Aims: Heme oxygenase-1 (HO-1, HMOX1) can prevent tumor initiation; while in various tumors, it has been demonstrated to promote growth, angiogenesis, and metastasis. Here, we investigated whether HMOX1 can modulate microRNAs (miRNAs) and regulate human non-small cell lung carcinoma (NSCLC) development. Results: Stable HMOX1 overexpression in NSCLC NCI-H292 cells up-regulated tumor-suppressive miRNAs, whereas it significantly diminished the expression of oncomirs and angiomirs. The most potently down-regulated was miR-378. HMOX1 also up-regulated p53, down-regulated angiopoietin-1 (Ang-1) and mucin-5AC ( MUC5AC), reduced proliferation, migration, and diminished angiogenic potential. Carbon monoxide was a mediator of HMOX1 effects on proliferation, migration, and miR-378 expression. In contrast, stable miR-378 overexpression decreased HMOX1 and p53; while enhanced expression of MUC5AC, vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), and Ang-1, and consequently increased proliferation, migration, and stimulation of endothelial cells. Adenoviral delivery of HMOX1 reversed miR-378 effect on the proliferation and migration of cancer cells. In vivo, HMOX1 overexpressing tumors were smaller, less vascularized and oxygenated, and less metastatic. Overexpression of miR-378 exerted opposite effects. Accordingly, in patients with NSCLC, HMOX1 expression was lower in metastases to lymph nodes than in primary tumors. Innovation and Conclusion: In vitro and in vivo data indicate that the interplay between HMOX1 and miR-378 significantly modulates NSCLC progression and angiogenesis, suggesting miR-378 as a new therapeutic target. Rebound Track: This work was rejected during standard peer review and rescued by Rebound Peer Review (Antioxid Redox Signal 16, 293-296, 2012) with the following serving as open reviewers:
Nonsuction drainage is more effective than suction drainage with regard to drainage volume, drainage duration, and incidence of persistent air leakage. However, it is associated with a higher incidence of asymptomatic residual air spaces.
Proangiogenic enzyme thymidine phosphorylase (TP) is a promising target for anticancer therapy, yet its action in non-small cell lung carcinoma (NSCLC) is not fully understood. To elucidate its role in NSCLC tumor growth, NCI-H292 lung mucoepidermoid carcinoma cells and endothelial cells were engineered to overexpress TP by viral vector transduction. NSCLC cells with altered expression of transcription factor Nrf2 or its target gene heme oxygenase-1 (HO-1) were used to study the regulation of TP and the findings from pre-clinical models were related to gene expression data from clinical NSCLC specimens. Overexpression of Nrf2 or HO-1 resulted in upregulation of TP in NCI-H292 cells, an effect mimicked by treatment with an antioxidant N-acetylcysteine and partially reversed by HO-1 knockdown. Overexpression of TP attenuated cell proliferation and migration in vitro, but simultaneously enhanced angiogenic potential of cancer cells supplemented with thymidine. The latter was also observed for SK-MES-1 squamous cell carcinoma and NCI-H460 large cell carcinoma cells. TP-overexpressing NCI-H292 tumors in vivo exhibited better oxygenation and higher expression of IL-8, IL-1β and IL-6. TP overexpression in endothelial cells augmented their angiogenic properties which was associated with enhanced generation of HO-1 and VEGF. Correlation of TP with the expression of HO-1 and inflammatory cytokines was confirmed in clinical samples of NSCLC. Altogether, the increased expression of IL-1β and IL-6 together with proangiogenic effects of TP-expressing NSCLC on endothelium can contribute to tumor growth, implying TP as a target for antiangiogenesis in NSCLC.
IntroductionIatrogenic tracheobronchial injuries are rare.AimTo analyse the mechanism of injury, symptoms and treatment of these patients.Material and methodsRetrospective analysis of hospital records of all patients treated for main airway injuries between 1990 and 2012 was performed.ResultsThere were 24 patients, including 21 women and 3 men. Mean time between injury and initiation of treatment was 12 hours (range: 2-48). In 16 patients the injury occurred during tracheal intubation, in 1 during rigid bronchoscopy, in 1 during rigid oesophagoscopy, in 1 during mediastinoscopy and in 5 during open surgery. Mean length of airway tear was 3.8 cm (range: 1.5-8). In 1 patient there was an injury to the cervical trachea and in the remaining 23 in the thoracic part of the airway. The treatment included repair of the membranous part of the trachea performed via right thoracotomy in 10 patients (in 1 patient additionally coverage with a pedicled intercostal muscle flap was used), a self-expanding metallic stent in 1 patient, suture of the right main bronchus and the oesophagus in 1, left upper sleeve lobectomy in 1, right upper lobectomy in 1, implantation of a silicone Y stent in 3, mini-tracheostomy in 1, and conservative treatment in 5 patients.ConclusionsIntubation is the most frequent cause of iatrogenic main airway injuries. Patients with these life-threatening complications require an individualised approach and treatment in a reference centre.
