Aquaporin 3 knockdown suppresses tumour growth and angiogenesis in experimental non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the most common diseases encountered in medical oncology practice. The aim of the present study was to test the antitumour effects of short-hairpin RNA targeting aquaporin 3 (AQP3) in experimental NSCLC. Expression of AQP3 was suppressed in human A549 and H1299 NSCLC cell lines by short-hairpin RNA-mediated silencing. Therapeutic effects were assessed by examining tumorigenicity using a subcutaneous xenograft mouse model of NSCLC. Aquaporin 3 knockdown inhibited tumour growth and prolonged survival of mice with tumours. Aquaporin 3 knockdown suppressed tumour proliferation, marked by enhanced expression of p53, an increased ratio of cleaved caspase 3 to pro-caspase 3 and reduced expression of proliferating cell nuclear antigen and B-cell lymphoma-2 (bcl-2). Aquaporin 3 knockdown inhibited tumour angiogenesis, marked by decreased CD31 immunostaining and reduced expression of hypoxia-inducible factor-2α and vascular endothelial growth factor. Aquaporin 3 knockdown reduced cellular glycerol content and suppressed mitochondrial ATP formation. Aquaporin 3 knockdown in vitro significantly suppressed activities of matrix metalloproteinases MMP2 and MMP9, reduced AKT phosphorylation and decreased cell invasiveness of A549 and H1299 cells. In conclusion, AQP3 knockdown suppressed tumour growth and reduced angiogenesis in human NSCLS xenografts. Aquaporin 3 could thus be envisaged as a novel therapeutic target for NSCLC.

Andrographolide antagonizes cigarette smoke extract-induced inflammatory response and oxidative stress in human alveolar epithelial A549 cells through induction of microRNA-218.

Andrographolide is a major bioactive labdane diterpenoid isolated from Andrographis paniculata and has protective effects against cigarette smoke (CS)-induced lung injury. This study was done to determine whether such protective effects were mediated through modulation of microRNA (miR)-218 expression. Therefore, we exposed human alveolar epithelial A549 cells to cigarette smoke extract (CSE) with or without andrographolide pretreatment and measured the level of glutathione, nuclear factor-kappaB (NF-κB) activation, proinflammatory cytokine production, and miR-218 expression. We found that andrographolide pretreatment significantly restored the glutathione level in CSE-exposed A549 cells, coupled with reduced inhibitor κB (IκB)-α phosphorylation and p65 nuclear translocation and interleukin (IL)-8 and IL-6 secretion. The miR-218 expression was significantly upregulated by andrographolide pretreatment. To determine the biological role of miR-218, we overexpressed and downregulated its expression using miR-218 mimic and anti-miR-218 inhibitor, respectively. We observed that miR-218 overexpression led to a marked reduction in IκB-α phosphorylation, p65 nuclear accumulation, and NF-κB-dependent transcriptional activity in CSE-treated A549 cells. In contrast, miR-218 silencing enhanced IκB-α phosphorylation and p65 nuclear accumulation in cells with andrographolide pretreatment and reversed andrographolide-mediated reduction of IL-6 and IL-8 production. In addition, depletion of miR-218 significantly reversed the upregulation of glutathione levels in A549 cells by andrographolide. Taken together, our results demonstrate that andrographolide mitigates CSE-induced inflammatory response in A549 cells, largely through inhibition of NF-κB activation via upregulation of miR-218, and thus has preventive benefits in CS-induced inflammatory lung diseases.

[Combined effects of interferon γ and γ ray irradiation on A549 cells in vitro].

OBJECTIVE: To define the role of interferon-γ on radiotherapy of lung cancer and explore a new way to clinical treatment. METHODS: A549 cells were exposed to γ ray with or without IFN-γ co-treatment. MTT assay was performed to evaluate cell viability. Western blot was used to observe the expression of P53 protein. RESULTS: The results showed that co-treatment of IFN-γ decreased the cell viability significantly compared with the γ ray irradiation group (71.4% ± 2.1% vs 44.1% ± 3.1%, n = 7, P < 0.01). In addition, the expression of P53 protein also increased significantly after co-treatment (P < 0.01); Furthermore, the cell cycle was changed obviously in co-treatment group compared with γ ray irradiation group, S phase increased (12.9% vs 20.9%, n = 5, P < 0.05) and also blocked the G2/M phase (28.8% vs 38.9%, n = 5, P < 0.05). CONCLUSIONS: The results suggested that γ ray irradiation combined with IFN-γ can increase the efficiency of radiotherapy on A549 cells and there is much broad prospect in the clinical treatment of lung cancer.

