Hsa-miR-1246 and hsa-miR-1290 are associated with stemness and invasiveness of non-small cell lung cancer.

OBJECTIVES: Cancer stem cells (CSCs) are considered to play a pivotal role in the process of invasion, metastasis and chemotherapy resistance. Diverse aberrantly expressed microRNAs (miRNAs) have been reported in lung cancer cells. However, there have been few reports about miRNAs that were associated with stemness and invasion of lung cancer. We investigated the role of miRNAs associated with characteristics of CSCs in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We cultured A549 cells (lung adenocarcinoma) and HCC1588 cells (lung squamous cell carcinoma) in serum free media condition. We isolated sphere-forming NSCLC cells and examined the microRNA expression by microarray and qRT-PCT. By inhibition of CSC-associated microRNAs, we identified the changes of stemness and invasiveness in NSCLC. RESULTS AND CONCLUSION: We discovered 44 over-expressed, 42 down-regulated miRNAs in the sphere-forming cells compared with the parent cells of NSCLC. By in-silico database search, we selected miR-1246 and miR-1290 that were suspected to be associated with CSCs among aberrantly expressed miRNAs. Inhibition of miR-1246 and miR-1290 showed decreased stemness markers and epithelial-mesenchymal transition (EMT) markers in NSCLC. Anti-miR-1246 and anti-miR-1290 suppressed proliferation, sphere-formation, colony formation and invasion of NSCLC. CSCs-associated miR-1246, or miR-1290 may be important in the invasion or metastasis of NSCLC.

Human papillomavirus type-16 positive endobronchial metastasis from uterine cervical cancer.

Although the lung is the most common site of metastasis from extrapulmonary malignancies, endobronchial metastases (EBM) are relatively rare. EBM typically originate from breast, colorectal, or kidney cancer. EBM from uterine cervical cancer is relatively rare and is difficult to confirm. In this study, we report a case of EBM in a patient with previously treated uterine cervical cancer. In this case, differentiation of the EBM from primary bronchogenic carcinoma with clinical, radiological, and pathologic findings was difficult. As identical human papillomavirus (HPV)-16 DNA was detected in both the EBM and in previously resected tissues from the prior uterine cervical cancer, the patient was diagnosed with EBM from uterine cervical cancer. HPV genotyping may aid in discriminating EBM from primary bronchogenic carcinoma in patients with uterine cervical cancer.

A case of pulmonary artery sarcoma presented as cavitary pulmonary lesions.

Pulmonary artery sarcoma (PAS) is a rare, poorly differentiated malignancy arising from the intimal layer of the pulmonary artery. Contrast-enhanced chest computed tomography (CT) is a good diagnostic modality that shows a low-attenuation filling defect of the pulmonary artery in PAS patients. An 18-year-old man was referred to our hospital for the evaluation and management of cavitary pulmonary lesions that did not respond to treatment. A contrast-enhanced CT of the chest was performed, which showed a filling defect within the right interlobar pulmonary artery. The patient underwent a curative right pneumonectomy after confirmation of PAS. Although lung parenchymal lesions of PAS are generally nonspecific, it can be presented as cavities indicate pulmonary infarcts. Clinicians must consider the possibility of PAS as well as pulmonary thromboembolism in patients with pulmonary infarcts. So, we report the case with PAS that was diagnosed during the evaluation of cavitary pulmonary lesions and reviewed the literatures.

Endobronchial metastases from extrathoracic malignancies: recent 10 years' experience in a single university hospital.

BACKGROUND: Although the lung is a common site of metastasis, endobronchial metastases (EBM) from extrathoracic malignancies are rare. Previous studies were retrospective reviews of the cases from each single institute, and the last one was performed between 1992 and 2002. We evaluated the characteristics of patients with EBM who had been diagnosed in recent 10 years in our hospital. METHODS: We retrospectively reviewed 1,275 patients who had undergone diagnostic bronchoscopic procedures between 2001 and 2011. An EBM was defined as bronchoscopically notable lesion, which was histopathologically identical to the primary tumor. RESULTS: A total of 18 cases of EBM were identified. The mean age was 53 years, and 12 cases of the 18 patients were female. The most common primary malignancies were colorectal cancer and breast cancer (4 cases each), followed by cervix cancer (3 cases) and renal cell carcinoma (2 cases). Cough was the most common symptom. The most common radiologic finding was atelectasis, which was identified in 27.7% of the cases. The median interval from the diagnosis of primary malignancy to the diagnosis of EBM was 14 months (range, 0-112 months). The median survival time from the diagnosis of EBM was 10 months (range, 1-39 months). CONCLUSION: EBM from extrathoracic malignancies were rare. Colorectal cancer and breast cancer were common as primary malignancies. Fiberoptic bronchoscopy should be performed in all patients, who are suspected of having EBM. If atypical clinical and pathological features are present, appropriate diagnostic studies should be undertaken.

