Within our restricted I-BET-762 concentration “”T4 phages”" genus, four subtypes were identified (T4-type, 44RR2.8t-type, RB43-type and the RB49-type viruses). This is confirmed by the phylogenetic studies of Filée et al. [5] and our unpublished results. Since these subtypes include different species, no equivalent taxonomic level is currently available in the official ICTV classification. Perhaps the introduction of a “”subgenus”" level should be considered in order to account for the complexity of T4-related phages. Alternately, a general elevation of

all taxonomic levels (from the subfamily level) may be envisioned. This study illustrates the great diversity and biological richness of tailed phages. The number of independent genera is not surprising in view of the antiquity of tailed

bacteriophages, which are found in archaea and bacteria and may predate the separation of these domains. It can be expected that many more phage groups will be found or individualized in the future. For example, this study does not include giant Bacillus phage G, the largest bacterial virus with a genome of 497,513 bp and 684 genes [102] whose sequence is not yet available for comparison. We reiterate our statement in our publication on the taxonomy of the Podoviridae, “”We highly recommend that the entire genome of any newly sequenced phage be thoroughly screened (BLASTX) against the Entrez Query “”Viruses [ORGN]“” databases to reveal all similarities for quick identification of potential relationships. A validation step using CoreGenes is essential and more precise for individual comparisons Smad inhibitor [2].”" Conclusion Myoviridae can be classified by their proteomes into subfamilies and genera. This classification is in close agreement with ICTV – and other informatics-based classifications. Methods Phages and bioinformatic tools This study is limited to the genomes of completely sequenced, viable Myoviridae

from the databases of NCBI http://​www.​ncbi.​nlm.​nih.​gov/​ and the Tulane University at New Orleans, LA (GT4P, “”Genomes of the T4 Phages”"; http://​phage.​bioc.​tulane.​edu/​, excluding prophages without a virion stage. We follow here the ICTV which classifies viable viruses only. Prophages and proviruses, prophage fragments, defective viruses, phage-like “”bacteriocins”", virus-like or phage-likes particles Nitroxoline from sections or the environment, viroids, satellite viruses, plasmids, or transposons, or artificial virus hybrids are not considered. CoreExtractor and CoreGenes software were used as described previously [2]. In the case of CoreExtractor, the BLASTX analysis of phage gene products was performed using the NCBI Batch BLAST server, http://​greengene.​uml.​edu/​programs/​NCBI_​Blast.​html hosted by the University of Massachusetts at Lowell, MA. Searches were performed against the NCBI nonredundant database (BLOSUM45 matrix, with a 0.05 expectancy cut-off value) (Additional Figure 2).

coli TOP10 One Shot® chemically competent cells. The correct orientation and frame of the inserted gene sequence was verified by

sequencing. The Doxorubicin research buy bait containing plasmid was isolated using Fast Plasmid™Mini technology (Brinkmann Instruments) and used to transform competent S. cerevisiae yeast cells (Y187) with the YEAST- MAKER™ Yeast Transformation System 2 (Clontech Laboratories Inc.). Tests for autonomous gene activation and cell toxicity were carried out as described by the manufacturer. A cDNA library using S. schenckii yeast RNA was constructed as described previously in AH109 cells [58]. Transformants were selected in SD/-Leu plates, harvested and used for mating with the bait containing S. cerevisiae strain Y187. Mating of S. cerevisiae yeast cells strains Y187 (Mat-α) and AH109 (Mat-a) was done according to the manufacturer’s instructions as described previously. Colonies growing in triple dropout medium (TDO) SD/-Ade/-Leu/-Trp were tested for growth

in quadruple dropout medium (QDO) SD/-Ade/-His/-Leu/-Trp. These positive colonies were re-plated in QDO medium to verify that they maintained the correct phenotype. Colony PCR was used to corroborate the presence of both plasmids selleck kinase inhibitor in the diploid cells using the T7/3′BD sequencing primer pair for the pGBKT7/SSCMK1 plasmid and the T7/3′AD primer pair for the pGADT7-Rec library plasmid and yeast colony suspension as template. The Ready-to-Go™ Beads (Amersham

