Cell regulation, differentiation and their sequelae in the Helicobacter pylori inflamed and eradicated stomach
The issues of cell regulation and turnover in the stomach are of critical importance as they impact directly on the important lesions of erosions, ulcers and cancer, the major complications of H. pylori disease. In uncomplicated H. pylori-associated gastritis and duodenitis an erosion or ulcer results from the inability of the epithelial dynamics adequately to maintain or repair the epithelium at an adequate rate. Further, a persistent long-term increase in epithelial turnover in many organs may predispose to neoplastic sequelae, and in this regard the stomach is no exception. The theory is that increased cell turnover results from increased mitotic activity, and this in turn provides greater opportunities for the production of abnormal cells from which clones may arise, and from which neoplasms may ultimately develop. Further, it is increasingly apparent that while regular cell turnover is associated with a 3–5-day turnover at the surface, and a turnover time measured in months in the pits, that there is a second method of cell degeneration that must be taken into account in epithelial dynamics, which is that of cell apoptosis. Further, the relationships between cell turnover, the inflammatory response and H. pylori itself need to be separated as far as possible. Because H. pylori infection in humans is always associated with at least some degree of chronic inflammatory infiltrate, some of these data necessarily come from animal sources.
KeywordsGastric Cancer Pylorus Infection Intestinal Metaplasia Atrophic Gastritis Oxyntic Mucosa
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Huang LL, Cave DR, Gilbert JV, Wright A. Cloning and sequencing of the gene encoding an acid inhibitory protein in Helicobacter pylori
. Gastroenterology. 1996;110:A927.Google Scholar
Kuipers EJ, Uyterlinde AM, Peña AS et al.
Long-term sequelae of Helicobacter pylori
gastritis. Lancet. 1995;345:1525–8.PubMedCrossRefGoogle Scholar
Klinkenberg-Knol EC, Festen HPM, Jansen JBMJ et al.
Long-term treatment with omeprazole for refractory reflux esophagitis: efficacy and safety. Ann Intern Med. 1994;121:161–7.PubMedGoogle Scholar
Havard TJ, Sarsfield P, Wotherspoon AC, Steer HW. Increased gastric epithelial cell proliferation in Helicobacter pylori
associated follicular gastritis. J Clin Pathol. 1996;49:68–71.PubMedCrossRefGoogle Scholar
Ladas SD, Katsogridakis J, Malamou H, Giannopoulou H, Kesse-Elia M, Raptis SA. Helicobacter pylori
may induce bile reflux: link between H. pylori
and bile induced injury to gastric epithelium. Gut. 1996;38:15–18.PubMedCrossRefGoogle Scholar
Fan XG, Kelleher D, Fan XJ, Xia HX, Keeling PWN. Helicobacter pylori
increases proliferation of gastric epithelial cells. Gut. 1996;38:19–22.PubMedCrossRefGoogle Scholar
Cahill RJ, Xia H, Kilgallen C, Beattie S, Hamilton H, O’Morain C. Effect of eradication of Helicobacter pylori
infection on gastric epithelial cell proliferation. Dig Dis Sci. 1995;40: 1627–31.PubMedCrossRefGoogle Scholar
Cahill RJ, Kilgallen C, Beattie S, Hamilton H, O’Morain C. Gastric epithelial cell kinetics in the progression from normal mucosa to gastric carcinoma. Gut. 1996;38:177–81.PubMedCrossRefGoogle Scholar
Lynch DA, Axon AT. Helicobacter pylori
, gastric cancer and gastric epithelial kinetics. Eur J Gastroenterol Hepatol. 1995;7(Suppl. 1):S17–23.PubMedGoogle Scholar
Fraser AG, Sim R, Sankey EA, Dhillon AP, Pounder RE. Effect of eradication of Helicobacter pylori
in gastric epithelial cell proliferation. Aliment Pharmacol Ther. 1994;8:167–73.PubMedCrossRefGoogle Scholar
Brenes F, Ruiz B, Correa P et al. Helicobacter pylori
causes hyperproliferation of the gastric epithelium: pre and post eradication indices of proliferating cell nuclear antigen. Am J Gastroenterol. 1993;88:1870–5.PubMedGoogle Scholar
Solcia E, Villani L, Luinetti O, Fiocca R. Proton-pump inhibitors, enterochromaffin-like cell growth, and Helicobacter pylori
gastritis. Aliment Pharmacol Ther. 1993;7(Suppl. 1):29–31.Google Scholar
Taniguchi Y, Ido K, Kimura K et al.
