Direct bilirubin levels are prognostic in non-small cell lung cancer.

We investigated the prognostic value of serum bilirubin levels in stage I-II non-small cell lung cancer (NSCLC) patients and evaluated the relationship between bilirubin levels and response to first-line platinum-based chemotherapy. We divided 634 NSCLC patients from a single hospital in China into retrospective training (n = 307) and prospective validation (n = 327) cohorts. X-tile was used to identify the optimal serum bilirubin cutoff value for sorting retrospective cohort patients into low and high overall survival (OS) groups. TNM stage and serum bilirubin levels were associated with OS on univariate analysis. Direct bilirubin (DBIL) levels were correlated with tumor progression and response to first-line platinum-based chemotherapy, and were associated with OS after adjusting for TNM stage. Our findings indicate a DBIL-based prognostic nomogram is more accurate than the TNM staging system in predicting clinical outcomes, and that the DBIL level is an independent predictor of OS in NSCLC. Thus, an index that combines DBIL with TNM stage may better predict patient outcomes than TNM stage alone.

Juglanin inhibits lung cancer by regulation of apoptosis, ROS and autophagy induction.

Juglanin (Jug) is obtained from the crude extract of Polygonum aviculare, exerting suppressive activity against cancer cell progression in vitro and in vivo. Juglanin administration causes apoptosis and reactive oxygen species (ROS) in different types of cells through regulating various signaling pathways. In our study, the effects of juglanin on non-small cell lung cancer were investigated. A significant role of juglanin in suppressing lung cancer growth was observed. Juglanin promoted apoptosis in lung cancer cells through increasing Caspase-3 and poly ADP-ribose polymerase (PARP) cleavage, which is regulated by TNF-related apoptosis-inducing ligand/Death receptors (TRAIL/DRs) relied on p53 activation. Anti-apoptotic members Bcl-2 and Bcl-xl were reduced, and pro-apoptotic members Bax and Bad were enhanced in cells and animals receiving juglanin. Additionally, nuclear factor-κB (NF-κB), phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinases (MAPKs) activation were inhibited by juglanin. Further, juglanin improved ROS and induced autophagy. ROS inhibitor N-acetyl-l-cysteine (NAC) reversed apoptosis induced by juglanin in cancer cells. The formation of autophagic vacoules and LC3/autophagy gene7 (ATG7)/Beclin1 (ATG6) over-expression were observed in juglanin-treated cells. Also, juglanin administration to mouse xenograft models inhibited lung cancer progression. Our study demonstrated that juglanin could be a promising candidate against human lung cancer progression.

Lymphocyte to monocyte ratio is associated with response to first-line platinum-based chemotherapy and prognosis of early-stage non-small cell lung cancer patients.

Lymphocyte to monocyte ratio (LMR) has shown prognostic value in different types of cancer. This study assessed the prognostic performance of LMR in early-stage non-small cell lung cancer (NSCLC) patients and investigated the influence of LMR on the treatment response in patients receiving first-line platinum-based chemotherapy. Four hundred eighty-eight NSCLC patients and 500 healthy donors were enrolled in this study. The cutoff value for LMR was chosen by receiver operating characteristic curve analysis. The prognostic significance of markers was assessed by univariate and multivariate Cox regression models. The median overall survival was 43 months, and the median progression-free survival was 38 months. LMR was associated with disease status and the treatment response of first-line platinum-based chemotherapy. Multivariate analysis showed that LMR was an independent prognostic factor for both overall survival (hazard ratio = 1.53, 95 % confidence interval = 1.09-2.14, P = 0.015) and progression-free survival (hazard ratio = 1.20, 95 % confidence interval = 1.02-1.67, P = 0.028). Furthermore, integration of LMR into a prognostic model including TNM stage, tumor status, chemotherapy, and histological type generated a nomogram, which predicted accurately overall survival for NSCLC patients. Decreased LMR may be a potential biomarker of disease status, worse response to first-line platinum-based chemotherapy, and worse survival for NSCLC patients. A prospective study is warranted for further validation of our findings.

Complete mitochondrial genome sequence and mutations of the cardiac hypertrophy model inbred rat strain (Muridae; Rattus).

In the present work we undertook the complete mitochondrial genome sequencing of a important cardiac hypertrophy model inbred rat strain for the first time. The total length of the mitogenome was 16,308 bp. It harbored 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 non-coding control region (D-loop region). The mutation events were also reported.