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Background: The aim of this study was to evaluate the potential of liquid biopsy for prediction of the efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment and for assessment of the changes in genetic alterations during such treatment.Methods: Plasma samples were prospectively collected from non-small cell lung cancer patients with EGFR-activating mutations during EGFR-TKI treatment until disease progression and were analyzed for such mutations with droplet digital polymerase chain reaction and for other somatic alterations with next-generation sequencing.Results: One hundred patients, including 87 who were EGFR-TKI naïve, were enrolled. Median progression-free survival was significantly shorter for EGFR-TKI-naïve patients with EGFR-activating mutations detected in plasma at baseline than for those without them (7.9 vs 19.0 months; P < .001), with the values being significantly longer for initially positive patients who became negative for these mutations at 12 or 24 weeks than for those who remained positive. An increase in the number of alleles positive for EGFR-activating mutations in plasma during treatment was associated with disease progression, with a hazard ratio of 4.72 (95% CI, 2.07-10.79; P < .001) for EGFR-TKI-naïve patients showing an increase within 36 weeks. For 55 patients with available samples, the total number of somatic alterations (other than activating mutations or T790M of EGFR) in plasma was higher at disease progression than at baseline (33 vs 19; P = 0.04).Conclusion: Liquid biopsy shows potential for prediction of EGFR-TKI efficacy and elucidation of clonal tumor evolution during targeted therapy. [ABSTRACT FROM AUTHOR]

Malignant mesothelioma ( MM) incidence is increasing drastically worldwide as an occupational disease resulting from asbestos exposure. However, no curative treatment for MM of advanced stage is available. Thus, new therapeutic approaches for MM are required. Because malignant pleural mesothelioma ( MPM) cells spread along the pleural surface in most patients, MPM can be targeted using intrapleural therapeutic approaches. In this study, we investigated the effectiveness of the intrapleural instillation of a replication-competent adenovirus as an oncolytic agent against MPM. We constructed a vascular endothelial growth factor promoter-based conditionally replicative adenovirus ( VEGF- CRAd) that replicates exclusively in VEGF-expressing cells. All of the MM cell lines that we tested expressed VEGF mRNA, and VEGF- CRAd selectively replicated in these MM cells and exerted a direct concentration-dependent oncolytic effect in vitro. Furthermore, our in vivo studies showed that pre-infection of MM cells with VEGF- CRAd potently suppressed MPM tumor formation in nude mice, and that intrapleural instillation of VEGF- CRAd prolonged the survival time of tumor-bearing mice. Our results indicate that VEGF- CRAd exerts an oncolytic effect on MM cells and that intrapleural instillation of VEGF- CRAd is safe and might represent a promising therapeutic strategy for MPM. [ABSTRACT FROM AUTHOR]

Lessons Learned: Alectinib confers a pronounced survival benefit in patients with ALK rearrangement‐positive non‐small cell lung cancer and a poor performance status.Survival benefit of alectinib for patients with a poor performance status was consistent regardless of the presence of central nervous system metastases. Background: We previously reported a marked objective response rate (ORR) and safety for alectinib treatment in patients with ALK rearrangement‐positive non‐small cell lung cancer (NSCLC) and a poor performance status (PS) in the Lung Oncology Group in Kyushu (LOGiK) 1401 study. It remained unclear, however, whether alectinib might also confer a long‐term survival benefit in such patients. Methods: Eighteen patients with ALK rearrangement‐positive advanced NSCLC and a PS of 2, 3, or 4 (n = 12, 5, and 1, respectively) were enrolled in LOGiK1401 between September 2014 and December 2015 and received alectinib. We have now updated the survival data for the study. Results: The median follow‐up time for all patients was 27.3 months. The median progression‐free survival (PFS) was 16.2 months (95% confidence interval [CI], 7.1–30.8 months), and the median survival time (MST) and the 3‐year overall survival rate were 30.3 months (95% CI, 11.5 months to not reached) and 43.8% (95% CI, 20.8–64.7%), respectively. This survival benefit was similarly manifest in patients with a PS of 2 (MST, 20.5 months) and those with a PS of ≥3 (MST, not reached). PFS did not differ between patients with or without central nervous system (CNS) metastases at baseline (median of 17.5 and 16.2 months, respectively, p =.886). Conclusion: Alectinib showed a pronounced survival benefit for patients with ALK rearrangement‐positive NSCLC and a poor PS regardless of the presence of CNS metastases, a patient population for which chemotherapy is not indicated. [ABSTRACT FROM AUTHOR]

Objectives: In this study, we attempted to perform inhalative administration of insulin using a new "bubble jet" atomization device based on ink jet printing technology and developed by Canon Inc. The aim of this study was to confirm the usefulness of the new device for achieving a hypoglycemic effect by insulin inhalation in normal rats., Methods: Inhaled insulin (15 U/kg) or a control solution without insulin was administrated to each Wistar rat intratracheally using the bubble-jet atomization device. Blood glucose concentrations were measured at 0, 10, 20, 30, 60, 90 and 120 min after administration of insulin or control solution., Results: The blood glucose concentrations in the inhaled insulin group were 63 +/- 10 mg/dl (20 min), 43 +/- 8 mg/dl (60 min) and 35 +/- 9 mg/dl (120 min), while those in the control solution group were 80 +/- 9 mg/dl (p = 0.016), 75 +/- 10 mg/dl (p < 0.001) and 85 +/- 27 mg/dl (p < 0.001). The blood glucose concentrations after administration of inhaled insulin were significantly lower than those after administration of control solution at all time points (p < 0.05) except 0 and 10 min., Conclusions: We confirmed the hypoglycemic effect of inhaled insulin using the new bubble jet atomization device. These results proved that the new device could atomize insulin while maintaining its bioactivity.