Morphological aspects of the cytotoxic action of Helicobacter pylori
. Eur J Gastroenterol Hepatol. 1994;6(Suppl. 1):S17–21.PubMedGoogle Scholar
Chang K, Fujiwara Y, Wyle F, Tarnawski A. Helicobacter pylori
toxin inhibits growth and proliferation of cultured gastric cancer cells-Kato II. J Physiol Pharmacol. 1993;44:17–22.PubMedGoogle Scholar
Matsui T, Matsukawa Y, Sakai T, Nakamura K, Aoike A, Kawai K. Effect of ammonia on cell cycle progression of human gastric cancer cells. Eur J Gastroenterol Hepatol. 1995;7(Suppl. 1): S79–81.PubMedGoogle Scholar
Crabtree JE, Farmery SM. Helicobacter pylori
and gastric mucosal cytokines: evidence that CagA-positive strains are more virulent. Lab Invest. 1995;73:742–5.PubMedGoogle Scholar
Peek RM Jr, Miller GG, Tham KT et al.
Heightened inflammatory response and cytokine expression in vivo
to cagA+ Helicobacter pylori
strains. Lab Invest. 1995;73:760–70.PubMedGoogle Scholar
Husson MO, Gottrand F, Vachee A et al.
Importance in diagnosis of gastritis of detection by PCR of the cagA
gene in Helicobacter pylori
strains isolated from children. J Clin Microbiol. 1995;33: 3300–3.PubMedGoogle Scholar
Kuipers EJ, Pérez-Pérez GI, Meuwissen SGM, Blaser MJ. Helicobacter pylori
and atrophic gastritis: importance of the cagA status. J Natl Cancer Inst. 1995;87:1777–80.PubMedCrossRefGoogle Scholar
Weel JFL, Van der Hulst RWM, Gerrits Y et al.
The interrelationship between cytotoxin-associated gene A, vacuolating cytotoxin, and Helicobacter pylori-related
diseases. J Infect Dis. 1996; 173: 1171–5.PubMedCrossRefGoogle Scholar
Ching CK, Wong BCY, Kwok E, Ong L, Covacci A, Lam SK. Prevalence of CagA-bearing Helicobacter pylori
strains detected by the anti-CagA assay in patients with peptic ulcer disease and in controls. Am J Gastroenterol. 1996;91:949–53.PubMedGoogle Scholar
Tee W, Lambert JR, Dwyer B. Cytotoxin production by Helicobacter pylori
from patients with upper gastrointestinal tract disease. J Clin Microbiol. 1995;33:1203–5.PubMedGoogle Scholar
Murakita H, Hirai M, Ito S, Azuma T, Kato T, Kohli Y. Vacuolating cytotoxin production by Helicobacter pylori
isolates from peptic ulcer, atrophic gastritis and gastric carcinoma. Eur J Gastroenterol Hepatol. 1994;6(Suppl. 1):S29–31.PubMedGoogle Scholar
Sipponen P, Kimura K. Intestinal metaplasia, atrophie gastritis and stomach cancer: trends over time. Eur J Gastroenterol Hepatol. 1994;6(Suppl. 1):S79–83.PubMedGoogle Scholar
Sharp R, Babyatski R, Takagi H et al.
