Rivka Koren

Relationship between Helicobacter pylori CagA status and colorectal cancer

OBJECTIVES:Infection with Helicobacter pylori, particularly with strains positive for CagA protein, increases the risk of gastric adenocarcinoma. Few studies have explored the possible association between H. pylori infection and colorectal cancer. This study evaluated whether the seroprevalence of CagA in H. pylori-infected patients affected risk for colorectal cancer independently of H. pylori status.METHODS:In this study, we tested serum IgG antibodies against H. pylori (ELISA) and CagA protein (Western blot assay) in 67 patients with colorectal adenocarcinoma, 36 with gastric adenocarcinoma, 47 with other malignancies (cancer controls), and 45 hospitalized for transesophageal echocardiography (TEE controls). Colonic cancer and gastric cancer patients with H. pylori infection were compared to each control group and to the pooled controls using simple and adjusted analyses.RESULTS:H. pylori infection was noted in 50 colon cancer patients, 31 gastric cancer patients, 31 cancer controls, and 32 TEE controls. In all, 41 (82%), 29 (94%), 11 (35%), and 13 (41%), respectively, of these H. pylori-positive sera expressed CagA reactivity (p < 0.001 for all pairwise comparisons between cases and controls). In the adjusted analysis, infection with H. pylori CagA+ compared to H. pylori CagA− was associated with increased risk for colorectal adenocarcinoma (odds ratio = 10.6; 95% CI = 2.7–41.3; p = 0.001) and gastric adenocarcinoma (odds ratio = 88.1; 95% CI = 6.3–1229.2; p = 0.001).CONCLUSIONS:Among patients infected with H. pylori, CagA+ seropositivity is associated with increased risk for both gastric and colonic cancer. This finding should stimulate additional research into the role of cagA+ H. pylori infection in the development of colorectal cancer.

Does Helicobacter pylori affect gastric mucin expression? Relationship between gastric antral mucin expression and H. pylori colonization

BACKGROUND/OBJECTIVE: Helicobacter pylori colonizes the gastric mucous gel layer, the surface epithelium and glands. It has been shown that H. pylori infection causes aberrant expression of gastric mucins MUC 5 and MUC 6. This study aimed to determine the distribution of MUC 5 and MUC 6 in the gastric antrum of dyspeptic patients, and to investigate changes in this pattern in the presence of H. pylori and after successful eradication. MATERIALS AND METHODS: Gastric antrum biopsy specimens were examined by immunohistochemistry for mucin gene (MUC 5 and MUC 6) expression. Polyclonal antibodies were used to detect amino acid tandem repeats of each protein. A scoring system (0-3) was used to assess staining intensity at three sites: foveola, mucous neck cells and glands. H. pylori status was determined by histology and rapid urease test, and considered positive or negative when both tests were positive or negative, respectively. The study included 49 patients positive for H. pylori, in 36 of whom successful eradication was performed, and 11 H. pylori-negative patients. RESULTS: There was a gradient of MUC 5 expression, higher to lower, from the surface to the glands, which was more pronounced before eradication. Increased MUC 5 synthesis in the mucous neck cells and in the glands was found after H. pylori eradication (P = 0.016). MUC 6 was synthesized in the glands more than in the mucous neck cells or foveola. MUC 6 was also secreted into the lumen and probably comprised the superficial part of the unstirred mucous layer. CONCLUSION: The change in MUC 5 synthesis may reflect H. pylori colonization.

13C-urea breath test, referral patterns, and results in children.