[Wedge resection and thermal cautery for malignant pleural effusion caused by lung cancer under vats].

OBJECTIVE: To discuss the treatment effect of wedge resection and thermal cautery of pleura for patients with malignant pleural effusion (MPE) caused by lung cancer under VATS. METHODS: 37 patients with MPE underwent wedge resection and thermal cautery of pleura under VATS, from June 2005 to December 2008. Postoperative tumor markers level was contrasted with the preoperative, and the control rate of pleural effusion and survival rate of the patients were compared with control group, including 25 patients undergoing intrapleural chemotherapeutics in the same period. RESULT: In the group, the control rate of pleural effusion was 100%, but 60% in control group (P = 0.005). The 1-year survival rate of the group and the control group was 78.38% and 60% respectively (P = 0.003). CEA and CA-125 were descended obviously in postoperative day 7 in the group(P = 0.002);in control group, there were no significant change of CEA and CA125 after treatment (P = 0.797). CONCLUSION: Wedge resection and thermal cautery of pleura under VATS can reduce tumor burden of patients with MPE to the maximum, and control MPE effectively and improve the quality of life for lung cancer patients with MPE.

[Diagnosis and surgical treatment of congenital bronchoesophageal fistula in adult].

OBJECTIVE: To explore the clinical characteristics, diagnosis and surgical treatment of adult congenital bronchoesophageal fistula. METHODS: Eleven cases of adult congenital bronchoesophageal fistula that were diagnosed and surgically treated between May 1990 and August 2010 had been reviewed. There were 7 male and 4 female patients, ranging in age from 28 to 66 years (mean 48.7 years). The chief clinical presentation included coughing and sputum in 10 cases, recurrent bouts of coughing after drinking liquid food in 6 cases, hemoptysis in 6 cases, low fever in 4 cases, chest pain in 3 cases. The duration of symptoms before diagnosis ranged from 5 to 36 years (mean 16.8 years). The diagnosis of bronchoesophageal fistula was confirmed most by esophagography. Associated diseased lung was resected in all patients (lobectomy in 10 cases and pneumonectomy in 1 case). The operation included right thoracotomy in 7 cases and left thoracotomy in 4 cases. The fistula was completely resected in 10 cases. The tract was simply divided and the end was sutured in 1 case. RESULTS: The postoperative course was uneventful in 10 patients who were discharged from hospital 10 to 18 d after operation. One patient suffered from esophageal fistula and received second operation. Regular follow-up was conducted on all 11 patients, proving that 3-year survival rate was 11/11 and 5-year survival rate was 9/11. CONCLUSION: Persistence of congenital bronchoesophageal fistula into adulthood is rare. The main symptom is nonspecific coughing and bouts of coughing after drinking liquid food. The most useful diagnostic method is the esophagography. Even though it is benign disease, life-threatening complications might occur and it must be treated surgically as soon as the diagnosis is established.

[The impact of antibiotic treatment in patients with influenza-like illness].

