lewis-y-antigen and Stomach-Ulcer

Helicobacter pylori (H. pylori) is a major causative agent for the induction of chronic gastritis, gastric ulcer and gastric cancer. Celecoxib (COX-2 inhibitor) inhibits gastric cancer cell proliferation, but with low treatment efficacy, limiting its applications. It is important to develop a better strategy to improve the efficacy of celecoxib. Lewis Y (LeY) is a difucosylated oligosaccharide, highly expressed in 60-90% of human epithelial cancers, including gastric cancer. We previously found that H. pylori infection was associated with high level of LeY in gastric cancer.. Herein, we analyzed the correlation between H. pylori and cyclo-oxygenase-2 (COX-2), LeY, gastric markers (CA724 and GRN) in gastric patient's tissue and serum samples by IHC and ELISA. Furthermore, we treated the primary gastric cancer cells with celecoxib, anti-LeY antibody or the combination, and analyzed their therapeutic efficacy on CA724, GRN and COX-2 expression by Western blot, flow cytometry and ELISA.. We found that gastric cancer had significantly high expression of H. pylori, COX-2, CA724, and GRN compared to gastric ulcers and chronic gastritis (P < 0.0001). H. pylori level showed significant correlation with COX-2 (R--0.552), LeY (R--0.861), CA724 (R--0.714) and GRN (R--0.664) (P < 0.0001). Additionally, the combination therapy led to impressive inhibition of gastric cancer cell proliferation, with decreased expression of COX-2, CA724 and GRN through downregulation of MAPKs/COX-2 pathway (P < 0.01).. Our findings suggest that anti-LeY antibody enhances the cancer cell proliferation inhibitory effects of celecoxib, which might be a new feasible way for gastric cancer therapy.

Topics: Adult; Aged; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Celecoxib; Cyclooxygenase 2; Down-Regulation; Drug Synergism; Helicobacter Infections; Helicobacter pylori; Humans; Lewis Blood Group Antigens; MAP Kinase Signaling System; Middle Aged; Pyrazoles; Signal Transduction; Stomach Neoplasms; Stomach Ulcer; Sulfonamides; Treatment Outcome; Tumor Cells, Cultured

There are no reports, to our knowledge, on the expression of Lewis (Le) antigens in Helicobacter pylori isolates from children. The aim of this study was to compare the expression of Le antigens by H. pylori isolates from children and from adults. Totals of 278 clones from 22 children with recurrent abdominal pain and 293 clones from 22 adults with (n=10) or without (n=12) duodenal ulcer were studied. Expression of Le(x) and Le(y) antigens was determined by ELISA, using monoclonal anti-Le antibodies. The Le phenotype of the patients was determined in gastric juice with a hemagglutination assay. Clones expressing Le(x) were more common in children than in adults (55.4% vs. 33.4%, respectively; P<.001), and Le(y) was more common in adults than in children (81.6% vs. 66%, respectively; P<.01). A trend analysis showed a significant decline in frequency of clones expressing Le(x) with age (P=.021). In this community, expression of Le antigens differs in H. pylori isolates obtained from children versus adults.

Topics: Abdominal Pain; Adolescent; Adult; Aged; Antigens, Bacterial; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; Gastric Juice; Helicobacter pylori; Humans; Lewis Blood Group Antigens; Lewis X Antigen; Male; Middle Aged; Stomach Ulcer

Helicobacter pylori infection induces autoantibodies that cross-react with human gastric mucosa from infected individuals. Candidates for the antigens responsible for molecular mimicry causing autoreactivity include the heat-shock protein HspB (Hsp60, sometimes called Hsp54) or Lewis x and Lewis y carbohydrate antigens.. Our goal was to investigate the involvement of HspB (Hsp60) in autoreactivity between H. pylori and gastric biopsy tissue.. Immunoelectron microscopy was used to study cross-reactivity among biopsy tissues from a patient with gastritis, gastric ulcer, and duodenal ulcer and his own serum as well as reactivity with serum raised against HspB from H. pylori and monoclonal antibodies against Lewis antigens.. The patient serum reacted with gastric mucosa, and the antibodies involved were predominantly IgG. Antibody raised to H. pylori HspB (Hsp60) reacted only with H. pylori cells but not with gastric mucosal tissue. In contrast, monoclonal antibodies specific for Lewis x and Lewis y antigens reacted with both H. pylori and human gastric epithelial tissue.. Hsp60 (Hsp54) is unlikely to be involved in autoreactivity seen in individuals infected with H. pylori. In contrast, we could not rule out the role of Lewis x and Lewis y carbohydrate antigens, expressed as a component of H. pylori lipopolysaccharides, in molecular mimicry and autoantibody production.

Topics: Adult; Antigens, Bacterial; Autoantibodies; Autoimmunity; Chaperonin 60; Cross Reactions; Duodenal Ulcer; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Lewis Blood Group Antigens; Lewis X Antigen; Male; Microscopy, Immunoelectron; Molecular Mimicry; Stomach Ulcer

Monoclonal antibodies were used in an enzyme-linked immunosorbent assay for the detection of human Lewis immunodeterminants in the lipopolysaccharide of Helicobacter pylori. In 94 H. pylori isolates, expression of Lewis(x) (Le(x)) and Le(y) was a stable phenotypic marker independent of the growth medium and cell age; 46 (49%) of the isolates expressed both and 34 (36%) of the isolates expressed either Le(x) or Le(y); 14 (15%) were negative for both determinants. Twelve (13%) isolates expressed Le(b), 3 (3%) expressed Le(a), and 2 (2%) expressed sialyl-Le(x). H. pylori isolates positive for both Le(x) and Le(y) were predominantly cagA+ (P < 0.001) and possessed the s1 signal sequence (P < 0.05) and the m1 midregion type (P = 0.033) of vacA. Isogenic mutants of H. pylori CPY3401 were created by interruption of the cagA, picB, or ureA gene. The cagA-ablated strain (but not the picB- and ureA-ablated mutant strains) had significantly (P < 0.01) diminished expression of Le(y) compared with that of the wild-type strain; for all four strains, expression of Le(x) was similar. In conclusion, 89% of H. pylori isolates express Le determinants in their lipopolysaccharide, mimicking human cell surface glycoconjugates. Strong expression of Le(x) and Le(y) by cagA+ isolates could counterbalance their enhanced proinflammatory activities and thereby facilitate persistence.

Topics: Antibodies, Monoclonal; Antigens, Bacterial; Bacterial Proteins; Carbohydrate Conformation; Carbohydrate Sequence; Culture Media; Enzyme-Linked Immunosorbent Assay; Helicobacter pylori; Humans; Lewis Blood Group Antigens; Lewis X Antigen; Lipopolysaccharides; Molecular Sequence Data; Mutation; Oligosaccharides; Phenotype; Sialyl Lewis X Antigen; Stomach Ulcer