No abstract

Sinulariolide, an isolated compound from the soft coral Sinularia flexibilis, possesses the anti-proliferative, anti-migratory and apoptosis-inducing activities against the TSGH bladder carcinoma cell. The anti-tumor effects of sinulariolide were determined by 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, cell migration assay and flow cytometry, respectively. Sinulariolide inhibited the growth and migration of bladder carcinoma cells in a dose-dependent manner, as well as induced both early and late apoptosis as determined by the flow cytometer. Also, the sinulariolide-induced apoptosis is related to the mitochondrial-mediated apoptosis via caspase-dependent pathways, elucidated by the loss of mitochondrial membrane potential, release of cytochrome C, activation of caspase-3/-9, Bax and Bad, as well as suppression of Bcl-2/Bcl-xL/Mcl-1. Detection of the PARP-1 cleaved product suggested the partial involvement of caspase-independent pathways. Moreover, inhibition of p38MAPK activity leads to the rescue of the cell cytotoxicity of sinulariolide-treated TSGH cells, indicating that the p38MAPK pathway is also involved in the sinulariolide-induced cell apoptosis. Altogether, these results suggest that sinulariolide induces apoptosis against bladder cancer cells through mitochondrial-related and p38MAPK pathways.

No abstract

Esophageal squamous cell cancer (ESCC) is one of the most common fatal human cancers. The identification of biomarkers for early detection could be a promising strategy to decrease mortality. Previous studies utilized microarray techniques to identify more than one hundred genes; however, it is desirable to identify a small set of biomarkers for clinical use. This study proposes a sequential forward feature selection algorithm to design decision tree models for discriminating ESCC from normal tissues. Two potential biomarkers of RUVBL1 and CNIH were identified and validated based on two public available microarray datasets. To test the discrimination ability of the two biomarkers, 17 pairs of expression profiles of ESCC and normal tissues from Taiwanese male patients were measured by using microarray techniques. The classification accuracies of the two biomarkers in all three datasets were higher than 90%. Interpretable decision tree models were constructed to analyze expression patterns of the two biomarkers. RUVBL1 was consistently overexpressed in all three datasets, although we found inconsistent CNIH expression possibly affected by the diverse major risk factors for ESCC across different areas.

Using a microarray technique, we found decorin to be underexpressed, but osteopontin (OPN) to be overexpressed, in esophageal squamous cell carcinoma (ESCC). This study aims to examine whether plasma decorin and OPN plus personal substances use (tobacco, alcohol and areca) can serve as suitable clinical markers to predict the presence of ESCC. In total, 570 archived plasma specimens (275 patients and 295 controls) were collected from 2 medical centers in Taiwan between 2000 and 2008. Decorin and OPN protein levels were measured by ELISA. Means and standard deviation of plasma decorin were 5.6 6 3.6 ng/ml in case patients, which were significantly lower than those in controls (7.8 6 3.1, p < 0.0001). Plasma OPN levels in case patients were not significantly different from controls (p 5 0.33). When compared to subjects with the lowest quartile of plasma decorin, those with the highest quartile one had a significantly lower risk to have ESCC (Adjusted OR 5 0.03, p < 0.001). Receiver operator characteristic (ROC) analysis was performed for the combination of plasma decorin and 3 substances use (smoke, alcohol and areca) for the patients compared with the controls. The area under the curve was 88.6% and the optimal cut-point of ROC curve (any 3 factors) had 73.5% sensitivity and 90.2% specificity with~82% of corrected classification. Plasma decorin, but not OPN, is a potential clinical marker for the detection of ESCC. When plasma decorin plus the use of the 3 substances are combined, this factor cluster could be used to detect the presence of ESCC.Esophageal cancer is the 8th most common malignancy worldwide.1 In Taiwanese males, esophageal cancer, predominantly esophageal squamous cell carcinoma (ESCC), is the 6th leading cause of cancer deaths.2,3 Once diagnosed with ESCC, the prognosis is very poor with a 5-year survival rate below 10%. [4][5][6] Thus, identification of the novel markers with the use of a simple, easy and relatively noninvasive technique to measure them and apply the findings to clinical settings for detecting the presence of ESCC becomes crucial.Decorin is a small leucine-rich proteoglycan. Decorin has been shown to phosphorylate and degrade epidermal growth factor receptor, to activate mitogen-activated protein kinase, and to upregulate p21 WAF , the cell-cycle inhibitor, of tumor cells that leads to growth suppression. [7][8][9] Although many studies have found that the low expression of decorin is associated with advanced grades of malignancies such as myeloma, breast cancer and oral cancer, 9-11 few have examined the effect of its expression in esophageal cancer. Only 1 recent study has shown decorin expression decreases, but not significantly, in esophageal cancer patients. 12Osteopontin (OPN) is a secreted adhesive glycoprotein that may play a role in the process of carcinogenesis. [13][14][15][16] Several studies, including ours, have shown increased OPN mRNA or protein expression in the tumor tissues of ESCC,