OBJECTIVE: To study the etiology of influenza-like illness (ILI) in Beijing, and to investigate the impact of antibiotic treatment on outcomes. METHODS: This was a prospective cohort study. Patients with diagnosis of influenza-like illness were prospectively enrolled for study of bacterial and viral pathogens. Demographic characteristics, underlying diseases, respiratory and extrapulmonary symptoms, laboratory tests were also collected for analysis of relationship between drug therapy and outcomes. RESULTS: A total of 476 cases were enrolled between Dec. 2006 and Apr. 2007, of whom 454 cases were used for analysis. Influenza virus was the most common pathogen( n = 197, 43.4%), with other pathogens rarely seen. The mean age of the patients was (33 +/- 13) years, and the ratio of male to female was 1.1:1. Twenty four patients (5.3% ) received influenza vaccine. The rate of antibiotic prescription after onset of illness was 63.4%, but none received antiviral drugs such as Oseltamivir and amantadine. Compared with influenza-negative patients, patients with influenza were older, had more underlying diseases and had greater severity of symptoms such as cough, sore throat, headache and myalgia (but with no statistical differences). The influenza syndrome (T > or = 39 degrees C plus cough, sore throat and headache or myalgia) was more common in the influenza group compared to the influenza-negative patients (P < 0.05). The ratio of antibiotic prescription was 67% in the influenza group, and the total white blood cell and platelet count, percentage of neutrophils were higher in antibiotic treatment patients compared with non-antibiotic treatment patients (P < 0.01). The cost in patients who received antibiotics was twice as much as non-antibiotic treatment patients (P < 0.05), but the defervescence time and respiratory symptom alleviation time did not differ. Cox regression analysis showed that the total white blood count and the differentials (OR value 1.049 and 1.014, respectively), but not antibiotic use were the independent risk factors for longer defervescence time. CONCLUSION: Influenza virus was the most common pathogen for adult patients with ILI in Beijing city during the winter and the spring seasons. Antibiotic treatment of adult patients with ILI did not improve illness resolution, while the cost was increased significantly.

[Clinicopathological features and prognosis of bronchial mucoepidermoid carcinoma: analysis of 21 cases].

OBJECTIVE: To investigate the clinicopathological features and prognosis of bronchial mucoepidermoid carcinoma. METHODS: Twenty-one with mucoepidermoid carcinoma, 16 males and 5 females, aged 40.8 (15 ~ 72) underwent surgical treatment, 13 cases undergoing lobectomy, 3 sleeve lobectomy, 4 pneumonectomy, and 1 case thoracic exploration, from February 1988 to June 2005. Bronchoscopy was done in all patients before operation. Follow-up was made for 68.3 months on average. RESULTS: Most patients presented the respiratory symptoms such as cough, dyspnea, hemoptysis, and obstructive pneumonia. Biopsy examination through bronchoscopy confirmed the diagnosis of bronchial mucoepidermoid carcinoma in 16 cases. Pathology showed 17 cases of low grade tumor and 4 cases of high grade tumor. Follow-up showed that 17 cases of low-grade group (stage T(1 - 3)N(0 - 1)M(0)) all survived, 8 of which had survived for more than 5 years, including one patient with hilar lymph node metastasis. However, none of the 4 cases with high-grade tumor survived for more than 1 year except one that survived for 13 months. CONCLUSION: Patients with low-grade mucoepidermoid carcinoma can be expected to be cured through curative resection, however, patients in high-grade group have poor prognosis because of metastasis. TNM staging, malignancy grade, and local lymph node metastasis play the key roles in prediction of prognosis.

[Enhanced-real time PCR: a highly sensitive method for SARS-coronavirus detection].

An enhanced real-time polymerase chain reaction (ERT-PCR) assay to detect the coronavirus associated with severe acute respiratory syndrome (SARS-Cov) has been designed for detection of SARS-Cov with high sensitivity and easy-to-interpret results, in which a target gene pre-amplification step preceded TaqMan real-time fluorescent PCR. The limit of detection of the ERT-PCR method was 10(-2) higher than the standard real-time PCR assay and 10(-7) higher than conventional PCR methods. The increased sensitivity of the assay would have major benefits in screening suspected SARS patients rapidly and efficiently and may help control the spread of SARS and other infectious diseases during future outbreak.

[Clinical diagnosis and surgical treatment of primary pulmonary lymphoma].

