Paraffin sections from 239 cases of surgical resected mammary gland carcinomas were assessed to determine the role of BRCA1 gene methylation in sporadic triple-negative breast cancer and to evaluate the relationship between BRCA1 gene methylation and clinicopathologic features of triple-negative breast cancer in the National Cancer Center, China. Diagnostic tissues collected from patients received mastectomy in the National Cancer Center from January 1, 1999 to December 31, 2008 were reviewed. Tissue microarrays were constructed using 239 triple-negative breast cancer cases and stained with estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, cytokeratin 5/6, and epidermal growth factor receptor. Methylation status of the BRCA1 promoter was measured by methylation-specific PCR and analyzed against clinicopathologic characteristics, subtypes, and prognosis using standard statistical methods. Among the 239 triple-negative breast cancer cases, 137 (57.3 %) showed methylation of the BRCA1. According to the immunohistochemistry results, triple-negative breast cancer cases were classified into basal-like breast cancer (60.7 %) and non-basal-like breast cancer (39.3 %). The frequency of BRCA1 methylation was significantly higher in basal-like breast cancer subtype (71.7 %) than the non-basal subtype (35.1 %). Thus, BRCA1 methylation is statistically significantly correlated with basal-like breast cancer subtype (p < 0.001). Multivariate analyses further showed that BRCA1 promoter methylation is an independently predictor of overall survival (p = 0.023; HR 2.32; 95 % CI 1.12-4.81) and disease-free survival (p = 0.022; HR 2.36; 95 % CI 1.13-4.90) in triple-negative breast cancer. Here we demonstrated that epigenetic alteration of key tumor suppressor gene can be a promising biomarker for the prognosis of triple-negative breast cancer/basal-like breast cancer. Specifically our finding revealed that BRCA1 methylation is closely associated with a significant decrease in overall survival and disease-free survival, highlighting BRCA1 promoter methylation as promising and powerful biomarkers for effect and better prognosis of DNA damaging agents for triple-negative breast cancer/basal-like breast cancer.

We previously showed that pre-exposure of the cornea to Toll-like receptor 5 ligand flagellin induces profound mucosal innate protection against infections by modifying gene expression. Taking advantage of easily procurable epithelial cell population, this study is the first report to use genome-wide cDNA microarray approach to document genes associated with flagellin-induced protection against Pseudomonas aeruginosa in corneal epithelial cells (CECs). Infection altered the expression of 675 genes (497 up and 178 down), while flagellin pretreatment followed by infection resulted in a great increase in 890 gene upregulated and 37 genes downregulated. Comparing these two groups showed 209 differentially expressed genes (157 up, 52 down). Notably, among 114 genes categorized as defense related, S100A8/A9 are the two most highly induced genes by flagellin, and their expression in the corneal was confirmed by realtime PCR and immunohistochemistry. Neutralization of S100A8 and, to a less extent, A9, resulted in significantly increased bacterial burden and severe keratitis. Collectively, our study identifies many differentially expressed genes by flagellin in CECs in response to Pseudomonas. These novel gene expression signatures provide new insights and clues into the nature of protective mechanisms established by flagellin and new therapeutic targets for reducing inflammation and for controlling microbial infection.

Palladium diselenide (𝑃𝑑𝑆𝑒 2 ) is a recently isolated layered material that has attracted a lot of interest for the pentagonal structure, the air stability and the electrical properties largely tunable by the number of layers. In this work, 𝑃𝑑𝑆𝑒 2 is used in the form of multilayer as the channel of back-gate field-effect transistors, which are studied under repeated electron irradiations. Source-drain 𝑃𝑑 leads enable contacts with resistance below 350 𝑘Ω • 𝜇𝑚. The transistors exhibit a prevailing n-type conduction in high vacuum, which reversibly turns into ambipolar electric transport at atmospheric pressure. Irradiation by 10 𝑘𝑒𝑉 electrons suppresses the channel conductance and promptly transforms the device from n-type to p-type. An electron fluence as low as 160 𝑒 − /𝑛𝑚 2 dramatically change the transistor behavior demonstrating a high sensitivity of 𝑃𝑑𝑆𝑒 2 to electron irradiation. The sensitivity is lost after few exposures, that is a saturation condition is reached for fluence higher than ∼ 4000 𝑒 − /𝑛𝑚 2 . The damage induced by high electron fluence is irreversible as the device persist in the radiation-modified state for several hours, if kept in vacuum and at room temperature. With the support of numerical simulation, we explain such a behavior by electron-induced Se atom vacancy formation and charge trapping in slow trap states at the 𝑆𝑖/𝑆𝑖𝑂 2 interface.