Background The family is the core unit for Helicobacter pylori (Hp) infection. In most instances, Hp colonization occurs in early childhood, and correlates with socioeconomic parameters. Helicobacter pylori infection is highly prevalent in many countries, and may cause chronic gastritis and peptic ulcer in adults and in children. Gastritis induced by Hp may be associated with recurrent abdominal pain in children, and eradication of the bacterium may improve the clinical symptoms. Aim The primary aim of this study is to characterize the group of pediatric patients according to the referral patterns and results of 13C-urea breath test (13C -UBT) in our laboratory. The secondary aim is to investigate the result of different treatment combinations for Hp eradication. Methods The 13C-UBT was performed with 75 mg urea labeled with 13C in 200 mL orange juice. Breath samples were collected at 0 and 30 minutes, and the results expressed as the change in the 13C/12C ratio at T30´ minus T0´ The cutoff for Hp eradication was 3.5. The physicians who ordered the test completed a questionnaire covering demographic data (age, gender, and origin), indication for the test was use of a proton pump inhibitor (PPI), and type of combination eradication therapy. Results The study sample consisted of 1655 children, aged 1 to 18 years, 992 (59.9%) boys and 663 (40.1%) girls, from all parts of the country. The 13C-UBT was positive in 763 (46.1%). The prevalence of positive results was directly correlated with age. History of peptic disease was the main indication for the test, in 1346 (81.4%) cases. Details on eradication therapy were available for 435 children of whom 42.5% had a positive 13C-UBT, indicating a successful eradication rate of 57.5%. Compared with Israeli and American–European origin, children of Asian–African origin had a higher rate of referrals for reason of validation of successful Hp eradication, greater long-term PPI use, and a higher rate of 13C-UBT positivity. No significant difference was demonstrated between the triple therapy regimens used. Conclusion 13C-UBT may be performed in children of all age groups. The main indication is a history of peptic ulcer disease. The prevalence of Hp infection increased with age and the only factor associated with increased Hp infection was Asian–African origin. The most frequent eradication therapy used in childdren is a combination of omeprazole, amoxicillin, and clarithromycin.

Gastric corpus mucin expression after partial gastrectomy, in relation to colonization with Helicobacter pylori.

Twelve different genes for mucin have been described. MUC5AC and MUC6 encode the secreted apomucins of the stomach. A gradient from the surface epithelium (foveola) to the glands is typical for MUC5AC synthesis, whereas a gradient in the opposite direction was found for MUC6. Our goal was to determine the distribution of MUC5AC and MUC6 in the postoperative stomach, with relation to the H. pylori status. Gastric corpus biopsy specimens from patients who underwent partial gastrectomy were examined by immunohistochemistry for mucin gene (MUC5AC and MUC6) apoproteins. We used polyclonal antibodies for amino acid tandem repeats of both proteins. A scoring system (0-3) was used to assess staining intensity at four sites: the lumen, the foveola, the mucous neck cells, and the glands. Helicobacter pylori status was determined by histology and rapid urease test and was considered positive or negative when both tests were positive or negative, respectively. We studied 19 H. pylori-positive and 32 H. pylori-negative patients. No significant change in MUC5AC or MUC6 synthesis and secretion was demonstrated between H. pylori-positive or -negative patients. A gradient similar to that shown for the intact stomach (from the surface epithelium to the glands) for MUC5AC protein and an increase of MUC6 protein presentation from the mucous neck cell to the glands were demonstrated. The pattern of MUC5AC protein synthesis was not different between H. pylori-positive and -negative patients in the postoperative stomach. MUC6 expression was higher in the foveola in H. pylori-positive patients, whereas there was no difference in the other cell layers.

Association between Gastric Acid and Mucin Secretion in Dyspeptic Patients

Background and Aims: The maintenance of an intact gastric mucosa implies a balance between aggressive, such as acid, and protective factors such as mucin. We examined gastric aspirates to determine a possible correlation between gastric acid and mucin contents. Methods: Gastric contents were aspirated at gastroscopy in 14 patients. Acid content was evaluated by titration, and mucin content by gel filtration. In 4 other patients these measurements were also performed for 1-hour basal gastric secretion, and after pentagastrin stimulation. Western blot and dot blot for mucin protein were performed with polyclonal antibodies to the protein of MUC 5AC and MUC 6. Results: A positive correlation was demonstrated between acid and mucin content in 14 patients, r = 0.77. In 4 other patients mucin secretion, after pentagastrin injection, increased by 3–46 fold in comparison with basal secretion. A positive correlation was demonstrated between basal acid and mucin secretion, and stimulated acid and mucin secretion. In dot blot experiments, MUC 5AC had a significant higher dot blot intensity than MUC 6. Conclusions: There is a correlation between acid and mucin secretion rates. Secretagogue that causes acid secretion may also cause secretion of protective mucin.

