No abstract

Estrogen exhibits mitogenic activity in early ovarian carcinogenesis and plays an important role in ovarian tumorigenesis. Due to the increased expression of ERa and decreased expression of the ERb, the ratio of ERa and ERb is markedly increased in ovarian cancer. We have recently reported that PES1 regulates the balance of ERa and ERb at the posttranscriptional level in breast cancer. Here, we report that PES1 inversely regulates the expression of ERa and ERb in addition to their transcriptional activities in epithelial ovarian cancer. We found that the ablation of PES1 resulted in the significant downregulation of ERa and estrogen-responsive genes such as cylin D1, HIF-1a and VEGF and the up-regulation of ERb and p21WAF1. Cell proliferation in both tested ovarian cell lines was markedly inhibited and cells were arrested in G2 after PES1 was ablated. Further analysis of clinical samples showed that expression of PES1 correlated positively with ERa expression and negatively with ERb expression. Our results demonstrate that PES1 may play important role in the progression of ovarian cancer by inversely regulating the ERa and ERb expression. PES1 may be a new target for ovarian cancer therapy.

Gastric cancer is one of the leading causes of cancer death worldwide. However, precise molecular mechanisms underlining its development are far from clear. We recently reported that PES1 promoted development of breast cancer and ovarian cancer as an oncogene. In this study, we reported that ablation of endogenous PES1 resulted in significant suppression of cell proliferation and growth and led to cell cycle arrest in G2 or G1 phase, respectively, in two gastric cancer cell lines (AGS and N87) in vitro. Meanwhile, silencing of PES1 obviously decreased expressions of cyclin D1, HIF-1α, and vascular endothelial growth factor (VEGF) expressions and increased p21WAF1 expression. Re-expression of PES1 in these two kinds of PES1 knockdown cells rescued these effects. In vivo, repression of endogenous PES1 expression suppressed gastric tumor growth in nude mice. In addition, 40.7 % (24/59) of gastric cancer tissues showed PES1 expression via immunohistochemical (IHC) staining. However, there were not any positive PES1 stainings in matched adjacent tissues. Our results demonstrated that repression of PES1 changed expressions of some cell proliferation- and angiogenesis-related genes and inhibited gastric cancer growth, and PES1 expression increased in gastric cancer tissues. These results suggest that PES1 may play an important role in development of gastric cancer. PES1 may be a potential target for gastric cancer therapy.

A multivariate time-series analysis employing a state-space embedding strategy and singular value decomposition is presented in this article to detect infrastructure damage. After summarizing the current state-space reconstruction method, the univariate state-space reconstruction is extended to multivariate (or global) reconstruction for observed time series at multiple locations. Under the hypothesis that reconstructed phase state geometry will change with damage, a reduced feature based on Mahalanobis distance of the most significant singular value vector, which is calculated from the reconstructed trajectory, is proposed. Both the area under receiver operating characteristic curve and deflection coefficient are used as comparison metrics to illustrate the presence and severity of damage. The advantage of this proposed approach is computational efficiency and easy implementation using state-space methodology since it does not require high-dimensional neighbor searches, as previous methods have proposed. Validation of the approach is demonstrated using a 6-degree-of-freedom linear spring-mass system and the IASC-ASCE 4-story benchmark experimental structure. Results from both test beds show that damage occurrence and severity can be successfully identified.

No abstract