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The meta-analysis evaluated the efficacy and safety of chemotherapy or tyrosine kinase inhibitors combined with bevacizumab versus chemotherapy or tyrosine kinase inhibitors alone in the treatment of non-small cell lung cancer (NSCLC). The PubMed/MEDLINE, Ovid, Web of Science, CNKI, and the Cochrane Library database were searched for eligible randomized controlled trials comparing the combination of chemotherapy or epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) with bevacizumab to chemotherapy or EGFR-TKI alone. Main outcome measures were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse effects. The pooled data were analyzed by STATA 12.0 and expressed as hazard ratio (HR) or risk ratio (RR), with their corresponding 95 % confidence intervals (95 % CI). Nine eligible trials comprising 3,547 patients (1,779 for bevacizumab and 1,768 for controls) were included in the study. Chemotherapy or TKIs in combination with bevacizumab significantly prolonged PFS (HR 0.72, 95 % CI 0.66-0.79, P < 0.001) and OS (HR 0.90, 95 % CI 0.82-0.99, P = 0.029) as first-line treatment for NSCLC compared with chemotherapy or TKIs alone. Bevacizumab combination regimens significantly prolonged PFS (HR 0.62, 95 % CI 0.52-0.74, P < 0.001) as second-line treatment; however, no benefit regarding OS was observed with the addition of bevacizumab (HR 0.94, 95 % CI 0.78-1.12, P = 0.479). The bevacizumab group showed increased ORR in both first- and second-line treatments. The high-dose bevacizumab subgroup in combination with chemotherapy showed a statistically significant improvement in OS, PFS, and ORR (HR 0.89, 95 % CI 0.80-0.99, P 0.037; HR 0.71, 95 % CI 0.64-0.79, P < 0.01, RR 1.85, 95 % CI 1.59-2.15, P < 0.001, respectively); however, the low-dose bevacizumab subgroup did not show enhanced OS (HR 0.91, 95 % CI 0.77-1.07, P = 0.263), and a moderate improvement of PFS and ORR (HR 0.85, 95 % CI 0.72-1.00, P = 0.049; RR 1.60, 95 % CI 1.28-2.0, P < 0.001). Erlotinib in combination with bevacizumab significantly prolonged PFS (HR 0.60, P < 0.001, 95 % CI 0.51-0.71) and increased ORR (RR 1.21, 95 % CI 0.98-1.49, P = 0.067) compared with erlotinib alone. A higher incidence of grade ≥3 adverse events such as proteinuria, hypertension, and hemorrhage was observed in the bevacizumab combination group than in the control group without bevacizumab ( P < 0.05). The addition of bevacizumab to chemotherapy or erlotinib can significantly improve PFS and ORR both in first- and second-line treatments of advanced NSCLC, with an acceptable risk of bleeding events, hypertension, proteinuria, and rash. Combination therapy with bevacizumab and chemotherapy is beneficial regarding OS; however, whether bevacizumab plus erlotinib can prolong OS need further validation. [ABSTRACT FROM AUTHOR]

Purpose: This study was to evaluate the influence of mtDNA deletion on the lung cancer cells under the conditions of hypoxia or irradiation. Method: The treatment conditions of lung cancer cell lines with (A549) and without mtDNA (ρ0A549: obtained by inducing from A549) included 2 h of hypoxia and 4 Gy irradiation (group 1: without treatment; group 2: 2 h of hypoxia; group 3: 4 Gy irradiation; group 4: 2 h of hypoxia plus 4 Gy irradiation). The Human OneArray™ microarray was used to hybridize with the Cy5-labeled aRNA in microarray sample preparation. Differentially expressed genes (DEGs) between the lung cancer cells with and without mtDNA were identified using NOISeq package in R. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the online tool of DAVID. Result: In the KEGG pathway analysis of down-regulated DEGs, nineteen pathways were simultaneously enriched in the four groups, which were mainly metabolism- and biosynthesis-related pathways. Nine lung cancer-related pathways were enriched in group 4, and more cancer-associated DEGs, such as MYC, MAX, and E2F1 were found in group 4 than in the other groups. Conclusion: The mtDNA deletion could inhibit the biosynthesis and metabolism of lung cancer cells and promote the effect of hypoxia and radiation on lung cancer cells. MYC might be the key gene of the cooperation of hypoxia and radiation and MYC, MAX, and E2F1 might play roles in hypoxia- and radiation-induced cell death in lung cancer cells without mtDNA. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article related to KRAS gene that is used as a biomarker, published in the previous issue of the periodical.

A retraction of the article "The Influence of mtDNA Deletion on Lung Cancer Cells Under the Conditions of Hypoxia and Irradiation" by Cheng-Bo Han and colleagues in the 2014 issue is presented.