Transforming growth factor alpha disrupts the normal program of cellular differentiation in the gastric mucosa of transgenic mice. Development. 1995; 121:149–61.PubMedGoogle Scholar
Tsujii M, Kawano S, Tsuji S et al.
Cell kinetics of mucosal atrophy in rat stomach induced by long-term administration of ammonia. Gastroenterology. 1993;104:796–801.PubMedGoogle Scholar
Li H, Heiander HF. Hypergastrinemia increases proliferation of gastroduodenal epithelium during gastric ulcer healing in rats. Dig Dis Sci. 1996;41:40–8.PubMedCrossRefGoogle Scholar
Jones NL, Yeger H, Cutz E, Sherman PM. Helicobacter pylori
induces apoptosis of gastric antral epithelial cells in vivo
. Gastroenterology. 1996; 110:A933.Google Scholar
Zhu GH, Ching CK, Lam SK, Sheng JZ, Wong TM, Ding SZ. Sialic acid dependent H. pylori
lectin as an activator of calcium signal in cultured epithelial cells. Gastroenterology. 1996;110:A307.Google Scholar
Fukuda T, Arakawa Y, Fujiwara Y et al.
Nitric oxide induces apoptosis in gastric mucosal cells. Gastroenterology. 1996; 110: A111.Google Scholar
Naito Y, Yoshikawa T, Yagi N et al.
Cell growth inhibition and apoptosis induced by monochloramine in a gastric mucosal cell line. Gastroenterology. 1996; 110:A205.Google Scholar
Kato K, Sasano H, Ohara S et al.
DNA damages caused by ammonia administration in rat stomach. Gastroenterology. 1996; 110: A150.Google Scholar
Higashide S, Gomez G, Rajaraman S, Thompson JC, Townsend CM Jr. The effects of gastrin and bombesin on apoptosis induced by fasting in the rat stomach. Gastroenterology. 1996; 110:A529.CrossRefGoogle Scholar
Saegusa M, Takano Y, Okayasu I. Bcl-2 expression and its association with cell kinetics in human gastric carcinoma and intestinal metaplasia. J Cancer Res Clin Oncol. 1995;121:357–63.PubMedCrossRefGoogle Scholar
Lauwers GY, Scott GV, Hendricks J. Immunohistochemical evidence of aberrant bcl-2 expression in gastric epithelial dysplasia. Cancer. 1994;73:2900–4.PubMedCrossRefGoogle Scholar
Okuyama S, Yokota K, Yuki M. Cell proliferation and cell death (apoptosis) in epithelial tumors of the stomach — analysis of tumor tissues by the endoscopie mucosal resection. Jpn J Gastroenterol. 1995;92:130–9.Google Scholar
Uemura M, Mukai T, Okamoto S et al. Helicobacter pylori
eradication inhibits the growth of intestinal type of gastric cancer in initial stage. Gastroenterology. 1996;110:A282.Google Scholar
O’Connor E, Buckley M, O’Morain C. Intestinal metaplasia and the gastric cancer cascade. Gastroenterology. 1996; 110: A214.Google Scholar
Khulusi S, Mendall MA, Badve S, Finlayson C, Northfield TC. Effect of Helicobacter pylori
eradication on gastric metaplasia in the duodenum. Gut. 1995;36:193–7.PubMedCrossRefGoogle Scholar
Hansson LE, Engstrand L, Nyrén O, Lindgren A. Prevalence of Helicobacter pylori
infection in subtypes of gastric cancer. Gastroenterology. 1995;109:885–8.PubMedCrossRefGoogle Scholar
Huang JQ, Sridhar S, Chen Y, Wilkinson J, Hunt RH. Do younger patients with Helicobacter pylori
have a higher risk of gastric cancer? A meta-analysis between Hp
seropositivity and gastric cancer. Gastroenterology. 1996;110:A532.Google Scholar
© Kluwer Academic Publishers and Axcan Pharma 1996