AMPK α1 Downregulates ROS Levels Through Regulating Trx Leading to Dysfunction of Apoptosis in Non-Small Cell Lung Cancer.

PURPOSE: AMP-activated protein kinase α1 (AMPK α1) associates closely with cancers. However, the relationship between AMPK α1 and non-small cell lung cancer (NSCLC) is not fully understood. In this study, we aim to explore the role and mechanism of AMPK α1 in NSCLC initiation and progression. MATERIALS AND METHODS: A total of 165 clinical NSCLC specimens were included in the formalin-fixed and paraffin-embedded (FFPE) lung cancer tissue arrays. The expression levels of AMPK α1 and thioredoxin (Trx) in NSCLC cancer tissues and adjacent non-tumor lung tissues were measured through using immunohistochemistry. MTT assay was used to detect cell proliferation. Intracellular ROS levels were measured by using H2DCFDA reagent. Lentiviruses including LV-PRKAA1-RNAi, LV-PRKAA1 and a negative LV-control were used to infect A549 cells to modulate AMPK α1 expression in vitro. Immunoblotting was used to determine the modulation relationship between AMPK α1 and Trx. Log rank test and Kaplan-Meier survival analysis were performed to evaluate the significances of AMPK α1 and Trx expression levels on NSCLC patients' prognoses. RESULTS: AMPK α1 was highly expressed in NSCLC cancer tissues and correlated with poor prognosis in patients with NSCLC. In A549 cells, overexpression of AMPK α1 promoted proliferation, suppressed ROS levels and inhibited apoptosis. Moreover, inhibition of AMPK α1 expression achieved the opposite effects. Trx was significantly overexpressed in NSCLC cancer tissues; furthermore, Trx expressed much more in cytoplasm when compared with cell nucleus. Trx expression levels were positively correlated with AMPK α1 expression levels in NSCLC tissues. AMPK α1 could regulate Trx in A549 cells. No significant correlations were observed between Trx expression variances and prognoses in NSCLC patients. Combination of AMPK α1 and Trx had no advantage in predicting prognoses of NSCLC patients. CONCLUSION: These results suggest that AMPK α1 serves a carcinogenic role at least in part through the regulation of Trx expression, and thus represents a potential treatment target in patients with NSCLC.

Meta-analysis of deep inspiration breath hold (DIBH) versus free breathing (FB) in postoperative radiotherapy for left-side breast cancer.

OBJECTIVES: This meta-analysis evaluates the difference in deep inspiration breath hold (DIBH) versus free breathing (FB) for patients receiving postoperative radiotherapy for left breast cancer and provides a useful reference for clinical practice. METHODS: The relevant controlled trials of DIBH versus FB in postoperative radiotherapy for left-side breast cancer were retrieved from the databases of PubMed, Science Direct, Cochrane Library, and Web of Science databases. The principal outcome of interest was heart dose, left anterior descending coronary artery (LADCA) dose, and left lung dose and target coverage. We calculated summary standardized mean difference (SMD) and 95% confidence intervals (CI). The meta-analysis was performed using RevMan 5.3 software. RESULTS: The analysis included 1019 patients from 12 observational studies, of which 576 cases were in the DIBH group and 443 cases in the FB group. Compared with the FB group, the DIBH group can have lower heart dose, left anterior descending coronary artery (LADCA) dose, and left lung dose more effectively, and the difference was statistically significant (heart dose, SMD = - 1.36, 95% CI - 1.64 ~ - 1.09, P < 0.01. LADCA dose, SMD = - 1.45, 95% CI - 1.62 ~ - 1.27, P < 0.01. Left lung dose, SMD = - 0.52, 95% CI - 0.81 ~ - 0.23, P < 0.01). There was no significant difference in target coverage between the two groups (SMD = 0.03, 95% CI - 0.11 ~ 0.18, P = 0.64). CONCLUSION: By this meta-analysis, we found that implementation of DIBH in postoperative radiotherapy for left-side breast cancer can reduce irradiation of heart dose, LADCA dose and left lung dose, without compromising target coverage.

The demographic and treatment options for patients with large cell neuroendocrine carcinoma of the lung.

INTRODUCTION: Lung large cell neuroendocrine carcinoma (L-LCNEC) is a rare, aggressive tumor, for which the optimal treatment strategies for LCNEC have not yet been established. In order to explore how to improve the outcome of prognosis for patients with LCNEC, this study investigated the effect of different treatments based on the data obtained from the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: A total of 2594 LCNEC cases with conditional information were extracted from SEER database. Propensity Score Matching (PSM) method was conducted to reduce possible bias between groups. One-way ANOVA was used to test the differences of characteristics between groups. Univariate and multivariate Cox proportional hazard models were applied to identify prognostic factors. RESULTS: Clinicopathologic characteristics including gender, age, TNM stage, T stage, N stage, and M stage were all identified as independent prognostic factors. Surgery benefited stage I, II, and III LCNEC patients' prognoses. The combination treatment that surgery combining with chemotherapy was the optimal treatment for stage I, II, and III LCENC patients. Compared with palliative treatment, stage IV patients obtained better prognoses with the treatment of radiation, chemotherapy, or chemoradiation. When comparing the effect of the three treatments (radiation, chemotherapy, and chemoradiation) in achieving better prognosis for stage IV patients, chemotherapy alone was better than the other treatments. CONCLUSION: Surgery combining with chemotherapy was the optimal treatment for stage I, II, and III LCNEC patients; chemotherapy alone achieves more benefit than the other treatments for stage IV patients.