The impact of Metastasis Suppressor-1, MTSS1, on oesophageal squamous cell carcinoma and its clinical significance

<p>Abstract</p> <p>Background</p> <p>Metastasis suppressor-1 (MTSS1) has been proposed to function as a cytoskeletal protein with a role in cancer metastasis. Recent studies have demonstrated the clinical significance of MTSS1 in certain type of cancers, yet the clinical relevance of MTSS1 in oesophageal squamous cell carcinoma (ESCC) has not been reported.</p> <p>Methods</p> <p>In this study, we assessed the expression levels of MTSS1 in tumours and its matched adjacent non-tumour tissues obtained from 105 ESCC patients. We also used ESCC cells with differing MTSS1 expression and assessed the influence of MTSS1 on ESCC cells.</p> <p>Results</p> <p>Down-regulation of MTSS1 expression was observed both in oesophageal tumour tissues and ESCC cancer cell lines. We also reported that MTSS1 expression was associated with tumour grade (p = 0.024), lymph node metastasis (p = 0.010) and overall survival (p = 0.035). Patients with high levels of MTSS1 transcripts had a favorable prognosis in comparison with those who had reduced or absent expression levels. Using over-expression and knockdown approach, we created sublines from ESCC cells and further demonstrated that MTSS1 expression in ESCC cells significantly influenced the aggressiveness of the oesophageal cancer cells, by reducing their cellular migration and in vitro invasiveness.</p> <p>Conclusion</p> <p>MTSS1 serves as a potential prognostic indicator in human ESCC and may be an important target for cancer therapy.</p

Molecular impact of bone morphogenetic protein 7, on lung cancer cells and its clinical significance

The aim of this study was to investigate the expression of bone morphogenetic protein 7 (BMP7), in human pulmonary cancer tissues/cells and to evaluate the cellular impact of bone morphogenetic proteins on pulmonary cancer cells. BMP7 expression was determined in human lung cancer cell lines. The invasiveness and growth of cells transfected with BMP7, in vitro, were evaluated using the in vitro invasion assay and in vitro tumour models. Cellular migration was analysed using wounding assays. BMP7-positive tumours correlated with the absence of bone metastasis (P=0.040). In this analysis, we identified that 4 of 4 small cell lung cancer (SCLC) tissue specimens had no BMP7 expression, which illustrated that BMP7 may have no role in SCLC. BMP7 expression was not correlated with the overall survival time in lung cancer patients. Downregulation of BMP7 expression significantly inhibited the invasiveness of SPC-A1 cells (P0.5 respectively). In conclusion, we have demonstrated that BMP7 has an important role in controlling lung cancer cell motility and invasiveness, without affecting the growth process, cell proliferation and cell apoptosis. A higher BMP7 expression may be an indicator for bone metastasis. The therapeutic role of BMP7 warrants further investigation

Three Gorges Dam: Friend or Foe of Riverine Greenhouse Gases?

International audienceDams are often regarded as greenhouse gas (GHG) emitters. However, our study indicated that the world's largest dam, the Three Gorges Dam (TGD), has caused significant drops in annual average emissions of CO$_2$, CH$_4$ and N$_2$O over 4300 km along the Yangtze River, accompanied by remarkable reductions in the annual export of CO$_2$ (79%), CH$_4$ (50%) and N$_2$O (9%) to the sea. Since the commencement of its operation in 2003, the TGD has altered the carbonate equilibrium in the reservoir area, enhanced methanogenesis in the upstream, and restrained methanogenesis and denitrification via modifying anoxic habitats through long-distance scouring in the downstream. These findings suggest that 'large-dam effects' are far beyond our previous understanding spatiotemporally, which highlights the fundamental importance of whole-system budgeting of GHGs under the profound impacts of huge dams

Expert consensus on postoperative rehabilitation nursing of patients with head and neck cancer

