: There was no difference in the levels of nitrite, nitrite + nitrate, S-nitrosothiols, and nitrotyrosine in the exhaled breath condensate at the baseline visit between smokers and non-smokers. After smoking, nitrite + nitrate levels were significantly but transiently increased (from 20.2 (2.8) microM to 29.8 (3.4) microM, p<0.05). There was no significant change in the levels of exhaled NO, nitrite, S-nitrosothiols, or nitrotyrosine 30 and 90 minutes after smoking. CONCLUSIONS: These findings suggest that acute smoking can increase the level of nitrate, but not nitrite, S-nitrosothiols, or nitrotyrosine in breath condensate. The deleterious effect of oxidant radicals induced by smoking may contribute to the epithelial damage of airways seen in smokers.
Assuntos
Óxido Nítrico/metabolismo , Fumar/metabolismo , Adulto , Análise de Variância , Testes Respiratórios/métodos , Monóxido de Carbono/metabolismo , Feminino , Humanos , Masculino , Nitratos/metabolismo , Nitritos/metabolismo , Compostos Nitrosos/metabolismo , Estresse Oxidativo , Fumar/efeitos adversosRESUMO
OBJECTIVES: The use of mobile phones with the resulting generation of potentially harmful electromagnetic fields (EMF) is the focus of public interest. Heat generation and the activation of the inducible form of nitric oxide (NO) synthase may be possible causes of the biological effects of EMF exposure. We investigated if a mobile telephone conversation can modify skin temperature, NO, and nasal resistance. METHODS: We studied the effect of an EMF (900 MHz) generated by a commercially available cellular phone during a 30-minute telephone conversation on skin temperature, nasal NO measured by chemiluminescence, and nasal minimal cross-sectional area (MCA) measured by rhinometry. Eleven normal subjects (mean age +/- standard error of mean [SEM], 32 +/- 5 y; 10 male) were studied. RESULTS: There was a similar and significant increase in skin temperature of the nostril and occipital area on the same side as the telephone (maximal increase 2.3 +/- 0.2 degrees C at 6 min) as well as a tendency for higher nasal NO levels (maximal increase 12.9 +/- 4.9% at 10 min), whereas the MCA was significantly reduced (maximal decrease -27 +/- 6% at 15 min). Such changes were not recorded when an earpiece was used to avoid the direct exposure to the electromagnetic field. There were no changes in the skin temperature and nasal NO measured on the opposite side to the mobile phone, whereas the MCA was significantly increased (38 +/- 10%). CONCLUSIONS: Exposure to EMF produced by a mobile phone produces biological effects that can be easily measured. Microwaves may increase skin temperature and therefore cause vasodilation and reduce MCA. Further studies are needed to study the long-term effects of mobile phone use and the relation among NO production, vasodilation, and temperature.