Role of ERCC1 variants in response to chemotherapy and clinical outcome of advanced non-small cell lung cancer.

Excision repair cross-complementation group 1 (ERCC1) and xeroderma pigmentosum-F (XPF) in the nucleotide excision repair pathway have been effectively repairing DNA damage induced by chemotherapeutic agents. We conducted a cohort study to assess the associations of ERCC1 and XPF polymorphisms with response to platinum-based chemotherapy and clinical outcome of non-small-cell lung cancer (NSCLC). One hundred eighty-seven NSCLC cases treated with platinum-based chemotherapy were prospectively analyzed. The predictive value of four SNPs in ERCC1 and two SNPs in XPF in patient's response and survival related to platinum-based chemotherapy were analyzed using χ(2) tests, Kaplan-Meier method, log-rank test, and Cox proportional hazards regression. The overall chemotherapy response rate for treatment was 51.18%. One hundred eighty-seven patients were followed up, and the median survival time is 17.6 months (ranged from 1 to 50 months). A total of 106 patients (56.68%) died from NSCLC during the follow-up period. Carriers of the rs3212986 AA and A allele had a borderline significantly lower response rate to the chemotherapy. In the Cox proportional hazards model, patients carrying the ERCC1 rs3212986 AA genotype were significantly associated with increased risk of death from NSCLC when compared with those with CC genotype as a reference variable. This study reported that variants in ERCC1 can be used as a prognostic maker to platinum-based chemotherapy in NSCLC patients.

Andrographolide protects against LPS-induced acute lung injury by inactivation of NF-κB.

BACKGROUND: Nuclear factor-κB (NF-κB) is a central transcriptional factor and a pleiotropic regulator of many genes involved in acute lung injury. Andrographolide is found in the plant of Andrographis paniculata and widely used in Traditional Chinese Medicine, exhibiting potently anti-inflammatory property by inhibiting NF-κB activity. The purpose of our investigation was designed to reveal the effect of andrographolide on various aspects of LPS induced inflammation in vivo and in vitro. METHODS AND RESULTS: In vivo, BALB/C mice were subjected to LPS injection with or without andrographolide treatments to induce ALI model. In vitro, MLE-12 cells were stimulated with LPS in the presence and absence of andrographolide. In vivo, pulmonary inflammation, pulmonary edema, ultrastructure changes of type II alveolar epithelial cells, MPO activity, total cells, neutrophils, macrophages, TNF-α, IL-6 and IL-1ß in BALF, along with the expression of VCAM-1 and VEGF were dose-dependently attenuated by andrographolide. Meanwhile, in vitro, the expression of VCAM-1 and VEGF was also reduced by andrographolide. Moreover, our data showed that andrographolide significantly inhibited the ratios of phospho-IKKß/total IKKß, phospho-IκBα/total IκBα and phospho-NF-κB p65/total NF-κB p65, and NF-κB p65 DNA binding activities, both in vivo and in vitro. CONCLUSIONS: These results indicate that andrographolide dose-dependently suppressed the severity of LPS-induced ALI, more likely by virtue of andrographolide-mediated NF-κB inhibition at the level of IKKß activation. These results suggest andrographolide may be considered as an effective and safe drug for the potential treatment of ALI.

Physical activity and risk of lung cancer: a meta-analysis of prospective cohort studies.

BACKGROUND: Previous studies investigating the association of physical activity with risk of lung cancer reported conflicting results. In order to update and improve available evidence on any link, a meta-analysis was performed. METHOD: We searched the PubMed database for prospective cohort studies investigating the relation of physical activity with risk of lung cancer. The pooled relative risk (RR) with its 95% confidence intervals (95%CI) was used to assess the association. RESULTS: We included 14 prospective studies with a total of 1,644,305 participants, with 14,074 incident lung cancer cases documented during follow-up. Meta-analysis of all 14 studies suggested both high and medium levels of physical activity to be associated with decreased risk of lung cancer compared to the reference group with low level of physical activity (for high level, RR = 0.77, 95%CI 0.73-0.81, P < 0.001; for medium level, RR = 0.87, 95%CI 0.83-0.90, P < 0.001). Subgroup analyses by gender found obvious associations in both men and women. No publication bias was observed. CONCLUSION: Our findings suggest that high and medium levels of physical activity have a beneficial effect on lung cancer by reducing the overall risk of tumour development among both men and women.

[Effect of RNA interference on CTGF expression and collagen synthesis induced by hypoxia in rat cardiac fibroblasts].

OBJECTIVE: To investigate the effect of the lentiviral vector pGCL-GFP transferred connective tissue growth factor (CTGF) short hairpin RNA (CTGF-ShRNA) on CTGF expression, cell proliferation and collagen synthesis induced by hypoxia in rat cardiac fibroblasts (CFs). METHODS: CTGF-ShRNA plasmids successfully constructed and screened. CFs of adult Sprague-Dawley (SD) rats isolated with the method of trypsin digestion and differential anchoring velocity which randomly divided into the control group, the hypoxia group, Hypo+pGCL-GFP group and Hypo+CTGF-ShRNA group. The mRNA and protein levels of CTGF were detected by means of semi-quantitative reverse transcriptional polymerase chain reaction (RT-PCR) and Western blot 24 h later. Proliferation of CFs was observed by WST-1 coloricmetric assay and synthesis of collagen was observed by the hydroxyproline. RESULTS: Successfully constructed and screened CTGF short hairpin RNA. Compared with control group, the expression of CTGF mRNA and protein levels induced by hypoxia in CFs were markedly up-regulated in Hypoxia, Hypo + pGCL-GFP and Hypo + CTGF-ShRNA group (P < 0.05). CFs proliferation and collagen synthesis in Hypoxia, Hypo+pGCL-GFP and Hypo+CTGF-ShRNA group were significantly higher than that of the control group (P < 0.05). In comparison to Hypoxia and Hypo+pGCL-GFP group, the CTGF mRNA and protein levels induced by hypoxia in CFs were markedly down-regulated in Hypo + CTGF-ShRNA group (P < 0.01). CFs proliferation and collagen synthesis in Hypo+CTGF-ShRNA group were significantly lower than that of the Hypoxia and Hypo+pGCL-GFP group (P < 0.01). CONCLUSION: CTGF mRNA and protein expression, CFs proliferation and collagen synthesis induced by hypoxia in CFs effectively inhibited by CTGF-ShRNA.