Biosciences) were used for PCR. The amplification parameters were those described previously [58]. PCR products were analyzed on agarose gels and the DNA recovered using Spin-X Centrifuge Tube Filters as described by the manufacturer (0.22 μm, Corning Costar Corp.). The PCR products were cloned and amplified as described previously [58]. Plasmid preparations were obtained using the Fast Plasmid™ Mini technology (Brinkmann over Instruments) and the inserts sequenced using commercial sequencing services from SeqWright (Fisher Scientific, Houston, TX, USA) and Retrogen DNA Sequencing (Retrogen Inc., San Diego, CA, USA)). Co-immunoprecipitation (Co-IP) and Western blots Co-immunoprecipitation followed by Western blot was used to confirm the interaction of HSP90 identified in the yeast two-hybrid analysis as interacting with SSCMK1 as described previously [58]. S. cerevisiae diploids obtained in the yeast two-hybrid assay were grown in QDO, harvested by centrifugation and resuspended in 8 ml containing phosphate buffer saline (800 μl) with phosphatase (400 μl), deacetylase (80 μl) and protease inhibitors (50 μl), and PMSF (50 μl). The cells were broken as described previously [59]. The cell extract was centrifuged and the supernatant used for Co-IP using the Immunoprecipitation Starter Pack (GE Healthcare, Bio-Sciences AB, Bjorkgatan, Sweden).

The canonical hexa-acylated LPS of Escherichia coli JM 83-wild type strain was used as the reference [66]. Cell culture

HGFs were PD0325901 research buy obtained from Sciencell research laboratories (Carlsbad, CA, USA) and cultured according to the manufacturer’s instructions [67, 68]. Continuous subcultures up to 10th passage contained homogeneous, slim and spindle-shaped cells growing in characteristic swirls. Third to fourth passages of HGFs without any signs of senescence were used for all experiments as described in our previous study [4]. Stimulation of HGFs by heterogeneous P. gingivalis LPS The cells suspended at 105 cell/ml were seeded on six-well-plates and grown until click here confluent at 37°C with 5% CO2 in a culture medium for fibroblasts consisting of basal medium with 2% fetal bovine serum, penicillin/streptomycin (0.01% w/v) and fibroblast growth supplement. Once the cells were over 90% confluent, fibroblast medium (FM) was replaced entirely with serum free and animal component free-medium (FM-acf) for the dose- and time-dependent experiments. In the dose-dependent assay, cells were stimulated with P. gingivalis LPS1435/1449, P. gingivalis LPS1690 or E. coli LPS in the media containing various doses of LPS (0.001 μg/ml −10 μg/ml). Subsequently, 1 μg of LPS was selected as the appropriate

dose for the following time-dependent experiments. Cells were incubated with P. gingivalis LPS or E. coli LPS at 1 μg/ml and harvested at 2, 12, 24 and 48 h. Cells without LPS treatment were designated as the controls. Culture supernatants

were collected and centrifuged to remove the cellular debris and stored at −70°C for Microtubule Associated inhibitor subsequent protein assays. Cellular fraction was then washed with PBS and collected for mRNA and protein extraction. RNA extraction, cDNA synthesis and real-time qPCR Total RNA extraction, cDNA transcription and real-time qPCR for MMPs1-3 and TIMP-1 were performed as previously described [17]. In brief, total RNA was extracted from the homogenized HGFs using RNeasy Mini Kit (Qiagen, Hilden, Germany) according to the manufacturer’s instructions [35]. cDNA was synthesized by reverse transcriptase-PCR at 43°C for 90 min in a 20 μl of reaction mixture containing 1 μg of total RNA, 1 μl (200 U) of SuperScript™ First-Strand Synthesis System (Invitrogen Corp., Carlsbad, CA, USA), 0.5 μg of oligo dT-primer, first-strand buffer, 10 mM DTT, and 1 mM dNTPs. A control reaction was performed without reverse transcriptase for all samples to verify the absence of genomic DNA contamination. Real-time qPCR was then performed by using the StepOne Real-Time PCR System (Applied Biosystems, Foster City, CA) in at least three separate experiments.

Alternatively spliced fibronectin (FN) variants containing extra FN type 3 repeats, referred to as cellular or “oncofetal” FN, are major constituents Selleck GSK1120212 of the extracellular matrix surrounding angiogenic blood vessels and carcinoma-activated fibroblasts. Whereas cellular FN is virtually absent from normal adult tissue, a massive upregulation is observed in highly angiogenic and invasive tumors, suggesting that cellular FN and signaling components that control its expression, assembly and rigidification may represent key targets for anti-tumoral therapies.

