Epstein-Barr virus (EBV) is associated with Burkitt lymphoma, nasopharyngeal carcinoma, opportunistic lymphomas in immunocompromised hosts, and a fraction of gastric cancers. Aberrant promoter methylation accompanies human gastric carcinogenesis, though the contribution of EBV to such somatic methylation changes has not been fully clarified. We analyzed promoter methylation in gastric cancer cases with Illumina's Infinium BeadArray and used hierarchical clustering analysis to classify gastric cancers into 3 subgroups: EBV À /low methylation, EBV À /high methylation, and EBV þ /high methylation. The 3 epigenotypes were characterized by 3 groups of genes: genes methylated specifically in the EBV þ tumors (e.g., CXXC4, TIMP2, and PLXND1), genes methylated both in EBV þ and EBV À /high tumors (e.g., COL9A2, EYA1, and ZNF365), and genes methylated in all of the gastric cancers (e.g., AMPH, SORCS3, and AJAP1). Polycomb repressive complex (PRC) target genes in embryonic stem cells were significantly enriched among EBV À /high-methylation genes and commonly methylated gastric cancer genes (P ¼ 2 Â 10 -15 and 2 Â 10 -34 , respectively), but not among EBV þ tumor-specific methylation genes (P ¼ 0.2), suggesting a different cause for EBV þ -associated de novo methylation. When recombinant EBV was introduced into the EBV À /low-methylation epigenotype gastric cancer cell, MKN7, 3 independently established subclones displayed increases in DNA methylation. The promoters targeted by methylation were mostly shared among the 3 subclones, and the new methylation changes caused gene repression. In summary, DNA methylation profiling classified gastric cancer into 3 epigenotypes, and EBV þ gastric cancers showed distinct methylation patterns likely attributable to EBV infection. Cancer Res; 71(23); 7187-97. Ó2011 AACR.

We present rapidly rising transients discovered by a high-cadence transient survey with the Subaru telescope and Hyper Suprime-Cam. We discovered five transients at z=0.384-0.821, showing a rate of rise faster than 1 mag per day in the restframe near-ultraviolet wavelengths. The fast rate of rise and brightness are most similar to SN 2010aq and PS1-13arp, for which ultraviolet emission was detected within a few days after the shock breakout. The lower limit of the event rate of rapidly rising transients is ∼9% of core-collapse supernova rates, assuming the duration of rapid rise to be 1 day. We show that the light curves of the three faint objects agree with the cooling envelope emission from the explosion of red supergiants. The other two luminous objects, however, are brighter and faster than the cooling envelope emission. We interpret these two objects to be the shock breakout from a dense wind with a mass loss rate of ∼10 −3 M  yr −1 , as also proposed for PS1-13arp. This mass loss rate is higher than that typically observed for red supergiants. The event rate of these luminous objects is 1% of the corecollapse supernova rate, and thus our study implies that more than ∼1% of massive stars can experience intense mass loss a few years before the explosion.

Breast cancer remains a common malignancy in women, but the take-up for breast cancer screening programs in Japan is still low, possibly due to its perceived inconvenience. TFF1 and TFF3 are expressed in both breast cancer tissue and normal breast. Serum trefoil proteins were reported as cancer screening markers for gastric, prostate, lung, pancreatic cancer and cholangio carcinoma. The purpose of this study was to examine whether serum trefoil proteins could be screening biomarkers for breast cancer. Serum trefoil proteins in 94 breast cancer patients and 84 health check females were measured by ELISA. Serum TFF1 and TFF3 were significantly higher and serum TFF2 was significantly lower in breast cancer patients. Area under the curve of receiver operating characteristic of TFF1, TFF2, and TFF3 was 0.69, 0.83, and. 0.72, respectively. AUC of the combination of TFF1, TFF2, and TFF3 was 0.96. Immunohistochemically, TFF1 expression was positive in 56.5% and TFF3 was positive in 73.9% of breast cancers, while TFF2 was negative in all tumors. Serum TFF1 had positive correlation with expression of TFF1 in breast cancer tissue. Serum concentrations of TFF1 and TFF3 but not TFF2 are higher in women with breast cancer than in women without breast cancer.