OBJECTIVE: To study the clinical characteristics, the principles of diagnosis and surgical treatment for primary pulmonary lymphoma. METHOD: Ten patients with primary pulmonary lymphoma were treated surgically and their clinical characteristics, the experiences of clinical diagnosis and surgical treatment were analyzed. The tumors located in left upper lobe in 2, left lower lobe in 1, right upper lobe in 3, right middle lobe in 3 and right lower lobe in 1. The main symptoms were cough and (or) hemoptysis. Imageological representations (X-ray and CT scanning of thorax) were similar to primary pulmonary carcinoma. Broncho-fibroscopic examination was performed on all cases with negative findings. Eight cases were mistakenly diagnosed as primary pulmonary carcinoma by imageological representations. Only 2 cases were diagnosed as primary pulmonary lymphoma by percutaneous needle biopsy and pathologic examination. All cases received pneumonectomy, ipsilateral hilar and mediastinal lymphadenectomy. All cases with non-Hodgkin's lymphoma received regular chemotherapy (MOPP and ABVD scheme for 1 case with Hodgkin's disease respectively, CHOP for 8 cases with non-Hodgkin's lymphoma), and 3 cases received radiotherapy postoperatively. RESULTS: Eight cases were non-Hodgkin's lymphoma (B-type) and 2 cases were Hodgkin's disease (mixed type) confirmed by pathological examination. Six cases with non-Hodgkin's lymphoma (3 cases for stage IE, 2 cases for stage II 1E, and 1 case for stage II 2E W) had been surviving for 18-42 months until the follow-up. Two cases with non-Hodgkin's lymphoma (stage II 2E, B-cell, low-grade) and 2 cases with Hodgkin's disease (stage IE and II 2E, mixed type) died in 24, 32, 8 and 17 months postoperatively respectively. CONCLUSIONS: Primary pulmonary lymphoma is a rare type of malignant lung neoplasm without special clinical features. The preoperative diagnosis is difficult. Treatment modalities include surgical treatment, radiotherapy and regular chemotherapy postoperatively.

[Fluorine-18 fluorodeoxyglucose uptake in patients with benign pulmonary nodules].

OBJECTIVE: To assess the features of fluorine-18 fluorodeoxyglucose (FDG) uptake in patients with benign pulmonary nodules. METHODS: From October 1998 to July 2004, 47 patients with benign pulmonary nodules were imaged with FDG-positron emission tomography (PET). Diagnoses were confirmed by surgery. FDG-PET data was analyzed by visual method and semi-quantitive method. When pulmonary nodules with abnormal FDG intake appeared in PET scans confirmed by visual method, their maximum and mean standard uptake value (SUVmax and SUVmean) and SUV of normal lung (SUVlung) were measured using semiquantitative method. RESULTS: Twenty-one cases showed nothing abnormal in PET scans, including 17 calcification and fibrosis, 2 hamartomas and 2 sclerosing hemangiomas. 26 pulmonary nodules were detected by FDG-PET (17 active tuberculous, 6 inflammatory pseudotumors, 3 cryptococcosis). FDG uptake of these 26 nodules was higher than that of normal lung (SUVmax, SUVmean and SUVlung were 3.04 +/- 1.65, 2.48 +/- 1.35 and 0.40 +/- 0.07, respectively, P < 0.001). Correlations were not found between FDG uptake and nodule size or SUV of normal lung or age or blood glucose level in these 26 patients (P > 0.05). SUV in 9 cases (9/26, 35%) were beyond 2.5. CONCLUSIONS: Some benign pulmonary nodules were FDG avid.

[Value of carbon-11 choline positron emission tomography in patients with pulmonary abnormalities].

OBJECTIVE: To assess the value of carbon-11 choline (CH) positron emission tomography (PET) in patients with pulmonary nodules. METHODS: From September 2002 to December 2004, 39 patients with pulmonary nodules were imaged with CH-PET. CH-PET data was analyzed by visual method and semiquantitative method. When pulmonary nodules with abnormal CH uptake appeared in PET scans confirmed by visual method, their maximum and mean standard uptake value (SUVmax and SUVmean) were measured using semiquantitative method. Diagnoses were confirmed by surgery or biopsy and follow-up survey. RESULTS: Twenty-four cancerous and 3 inflammatory nodules and 1 bronchogenic cyst were detected by CH-PET and were diagnosed malignant with visual method. Three bronchial alveolar carcinoma, 2 metastatic tumor from kidney and colon, 3 fibrous nodules, 1 cryptococcosis, 1 hamartoma and 1 sclerosing hemangioma showed nothing abnormal in PET scans. For identification of pulmonary nodules with CH-PET, the sensitivity was 89% (24/29), the specificity was 60% (6/10), and the accuracy was 77% (30/39). There were differences in SUV between 8 squamous cell carcinomas and 9 adenocarcinomas (Z = -2.937, -2.887, P < 0.01). In diagnosing 70 resected enlarged lymph nodes beyond 1 cm in 17 lung cancer patients, CH-PET had the sensitivity of 86% (25/29), the specificity of 90% (37/41), and the accuracy of 89% (62/70). CH-PET confirmed 7 distant metastases in 25 lung cancer patients. In 5 cases suspected brain metastases CH-PET identified 2 cases positive correctly. CONCLUSIONS: CH-PET can confirm malignant pulmonary nodules, but still there were false positive and false negative cases. CH-PET can evaluate N stage effectively in patients with lung cancer. CH-PET can depict brain metastases accurately.