We have examined the role and functional redundancy of cellular FN variants ED-B and ED-A (Extra Domains-B and -A) in vascular endothelial cells by isoform-selective RNA interference. FN-depleted cells fail to assemble a subendothelial matrix indicating that FN fibrillogenesis is a cell autonomous process in endothelial cells in which basal secretion of FN is tightly coupled to integrin-dependent assembly. Isoform-specific FN knock down alters integrin usage and impacts on downstream signaling events that regulate cytoskeletal organization, motility, cell-cell adhesion and capillary morphogenesis on a basement

membrane matrix. In cells lacking FN, the integrin beta subunit partner ILK (Integrin-linked Kinase) shifts from alpha5beta1 fibrillar adhesions to alphavbeta3 adhesive structures. This integrin switch is accompanied by the disruption of adherens junctions and abrogation of loss of monolayer integrity. Altogether, these results highlight the importance of autocrine FN for angiogenic

JAK inhibitors in development blood vessel remodeling and allow us to propose that cellular FN expression provides a spatially and temporally restricted control of vascular network NADPH-cytochrome-c2 reductase formation and stability. O42 Tumor-Derived, Low-Level TNFa Expression Augments the Formation of Tumor-Promoting Myeloid Subtype of Vascular Leukocytes through the Upregulation of Integrin a 5 and Enhanced Binding to Fibronectin Bin Li1, Alicia Vincent1, Pampee Young 1 1 Pathology and Medicine, Vanderbilt University Medical Center, Nashville, TN, USA Tumor associated myeloid cells are believed to promote tumor development by stimulating tumor growth, angiogenesis, invasion and metastasis. These tumor-associated myeloid cells are believed to be a heterogeneous population. There is growing data from multiple laboratories that tumor associated myeloid cells that co-express endothelial and myeloid markers represent a pro-angiogenic subtype of tumor associated myeloid cell known as vascular leukocytes. Recently, we demonstrated that tumor-derived TNFa promotes local tumor growth and vascularity, in part by increasing numbers of tumor-associated vascular leukocytes (Can Res. 2009; 69:338). We wished to explore the mechanism by which TNFa mediates endothelial differentiation of myeloid cells. Published studies have shown that fibronectin is a critical promoter of endothelial differentiation of blood mononuclear cells in vitro.

9 3.75 ± 10.9 3.75 ± 10.9 p value compared to V1   0.058 <0.0001 <0.0001 Patients of both groups stated that they were satisfied with the therapy, in fact all the patients answered yes to the question: ""Are you satisfied with your analgesic treatment?"" Adverse events Transdermal opioid switching reduced the incidence of adverse events. Nausea GSK2118436 cost and vomiting persisted in patients suffering from gall bladder cancer and gastric cancer (three patients). The number of patients with constipation was also reduced; BTDS group: V1 11 pts, V2 4 pts, V3 5 pts, V4 5 pts and similarly in the FTDS group: V1 10 pts, V2 6 pts, V3 4 pts, V4 5 pts

(table 4 and table 5). Constipation persisted only in patients suffering from colon, brain and lung cancer (9 patients). Moreover, in both groups, dysphoria and sedation disappeared completely after the first week (tables 4 and 5). Table 4     Number of patients with Nausea and/or vomiting Number of patients with constipation Number of patients with dysphoria   V1 V2 V3 V4 V1

V2 V3 V4 V1 V2 V3 V4 FTDS 9 6 5 3 10 6 4 5 0 0 0 0 BTDS 8 5 4 2 11 4 5 4 2 0 0 0 Table 5 SEDATION SCALE   SEDATION SCALE   Number of patients without Sedation Number of patients with slight sedation Number of patients with moderate sedation Number of patients with severe sedation   V1 V2 V3 V4 V1 V2 V3 V4 V1 V2 V3 V4 V1 V2 V3 V4 FTDS 10 16 16 16 2 0 0 0 4 0 0 0 0 0 0 0 BTDS 12 16 16 16 3 0 0 0 1 0 0 0 0 0 0 0 Discussion Opioid

switching is a fundamentally useful strategy in long-term treatment of cancer pain, where tolerance phenomena selleckchem and the large number of side-effects can limit the use of these medicines and further diminish the patients’ quality of life [6, 8]. In these cases, switching from one opioid to another is a useful means to establish a more favourable balance between analgesia and toxicity and is regulated in conversion tables in order to ensure fewer side-effects and an improvement in pain symptoms. [7, 9, 10, 12]. The development of tolerance suggests the necessity to increase the drug dose in order to obtain the same analgesic effect [13, 14]. Tolerance development may also be associated with pharmacodynamic, pharmacokinetic and psychological processes resulting ADAMTS5 in an increase in side effects connected not only with the drug, but also with its metabolites. It may be supposed that by changing the opioid and using lower doses than indicated in conversion tables it is possible, in most cases, to reduce toxicity and improve pain symptoms [6, 15, 16]. According to available data, many factors may influence opioid treatment such as individual variability, genetic factors, relation among active metabolites, intrinsic activity, number and types of receptors, as well as issues of efficacy, toxicity and tolerance.

