Purpose: Concurrent proton pump inhibitor (PPI) use might reduce the plasma concentration of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). Clinically, the adverse effect of PPIs on patients with non-small cell lung cancer (NSCLC) treated with first-line EGFR TKIs remains controversial. This study was conducted to evaluate whether the combined use of gefitinib with PPIs affected NSCLC outcomes. Patients and methods: We performed a nationwide cohort study of patients newly diagnosed with NSCLC between 1997 and 2013 using the Taiwan Cancer Registry and Taiwan National Health Insurance databases. We identified patients who were treated with first-line EGFR TKIs and analyzed the association between use of PPIs and TKI treatment outcome. We defined the coverage ratio of PPIs as duration of PPI treatment in days divided by duration of TKIs in days. Patients who exhibited an overlap of >20% between PPI and TKI usage days were defined as having a high coverage ratio. Results: A total of 1278 patients were treated with first-line gefitinib, 309 of which took PPIs at the same time and 145 had a high PPI coverage ratio. Patients had similar time to failure regardless of their PPI coverage ratio during gefitinib treatment. However, higher PPI coverage ratio significantly decreased overall survival (OS) compared with that of patients with a lower PPI coverage ratio or no PPI treatment in univariate analysis (median OS, 13.5, 16.7, and 21.8 months, respectively, p<0.01) and multivariate analyses (high coverage ratio HR: 1.67; low coverage ratio HR: 1.29). Exposure to PPIs during first line gefitinib treatment significantly decreased overall survival of patients with NSCLC. Conclusion: Concurrent use of PPIs was associated with lower overall survival in patients with EGFR-mutant NSCLC under first-line gefitinib treatment.

For rapid and unlimited cell growth and proliferation, cancer cells require large quantities of nutrients. Many metabolic pathways and nutrient uptake systems are frequently reprogrammed and upregulated to meet the demand from cancer cells, including the demand for lipids. The lipids for most adult normal cells are mainly acquired from the circulatory system. Whether different cancer cells adopt identical mechanisms to ensure sufficient lipid supply, and whether the lipid demand and supply meet each other, remains unclear, and was investigated in lung cancer cells. Results showed that, despite frequent upregulation in de novo lipogenesis and the lipid transporter system, different lung cancer cells adopt different proteins to acquire sufficient lipids, and the lipid supply frequently exceeds the demand, as significant amounts of lipids stored in the lipid droplets could be found within lung cancer cells. Lipid droplet surface protein, PLIN3, was found frequently overexpressed since the early stage in lung cancer tissues. Although the expression is not significantly associated with a specific gender, age, histology type, disease stage, and smoking habit, the frequently elevated expression of PLIN3 protein indicates the importance of lipid droplets for lung cancer. These lipid droplets are not only for nutrient storage, but are also crucial for tumor growth and proliferation, as well as survival in starvation. These results suggest that manipulation of lipid droplet formation or TG storage in lung cancer cells could potentially decrease the progression of lung cancer. Further exploration of lipid biology in lung cancer could help design novel treatment strategies.

Background: Casein kinase 2 (CK2) is dysregulated in various human cancers and is a promising target for cancer therapy. To date, there is no small molecular CK2 inhibitor in clinical trial yet. With the aim to identify novel CK2 inhibitors, we screened a natural product library. Methods: We adopted cell-based proliferation and CK2 kinase assays to screen CK2 inhibitors from a natural compound library. Dose-dependent response of CK2 inhibitors in vitro was determined by a radioisotope kinase assay. Western blot analysis was used to evaluate down stream Akt phosphorylation and apoptosis. Apoptosis was also evaluated by annexin-V/propidium iodide (PI) labeling method using flow cytometry. Inhibition effects of CK2 inhibitors on the growth of cancer and normal cells were evaluated by cell proliferation and viability assays. Results: Hematein was identified as a novel CK2 inhibitor that is highly selective among a panel of kinases. It appears to be an ATP non-competitive and partially reversible CK2 inhibitor with an IC₅₀ value of 0.55 μM. In addition, hematein inhibited cancer cell growth partially through down-regulation of Akt phosphorylation and induced apoptosis in these cells. Furthermore, hematein exerted stronger inhibition effects on the growth of cancer cells than in normal cells. Conclusion: In this study, we showed that hematein is a novel selective and cell permeable small molecule CK2 inhibitor. Hematein showed stronger growth inhibition effects to cancer cells when compared to normal cells. This compound may represent a promising class of CK2 inhibitors.

