Third CECOG consensus on the systemic treatment of non-small-cell lung cancer

The current third consensus on the systemic treatment of non-small-cell lung cancer (NSCLC) builds upon and updates similar publications on the subject by the Central European Cooperative Oncology Group (CECOG), which has published such consensus statements in the years 2002 and 2005 (Zielinski CC, Beinert T, Crawford J et al. Consensus on medical treatment of non-small-cell lung cancer—update 2004. Lung Cancer 2005; 50: 129-137). The principle of all CECOG consensus is such that evidence-based recommendations for state-of-the-art treatment are given upon which all participants and authors of the manuscript have to agree (Beslija S, Bonneterre J, Burstein HJ et al. Third consensus on medical treatment of metastatic breast cancer. Ann Oncol 2009; 20 (11): 1771-1785). This is of particular importance in diseases in which treatment options depend on very particular clinical and biologic variables (Zielinski CC, Beinert T, Crawford J et al. Consensus on medical treatment of non-small-cell lung cancer—update 2004. Lung Cancer 2005; 50: 129-137; Beslija S, Bonneterre J, Burstein HJ et al. Third consensus on medical treatment of metastatic breast cancer. Ann Oncol 2009; 20 (11): 1771-1785). Since the publication of the last CECOG consensus on the medical treatment of NSCLC, a series of diagnostic tools for the characterization of biomarkers for personalized therapy for NSCLC as well as therapeutic options including adjuvant treatment, targeted therapy, and maintenance treatment have emerged and strongly influenced the field. Thus, the present third consensus was generated that not only readdresses previous disease-related issues but also expands toward recent developments in the management of NSCLC. It is the aim of the present consensus to summarize minimal quality-oriented requirements for individual patients with NSCLC in its various stages based upon levels of evidence in the light of a rapidly expanding array of individual therapeutic option

DNA methylation transcriptionally regulates the putative tumor cell growth suppressor ZNF677 in non-small cell lung cancers

In our study, we investigated the role of ZNF677 in non-small cell lung cancers (NSCLC). By comparing ZNF677 expression in primary tumor (TU) and in the majority of cases also of corresponding non-malignant lung tissue (NL) samples from > 1,000 NSCLC patients, we found tumor-specific downregulation of ZNF677 expression (adjusted p-values < 0.001). We identified methylation as main mechanism for ZNF677 downregulation in NSCLC cells and we observed tumor-specific ZNF677 methylation in NSCLC patients (p < 0.0001). In the majority of TUs, ZNF677 methylation was associated with loss of ZNF677 expression. Moreover, ZNF677 overexpression in NSCLC cells was associated with reduced cell proliferation and cell migration. ZNF677 was identified to regulate expression of many genes mainly involved in growth hormone regulation and interferon signalling. Finally, patients with ZNF677 methylated TUs had a shorter overall survival compared to patients with ZNF677 not methylated TUs (p = 0.013). Overall, our results demonstrate that ZNF677 is trancriptionally regulated by methylation in NSCLCs, suggest that ZNF677 has tumor cell growth suppressing properties in NSCLCs and that ZNF677 methylation might serve as prognostic parameter in these patients

Irish Journal of Medical Science (1971 -) / Long-term endurance training increases serum cathepsin S levels in healthy female subjects

Background Circulating cathepsin S (CS) has been associated with a lower risk for breast cancer in a large Swedish cohort. Long-term physical activity has been shown to have beneficial effects on the development of various cancer subtypes, in particular breast and colorectal cancers. The aim of this study was to investigate the effect of long-term endurance sport on CS levels in females. Material and methods Thirty-six of 40 subjects completed the study. Subjects were told to increase their activity pensum for 8 months reaching 150 min/week moderate or 75 min/week intense exercise. Ergometries were performed at the beginning and the end of the study to prove/quantify the performance gain. Blood samples were drawn at baseline and every 2 months. Serum CS levels were measured by ELISA. To analyse the change and the progression of CS, Wilcoxon rank sum and Friedman tests were used. Results The sportive group (performance gain by > 4.9%) showed a significant increase of CS levels from 3.32/2.73/4.09 to 4.00/3.09/5.04 ng/ml (p = 0.008) corresponding to an increase of 20.5%. Conclusions We could show a significant increase of circulating CS levels in healthy female subjects induced by long-term physical activity. CS, occurring in the tumour microenvironment, is well-known to promote tumour growth, e.g. by ameliorating angiogenesis. However, the role of circulating CS in cancer growth is not clear. As physical activity is known as preventive intervention, in particular concerning breast and colorectal cancers, and long-term physical activity leads to an increase of CS levels in female subjects, circulating CS might even be involved in this protective effect. Trial registration Clinical trial registration: NCT02097199(VLID)366407