Persistent hypoxia stimulation, one of the most critical microenvironmental factors, accelerates the acquisition of epithelial–mesenchymal transition (EMT) phenotypes in lung cancer cells. Loss of phosphatase and tensin homologue deleted from chromosome 10 (PTEN) expression might accelerate the development of lung cancer in vivo. Recent studies suggest that tumor microenvironmental factors might modulate the PTEN activity though a decrease in total PTEN expression and an increase in phosphorylation of the PTEN C-terminus (p-PTEN), resulting in the acquisition of the EMT phenotypes. Nevertheless, it is not known whether persistent hypoxia can modulate PTEN phosphatase activity or whether hypoxia-induced EMT phenotypes are negatively regulated by the PTEN phosphatase activity. We aimed to investigate hypoxia-induced modulation of PTEN activity and EMT phenotypes in lung cancers. Western blotting was performed in five lung cancer cell lines to evaluate total PTEN expression levels and the PTEN activation. In a xenograft model of lung cancer cells with endogenous PTEN expression, the PTEN expression was evaluated by immunohistochemistry. To examine the effect of hypoxia on phenotypic alterations in lung cancer cells in vitro, the cells were cultured under hypoxia. The effect of unphosphorylated PTEN (PTEN4A) induction on hypoxia-induced EMT phenotypes was evaluated, by using a Dox-dependent gene expression system. Lung cancer cells involving the EMT phenotypes showed a decrease in total PTEN expression and an increase in p-PTEN. In a xenograft model, loss of PTEN expression was observed in the tumor lesions showing tissue hypoxia. Persistent hypoxia yielded an approximately eight-fold increase in the p-PTEN/PTEN ratio in vitro. PTEN4A did not affect stabilization of hypoxia-inducible factor 1α. PTEN4A blunted hypoxia-induced EMT via inhibition of β-catenin translocation into the cytoplasm and nucleus. Our study strengthens the therapeutic possibility that compensatory induction of unphosphorylated PTEN may inhibit the acquisition of EMT phenotypes in lung cancer cells under persistent hypoxia.

We have reported that the reaction of ethyl bromodifluoroacetate (1) with alkenyl iodides in the presence of copper powder gives ethyl alkenyldifluoroacetates. As an extension of this reaction, reaction of 1 with Michael acceptors in the Presence of copper powder was examined and found to give 1, 4-addition products selectively, unless the acceptor has a group stabilizing a radical intermediate, such as a phenyl group.

Impact of mild to moderate COPD on feasibility and prognosis in non-small cell lung cancer patients who received chemotherapy Norihito Omote, Naozumi Hashimoto, Masahiro Morise, Koji Sakamoto, Shinichi Miyazaki, Akira Ando, Yoshio Nakahara, Yoshinori Hasegawa Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan Background: Non-small cell lung cancer (NSCLC) is the predominant cause of death in patients with COPD, and the severity of COPD in NSCLC patients is classified mainly as mild to moderate. Most advanced NSCLC patients with mild to moderate COPD are treated with chemotherapy; however, the feasibility for and prognosis after chemotherapy of these patients are not well understood. The aim of this study was to elucidate the impact of mild to moderate COPD on the feasibility for and prognosis after chemotherapy in NSCLC patients.Patients and methods: A retrospective review was performed on 268 NSCLC patients who received first-line chemotherapy from 2009 to 2014 in our institution. Finally, 85 evaluable patients were included in this study. The clinical characteristics, toxicity profile, objective response rate, and prognosis were analyzed and compared between patients with mild to moderate COPD and those without COPD (non-COPD).Results: Forty-three patients were classified as COPD (27 cases mild and 16 cases moderate) and 42 patients as non-COPD. The COPD group were older and had fewer never-smokers than the non-COPD group. The objective response rate did not differ between groups (p=0.14). There was no significant difference in overall survival between COPD and non-COPD groups (15.0 and 17.0 months, log-rank test p=0.57). In the multivariate Cox’s proportional hazard model, the adjusted hazard ratio (HRadj) was statistically significant for male sex (HRadj =5.382, 95% CI: 1.496–19.359; p=0.010), pathological diagnosis of adenocarcinoma (HRadj =0.460, 95% CI: 0.223–0.948; p=0.035), and epithelial growth factor receptor negative mutation (HRadj =6.040, 95% CI: 1.158–31.497; p=0.033), but not for the presence of COPD (HRadj =0.661, 95% CI: 0.330–1.325; p=0.24). Toxicity profile in COPD group was favorable, as in the non-COPD group.Conclusion: Mild to moderate COPD did not have a significant deleterious impact on toxicity and prognosis in NSCLC patients. Keywords: toxicity, survival, prognostic factors

The texture of feeble magnetic ceramics can be controlled by a strong magnetic field. When the magnetic susceptibility of the $c$ axis is smaller than that of the other axes, the $c$ axis aligns perpendicular to the magnetic field; however, the direction is randomly oriented on the plane perpendicular to the magnetic field. The authors demonstrate in this letter that a highly controlled texture in bismuth titanate, which has a $c$ -axis susceptibility smaller than the other axes, can be achieved using a two-step magnetic field procedure. This highly controlled orientation is effective for improving the electromechanical coupling coefficient.

There is only limited information on the impact of thin-section computed tomography (TSCT)-determined usual interstitial pneumonia (UIP) pattern in the decision-making for resection in newly diagnosed lung cancer patients. In this retrospective analysis, data were reviewed from 499 newly diagnosed lung cancer patients who received bronchoscopy between 2010 and 2014. The clinical impact of TSCT-determined UIP pattern on the decision-making process for resection in this cohort was evaluated. The prevalence rate of TSCT-determined fibrosis was 14.8% (74/499 cases), 86.5% (64/74 cases) of which also had TSCT-determined emphysema. The fibrosis group comprised 40 patients with possible UIP and 34 patients with the UIP pattern. Among surgical candidates, the number of surgeries performed was lower in the fibrosis group (60.8%) than in the normal and emphysema groups (84.7 and 77.3%, respectively). Although the proportion of possible UIP did not differ between surgical candidates and patients with resected lung cancer, the proportion of UIP pattern in patients with resected lung cancer was decreased by 8.5%, compared to the surgical candidates. Although measurement of diffusing capacity of the lung for carbon monoxide (DLCO) was performed in more than 97% of patients with thoracic surgery, only 58% of patients without thoracic surgery had DLCO measurement. Multivariate analysis showed that the finding of UIP pattern independently affects the decision-making process for thoracic surgery. The adjusted odds ratios for the comparison between the patients without fibrosis and the patients with UIP pattern was 0.266 (95% confidence intervals: 0.087–0.812). The presence of TSCT-determined UIP pattern might independently affect the decision-making process for proposing thoracic surgery with curative intent.