Modulation of Mucin Synthesis by γ-Interferon in Human Colon Adenocarcinoma Cells

Objectives: Recombinant human interferon has been shown to enhance the expression of histocompatibility antigens and certain tumor-associated antigens in a variety of carcinoma cell lines. Since many tumor-associated antigens are mucins, we investigated the effect of recombinant human γ-interferon on mucin production and secretion by colon cancer cell lines. Methods: Control and γ-interferon-treated cells were labeled with [3H]glucosamine in DMEM-H16 medium with 5% FCS for 24 h. Analysis was performed by gel filtration on Sepharose CL-4B columns, and the high-molecular-weight glycoprotein eluted at the void volume from the cytosol and medium was counted (expressed as dpm/4 × 106 cells). In another experiment the void volume was compared to concentration curves of standard mucins (expressed as mg/107 cells). Results: γ-Interferon increased mucin synthesis in HT-29 and LIM-6 cells, but not in LS174T and CACO2 cells. In HT-29 and LIM-6 cells, mucin synthesis was induced by γ-interferon in a dose-dependent manner. The percentage of mucin secreted into the medium was also increased. Conclusion: The heterogeneity of response of human colon cancer cell lines to γ-interferon by mucin production may limit the specific role of γ-interferon as a modulator of mucin-type tumor-associated antigens.

Gastric corpus mucin expression after partial gastrectomy, in relation to colonization with Helicobacter pylori

Twelve different genes for mucin have been described. MUC5AC and MUC6 encode the secreted apomucins of the stomach. A gradient from the surface epithelium (foveola) to the glands is typical for MUC5AC synthesis, whereas a gradient in the opposite direction was found for MUC6. Our goal was to determine the distribution of MUC5AC and MUC6 in the postoperative stomach, with relation to the H. pylori status. Gastric corpus biopsy specimens from patients who underwent partial gastrectomy were examined by immunohistochemistry for mucin gene (MUC5AC and MUC6) apoproteins. We used polyclonal antibodies for amino acid tandem repeats of both proteins. A scoring system (0–3) was used to assess staining intensity at four sites: the lumen, the foveola, the mucous neck cells, and the glands. Helicobacter pylori status was determined by histology and rapid urease test and was considered positive or negative when both tests were positive or negative, respectively. We studied 19 H. pylori-positive and 32 H. pylori-negative patients. No significant change in MUC5AC or MUC6 synthesis and secretion was demonstrated between H. pylori-positive or -negative patients. A gradient similar to that shown for the intact stomach (from the surface epithelium to the glands) for MUC5AC protein and an increase of MUC6 protein presentation from the mucous neck cell to the glands were demonstrated. The pattern of MUC5AC protein synthesis was not different between H. pylori-positive and -negative patients in the postoperative stomach. MUC6 expression was higher in the foveola in H. pylori-positive patients, whereas there was no difference in the other cell layers.

Does Helicobacter pylori effect gastric mucin expression? relationship between gastric mucin expression and H. pylori colonization

Background/objective Helicobacter pylori colonizes the gastric mucous gel layer, the surface epithelium and glands. It has been shown that H. pylori infection causes aberrant expression of gastric mucins MUC 5 and MUC 6. This study aimed to determine the distribution of MUC 5 and MUC 6 in the gastric antrum of dyspeptic patients, and to investigate changes in this pattern in the presence of H. pylori and after successful eradication. Materials and methods Gastric antrum biopsy specimens were examined by immunohistochemistry for mucin gene (MUC 5 and MUC 6) expression. Polyclonal antibodies were used to detect amino acid tandem repeats of each protein. A scoring system (0–3) was used to assess staining intensity at three sites: foveola, mucous neck cells and glands. H. pylori status was determined by histology and rapid urease test, and considered positive or negative when both tests were positive or negative, respectively. The study included 49 patients positive for H. pylori, in 36 of whom successful eradication was performed, and 11 H. pylori-negative patients. Results There was a gradient of MUC 5 expression, higher to lower, from the surface to the glands, which was more pronounced before eradication. Increased MUC 5 synthesis in the mucous neck cells and in the glands was found after H. pylori eradication (P = 0.016). MUC 6 was synthesized in the glands more than in the mucous neck cells or foveola. MUC 6 was also secreted into the lumen and probably comprised the superficial part of the unstirred mucous layer. Conclusion The change in MUC 5 synthesis may reflect H. pylori colonization.