Purpose: To assess the efficacy and safety of S-1, a novel oral fluoropyrimidine derivative, we conducted a multicenter late phase II study in patients with advanced gastric cancer. Patients and Methods: Fifty-one patients who had received no previous chemotherapy were enrolled. Fifty patients were eligible for efficacy and safety analyses. The overall response was evaluated for the 43 patients who had metastatic lesions. S-1 was administered orally after breakfast and dinner for 28 days, followed by a 14-day break. The dosages were assigned according to the patients’ body surface area (BSA): BSA <1.25 m², 40 mg; 1.25–1.5 m², 50 mg, and BSA ≥1.5 m², 60 mg, twice daily. Results: The overall response to treatment was evaluated as partial response in 19 of the 43 patients (44%; 95% confidence interval 30–59%). The median survival time in all patients was 207 days with 1- and 2-year survival rates of 36.0 and 14.0%, respectively. Grade 3 adverse reactions included decreased hemoglobin values in 2 patients, leukopenia, neutropenia and diarrhea in 1 patient each. No other grade 4 or unexpected adverse reactions were seen. Conclusions: S-1 is effective against advanced gastric cancer. This oral treatment is suitable for outpatients because of its mild toxicity. Further therapeutic benefits are likely to be obtained by combining S-1 with other chemotherapeutic agents.

We constructed a sensitive and quantitative assay system to examine human T-cell leukemia virus type I (HTLV-I) envelope (env) glycoprotein-mediated cell fusion in which T7 RNA polymerase in donor cells coexpressing env glycoproteins activates a reporter gene in recipient cells upon cell fusion. An efficient expression of HTLV-I env glycoproteins (gp46 and gp21) was observed in 293T cells transfected with an expression plasmid by both immunoblot and immunofluorescence analyses. The cells expressing env glycoproteins also exhibited self-fusion. By cocultivating the donor cells with recipient cells transfected with a reporter plasmid possessing the luciferase gene under the T7 promoter, the expression of luciferase was observed upon cell fusion. The activation of the luciferase gene was inhibited by either anti-env neutralizing antibody or synthetic peptide corresponding to env gp21, thus indicating the cell fusion to be specifically mediated by the HTLV-I env glycoproteins expressed in the donor cells. A broad range of cell lines exhibited susceptibility to HTLV-I env-mediated cell fusion by this assay. This newly established assay system may thus provide an efficient way both to study the fusion mechanisms mediated by HTLV-I env glycoproteins and to identify the HTLV-I receptor(s).

Exfoliation syndrome (XFS) is the commonest known risk factor for secondary glaucoma and a significant cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A have been previously associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results between populations, and to identify new variants associated with XFS. We identified a rare, protective allele at LOXL1 (p.407Phe, OR = 25, P =2.9 × 10−14) through deep resequencing of XFS cases and controls from 9 countries. This variant results in increased cellular adhesion strength compared to the wild-type (p.407Tyr) allele. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 × 10−8). Index variants at the new loci map to chromosomes 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS, and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.

These results suggest that differential activation of the Rho-Rho-kinase and the ERK-p70S6 kinase pathways may play a critical role in CHF, and the Rho-Rho-kinase pathway is involved in the pathogenesis of cardiac dysfunction and cardiovascular remodeling. Thus, inhibition of the Rho-kinase pathway may be at least a potential therapeutic strategy for CHF.

The fate and interactions with river organisms of zooplankton as they drift downriver from a reservoir on a fourth-order mountain stream (Hiji River, Japan) were investigated. Monthly samples were collected at the reservoir and six river sites, simultaneously, from May 2005 to May 2006. Aquatic macroinvertebrates and fish were colleted, and their stomach contents were analyzed in April and May, 2006, respectively. Drift from the reservoir was the primary source for the river plankton community; the abundance of zooplankton, particularly those of cladocerans and large rotifer, rapidly decreased within several kilometers of the dam. Analysis of the contents of fish stomachs showed that drifting zooplankton was the main food for fish, with strong food selectivity for cladocerans and large rotifers. However, fish and insect planktivores showed longitudinally different stomach contents, with progressively fewer zooplankton found in the stomachs at the downriver sites. The results suggest that the outflow of zooplankton from the reservoir is an important food source for the downstream predators, especially fish, but the drift of zooplankton and consequent food availability for the predators at lower sites are strongly limited by concentrated fish predation just below the reservoir dam.