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A pre-metastatic niche (PMN) facilitates cancer metastasis through mobilization and recruitment of bone marrow-derived cells (BMDCs) and associated factors. In bone marrow, hematogenous cells, including osteoclasts, macrophages and lymphocytes, and mesenchymal cells, including mesenchymal stem cells, osteoblasts and adipocytes, are involved in PMN formation. Patients with lung cancer and metastasis have a poor prognosis and shortened median survival time. Bone marrow has been considered fertile ground for dormant and proliferating tumor cells, and mobilizing and recruiting BMDCs and immune cells can establish a PMN. However, the role of BMDCs in PMN formation is not yet fully understood. The present study aimed to investigate the association between BMDCs and PMN in bone marrow tissue samples. The results demonstrated that bone marrow served an important role in lung cancer progression and that eight pathways were potentially involved, including 'T-cell receptor signaling pathway', 'osteoclast differentiation', 'MAPK signaling pathway', 'VEGF signaling pathway', 'leukocyte transendothelial migration', 'signaling pathways regulating the pluripotency of stem cells', 'oxytocin signaling pathway' and 'cell adhesion molecules (CAMs)'. In addition, the present study investigated the role of BMDCs in facilitating lung cancer metastasis. In conclusion, the results from the present study suggested that molecular alterations in gene expression may provide a novel signature in lung cancer, which may aid in the development of novel diagnostic and therapeutic strategies for patients with lung cancer and bone metastasis.

Lung cancer is the most devastating malignancy in the world. Beyond genetic research, epigenomic studies—especially investigations of microRNAs—have grown rapidly in quantity and quality in the past decade. This has enriched our understanding about basic cancer biology and lit up the opportunities for potential therapeutic development. In this review, we summarize the involvement of microRNAs in lung cancer carcinogenesis and behavior, by illustrating the relationship to each cancer hallmark capability, and in addition, we briefly describe the clinical applications of microRNAs in lung cancer diagnosis and prognosis. Finally, we discuss the potential therapeutic use of microRNAs in lung cancer.

The aryl hydrocarbon receptor (AhR) agonists may upregulate matrix metalloproteinases (MMPs) and contribute to many airway diseases, such as asthma and chronic obstructive pulmonary disease. Elucidation of the detailed molecular mechanisms regulating MMPs may provide the scientific basis for diagnostic and therapeutic opportunities to improve the care of various pulmonary diseases, especially those related to xenobiotic agents. In this study, we investigated the detailed mechanisms of how AhR agonists modulated the expressions and activities of MMPs in bronchial epithelial cells. Treating the cells (Beas-2B or HBE135-E6E7) with 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester or 2,3,7,8-tetrachlorodibenzo-p-dioxin, we found these AhR agonists increased the expression and activity of MMP-1 via a noncanonical AhR pathway and increased the activity of MMP-2 and MMP-9 in an MMP-1-dependent manner. AhR agonists increased the expression of MMP-1 via the activation of mitogen-activated protein kinase (MAPK) pathways by increased cytosolic calcium level and activated calcium/calmodulin-dependent protein kinase II (CaMKII). The activated MAPK pathways phosphorylated c-Jun, c-Fos, and ATF-2, resulting in their nuclear translocation and binding to the activator protein-1 (AP-1) elements of the MMP-1 promoter region. These findings correlated clinically to the significantly higher plasma/serum MMP-1 level in asthmatic patients. In conclusion, the present study demonstrated a novel signaling pathway by which AhR agonists elevated intracellular calcium levels, which activated CaMKII, leading to increased MMP-1 expression through MAPK pathways in bronchial epithelial cell lines. This novel regulatory pathway may serve as a potential target for the treatment of airway remodeling of many pulmonary diseases, such as asthma.AhR agonists increase MMP-1 expression in bronchial epithelial cells. The underlying AhR pathway involves CaMKII, MAPKs, and AP-1 elements. The upregulated MMP-1 further activated MMP-2 and MMP-9. Asthmatic patients have higher serum MMP-1 level. This novel regulatory pathway is a potential target for treating asthma.