[Fluorine-18 fluorodeoxyglucose-positron emission tomography imaging of carcinoma of cardia or fundus of stomach].

OBJECTIVE: To investigate the value of fluorine-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) in carcinoma of cardia or fundus of stomach. METHODS: From April 1999 to April 2005, 57 patients with carcinoma of cardia or fundus of stomach were imaged with FDG-PET. FDG-PET imaging were analyzed by visual method combined with semiquantitative analysis. The results were compared with pathological findings and follow-up results. RESULTS: In 29 untreated patients, 25 T(2) to T(4) tumors were all FDG avid and 4 T(1) cases showed nothing abnormal at the primary site. In 24 patients performed curative operation 40 resected enlarged lymph nodes beyond 1 cm were diagnosed correctly by FDG-PET. FDG-PET revealed distant metastases in 5 patients and corrected them from curative surgery candidates to late stage. In 28 treated patients FDG-PET confirmed 22 cases with recurrence or metastasis. CONCLUSIONS: FDG-PET has limited value in confirming T stage in carcinoma of cardia or fundus of stomach. It showed potential in N and M staging and predicting treatment response.

Inhibition of metabotropic glutamate receptor 1 suppresses tumor growth and angiogenesis in experimental non-small cell lung cancer.

Metabotropic glutamate receptor 1 (mGlu1 receptor) is expressed in many cancer cell types as compared to normal counterparts underscoring its potential role in tumor behavior. The aim of present study was to test the role of mGlu1 receptor in experimental non-small cell lung cancer (NSCLC). First, protein expression of mGlu1 receptor was higher in human NSCLC cell lines, including both adenocarcinoma and squamous carcinoma subtypes, when compared to normal bronchial epithelial cells. Inhibition of mGlu1 receptor by BAY36-7620 (an mGlu1 receptor-specific inhibitor) inhibited tumor growth and prolonged survival of mice with tumors of A549 or H1299. Treatment with BAY36-7620 suppressed AKT phosphorylation in A549 tumors and pre-treatment with BAY36-7620 blocked the L-quisqualate (a potent mGlu1 receptor agonist)-induced AKT phosphorylation in A549 cells. Treatment with BAY36-7620 reduced cellular proliferation of A549 cells. Treatment with BAY36-7620 enhanced cleaved PARP levels and reduced protein expression of bcl-2, HIF-1α, and VEGF. In contrast, treatment with L-quisqualate reduced cleaved PARP levels and enhanced protein expression of bcl-2, HIF-1α, VEGF, and IL-8, which was reversed by co-incubation with MK2206 (an AKT inhibitor). Pre-treatment with BAY36-7620 blocked the VEGF-induced AKT phosphorylation in HUVECs. Treatment of HUVECs with L-quisqualate resulted in enhancement of capillary tube formation, which was reversed by co-incubation with MK2206. Furthermore, mGlu1 receptor knockdown suppressed tumor growth and prolonged survival of mice with tumors of A549 or H1299. Collectively, inhibition of mGlu1 receptor suppressed tumor growth and angiogenesis in experimental NSCLC.

[Surgical treatment of primary pulmonary cryptococcosis].

