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Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of unknown cause. IPF has a distinct histopathological pattern of usual interstitial pneumonia in which fibroblastic foci (FF) represent the leading edge of fibrotic destruction of the lung. Currently there are three major hypotheses for how FF are generated: (1) from resident fibroblasts, (2) from bone marrow-derived progenitors of fibroblasts, and (3) from alveolar epithelial cells that have undergone epithelial-mesenchymal transition (EMT). We found that FF dissociated capillary vessels from the alveolar epithelia, the basement membranes of which are fused in normal physiological conditions, and pushed the capillaries and elastic fibers down ~100 μm below the alveolar epithelia. Furthermore, the alveolar epithelial cells covering the FF exhibited a partial EMT phenotype. In addition, normal human alveolar epithelial cells in vitro underwent dynamic EMT in response to transforming growth factor-β signaling within 72 h. Because it seems that resident fibroblasts or bone marrow-derived cells cannot easily infiltrate and form FF between the alveolar epithelia and capillaries in tight contact with each other, FF are more likely to be derived from the epithelial-to-mesenchymal transitioned alveolar epithelia located over them. Moreover, histology and immunohistochemistry suggested that the FF formed in the lung parenchyma disrupt blood flow to the alveolar septa, thus destroying them. Consequently, collapse of the alveolar septa is likely to be the first step toward honeycombing in the lung during late stage IPF. On the basis of these findings, inhibition of transforming growth factor-β signaling, which can suppress EMT of the alveolar epithelial cells in vitro, is a potential strategy for treating IPF.

A cell–cell adhesion protein, junctional adhesion molecule‐A (JAM‐A), has been shown to be involved in neoplasia of various organs. However, the fundamental role of JAM‐A in tumorigenesis is still under debate because dysregulated expression of this protein has distinct effects, playing opposite roles in carcinogenesis depending on the target tissues. In the present study, we found elevated levels of JAM‐A expression in lung adenocarcinoma and its preinvasive lesions, including atypical adenomatous hyperplasia and adenocarcinoma in situ by immunohistochemistry. We also showed that suppression of constitutive JAM‐A expression conferred target cells with increased susceptibility to apoptosis in lung adenocarcinoma cells. Consequently, inhibition of JAM‐A activity decreased colony‐forming capability in vitro and tumorigenicity in vivo. The transformed phenotype following suppression of JAM‐A expression was sufficient to reduce motile and invasive capacities. Importantly, knockout of JAM‐A had striking effects on cells. Our observations suggest that increased expression of JAM‐A promotes neoplasia of lung adenocarcinoma. In addition, an anti‐JAM‐A antibody efficiently reduced cell proliferation and provoked apoptosis, indicating the potential feasibility of JAM‐A‐inhibitory cancer therapy.

Background Completion lobectomy long after segmentectomy in the same lobe is extremely difficult because of severe adhesions around hilar structures, especially in cases involving video-assisted thoracoscopic surgery (VATS) completion lobectomy. We report and compare the surgical outcomes of patients who underwent VATS or thoracotomy completion lobectomy long after radical segmentectomy for lung cancer. Methods We retrospectively evaluated the surgical outcomes of completion lobectomies performed at our institute long after radical segmentectomies for lung cancer in the same lobe. The efficacy and safety of VATS completion lobectomy was compared to that of thoracotomy completion lobectomy. Results Ten of 228 patients who underwent radical segmentectomy for lung cancer between 2009 and 2018 underwent completion lobectomy at least a month after segmentectomy; five patients underwent VATS completion lobectomy. None of the patients underwent VATS left upper completion lobectomy, and conversion to thoracotomy was required in one patient. There were no significant differences between VATS and thoracotomy completion lobectomies in the median operative times (VATS 295 min, thoracotomy 339 min, p = 0.55), intraoperative blood loss volumes (VATS 350 mL, thoracotomy 500 mL, p = 0.84), intervals between initial segmentectomy and completion lobectomy (VATS 40 months, thoracotomy 48 months, p = 0.55), and number of patients with pulmonary artery injury (VATS 1, thoracotomy 2, p = 0.49). There was no operation-related mortality. Conclusions VATS completion lobectomy long after segmentectomy for lung cancer could be performed without fatal complications unless severe adhesions are observed around each main pulmonary artery.

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Dendritic cell (DC) maturation results in changes in antigen processing and presentation, governing the fate of adaptive immunity. Understanding the intracellular signaling pathways governing DC maturation is therefore critical. In this study, we observed that the kinase, GSK-3β, is present in its active form in resting immature DCs isolated from the spleen and bone marrow of mice. Induction of DC maturation using GM-CSF, IL-4 and TNFalpha resulted in GSK-3β inhibition, as reflected by increased phosphorylation of Serine 9 on the kinase, and concomitant stabilization of its substrate, beta-catenin. Treatment of immature DCs with a GSK-3β inhibitor increased cell surface expression of CD80, CD86 and CD40 on DCs, enhancing their ability to present antigen and activating IL-2 secretion by T cells. GSK-3β inhibition also parallels dendritic cell maturation in vivo. Our results show that GSK-3β signaling controls DC maturation and suggest that this kinase could be manipulated to modulate adaptive immunity.

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