Crohn’s disease (CD) is a systemic illness with a constellation of extraintestinal manifestations affecting various organs. Of these extraintestinal manifestations of CD, those involving the lung are relat...Crohn’s disease (CD) is a systemic illness with a constellation of extraintestinal manifestations affecting various organs. Of these extraintestinal manifestations of CD, those involving the lung are relatively rare. However, there is a wide array of lung manifestations, ranging from subclinical alterations, airway diseases and lung parenchymal diseases to pleural diseases and drug-related diseases. The most frequent manifestation is bronchial inflammation and suppuration with or without bronchiectasis. Bronchoalveolar lavage findings show an increased percentage of neutrophils. Drug-related pulmonary abnormalities include disorders which are directly induced by sulfasalazine, mesalamine and methotrexate, and opportunistic lung infections due to immunosuppressive treatment. In most patients, the development of pulmonary disease parallels that of intestinal disease activity. Although infrequent, clinicians dealing with CD must be aware of these, sometimes life-threatening, conditions to avoid further impairment of health status and to alleviate patient symptoms by prompt recognition and treatment. The treatment of CD-related respiratory disorders depends on the specific pattern of involvement, and in most patients, steroids are required in the initial management.展开更多
Crohn's disease is a granulomatous systemic disorder of unknown etiology. Obvious pulmonary involvement is exceptional. Tracheal involvement in Crohn's disease is even more unusual, only a few cases have been ...Crohn's disease is a granulomatous systemic disorder of unknown etiology. Obvious pulmonary involvement is exceptional. Tracheal involvement in Crohn's disease is even more unusual, only a few cases have been report-ed to date. We herein report a rare case of tracheobron-chial nodules and pulmonary infiltrates in both lungs as a complication of Crohn's disease. A 42-year-old man underwent pancolectomy for multiple broken colon caused by Crohn's disease. Forty days later pulmonary symptoms and radiologic abnormalities were noted. A search for bacterial (including mycobacteria) and fungal in the repeated sputum proved negative. The treatment consisted of intravenous antimicrobials for one month, but there was no improvement in pyrexia or cough and radiologic abnormalities. Fibreoptic bronchoscopy (FOB) was performed and revealed nodes in the trachea and the right upper lobe opening. Histopathology of tracheo-bronchial nodules and bronchial mucosa biopsy specimen both showed granulomatous inflammation with proliferation of capillaries and inflammatory cells. Oral steroid and salicylazosulfapyridine were commenced and led to marked improvement in symptoms and an almost complete resolution of his chest radiograph. Repeated FOB showed that nodes in the trachea disappeared and the ones in the right upper lobe opening diminished obviously. Crohn's disease can be associated with several respiratory manifestations. The form of tracheal and bronchopulmonary involvement in Crohn's disease is rare and responded well to steroids.展开更多
Background： The E3 ubiquitin ligasc neural precursor cell expressed developmentally downregulated 4-1（N EDD4-1） negatively regulates phosphatase and tensin homolog deleted on chromosome 10 （PTEN） protein levels t...Background： The E3 ubiquitin ligasc neural precursor cell expressed developmentally downregulated 4-1（N EDD4-1） negatively regulates phosphatase and tensin homolog deleted on chromosome 10 （PTEN） protein levels through polyubiquitination and proteolysis, but its significance in lung cancer is still unclear. This study investigated the expression and the role of NEDD4-1 in tumor developnaent and chemosensitivity of lung adenocarcinoma （ADC）. Methods： We retrospectively investigated the expression and significance ofNEDD4-1, PTEN, and p-Akt proteins in 135 paired A DC and adjacent noncancerous tissue specimens using immunohistochemistry. Furthemaore, we evaluated the relationship between NEDD4-1 expression and clinicopathologic characteristics and prognosis. The effects of small interfering RNA against NEDD4-1 on proliferation and chemosensitivity were examined in A549 cells in vitro using 3- （4,5-dimethylthiazol-2-yl） -5-（3-carboxymethoxyphenyl） -2-（4-sulfophenyl）- 2H-tetrazoliunl method. The ability of migration and invasion ofA549 cells was tested by transwell assay. Moreover, reverse-transcription quantitative polymerase chain reaction and Western blotting analyses were used to determine the expression of NEDD4-1, PTEN, phosphoinositide 3-kinase （PI3K）/Akt activity, and its downstream target proteins. Results： NEDD4-1 protein was significantly upregulated in lung ADC tissues, whereas it was weak or negative in normal lung epithelial cells. The expression ofNEDD4-1 in ADC （78.5%, 106/135） was significantly much higher than that in adjacent normal lung tissue （ 13.3%, 29/135, P 〈 0.01）, and it was associated with lymph node metastasis, tumor-node-metastasis （TNM） stage, and chemotherapy resistance. PTEN expression was downregulated in lung ADC （60.7% vs. 100.0% in noncancerous specimens, P - 0.007）, and was negatively correlated with lymph node metastasis, histological variants, clinical stage, chemoresistance. In addition, expression of p-Akt in ADC tissues （71.1% 96/135） was much higher than that in adjacent lung epithelial cells （6.7%, 9/135, P 〈 0.01 ）. Kaplan-Meier and multivariate analysis demonstrated that expressions ofNEDD4-1 and PTEN were both independent risk factors for survival in patients with lung ADC. NEDD4-1 knockdown in vivo decreased proliferation, migration, and invasion and improved chemosensitivity to cisplatin and paclitaxel in A549 cells. NEDD4-1 knockdown also significantly enhanced PTEN expression and inhibited p-Akt activity and downstream target proteins. Conclusions： NEDD4-1 upregulation may contribute to the progression of lung ADC. NEDD4-1 may regulate the proliferation, invasion, migration, and chemoresistance of lung ADC cells through the P13K/Akt pathway, suggesting that it may be regarded as a therapeutic target for the treatment of lung ADC.展开更多
文摘Crohn’s disease (CD) is a systemic illness with a constellation of extraintestinal manifestations affecting various organs. Of these extraintestinal manifestations of CD, those involving the lung are relatively rare. However, there is a wide array of lung manifestations, ranging from subclinical alterations, airway diseases and lung parenchymal diseases to pleural diseases and drug-related diseases. The most frequent manifestation is bronchial inflammation and suppuration with or without bronchiectasis. Bronchoalveolar lavage findings show an increased percentage of neutrophils. Drug-related pulmonary abnormalities include disorders which are directly induced by sulfasalazine, mesalamine and methotrexate, and opportunistic lung infections due to immunosuppressive treatment. In most patients, the development of pulmonary disease parallels that of intestinal disease activity. Although infrequent, clinicians dealing with CD must be aware of these, sometimes life-threatening, conditions to avoid further impairment of health status and to alleviate patient symptoms by prompt recognition and treatment. The treatment of CD-related respiratory disorders depends on the specific pattern of involvement, and in most patients, steroids are required in the initial management.