OBJECTIVE: To assess the clinical feature, diagnosis and treatment of primary pulmonary cryptococcosis. METHODS: From 1996 to 2004, 11 patients with primary pulmonary cryptococcosis were surgical treated and confirmed by histologic study. At the same period, 2715 patients with pulmonary abnormalities received surgery. Their clinical data were retrospectively reviewed. RESULTS: Sixty-four percent (7/11) of the patients were symptomatic at the time of diagnosis. All 11 cases were misdiagnosed as lung cancer or inflammatory or tuberculosis by X-ray and CT scan before surgery. Three cases received fluorine-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) scan and their primary pulmonary lesions showed FDG avid. All 11 patients were treated by antibiotics and antituberculosis therapy but no responses appeared. Primary pulmonary cryptococcosis was diagnosed by ultrasound-guided fine needle aspiration biopsy in only 2 cases, but antifungal therapy was not effective. All 11 patients underwent thoracotomy and their pulmonary cryptococcosis were resected. Only 1 patient with multiple nodules received antifungal therapy postoperatively. No recurrence was found in any patients. CONCLUSIONS: Primary pulmonary cryptococcosis is non-specific and can be confused with lung cancer, tuberculosis, etc. The pulmonary abnormalities should be resected unless the diagnosis is established. Antifungal therapy is not necessary in patients whose abnormality has been resected thoroughly.

[Long-term outcome of bronchoplastic procedures in the treatment of lung cancer].

OBJECTIVE: To assess the value of bronchoplastic procedures in surgical treatment for bronchogenic carcinoma. METHODS: Bronchoplastic procedures were performed in 78 patients with bronchogenic carcinoma from August 1976 to December 2002. There were 67 patients with squamous cell carcinoma (86%). Of the total, 57 patients underwent sleeve resection of the right upper lobe (including 2 undergoing bronchoplasty and angioplasty; 2 undergoing partial carinal plus lobar resection); 1 patient had sleeve bilobectomy of the right upper and middle lobes; 2 patients had sleeve bilobectomy of the right middle and lower lobes. Sleeve resection of the left upper lobe was accomplished in 12 patients (including 3, undergoing bronchoplasty and angioplasty), 5 patients had sleeve lobectomy of the left lower lobe. Postoperative pathological staging: 47 in stage I (60.2%), 23 in stage II (29.5%), 8 in stage III (10.3%). RESULTS: No operative death occurred in 30 days. Complications were noted in 5 patients (6.6%), including pneumonia (2 patients) and atelectasis (3 patients). The overall 5-year survival for 78 patients was 57.8% (26/45), 43% (6/14) respectively. The 5-year survival for patients in stage I, II and III was 68.7% (22/32), 36.4% (4/11) and 0 (0/2) respectively. CONCLUSION: Bronchoplastic procedures for bronchogenic carcinoma extends operative indication to some patients with complication rates comparable to pneumonectomy and improve life quality.

[Expression and clinical significance of methylthioadenosine phosphorylase gene in patients with non-small cell lung cancer].

OBJECTIVE: To investigate the change of expression of methylthioadenosine phosphorylase (MTAP) gene in patients with non-small cell lung cancer and its clinical significance. METHODS: Thirty fresh samples of cancer with adjacent tissues were collected from 15 patients with lung cancer, 12 males and 8 females, aged 53.6 (38 approximately 72), 8 with squamous cell carcinoma and 7 with adenocarcinoma. The expressions of MTAP mRNA and of its protein were analyzed by RT-PCR and Western blotting. RESULTS: In 11 out of the 15 tumor samples (73.3%) MTAP mRNA was not expressed or expressed only after the additional 5 circulations. However, the MTAP mRNA expression rate was 93.3% (14/15) in the adjacent tissues. The result in the 11 samples with none or low MTAP mRNA expression was confirmed by Western blot analysis. The low expression rates were not significantly different between lung adenocarcinoma and squamous cell carcinoma. But the low expression rate of MTAP in intermediate and poorly differentiated lung cancer was significantly higher than that in well-differentiated cancer. CONCLUSION: The low expression or loss of MTAP gene may be relevant closely to the differentiation degree in lung cancer.

[Value of fluorine-18 fluorode oxyglucose-positron emission tomography in patients with small cell lung cancer].

OBJECTIVE: To investigate the value of fluorine-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging in patients with small cell lung cancer. METHODS: From February 2000 to July 2003, 17 patients with small cell lung cancer were imaged with FDG-PET. FDG-PET scans were analyzed by visual method. The FDG-PET results were compared with the pathological results and results of follow-up survey. RESULTS: 15 primary tumors were all FDG avid. By visual method 63 areas metastatic lymph nodes in 15 cases were revealed and more distant metastases outside the hemithoraxes were confirmed by FDG-PET than by routine examinations. FDG-PET corrected the diagnosis 5 cases from local disease (LD) to extended disease (ED). CONCLUSION: FDG-PET has great value in staging and treatment of patients with small cell lung cancer.