Inhaled corticosteroid is associated with an increased risk of TB in patients with COPD.

BACKGROUND: It is well known that oral corticosteroid and anti-tumor necrosis factor-α agents increase the risk of TB. However, little is known about whether inhaled corticosteroid (ICS) increases the risk of TB. We performed this study to assess the risk of pulmonary TB among ICS users, based on the presence of the radiologic sequelae of pulmonary TB. METHODS: A retrospective cohort study was performed. Between January 1, 2000, and December 31, 2005, a total of 778 patients who had COPD were recruited. Among them, 162 patients were excluded according to the exclusion criteria. In total, 616 patients were followed until December 31, 2010. They were divided into four groups according to whether they used ICS and whether they had radiologic sequelae of prior pulmonary TB. RESULTS: A total of 20 patients developed pulmonary TB. Kaplan-Meier estimates showed an increased risk of pulmonary TB among the ICS users who had radiologic sequelae of prior pulmonary TB ( P , .001). Multivariate Cox regression showed that ICS use was an independent risk factor for the occurrence of pulmonary TB in patients who had a normal chest radiograph (hazard ratio, 9.079; 95% CI, 1.012-81.431; P 5 .049) and in patients who had radiologic sequelae of prior pulmonary TB (hazard ratio, 24.946; 95% CI, 3.090-201.365; P 5 .003). CONCLUSION: ICS use increases the risk of pulmonary TB in patients with COPD and the risk is greater in patients who have radiologic sequelae of prior pulmonary TB.

Endobronchial malignant fibrous histiocytoma: case report of an unusual presentation and palliative flexible bronchoscopic resection.

Primary malignant fibrous histiocytoma (MFH) of the lung is a very rare neoplasm that usually presents as a parenchymal mass. Here we report an unusual case of primary MFH of the bronchus, showing relatively benign clinical features. We performed a palliative resection via flexible bronchoscopy, using a polypectomy snare. The patient has survived for over 2 years after being diagnosed with an endobronchial mass, later found to be MFH, and 14 months post-debulking. There is a possibility that endobronchial MFH has a more favorable prognosis than MFH of other origins. If this is true, interventional bronchoscopy can be a reasonable option for non-operable cases of MFH.

Impaired colony-forming capacity of circulating endothelial progenitor cells in patients with emphysema.

Chronic obstructive pulmonary disease (COPD) is classified into emphysema and chronic bronchitis, which are thought to result from different pathophysiological pathways. Smoking-induced lung parenchymal destruction and inadequate repair are involved in the pathogenesis of emphysema. In addition, decreased expression of vascular endothelial growth factor and increased endothelial cell apoptosis in the lung may participate in emphysema pathogenesis. As stem cells, circulating endothelial progenitor cells (EPCs) may play a key role in the maintenance of vascular integrity by replacing and repairing the damaged endothelial cells in the tissues. To determine whether the lack of appropriate repair by circulating EPCs in cases of smoking-induced endothelial cell injury participates in emphysema pathogenesis, we determined the association between the colony-forming or migratory capacity of circulating EPCs and the presence of emphysema in 51 patients with COPD. The patients were divided into emphysema (n = 23) and non-emphysema groups (n = 28) based on high-resolution computed tomography. Twenty-two smokers with normal lung function and 14 normal non-smokers served as controls. Circulating EPCs isolated from patients with emphysema showed significantly lower colony-forming units (CFUs) than those from patients with non-emphysema group, smokers with normal lung function, and normal non-smokers. EPCs from patients with emphysema showed significantly lower migratory capacity than those from normal non-smoking controls (p < 0.05). On multivariate analysis, the EPC-CFU was independently associated with emphysema (OR 0.944, 95% CI = 0.903-0.987, p = 0.011). Thus, impaired functions of circulating EPCs may contribute to the development of emphysema.

p16Ink4a suppression of lung adenocarcinoma by Bmi-1 in the presence of p38 activation.