Features of airway remodelling have been described using tissue obtained from fatal cases of asthma and bronchial biopsies from mildly, moderately and severely asthmatic patients. Epithelial detachment and smooth muscle mass enhancement are common features of asthmatic bronchial tissue. This study is the first to investigate the inhibitory effect of nonylphenol (NP) on human bronchial epithelial cell lines BEAS-2B and HBE135-E6E7 (HBE). The results show that NP inhibits bronchial epithelial proliferation via the Fas/Fas ligand apoptotic system. We also treated BEAS-2B and HBE with NP and harvested the condition medium (CM), which was then added to bronchial smooth muscle cells (BSMC). Cultures of BSMC with NP-BEAS-2B-CM and NP-HBE-CM increased BSMC proliferation and migration. Exposure of BEAS-2B and HBE to NP caused epithelial cells to produce inflammatory cytokines IL-6 and IL-8, which subsequently induced BSMC proliferation and migration. Depleting both IL-6 and IL-8 completely reversed the effect of NP-BEAS-2B-CM- and NP-HBE-CM-mediated BSMC proliferation and migration, suggesting that this effect is a synergistic influence of IL-6 and IL-8. This study is the first to demonstrate that NP not only induces bronchial epithelial apoptosis via the Fas-mediated pathway but also stimulates the bronchial epithelium to secrete IL-6 and IL-8, which cause bronchial smooth muscle proliferation and migration - major features in asthma remodelling.

Pulmonary hyalinizing granuloma (PHG) is a rare disease characterized by multiple bilateral pulmonary nodules of uncertain etiology. We describe a 71-year-old female patient with thyroid papillary carcinoma in whom bilateral pulmonary nodules were found during a routine chest radiography examination. Subsequent fluorodeoxyglucose positron emission tomography/computed tomography scan gave the impression of multiple pulmonary metastases based on high maximum standardized uptake value. She underwent video-assisted thoracoscopic surgery with wedge resection, and PHG was diagnosed on the basis of histopathologic findings. To our knowledge, this is the first report of PHG developing in a patient as a solid cancer, mimicking multiple pulmonary metastases. We also present the first description of positron emission tomography in PHG, according to a Medline search.

Features of airway remodelling have been described using tissue obtained from fatal cases of asthma and bronchial biopsies from mildly, moderately and severely asthmatic patients. Epithelial detachment and smooth muscle mass enhancement are common features of asthmatic bronchial tissue. This study is the first to investigate the inhibitory effect of nonylphenol (NP) on human bronchial epithelial cell lines BEAS-2B and HBE135-E6E7 (HBE). The results show that NP inhibits bronchial epithelial proliferation via the Fas/Fas ligand apoptotic system. We also treated BEAS-2B and HBE with NP and harvested the condition medium (CM), which was then added to bronchial smooth muscle cells (BSMC). Cultures of BSMC with NP-BEAS-2B-CM and NP-HBE-CM increased BSMC proliferation and migration. Exposure of BEAS-2B and HBE to NP caused epithelial cells to produce inflammatory cytokines IL-6 and IL-8, which subsequently induced BSMC proliferation and migration. Depleting both IL-6 and IL-8 completely reversed the effect of NP-BEAS-2B-CM- and NP-HBE-CM-mediated BSMC proliferation and migration, suggesting that this effect is a synergistic influence of IL-6 and IL-8. This study is the first to demonstrate that NP not only induces bronchial epithelial apoptosis via the Fas-mediated pathway but also stimulates the bronchial epithelium to secrete IL-6 and IL-8, which cause bronchial smooth muscle proliferation and migration - major features in asthma remodelling.

This study reports the antimigration, anti-invasive effect of glabridin, a flavonoid obtained from licorice, in human non–small cell lung cancer A549 cells. Glabridin exhibited effective inhibition of cell metastasis by decreasing cancer cell migration and invasion of A549 cells. In addition, glabridin also decreased A549-mediated angiogenesis. Further investigation revealed that glabridin’s inhibition of cancer angiogenesis was also evident in a nude mice model. Blockade of A549 cells migration was associated with an increase of ανβ3 integrin proteosome degradation. Glabridin also decreased the active forms of FAK and Src, and enhanced levels of inactivated phosphorylated Src (Tyr 527), decreasing the interaction of FAK and Src. Inhibition of the FAK/Src complex by glabridin also blocked Akt activation, resulting in reduced activation of RhoA and myosin light chain phosphorylation. This study demonstrates that glabridin may be a novel anticancer agent for the treatment of lung cancer in 3 different ways: inhibition of migration, invasion, and angiogenesis.

Self-contained underwater breathing apparatus (scuba) diving is increasingly popular in Taiwan. There are few references in the literature regarding pulmonary hemorrhage as the sole manifestation of pulmonary barotrauma in scuba divers, and no study from Taiwan was found in the literature. We present the case of a 25-year-old man who suffered alveolar hemorrhage related to pulmonary barotrauma as a complication of scuba diving. To our knowledge, this is the first case report describing a Taiwanese subject suffering from non-fatal pulmonary hemorrhage after scuba diving.