To address this question we randomized the O-glycosylation

positions for all the proteins. In this new set of data, the proteins displayed the same number of O-glycosylation sites as predicted by NetOGlyc but their positions were chosen at random. When these hypothetical proteins were analyzed in search of pHGRs, we obtained the results presented in Figure 3. The number of proteins displaying pHGRs was considerably smaller when the positions of the O-glycosylation sites were randomized. Between 42.6% (S. cerevisiae) to 75.7% (M. grisea) of the proteins displaying pHGRs with the O-glycosylation sites predicted by NetOGlyc lost them with the randomization of the O-glycosylation positions, indicating that at least in the majority of proteins there is really a selective pressure to localize the O-glycosylation sites grouped in pHGRs. The total number Nutlin-3a order of pHGRs

was also lower with the randomized data (Figure 3B), although in this case the difference was not so big, and in the case of S. cerevisiae the total number of pHGRs actually increased with the randomization of the O-glycosylation positions. The Akt inhibitor reason for this result may be related to the presence of proteins predicted to have a very high number of O-glycosylation sites in this yeast, for which the randomization of the O-glycosylation positions leads to the scattering of the sites throughout the whole protein and the appearance of a greater number of smaller pHGRs. As discussed before, S. cerevisiae differentiates from the rest of the organisms under study in the sense that it possesses a higher proportion of these highly O-glycosylated proteins (Figure 2). Figure 3 Effect of the randomization of the position of the O -glycosylation sites on pHGR prediction. Number of proteins with pHGRs (A) and total number of pHGRs (B) found in every genome with the O-glycosylation positions predicted by NetOGlyc (blue columns) or the randomized positions (red columns). pHGRs

show a small tendency to be located at protein ends We then addressed the question of whether the location of pHGRs shows a random distribution along the length of the proteins or, alternatively, there is preference for any given regions such as the C- or N-terminus. The central positions of all pHGRs detected selleck inhibitor for any given organism were calculated and classified in ten different groups according to their relative location along their respective protein. The first group contained those pHGRs having their center in the N-terminal 10% of the protein sequence; the second group those with center in the second 10%, and so on. Figure 4A shows the frequency distribution of these ten groups for the eight fungi and indicates that there is no clear preference for any protein region, although slightly higher frequencies are observed for the N- and C-terminus, especially the latter, for almost all fungi examined. The clearer exception is S.

2006, 2008), whereas three major decay times are found for PSI: 5–20, 20–60, 80–130 ps (Turconi et al. 1994; Croce et al. 2000; Ihalainen et al. 2002, 2005; van Oort et al. 2008; Slavov et al. 2008). Because of the various complications, only FDA-approved Drug Library in vivo the average lifetimes (τave) measured for WT and dgd1 thylakoid membranes and intact leaves are compared in this article. The longer lifetime in dgd1 can most easily be explained by taking into account the lower PSI content of the membranes (Ivanov et al. 2006)—this photosystem exhibits short lifetimes

(e.g., van Oort et al. 2010). Further, excess amounts of LHCI might also contribute to the longer lifetimes—according to Ivanov et al. (2006) the amount AZD1208 of LHCI was unchanged; hence, a fraction of these antenna complexes might not be connected to the reaction center. As reported by the lipophilic fluorescence probe MC540, alterations in the lipid composition in dgd1 bring about changes in the lipid packing. The spectroscopic properties of MC540 are determined by the dielectric

constant of its local environment (Lelkes and Miller 1980). Thus, it exhibits different fluorescent lifetimes when present in different environments (interacting with lipids or solubilized in the aqueous phase). Earlier it has been shown that the shortest lifetime (200 ps) component originates from dyes in aqueous environment and the 1- and 2-ns components from MC540 in hydrophobic environments, i.e., in the lipid phase (Krumova et al. 2008a). These lifetimes might be assigned either to two discrete populations of the molecules, reflecting two different microenvironments