PURPOSE: Because evasion of tumor suppression is a critical step in cancer development, cancer cells have developed a variety of mechanisms to circumvent the influence of tumor suppressive pathways. Thus, genes that negatively regulate tumor suppressors could be considered novel types of oncogenes such as Bmi-1 repressing p16Ink4a and inhibiting p53 and were found to be frequently up-regulated in a variety of cancers. p38 mitogen-activated protein kinase (MAPK), which reportedly plays a crucial role as a tumor suppressor, is activated in number of lung adenocarcinomas, which is seemingly at odds with its role as a tumor suppressor. METHODS: We examined 10 lung adenocarcinomas and corresponding normal tissues and determined the expression levels of a variety of tumor suppressor proteins through real-time polymerase chain reaction and immunohistochemistry and measured p38 MAPK activity by immunoblotting or immunohistochemistry analysis. In the in vitro cellular model, p38 activation by H-Ras and consequent senescence induction was achieved through retro-viral gene transduction. Similarly, the suppression of p16Ink4a by Bmi-1 after the introduction of H-Ras was achieved through transient transfection with cationic liposome. RESULTS: We detected several lung adenocarcinomas that were positive for activated p38 MAPK but evidenced reduced levels of p16Ink4a expression. The suppression of p16Ink4a occurred in parallel with an increase in Bmi-1 and/or p16Ink4a promoter hypermethylation. Consistent with these observations, the H-Ras-stimulated induction of p16Ink4a was suppressed significantly through the coexpression of Bmi-1 in vitro. DISCUSSION: These results demonstrate that the suppression of p16Ink4a by either the induction of Bmi-1 or the hypermethylation of p16Ink4 may be an important step in avoiding tumor surveillance by p38 MAPK during the development of lung cancer.

Proteomic analysis of human small cell lung cancer tissues: up-regulation of coactosin-like protein-1.

Small cell lung cancer (SCLC) is the leading cause of cancer death, with a high propensity for aggressiveness and metastasis even in an early stage. Thus, identification of biomarkers as early diagnostics and treatment is needed. In this study, we investigated differentially regulated proteins between human SCLC tissues and normal bronchial epithelium by proteomic analysis using two-dimensional electrophoresis (2-DE) and MALDI-TOF mass spectrometry. Seven proteins and protein isoforms, including, γ-actin, tubulin α-1B, laminin B1, coactosin-like protein-1 (COTL-1), ubiquitin carboxyl-terminal esterase L1, ubiquitin-conjugating enzyme E2-25K, and carbonic anhydrase 1, were up-regulated more than 2 fold in SCLC tissues. In particular, up-regulated COTL-1 expression was validated by Western blot analysis, immunohistochemistry, and reverse transcription quantitative polymerase chain reaction (RT-qPCR). Moreover, most SCLC tissues (93%; 28/30) were COTL-1-positive in immunohistochemistry, whereas only 16% (10/64) of nonsmall cell lung cancer (NSLC) tissues were. Taken together, this SCLC proteomic data may help in establishing a human SCLC proteome database. COTL-1 may be a biomarker or a therapeutic target in SCLC patients.

Clinical characteristics of acute pulmonary thromboembolism in Korea.

BACKGROUND: Acute pulmonary thromboembolism (APTE) remains an important cause of morbidity and mortality in Western countries. In Korea, both the incidence and the mortality rate of APTE were thought to be low compared to Western countries. We performed the present study to investigate the current status of APTE in Korea. METHODS: Eight hundred and eight registry patients with APTE were analyzed with respect to clinical symptoms and signs, the presence of underlying diseases or predisposing factors, diagnostic methods, treatment and clinical course. RESULTS: The most common risk factors were prolonged immobilization (22.9%), deep venous thrombosis (22.0%), a recent operation (19.2%), and cancer (15.8%). The most common symptoms were dyspnea (78.6%), and chest pain (26.9%). The most common abnormality on chest radiography was effusion. The overall mortality rate at 3 months was 11.0%. Multivariate logistic regression analysis demonstrated that increased mortality risk was independently associated with the following baseline factors: onset in hospital (OR 1.88; 95% CI 1.03-3.42; p=0.03), lung cancer (OR 9.20; 95% CI 1.96-43.27; p=0.005), tachycardia (OR 3.50; 95% CI 1.86-6.60; p=0.0001), cardiogenic shock (OR 6.74; 95% CI 2.73-16.64; p=0.0001), and cyanosis (OR 3.45; 95% CI 1.27-9.44; p=0.01). CONCLUSIONS: Some differences did exist for the risk factors, symptoms, chest X-ray findings, mortality rate and prognostic factors as compared with those for Western patients. These results can prove especially helpful in the diagnosis as well as for the treatment of patients with APTE.