Meprin-ß regulates production of pro-inflammatory factors via a disintegrin and metalloproteinase-10 (ADAM-10) dependent pathway in macrophages.

Inflammatory response plays an important role not only in the normal physiology but also in the pathology such as atherosclerosis. Meprin, an astacin metalloproteinase, has exhibited proinflammatory effects in vivo and in vitro studies. Here, we tried to further investigate the proinflammatory potential of meprin-ß and the possible underlying mechanisms in primary human peripheral blood macrophages. In our current study, ELISA assay revealed that meprin-ß increased the production of pro-inflammatory cytokines, including interleukin-1ß (IL-1ß), interleukin-18 and interleukin-6 (IL-6) in macrophages. However, meprin-ß shows no effects on the level of ligands of epidermal growth factor receptor (EGFR), and the activation of EGFR. The molecular mechanism was associated with activation of a disintegrin and metalloproteinase 10 (ADAM10) and the phosphorylation of IκB. Further analysis of upstream mechanisms showed that activation of NF-κB by meprin-ß was mediated by inhibiting ADAM10-downstream extracellular signal regulated kinase (ERK1/2) pathway. Taken together, these results indicated that meprin-ß exhibited pro-inflammatory effects by targeting activating ADAM10, leading to ERK1/2-mediated activation of NF-κB in macrophages, and this would make meprin-ß a strong candidate for further study as proinflammatory target.

EZH2 silencing with RNAi enhances irradiation-induced inhibition of human lung cancer growth in vitro and in vivo.

Non-small cell lung cancer (NSCLC) has a high mortality rate and poor prognosis. The aim of the present study was to silence EZH2 and explore the antitumor effect of small interfering RNA (siRNA)-EZH2 in combination with radiotherapy, which is a main treatment for NSCLC. The results showed that irradiation in the presence of siRNA-EZH2 arrested A549 cells in the G(0) and G(1) phases, delayed cell cycle progression and effectively inhibited cell proliferation, compared with cells that received radiotherapy alone. The combined therapy enhanced the percentage of apoptotic A549 cells in vitro and reduced the tumor size, in addition to increasing the survival rate in tumor xenograft experiments. This study demonstrates the antitumor activity of ionizing radiation therapy in combination with siRNA-EZH2 in NSCLC, both in vitro and in vivo, as well as providing a scientific rationale for targeting EZH2 to enhance the sensitivity of cancer to radiotherapy in NSCLC patients.

Congenital bronchoesophageal fistula in adults.

AIM: To study the clinical characteristics, diagnosis and surgical treatment of congenital bronchoesophageal fistulae in adults. METHODS: Eleven adult cases of congenital bronchoesophageal fistula diagnosed and treated in our hospital between May 1990 and August 2010 were reviewed. Its clinical presentations, diagnostic methods, anatomic type, treatment, and follow-up were recorded. RESULTS: Of the chief clinical presentations, nonspecific cough and sputum were found in 10 (90.9%), recurrent bouts of cough after drinking liquid food in 6 (54.6%), hemoptysis in 6 (54.6%), low fever in 4 (36.4%), and chest pain in 3 (27.3%) of the 11 cases, respectively. The duration of symptoms before diagnosis ranged 5-36.5 years. The diagnosis of congenital bronchoesophageal fistulae was established in 9 patients by barium esophagography, in 1 patient by esophagoscopy and in 1 patient by bronchoscopy, respectively. The congenital bronchoesophageal fistulae communicated with a segmental bronchus, a main bronchus, and an intermediate bronchus in 8, 2 and 1 patients, respectively. The treatment of congenital bronchoesophageal fistulae involved excision of the fistula in 10 patients or division and suturing in 1 patient. The associated lung lesion was removed in all patients. No long-term sequelae were found during the postoperative follow-up except in 1 patient with bronchial fistula who accepted reoperation before recovery. CONCLUSION: Congenital bronchoesophageal fistula is rare in adults. Its most useful diagnostic method is esophagography. It must be treated surgically as soon as the diagnosis is established.