or to a broad distribution of lifetimes due to incorporation of MC540 in a variety of environments with small differences in their physical properties. Our data reveal significant differences in the lipid packing between dgd1 and WT membranes. Most prominently, the increased amplitude of the 200 ps component suggest that in dgd1 the MC540 molecules Teicoplanin are more exposed to the aqueous phase than in WT (Fig. 5). The lower extent of incorporation of MC540 in the thylakoid membranes isolated from dgd1 in comparison with WT membranes might be due to two factors: (i) tighter lipid packing in dgd1, which could be the consequence of modified lipid–protein interactions and changes in the macroorganization, and/or (ii) modified surface charge of the membrane, i.e., due to conformational changes in the protein complexes or to differences in lipid–protein interactions. Despite the altered lipid composition (increased non-bilayer:bilayer lipid ratio) and alterations in the lipid packing, the ΔA515 measurements indicate that the dgd1 thylakoid membranes are perfectly adjusted to generate and maintain the transmembrane electrochemical potential difference at 25°C (Fig. 6a). ΔA515 is a voltmeter of thylakoid membranes.

The data sets (baseline data, three questionnaires) were sent to C. Cooper (Southampton) for data analysis. The wrist

fracture questionnaire was scored as follows: Every question had five answer options from 1—healthy to 5—severe impact on quality of life. The scores on individual questions were summed up to a total score from 12 to 60, and this was recalculated to a score from 0 to 100. The Qualeffo-41 (spine) was scored Selleckchem INCB024360 as described previously with scores ranging from 0, representing the best, to 100, representing the worst quality of life [10]. The EQ-5D was scored according to the manual [14]. The overall score ranging from 0, the worst, to 1, the best quality of life, represents

utility and can be used to calculate quality-adjusted life years (QALY) losses. The test–retest reproducibility was assessed in the patients by comparing the results of the wrist fracture questionnaire STA-9090 ic50 at 12 weeks with the results at 14 weeks, as described above, using weighted Cohen kappa. The internal consistency was assessed by Cronbach alpha, comparing the wrist fracture questionnaire with the domains for pain and physical function of Qualeffo-41. Spearman rank correlations were calculated between similar domains of the three questionnaires. Wilcoxon signed-rank test was used to test for significant differences between each time point median score and the baseline median score. The sensitivity to change was assessed by regression

analysis comparing the IOF-wrist fracture questionnaire with Qualeffo-41 and EQ-5D. Results Data were collected in 105 patients (92 women, 13 men) with wrist fracture and 74 control subjects (61 women, 13 men). Baseline data are shown in Table 1. The fracture was on the right side in 38 patients (36.5%) and on the left side in 66 patients (63.5%), and in one patient, the side was not known. The fracture was on the dominant side in 43 patients and non-dominant side in 60 patients (two missing). Most fractures were Colles type; eltoprazine three were Smith-type fracture. Surgical treatment was done in 32 patients. Analgesics were taken by 25 of 63 patients (42 missing) and algodystrophy was observed in 5 of 82 patients, whilst in 23, it was not known. Data at 12 months were available from 87 patients. Test–retest repeatability, analysed in patients by comparing results at 12 and 14 weeks, was restricted to 19 patients who completed the repeat questionnaire within 11–17 days. The weighted kappa statistic ranged from 0.33 to 0.74, and all scores were higher than 0.30. Cronbach alpha was assessed at baseline by comparing the wrist fracture questionnaire with the domains of pain and physical function of Qualeffo-41 (spine). Cronbach alpha was 0.96.

Genomics 1996, 35: 207–14.CrossRefPubMed 20. Gelebart P, Opas M, Michalak M: Calreticulin, a Ca2+-binding chaperone of the endoplasmic reticulum. Int J Biochem Cell Biol 2005, 37: 260–6.CrossRefPubMed 21. Obeid M, Tesniere A, Panaretakis T, Tufi R, Joza N, van Endert P, Ghiringhelli F, Apetoh L, Chaput N, Flament C, Ullrich Selumetinib E, de Botton S, Zitvogel L, Kroemer G: Ecto-calreticulin in immunogenic chemotherapy. Immunol Rev 2007, 220: 22–34.CrossRefPubMed 22. Ghali JK, Smith WB, Torre-Amione G, Haynos W, Rayburn BK, Amato A, Zhang D, Cowart D, Valentini G, Carminati P, Gheorghiade M: A phase 1–2 dose-escalating study evaluating the safety and tolerability of istaroxime and specific

effects on electrocardiographic and hemodynamic parameters in patients with chronic heart failure with reduced systolic function. Am J Cardiol 2007, 99: 47A-56A.CrossRefPubMed Competing interests The authors declare that they have no competing interests. Authors’ contributions

