Immunogenic cell death (ICD) is a form of cell death that activates an adaptive immune response against dead-cell-associated antigens. Cancer cells killed via ICD can elicit antitumor immunity. ICD is efficiently induced by near-infrared photo-immunotherapy (NIR-PIT) that selectively kills target-cells on which antibody-photoabsorber conjugates bind and are activated by NIR light exposure. Advanced live cell microscopies showed that NIR-PIT caused rapid and irreversible damage to the cell membrane function leading to swelling and bursting, releasing intracellular components due to the influx of water into the cell. The process also induces relocation of ICD bio markers including calreticulin, Hsp70 and Hsp90 to the cell surface and the rapid release of immunogenic signals including ATP and HMGB1 followed by maturation of immature dendritic cells. Thus, NIR-PIT is a therapy that kills tumor cells by ICD, eliciting a host immune response against tumor.

Six strains (CB7 T , CB18, CB23, CB26, CB28 and CB35 T ) were isolated from human faeces. Based on phylogenetic analysis, phenotypic characteristics, cellular fatty acid profiles and menaquinone profiles, these strains could be included within the genus Prevotella and made up two clusters. 16S rRNA gene sequence analysis indicated that five strains were most closely related to Prevotella veroralis, sharing about 92 % sequence similarity; the remaining strain was most closely related to Prevotella shahii, sharing about 90 % sequence similarity. All six strains were obligately anaerobic, non-pigmented, non-spore-forming, non-motile, Gram-negative rods. The cellular fatty acid compositions of the six strains differed significantly from those of other Prevotella species. Five strains (CB7 T , CB18, CB23, CB26 and CB28) contained dimethyl acetals and the major menaquinones of these strains were MK-11, MK-12 and MK-13. The major menaquinones of CB35 T were MK-12 and MK-13. Based on phenotypic and phylogenetic findings, two novel species, Prevotella copri sp. nov. and Prevotella stercorea sp. nov., are proposed, representing the two different strain clusters. The DNA G+C contents of strains CB7 T and CB35 T were 45.3 and 48.2 mol%, respectively. The type strains of P. copri and P. stercorea are CB7 T (=JCM 13464 T =DSM 18205 T ) and CB35 T (=JCM 13469 T =DSM 18206 T ), respectively.The application of molecular biological techniques has enabled phylogenetic analysis of bacterial 16S rRNA genes in the human gut. In particular, phylogenetic analysis based on 16S rRNA genes has made it possible to clarify the dominant human faecal microbiota (Eckburg et al., 2005;Hold et al., 2002;Suau et al., 1999;Wilson & Blitchington, 1996;Zoetendal et al., 1998). A large number of species that have not yet been identified and characterized exists in the human gut. It has been reported that the human faecal microbiota could be analysed by 16S rRNA gene libraries and strictly anaerobic culture-based methods (Hayashi et al., 2002a, b). Many novel operational taxonomic units (OTUs) and isolates that have not yet been characterized were detected and phylogenetic correlation between novel isolated strains and 16S rRNA sequences has been shown. Some novel OTUs and isolates were phylogenetically related to the genus Prevotella. These isolates were the predominant species in human faeces. Suau et al. (1999) and Eckburg et al. (2005) also detected some novel OTUs belonging to the genus Prevotella from 16S rRNA gene library data. Although Prevotella species have been isolated mainly from the oral cavity, these species also inhabit the human gut. Here, two novel species within the genus Prevotella isolated from human faeces are reported.The strains used in the present study were maintained on Eggerth Gagnon (EG) agar (Merck) supplemented with 5 % (v/v) horse blood for 2 days at 37 u C, in an atmosphere containing 100 % CO 2 . Strains CB7 T , CB18, CB23, CB26, CB28 and CB35 T were isolated from faeces of a healthy Japanese male (52 years old) using...

Estrogen receptor-α (ER)-positive breast cancer cells undergo hormone-independent proliferation after deprivation of oestrogen, leading to endocrine therapy resistance. Up-regulation of the ER gene (ESR1) is critical for this process, but the underlying mechanisms remain unclear. Here we show that the combination of transcriptome and fluorescence in situ hybridization analyses revealed that oestrogen deprivation induced a cluster of noncoding RNAs that defined a large chromatin domain containing the ESR1 locus. We termed these RNAs as Eleanors (ESR1 locus enhancing and activating noncoding RNAs). Eleanors were present in ER-positive breast cancer tissues and localized at the transcriptionally active ESR1 locus to form RNA foci. Depletion of one Eleanor, upstream (u)-Eleanor, impaired cell growth and transcription of intragenic Eleanors and ESR1 mRNA, indicating that Eleanors cis-activate the ESR1 gene. Eleanor-mediated gene activation represents a new type of locus control mechanism and plays an essential role in the adaptation of breast cancer cells.

Estrogen receptor (ER) a plays a crucial role in normal breast development and has also been linked to mammary carcinogenesis and clinical outcome in breast cancer patients. However, the molecular mechanisms controlling the expression of ERa are as yet not fully understood. Gene amplification is one of the important factors regulating protein expression. Recent studies on the amplification of the ESR1 gene, which encodes ERa, have presented conflicting data. Using fluorescence in situ hybridization and real-time quantitative polymerase chain reaction analysis, we examined the ESR1 status in a series of breast cancer tissues and analyzed its clinical importance. ESR1 gene amplification and gain were found in 22.6 and 11.3% of samples, respectively, as determined by three-dimensional fluorescence in situ hybridization assay. Moreover, ESR1 amplification and amplification plus gain were significantly negatively correlated with tumor size, number of positive lymph nodes, negative ERa, and positive human epidermal growth factor receptor 2 status. It has also been shown that ESR1 amplification strongly correlates with higher expression levels of ER protein and that patients with ESR1 amplification in their tumors apparently experience longer disease-free survival than those without. Our data suggest that ESR1 amplification might prove to be helpful in selecting patients who may potentially benefit from endocrine