This article presents a case report of a patient suffering from bullous emphysema and chronic obstructive pulmonary disease, who was diagnosed with tension pneumothorax after undergoing endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA).Tension pneumothorax is a severe but rare complication of EBUS-TBNA. It can result from lung injury caused by the biopsy needle or, in patients suffering from bullous emphysema, from spontaneous rupture of an emphysematous bulla resulting from increased pressure in the chest cavity during cough caused by bronchofiberoscope insertion. The authors emphasize that patients should be carefully monitored after the biopsy, and, in the case of complications, provided with treatment immediately in proper hospital conditions. Patients burdened with a high risk of complications should be identified before the procedure and monitored with extreme care after its completion.
surgical staging. However, the universally accepted staging strategy is still lacking. According to the revised European Society of Thoracic Surgeons (ESTS) guidelines for preoperative mediastinal lymph node staging, primary surgery can be offered to patients with no positive lymph nodes on computed tomography (CT) and positron emission tomography (PET), primary tumor smaller than 3 cm, and the tumor located in the outer third of the lung. 1 However, literature data supporting the use of the minimally invasive regimen in patients with tumors larger than 3 cm and centrally located are scant. INTRODUCTION Lung cancer is the most common cause of cancer-related deaths. During the 19th century, lung cancer evolved from a rare disease to the most serious oncological problem in the world. The overall 5-year survival rate in Europe is 11.5, and it has not improved significantly over the last 2 decades. The most important issue in choosing an appropriate therapy is reliable staging. In patients with no distant metastases, the involvement of mediastinal nodes is the most important factor. Numerous techniques have been used for this purpose, including imaging, needle biopsies, and invasive
Background: A solitary pulmonary nodule (SPN) is a common and increasing clinical problem, mainly due to the lung cancer (LC) screening programs and easier access to complementary diagnostic tests. Differential diagnosis is broad and often challenging for decision making, particularly in small and not accessible lesions. The process of selecting the right strategy must address the probability of malignancy, nodule characteristics observed on CT/PET-CT, patient preferences and institutional-related expertise. The aim of this study was to evaluate the accuracy of the multidisciplinary lung cancer tumor (MLCT) board team in the management of SPN. Method: We retrospectively reviewed all SPN patients who underwent surgical resections between January 2015 and March 2017. All patients were evaluated at a MLCT meeting. We characterized demographic, clinical and radiological features, surgical procedure, histology and outcomes. Result: We included 73 patients, 37 male (50.7%), with a mean age of 63.3±10.2, 64.4% smokers (current or former) and none with asbestos/radon exposure. Twentyfive patients (34.2%) had previous history of cancer and 5 (6.8%) of tuberculosis. Emphysema was present in 21 patients (28.8%). Fifty-six were solid SPN (6e20 mm) and 17 sub solid SPN (9-18 mm): 15 with solid component (2-13.5 mm) and 2 pure ground glass nodules (10 and 12.3 mm). Of the 73 patients, 11 (15.1%) had a definitive histological result before the surgical intervention: 10 LC and 1 metastasis. Among patients without diagnosis (n¼62), frozen section was performed in 45 patients (61.6%): 31 of these (70%) were malignant disease (25 LC and 6 metastases) and 14 were benign lesions. In this group, we performed 17 lobectomies, 15 anatomic segmentectomies and 13 wedge resections. All patients with LC underwent mediastinal lymph node dissection (MLND). Among the 25 patients with LC, 7 were adenocarcinoma in situ and 18 invasive lesions (17 in stage I). In the other 17 cases without previous diagnosis, a direct surgery was performed, based either on the location of the lesion, size or clinical suspicion. Twelve of these patients (70.6%) were confirmed to have LC in the final pathology evaluation (all invasive LC in stage I). They underwent an upper bilobectomy, 10 lobectomies, 3 anatomic segmentectomies, all with MLND, and 3 wedge resections. No major complications were reported. Conclusion: This study suggests that surgery is a safe strategy in the diagnosis and treatment of SPN without previous diagnosis.Background: Sarcomas are known to be malignant and aggressive tumors, and often develop multiple pulmonary metastases. Although systemic therapy is a treatment of choice for metastatic lung tumors, effective treatments have not yet been established. Surgical resection for metastatic lung tumors is a therapeutic option to control the disease, while it is not a curative therapy. Method: Between 2006 and 2014, 129 sarcoma patients who underwent pulmonary metastasectomy in Okayama University Hospital were retrospectively reviewed. In total, 2...
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