RESUMEN
Immunoglobulins (Igs) play important immunomodulatory effects on allergic asthma. Among these, IgG has been reported to regulate allergic inflammation in previous studies about immunotherapy and intravenous immunoglobulin therapy. In this study, to examine the immunomodulatory mechanisms of IgG and FcRs we evaluated the effects of intravenous (i.v.) rabbit IgG administration (IVIgG) on allergic airway inflammation and lung antigen-presenting cells (APCs) in a murine model of ovalbumin (OVA) sensitization and challenge. In OVA-challenged mice, IVIgG attenuated airway eosinophilia, airway hyperresponsiveness and goblet cell hyperplasia and also inhibited the local T helper type (Th) 2 cytokine levels. Additionally, IVIgG attenuated the proliferation of OVA-specific CD4(+) T cells transplanted into OVA-challenged mice. Ex vivo co-culture with OVA-specific CD4(+) cells and lung CD11c(+) APCs from mice with IVIgG revealed the attenuated transcription level of Th2 cytokines, suggesting an inhibitory effect of IVIgG on CD11c(+) APCs to induce Th2 response. Next, to analyse the effects on Fcγ receptor IIb and dendritic cells (DCs), asthmatic features in Fcγ receptor IIb-deficient mice were analysed. IVIgG failed to attenuate airway eosinophilia, airway inflammation and goblet cell hyperplasia. However, the lacking effects of IVIgG on airway eosinophilia in Fcγ receptor IIb deficiency were restored by i.v. transplantation of wild-type bone marrow-derived CD11c(+) DCs. These results demonstrate that IVIgG attenuates asthmatic features and the function of lung CD11c(+) DCs via Fcγ receptor IIb in allergic airway inflammation. Targeting Fc portions of IgG and Fcγ receptor IIb on CD11c(+) DCs in allergic asthma is a promising therapeutic strategy.
Asunto(s)
Asma/terapia , Antígeno CD11c/metabolismo , Células Dendríticas/efectos de los fármacos , Inmunoglobulina G/farmacología , Inmunoglobulinas Intravenosas/farmacología , Receptores de IgG/genética , Traslado Adoptivo , Animales , Presentación de Antígeno/efectos de los fármacos , Presentación de Antígeno/inmunología , Asma/inmunología , Asma/patología , Asma/fisiopatología , Hiperreactividad Bronquial/fisiopatología , Hiperreactividad Bronquial/prevención & control , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Recuento de Células , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/inmunología , Proliferación Celular , Citocinas/metabolismo , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Células Dendríticas/trasplante , Modelos Animales de Enfermedad , Eosinófilos/citología , Femenino , Inmunoglobulina E/sangre , Inmunoglobulina G/uso terapéutico , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/farmacología , Factores Inmunológicos/uso terapéutico , Inflamación/inmunología , Inflamación/patología , Inflamación/prevención & control , Ratones , Ratones Endogámicos C57BL , Ovalbúmina/inmunología , Organismos Libres de Patógenos Específicos , Células Th2/inmunologíaRESUMEN
This study aimed to identify predictive factors associated with prognostic benefits of gefitinib. A total of 221 Japanese patients who received gefitinib (250 mg day(-1)) were examined retrospectively and potential predictive factors analysed. Overall response rate (ORR) was 24.4% and median survival time (MST) was 8.0 months. In a log-rank test, survival was significantly better in females, patients with adenocarcinoma, never-smokers, favourable performance status (PS) and patients with epidermal growth factor receptor (EGFR) mutation. The lower the smoking exposure (Brinkman Index (BI)=cigarettes per day x years smoked), the better the MST (BI 0: 14.5 months, BI <500: 9.5 months, BI 500 to <1000: 6.9 months, BI > or =1000: 4.0 months). Positive-EGFR mutation status and PS 0-1 were independent predictors of favourable prognosis by multivariate analysis. Prognosis was significantly different according to EGFR mutation status (with the same smoking status), but not according to smoking status (with the same EGFR mutation status). EGFR mutation status is the most important independent predictor of survival benefit with gefitinib treatment. Although differences in prognosis were observed according to relative smoking status and smoking exposure, the results suggested that smoking is not a direct predictor of prognosis, yet is a surrogate marker of EGFR mutation status.
Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Receptores ErbB/antagonistas & inhibidores , Neoplasias Pulmonares/tratamiento farmacológico , Quinazolinas/uso terapéutico , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Receptores ErbB/genética , Femenino , Gefitinib , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Mutación , Quinazolinas/efectos adversos , Estudios Retrospectivos , Fumar/efectos adversosRESUMEN
BAG-1 is a recently identified Bcl-2-interacting anti-apoptotic protein. The aim of our study was to investigate the immunohistochemical staining pattern of BAG-1 protein in patients with colorectal cancer and examine associations of BAG-1 expression with various clinicopathological factors and patient survival. Tumour samples were collected from 86 patients diagnosed with colorectal cancer. There was significant variation in the immunohistochemical staining patterns for BAG-1, including absent staining and staining of either the cytoplasm, nucleus or both. Twenty-one colorectal carcinomas (24.4%) exhibited a nuclear staining pattern whilst 56 (65.1%) exhibited cytoplasmic staining. The percentage of cases exhibiting nuclear BAG-1 positivity was significantly higher in distant metastasis-positive cases (55.6%) than in distant metastasis-negative cases (20.8%; P=0.036). Overall survival was significantly shorter for patients with tumours exhibiting BAG-1 positive nuclei than those with absent nuclear BAG-1-staining (P=0.011). In addition, the multivariate cox proportional hazard models indicated that nuclear BAG-1 expression was the only independent prognostic variable for mortality (P=0.013). These studies demonstrate that nuclear BAG-1 expression is a useful predictive factor for distant metastasis and a poor prognosis in patients with colorectal cancer.
Asunto(s)
Proteínas Portadoras/análisis , Núcleo Celular/química , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/química , Neoplasias Colorrectales/mortalidad , Citoplasma/química , Proteínas de Unión al ADN , Humanos , Inmunohistoquímica , Metástasis de la Neoplasia , Pronóstico , Factores de TranscripciónRESUMEN
A 41-year-old man fell into type II respiratory failure after catching a cold, and became dependent on a respirator. Chest radiography showed no abnormalities and the hyperventilation test showed improved arterial blood gas findings. His sleep study showed marked nocturnal desaturation due to hypopnea and apnea with a decrease of thoracic and abdominal movement during sleep. Therefore, we diagnosed him as primary alveolar hypoventilation syndrome (PAH). Seven years previously, his 2-year elder sister had suffered from similar respiratory failure during her second pregnancy and had been diagnosed as PAH. While myopathy was suspected in both cases, attenuation of muscle strength was slight and it appeared not to be the main cause of alveolar hypoventilation. Since medication was not effective in each case, they underwent non-invasive positive pressure ventilation (NIPPV). While sustained mild hypercapnia remained during the daytime, it improved their respiratory failure. To our knowledge, this is the first study of familial adult onset PAH.
Asunto(s)
Apnea Central del Sueño/diagnóstico , Adulto , Edad de Inicio , Femenino , Humanos , MasculinoRESUMEN
A 70-year-old woman was admitted in April 1997 because a coin lesion in the left middle lung field was observed on chest roentgenograms. The lesion had slightly increased in size since 1994, when it was first pointed out. Chest computed tomography elucidated a high density area with irregular borders in the center of the shadow in S 3 a. Transbronchial biopsy revealed adenocarcinoma, and a left upper lobectomy was performed. The resected specimen demonstrated a tumor with central ossification and pleural indentation. Histologic examination determined that the the tumor was a papillary adenocarcinoma with central ossification containing marrow tissue. Primary lung cancer with central ossification is very rare, and only 6 cases have been reported to date, including this case.
Asunto(s)
Adenocarcinoma Papilar/complicaciones , Neoplasias Pulmonares/complicaciones , Osificación Heterotópica/complicaciones , Adenocarcinoma Papilar/patología , Anciano , Femenino , Humanos , Neoplasias Pulmonares/patología , Osificación Heterotópica/patología , NeumonectomíaRESUMEN
The clinical case is 68 year old woman. The patient experienced dyspnea and back pain. Chest X-ray and CT showed a large well-defined mass from the left thorax expanding to the right. The tumor, which was derived from the left lobe of thymus, was removed. Cut surface of the resected tumor showed multilobar patterns and a yellow-white portion like a wedge in a part of the tumor. Histological examinations revealed that the multilobar portion was thymic carcinoid and a yellow-white portion was malignant fibrous histiocytoma. As far as we examined, literature pertaining to such double cancers has never been reported.