BackgroundTreatment failure for esophageal carcinoma is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in esophageal carcinoma cells in vitro and in vivo.MethodsA metastasis model using a Matrigel invasion clonal selection approach was employed to establish a highly invasive subline EC9706-P4 from the esophageal carcinoma cell (ESCC) line EC9706. The differentially expressed genes of the subline and the parental cells determined by gene microarrays were further analyzed by RT-PCR and Western blotting.ResultsWe identified sphingosine kinase 1 (SPHK1) as an invasion and metastasis-related gene of esophageal cancer. SPHK1 was overexpressed in the EC9706-P4 subline with high invasive capacity. Among six ESCC lines tested, KYSE2 and KYSE30 cells showed the highest SPHK1 mRNA and protein expressions as well as the most invasive phenotype. By Western blotting, in 7/12 cases (58%), SPHK1 expression was higher in esophageal carcinomas than in the companion normal tissue. In 23/30 cases (76%), SPHK1 protein expression was upregulated in the tumors compared to matched normal tissue by immunohistochemistry (IHC). Esophageal carcinoma tissue microarray analysis indicated that SPHK1 expression correlated with the depth of tumor invasion (P < 0.0001) and lymph node metastasis (P = 0.016). By Kaplan-Meier analysis, strong SPHK1 expression was significantly associated with clinical failure (P < 0.01), suggesting the involvement of SPHK1 in aggressiveness of human esophageal carcinoma. SPHK1 overexpression significantly increased the invasiveness of EC9706 cells in vitro and also increased EC9706 cell growth and spontaneous metastasis in vivo, promoting significant increases in tumor growth, tumor burden and spontaneous lung metastasis in nude mice. SPHK1 expression significantly correlated with the expression of many EGFR pathway genes associated with invasion of cancer cells. SPHK1 protein expression also significantly correlated with the phosphorylation of EGFR.ConclusionIn summary, our data implicate SPHK1 in the metastasis of esophageal cancer. Our study also identified downstream mediators of SPHK1 in esophageal cancer cells that may mediate enhanced malignant behavior, and several of these mediators may be useful as therapeutic targets.

In this, the first published study focusing on the efficacy of u-ACP and b-ACP in total arch replacement for type A aortic dissection, the b-ACP group did not demonstrate significantly lower 30-day mortality or PND rate compared with the u-ACP group. Future large-sample studies are warranted to thoroughly examine this critical issue.

Increasing evidence has indicated the intimate relationship between the gastrointestinal tract and respiratory tract. The microbial ecosystem has been confirmed to share key conceptual features with gut-lung microbiome disorder and dysregulation during chronic obstructive pulmonary disease (COPD) exacerbations. However, the dynamic changes of the gut-lung microbiome during COPD exacerbations and its potential role in disease etiology remain poorly understood. The present study investigated the dynamic changes of gut and lung microorganisms during acute exacerbation of chronic obstructive pulmonary disease (AECOPD). A longitudinal 16S ribosomal DNA survey of the gut and lung microbiome was completed on 90 feces and sputum samples collected from 15 subjects with AECOPD at three visits, which were defined as exacerbation, seven-day stable state. The present analysis revealed a dynamic gut-lung microbiota, where changes appeared to be associated with exacerbation events indicative of specific exacerbation phenotypes. Antibiotic and steroid treatments appeared to have differential effects on the gut-lung microbiome, and the microbiome was associated with disease progression, but not with severity. The abundance and diversity of the microbiome was strongly influenced by the disease progression and therapy. Using culture-independent methods to impact the gut and lung microbiota on AECOPD may be the key to understanding the interactions between the gut and lung, highlighting its potential as a biomarker, and possibly a target for future respiratory therapeutics. K E Y W O R D Sacute exacerbations of chronic obstructive pulmonary disease, dynamic changes, gut-lung, microbiome

These data suggest that the TRPV-1 channel is unimportant for normal mechanosensation in the cervix in the absence of estrogen, since capsaizepine failed to reduce responses to uterine cervical distension in rats without estrogen replacement. In contrast, TRPV-1 function is important for estrogen-induced sensitization. These data raise the possibility that acute and chronic pain coming from the cervix, such as labor or cancer, may be enhanced by estrogen and might be reduced by antagonists of TRPV-1.

BackgroundTreatment failure for breast cancer is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in breast cancer cells in vitro and in vivo. Identification of new targets will facilitate the developmental pace of new techniques in screening and early diagnosis. Improved abilities to predict progression and metastasis, therapeutic response and toxicity will help to increase survival of breast cancer patients.MethodsDifferential protein expression in two breast cancer cell lines, one with high and the other with low metastatic potential, was analyzed using two-dimensional liquid phase chromatographic fractionation (Proteome Lab PF 2D system) followed by matrix-assisted laser desorption/time-of-flight mass spectrometry (MALDI-TOF/MS).ResultsUp regulation of α-subunit of ATP synthase was identified in high metastatic cells compared with low metastatic cells. Immunohistochemical analysis of 168 human breast cancer specimens on tissue microarrays revealed a high frequency of ATP synthase α-subunit expression in breast cancer (94.6%) compared to normal (21.2%) and atypical hyperplasia (23%) breast tissues. Levels of ATP synthase expression levels strongly correlated with large tumor size, poor tumor differentiation and advanced tumor stages (P < 0.05). ATP synthase α-subunit over-expression was detected on the surface of a highly invasive breast cancer cell line. An antibody against the ATP synthase α-subunit inhibited proliferation, migration and invasion in these breast cancer cells but not that of a non-tumor derived breast cell line.ConclusionsOver-expression of ATP synthase α-subunit may be involved in the progression and metastasis of breast cancer, perhaps representing a potential biomarker for diagnosis, prognosis and a therapeutic target for breast cancer. This finding of this study will help us to better understand the molecular mechanism of tumor metastasis and to improve the screening, diagnosis, as well as prognosis and/or prediction of responses to therapy for breast cancer.

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Utilizing neuroimaging and machine learning (ML) to differentiate schizophrenia (SZ) patients from normal controls (NCs) and for detecting abnormal brain regions in schizophrenia has several benefits and can provide a reference for the clinical diagnosis of schizophrenia. In this study, structural magnetic resonance images (sMRIs) from SZ patients and NCs were used for discriminative analysis. is study proposed an ML framework based on coarse-to-fine feature selection. e proposed framework used two-sample t-tests to extract the differences between groups first, then further eliminated the nonrelevant and redundant features with recursive feature elimination (RFE), and finally utilized the support vector machine (SVM) to learn the decision models with selected gray matter (GM) and white matter (WM) features. Previous studies have tended to report differences at the group level instead of at the individual level and cannot be widely applied. e method proposed in this study extends the diagnosis to the individual level and has a higher recognition rate than previous methods. e experimental results of this study demonstrate that the proposed framework distinguishes SZ patients from NCs, with the highest classification accuracy reaching over 85%. e identified biomarkers are also consistent with previous literature findings. As a universal method, the proposed framework can be extended to diagnose other diseases.

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