AB conceived the study, carried out experiments on the Ca2+-signaling and drafted the manuscript. JK carried out experiments on the Ca2+-signaling and Western Blot analysis. AT and RMH participated in the study design and revised the manuscript critically for important intellectual Alpelisib cost content.”
“Background Human HCC (hepatocellular carcinomas) is the common hepatic highly malignant tumor. Most patients, especially in China, present at diagnosis with

a high stage. The etiopathogenisis and developments of HCC are not well known. Deregulation of cell proliferation and cell apoptosis underlies neoplastic initiation and development, which involves multiple gene alterations, and is regulated by complicated signal transduction Cediranib (AZD2171) pathways. It has become clear that deregulated apoptosis plays a pivotal role in tumorigenesis, malignancy and metastatic potential [1]. Accumulating evidence suggests that multiple intrinsic and extrinsic signaling molecules contribute to the resistance to death ligands- and chemotherapeutics-induced apoptosis in cancer cells. c-FLIP(cellular FLICE-inhibitory protein) is a novel member of IAP(inhibitor of apoptosis protein) family, which inhibits the apoptosis signaling mediated by the death receptors Fas, DR4, and DR5[2, 3]. c-FLIP plays a pivotal role in modulating the induction of apoptosis in variant cancer cells [4–6]. Down-regulating c-FLIP expression confers sensitivity to TRAIL- and Fas-induced apoptosis. c-FLIP has homology to caspase-8 and caspase-10, but lacks their protease activity due to the absence of key NH2 acid residues at the active site[7]. c-FLIP belongs to the potential negative regulators of the DR(death receptor) pathway by interfering with caspase-8 activation. Two splicing variants of c-FLIP, 55 kDa c-FLIPL(long form) and 25 kDa c-FLIPS(short form), have the capacity to block DR-mediated apoptosis.

g., Japan, Korea, China), intermediate-risk (e.g., Vietnam) or low-risk (e.g., Thailand and Indonesia). In contrast, the prevalence of H. pylori infection is similar among these countries, being relatively high in the elderly population [7, 8]. Thus, although the association between H. pylori infection and the development of

gastric cancer has been well established, it is still unclear why there is such a wide variation in the incidence of gastric cancer among Asian countries, an issue that has been referred to as the “”Asian enigma”" or “”Asian paradox”" [7, 9]. Recent molecular epidemiologic data suggest that genetic diversity of H. pylori might be partly responsible for this phenomenon. A large number of studies have investigated the roles of CP-673451 clinical trial putative virulence factors of H. pylori, the best studied being the cagA and vacA genes. The structure of the 3′ repeat region of the cagA gene varies between strains from Western countries and those from East Asian countries

[10–17]; East Asian type cagA strains are reported to be more virulent JQ1 chemical structure than their Western counterparts [14, 15]. H. pylori can be divided into five subtypes based on the structure of the right-end junction motif of the cag pathogeniCity island (PAI), which can be a useful molecular marker for distinguishing isolates from different geographical areas [18]. Generally, type I is common in isolates from Western countries, type II in East Asian countries, and type III mainly in South Asia [18]. Types IV and V are relatively rare compared with the other types, but type V has been found in a few strains from India and Thailand [12]. There is considerable variation in vacuolation activity among H. pylori strains [19, 20], primarily due to differences of vacA gene structure in the signal region (s1 and s2) and HSP90 the middle region (m1 and m2)

[21]. Among the s1 genotype, s1/m1 is toxic for a wider range of epithelial cells than s1/m2 [22]. The vacA s2/m2 strains are virtually non-toxic [21] and are rarely associated with diseases [23–25]. Importantly, most of the H. pylori strains isolated from countries with a high incidence of gastric cancer such as Japan and South Korea concurrently possess virulent genotypes such as vacA s1/m1 and East Asian type cagA [13, 14]. In contrast, in countries with a low incidence of gastric cancer such as Thailand and India, a considerable proportion of H. pylori isolates have less virulent genotypes, such as vacA m2 and Western type cagA [12, 13]. Vietnam is located on the borderline between regions with high and low risk of gastric cancer. Interestingly, the ASR of gastric cancer in Vietnam was 21.8 in 2002, which is considered to be intermediate (i.e., lower than Japan [62.0], Korea [69.7] and China [41.4], but higher than Thailand [4.3] and Indonesia [3.5]) http://​www-dep.​iarc.​fr/​.