文摘Crohn's disease is a granulomatous systemic disorder of unknown etiology. Obvious pulmonary involvement is exceptional. Tracheal involvement in Crohn's disease is even more unusual, only a few cases have been report-ed to date. We herein report a rare case of tracheobron-chial nodules and pulmonary infiltrates in both lungs as a complication of Crohn's disease. A 42-year-old man underwent pancolectomy for multiple broken colon caused by Crohn's disease. Forty days later pulmonary symptoms and radiologic abnormalities were noted. A search for bacterial (including mycobacteria) and fungal in the repeated sputum proved negative. The treatment consisted of intravenous antimicrobials for one month, but there was no improvement in pyrexia or cough and radiologic abnormalities. Fibreoptic bronchoscopy (FOB) was performed and revealed nodes in the trachea and the right upper lobe opening. Histopathology of tracheo-bronchial nodules and bronchial mucosa biopsy specimen both showed granulomatous inflammation with proliferation of capillaries and inflammatory cells. Oral steroid and salicylazosulfapyridine were commenced and led to marked improvement in symptoms and an almost complete resolution of his chest radiograph. Repeated FOB showed that nodes in the trachea disappeared and the ones in the right upper lobe opening diminished obviously. Crohn's disease can be associated with several respiratory manifestations. The form of tracheal and bronchopulmonary involvement in Crohn's disease is rare and responded well to steroids.
基金This work was supported by a grant from the National Natural Science Foundation of China （No. 81402185）.
文摘Background： The E3 ubiquitin ligasc neural precursor cell expressed developmentally downregulated 4-1（N EDD4-1） negatively regulates phosphatase and tensin homolog deleted on chromosome 10 （PTEN） protein levels through polyubiquitination and proteolysis, but its significance in lung cancer is still unclear. This study investigated the expression and the role of NEDD4-1 in tumor developnaent and chemosensitivity of lung adenocarcinoma （ADC）. Methods： We retrospectively investigated the expression and significance ofNEDD4-1, PTEN, and p-Akt proteins in 135 paired A DC and adjacent noncancerous tissue specimens using immunohistochemistry. Furthemaore, we evaluated the relationship between NEDD4-1 expression and clinicopathologic characteristics and prognosis. The effects of small interfering RNA against NEDD4-1 on proliferation and chemosensitivity were examined in A549 cells in vitro using 3- （4,5-dimethylthiazol-2-yl） -5-（3-carboxymethoxyphenyl） -2-（4-sulfophenyl）- 2H-tetrazoliunl method. The ability of migration and invasion ofA549 cells was tested by transwell assay. Moreover, reverse-transcription quantitative polymerase chain reaction and Western blotting analyses were used to determine the expression of NEDD4-1, PTEN, phosphoinositide 3-kinase （PI3K）/Akt activity, and its downstream target proteins. Results： NEDD4-1 protein was significantly upregulated in lung ADC tissues, whereas it was weak or negative in normal lung epithelial cells. The expression ofNEDD4-1 in ADC （78.5%, 106/135） was significantly much higher than that in adjacent normal lung tissue （ 13.3%, 29/135, P 〈 0.01）, and it was associated with lymph node metastasis, tumor-node-metastasis （TNM） stage, and chemotherapy resistance. PTEN expression was downregulated in lung ADC （60.7% vs. 100.0% in noncancerous specimens, P - 0.007）, and was negatively correlated with lymph node metastasis, histological variants, clinical stage, chemoresistance. In addition, expression of p-Akt in ADC tissues （71.1% 96/135） was much higher than that in adjacent lung epithelial cells （6.7%, 9/135, P 〈 0.01 ）. Kaplan-Meier and multivariate analysis demonstrated that expressions ofNEDD4-1 and PTEN were both independent risk factors for survival in patients with lung ADC. NEDD4-1 knockdown in vivo decreased proliferation, migration, and invasion and improved chemosensitivity to cisplatin and paclitaxel in A549 cells. NEDD4-1 knockdown also significantly enhanced PTEN expression and inhibited p-Akt activity and downstream target proteins. Conclusions： NEDD4-1 upregulation may contribute to the progression of lung ADC. NEDD4-1 may regulate the proliferation, invasion, migration, and chemoresistance of lung ADC cells through the P13K/Akt pathway, suggesting that it may be regarded as a therapeutic target for the treatment of lung ADC.
