S-1 is an effective adjuvant treatment for East Asian patients who have undergone a D2 dissection for locally advanced gastric cancer. (ClinicalTrials.gov number, NCT00152217 [ClinicalTrials.gov].).

JapicCTI-101021.

The RHO1 gene encodes a homologue of mammalian remains to be clarified whether these target proteins of RhoA small G-protein in the yeast Saccharomyces Rho are involved in the reorganization of actin cytocerevisiae. Rho1p is required for bud formation and is skeleton. Very recently, one of these proteins, Rho kinase, localized at a bud tip or a cytokinesis site. We have recently shown that Bni1p is a potential target of has been shown to inhibit the myosin phosphatase activity Rho1p. Bni1p shares the FH1 and FH2 domains with (Kimura et al., 1996), although its physiological significproteins involved in cytokinesis or establishment of ance remains to be clarified. cell polarity. In S.cerevisiae, there is an open reading Cells of the budding yeast Saccharomyces cerevisiae frame (YIL159W) which encodes another protein grow by budding for cell division, and the actin cytohaving the FH1 and FH2 domains and we have named skeleton plays a pivotal role in the budding process this gene BNR1 (BNI1 Related). Bnr1p interacts with (Drubin, 1991 Johnson and Pringle, 1990). mutant shows a severe temperature-sensitive growth RHO1 is a homologue of the mammalian RhoA gene and phenotype. Cells of the bni1 bnr1 mutant arrested we have shown that the rho1 mutants are deficient in at the restrictive temperature are deficient in bud the budding process (Yamochi et al., 1994). Moreover, emergence, exhibit a random distribution of cortical immunofluorescence microscopic studies indicate that actin patches and often become multinucleate. TheseRho1p is localized at the growth site with cortical actin phenotypes are similar to those of the mutant of patches, including the presumptive budding site, the bud PFY1, which encodes profilin, an actin-binding protein.tip and the cytokinesis site (Yamochi et al., 1994). These Moreover, yeast two-hybrid and biochemical studies results suggest that RHO1 regulates the processes of bud demonstrate that Bni1p and Bnr1p interact directly formation. Concerning the downstream targets of Rho1p, with profilin at the FH1 domains. These results indicate we have shown that one of them is a homologue of that Bni1p and Bnr1p are potential targets of the Rho mammalian protein kinase C, Pkc1p (Nonaka et al., 1995), family members, interact with profilin and regulate which regulates cell wall integrity through the activation the reorganization of actin cytoskeleton.of the MAP kinase cascade (Levin and Errede, 1995). We Keywords: actin cytoskeleton/profilin/Rho have also shown that another target of Rho1p is 1,3-β-glucan synthase (Drgonová et al., 1996;Qadota et al., 1996), which is involved in cell wall synthesis. Very recently, we have identified BNI1 as a third potential target

The RHO1 gene encodes a homolog of mammalian RhoA small GTP binding protein in the yeast Saccharomyces cerevisiae. Rho1p is localized at the growth sites, including the bud tip and the cytokinesis site, and is required for bud formation. We have recently shown that Pkc1p, a yeast homolog of mammalian protein kinase C, and glucan synthase are targets of Rho1p. Using the two‐hybrid screening system, we cloned a gene encoding a protein which interacted with the GTP‐bound form of Rho1p. This gene was identified as BNI1, known to be implicated in cytokinesis or establishment of cell polarity in S.cerevisiae. Bni1p shares homologous domains (FH1 and FH2 domains) with proteins involved in cytokinesis or establishment of cell polarity, including formin of mouse, capu and dia of Drosophila and FigA of Aspergillus. A temperature‐sensitive mutation in which the RHO1 gene was replaced by the mammalian RhoA gene showed a synthetically lethal interaction with the bni1 mutation and the RhoA bni1 mutant accumulated cells with a deficiency in cytokinesis. Furthermore, this synthetic lethality was caused by the incapability of RhoA to activate Pkc1p, but not glucan synthase. These results suggest that Rho1p regulates cytoskeletal reorganization at least through Bni1p and Pkc1p.

In total gastrectomy for proximal gastric cancer that does not invade the greater curvature, splenectomy should be avoided as it increases operative morbidity without improving survival.