Rearranged during transfection (RET) fusions have been newly identified in approximately 1% of patients with primary lung tumors. However, patient-derived lung cancer cell lines harboring RET fusions have not yet been established or identified, and therefore, the effectiveness of an RET inhibitor on lung tumors with endogenous RET fusion has not yet been studied. In this study, we report identification of CCDC6-RET fusion in the human lung adenocarcinoma cell line LC-2/ad. LC-2/ad showed distinctive sensitivity to the RET inhibitor, vandetanib, among 39 non-small lung cancer cell lines. The xenograft tumor of LC-2/ad showed cribriform acinar structures, a morphologic feature of primary RET fusion-positive lung adenocarcinomas. LC-2/ad cells could provide useful resources to analyze molecular functions of RET-fusion protein and its response to RET inhibitors.

Early pulmonary resection is indicated in patients with hemoptysis of multiple branches from the cavity and chest wall, such as in fungal infections. When a bronchial branch is the only bleeding focus, superselective embolotherapy should be considered prior to surgery even if the localized focus of the bronchial branch shows minor vascularity on the angiography.

Decreased cell-substratum adhesion is crucially involved in metastasis. Previous studies demonstrated that lung cancer with floating cell clusters in histology is more likely to develop metastasis. In the present study, we investigated whether cancer cells in long-term, three-dimensional low attachment cultures acquire high metastatic potential; these cells were then used to examine the mechanisms underlying metastasis. Two KRAS-mutated adenocarcinoma cell lines (A549 and H441) were cultured and selected on ultra-low attachment culture dishes, and the resulting cells were defined as FL (for floating) sublines. Cancer cells were inoculated into NOD/SCID mice via an intracardiac injection, and metastasis was evaluated using luciferase-based imaging and histopathology. In vitro cell growth (in attachment or suspension cultures), migration, and invasion were assayed. A whole genomic analysis was performed to identify key molecular alterations in FL sublines. Upon detachment on low-binding dishes, parental cells initially formed rounded spheroids with limited growth activity. However, over time in cultures, cells gradually formed smaller spheroids that grew slowly, and, after 3–4 months, we obtained FL sublines that regained prominent growth potential in suspension cultures. On ordinary dishes, FL cells reattached and exhibited a more spindle-shaped morphology than parental cells. No marked differences were observed in cell growth with attachment, migration, or invasion between FL sublines and parental cell lines; however, FL cells exhibited markedly increased growth potential under suspended conditions in vitro and stronger metastatic abilities in vivo. A genomic analysis identified epithelial-mesenchymal transition (EMT) and c-Myc amplification in A549-FL and H441-FL cells, respectively, as candidate mechanisms for metastasis. The growth potential of FL cells was markedly inhibited by lentiviral ZEB1 knockdown in A549-FL cells and by the inhibition of c-Myc through lentiviral knockdown or the pharmacological inhibitor JQ1 in H441-FL cells. Long-term three-dimensional low attachment cultures may become a useful method for investigating the mechanisms underlying metastasis mediated by decreased cell-substratum adhesion.

Symptomatic extralobar pulmonary sequestration (EPS) is extremely rare. Herein, we report two male patients (3 and 16 years of age) with EPS presenting as hemothorax. Thoracotomic resections of the sequestrated lungs were uneventful. Pathologic examinations revealed hemothorax caused by circulatory disorders within the EPSs.

A 49-year-old woman with a 20-year history of Sjögren's syndrome (SS) was incidentally found to have an abnormal chest X-ray along with dyspnea and desaturation. Chest CT findings showed multiple cystic shadows, ground glass opacity, and small nodule-like lymphocytic interstitial pneumonia (LIP), which have been previously reported. She was diagnosed by surgical lung biopsy to have mucosa-associated lymphoid tissue (MALT) lymphoma. It was difficult to detect the presence of lymphoma by the use of only CT findings. Pulmonary involvement of SS occurs in various forms so that SS patients with pulmonary involvement should undergo open biopsy to reach a definitive diagnosis.

Despite remarkable advances in oncology medicine, the prognosis of lung cancer patients has not greatly improved over the past few decades. To overcome the current limit, new classes of agents that specifically target particular cascades have been developed. Gefitinib and erlotinib, which are tyrosine kinase inhibitors specific for the epidermal growth factor receptor (EGFR), have provided hope for better survival. The relationship between the sensitivity to gefitinib and the tumors' EGFR mutations have allowed the selective and accelerated use of these therapies. However, their efficacy is still limited, predominantly due to side effects and drug resistance. Further development of rational clinical strategies will require greater clarification of the key signaling factors downstream of EGFR which are potential targets for cancer therapies. In this review, we describe the various observed abnormalities in EGFR, the mechanisms of activation of several critical signaling cascades in lung cancer. Summarizing the data gleaned from preclinical, and clinicopathological aspects, we discuss the molecular mechanisms that may underlie a possible successful response to the blockade of EGFR and/or its downstream signaling.

Reinforced endostapling can prevent postoperative air leakage from surgical stumps. We herein present a 58-year old woman with idiopathic interstitial pneumonia who developed lethal haemothorax after a thoracoscopic lung biopsy with the use of an endostapler preloaded with bioabsorbable tissue reinforcement material. This lethal haemothorax, which occurred on the day after the lung biopsy, required an emergency operation. The bleeding point was an intercostal artery of the inferior chest wall adjacent to the surgical stump. The operative findings suggested that the reinforced material on the surgical stump scratched the chest wall through respiratory movement.

Anatomical variations in the pulmonary vessels present a potential risk for intraoperative bleeding and damage to the pulmonary circulation during pulmonary resection. Here, we present a patient who underwent left upper lobectomy for lung cancer. The patient had a dangerous mediastinal basal pulmonary artery variation that could be mistaken for the mediastinal lingular pulmonary artery and be divided during left upper lobectomy.