Objectives: This paper reports on the findings of a population-based study to evaluate the relationship between atmospheric fine particulate matter (PM_2.5) levels and hospital admissions for chronic obstructive pulmonary disease (COPD) in southwestern Taiwan over a three-year period, 2008–2010. Methods: Data on hospital admissions for COPD and PM_2.5 levels were obtained from the National Health Insurance Research database (NHIRD) and the Environmental Protection Administration from 2008 to 2010, respectively. The lag structure of relative risks (RRs) of hospital admissions for COPD was estimated using a Poisson regression model. Results: During the study period, the overall average hospitalization rate of COPD and mean 24-h average level of PM_2.5 was 0.18% and 39.37 μg/m³, respectively. There were seasonal variations in PM_2.5 concentrations in southwestern Taiwan, with higher PM_2.5 concentrations in both spring (average: 48.54 μg/m³) and winter (49.96 μg/m³) than in summer (25.89 μg/m³) and autumn (33.37 μg/m³). Increased COPD admissions were significantly associated with PM_2.5 in both spring (February–April) and winter (October–January), with the relative risks (RRs) for every 10 μg/m³ increase in PM_2.5 being 1.25 (95% CI = 1.22–1.27) and 1.24 (95% CI = 1.23–1.26), respectively, at a lag zero days (i.e., no lag days). Lag effects on COPD admissions were observed for PM_2.5, with the elevated RRs beginning at lag zero days and larger RRs estimates tending to occur at longer lags (up to six days, i.e., lag 0–5 days). Conclusions: In general, findings reveal an association between atmospheric fine particulate matter (PM_2.5) and hospital admissions for COPD in southwestern Taiwan, especially during both spring and winter seasons.

Ambient particulate matter (PM) can trigger adverse reactions in the respiratory system, but less is known about the effect of indoor PM. In this longitudinal study, we investigated the relationships between indoor PM and clinical parameters in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). Indoor air quality (PM_2.5 and PM₁₀ levels) was monitored in the patients’ bedroom, kitchen, living room, and front door at baseline and every two months for one year. At each home visit, the patients were asked to complete spirometry and questionnaire testing. Exacerbations were assessed by chart review and questionnaires during home visits. Generalized estimating equation (GEE) analysis (n = 83) showed that the level of wheezing was significantly higher in patients whose living room and kitchen had abnormal (higher than ambient air quality standards in Taiwan) PM_2.5 and PM₁₀ levels. Patients who lived in houses with abnormal outdoor PM_2.5 levels had higher COPD Assessment Test scores (physical domain), and those who lived in houses with abnormal PM₁₀ levels in the living room and kitchen had higher London Chest Activity of Daily Living scores. Increased PM levels were associated with worse respiratory symptoms and increased risk of exacerbation in patients with moderate to very severe COPD.

The burden of illness resulting from adverse environmental exposure is significant. Numerous studies have examined self-care behaviors among patients with chronic obstructive pulmonary disease (COPD), but seldom assess these behaviors in relation to air pollution. The study aims to examine the effects of particulate matter (PM) education on prevention and self-care knowledge regarding air pollution, symptom changes, and indoor PM concentration levels among patients with COPD. A longitudinal, quasi-experimental design using a generalized estimating equation examined the effectiveness of the education intervention. Participants were 63 patients with COPD, of whom only 25 received intervention. Levels of PM_2.5 and PM₁₀ decreased in the first-month follow-up in the experimental group. Improvement of knowledge and prevention regarding PM in the first and third months were also greater in the experimental group compared to the control. Regarding the COPD assessment test and physical domain scores, the experimental group exhibited a greater improvement in the first-month follow-up. Scores on the psychological domain significantly changed in the sixth-month follow-up. The PM education coordinated by nurses improved the health of participants, maintaining six-month effects. Further studies should evaluate the practice barriers and effects of health education on preventive self-care behaviors regarding indoor PM among patients with COPD.