The location and size of tumors, treatment methods and prognosis of patients with head and neck cancer can seriously affect their oral function and neck activity, thereby affecting daily activities such as eating, speech and upper limb movement. Early rehabilitation after head and neck cancer surgery can accelerate functional recovery, alleviate discomfort symptoms, improve quality of life, and reduce unnecessary rehabilitation or treatment measures. Developing a clinical rehabilitation nursing pathway for head and neck cancer, forming personalized rehabilitation plans, and conducting early and effective nursing interventions are currently one of the key points of clinical work for patients with head and neck cancer. At present, domestic and foreign guidelines or consensus pays less attention to the impairments of speech function, chewing and swallowing function, neck and shoulder function etc., and lacks a systematic and comprehensive rehabilitation nursing guide or consensus to provide practical guidance for the care of patients with head and neck cancer. Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine organized relevant experts from Beijing, Shanghai, Sichuan, Shaanxi, Zhejiang and Anhui to draft Expert consensus on postoperative rehabilitation nursing of patients with head and neck cancer basing on previous literature and clinical nursing skills and experiences, of which the aim is to provide guidance for those patients in the aspects of oral care, nutritional support, flap donor area care, care after tracheotomy, chewing and swallowing rehabilitation, speech function rehabilitation, neck and shoulder function rehabilitation, restricted mouth opening rehabilitation, risk identification and prevention and follow-up

Prediction of overall survival for patients with metastatic castration-resistant prostate cancer : development of a prognostic model through a crowdsourced challenge with open clinical trial data

Background Improvements to prognostic models in metastatic castration-resistant prostate cancer have the potential to augment clinical trial design and guide treatment strategies. In partnership with Project Data Sphere, a not-for-profit initiative allowing data from cancer clinical trials to be shared broadly with researchers, we designed an open-data, crowdsourced, DREAM (Dialogue for Reverse Engineering Assessments and Methods) challenge to not only identify a better prognostic model for prediction of survival in patients with metastatic castration-resistant prostate cancer but also engage a community of international data scientists to study this disease. Methods Data from the comparator arms of four phase 3 clinical trials in first-line metastatic castration-resistant prostate cancer were obtained from Project Data Sphere, comprising 476 patients treated with docetaxel and prednisone from the ASCENT2 trial, 526 patients treated with docetaxel, prednisone, and placebo in the MAINSAIL trial, 598 patients treated with docetaxel, prednisone or prednisolone, and placebo in the VENICE trial, and 470 patients treated with docetaxel and placebo in the ENTHUSE 33 trial. Datasets consisting of more than 150 clinical variables were curated centrally, including demographics, laboratory values, medical history, lesion sites, and previous treatments. Data from ASCENT2, MAINSAIL, and VENICE were released publicly to be used as training data to predict the outcome of interest-namely, overall survival. Clinical data were also released for ENTHUSE 33, but data for outcome variables (overall survival and event status) were hidden from the challenge participants so that ENTHUSE 33 could be used for independent validation. Methods were evaluated using the integrated time-dependent area under the curve (iAUC). The reference model, based on eight clinical variables and a penalised Cox proportional-hazards model, was used to compare method performance. Further validation was done using data from a fifth trial-ENTHUSE M1-in which 266 patients with metastatic castration-resistant prostate cancer were treated with placebo alone. Findings 50 independent methods were developed to predict overall survival and were evaluated through the DREAM challenge. The top performer was based on an ensemble of penalised Cox regression models (ePCR), which uniquely identified predictive interaction effects with immune biomarkers and markers of hepatic and renal function. Overall, ePCR outperformed all other methods (iAUC 0.791; Bayes factor >5) and surpassed the reference model (iAUC 0.743; Bayes factor >20). Both the ePCR model and reference models stratified patients in the ENTHUSE 33 trial into high-risk and low-risk groups with significantly different overall survival (ePCR: hazard ratio 3.32, 95% CI 2.39-4.62, p Interpretation Novel prognostic factors were delineated, and the assessment of 50 methods developed by independent international teams establishes a benchmark for development of methods in the future. The results of this effort show that data-sharing, when combined with a crowdsourced challenge, is a robust and powerful framework to develop new prognostic models in advanced prostate cancer.Peer reviewe

Mean-range based distribution-free procedures to minimize overage and underage costs

Mean-Range Based Distribution-Free Procedures to Minimize ”Overage ” and ”Underage ” Costs We introduce and discuss several mean-range based distribution-free decision procedures to minimize several “overage ” and “underage ” cost functions. For a general cost function, we identify the most favorable distribution and the least favorable distribution associated with the random variable and determine the upper and lower bounds for the cost function. For the quadratic cost function, we recommend the min-max distribution-free decision. For the linear cost function, we identify the range of potential optimal solutions (decisions) and recommend a hybrid distribution-free decision that has serval favorable properties. Several numerical examples are provided to demonstrate the robustness of the proposed distributionfree decisions