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Gene Expression of Ornithine Decarboxylase, Cyclooxygenase-2, and Gastrin in Atrophic Gastric Mucosa Infected with Helicobacter pylori Before and After Eradication Therapy

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Abstract

H. pylori (Hp) -induced atrophic gastritis is a well-known risk factor for the development of gastric cancer. Whether Hp eradication can prevent or retard the progress of atrophy and metaplasia has been the topic of numerous studies but the subject remains controversial. Recently, the increased expression of ornithine decarboxylase (ODC), gastrin and cyclooxygenase (COX)-2 has been shown to be increased in premalignant lesions in gastric mucosa and to play an essential role in the malignant transformation. The aim of the study is to assess the effect of eradication therapy on atrophic gastritis and analyze the gene expression for ODC, COX-2 and gastrin in gastric mucosa after succesful eradication in patients with atrophic gastritis. Twenty patients with chronic atrophic gastritis including both corpus and antrum of the stomach were included in this study. Four antral mucosal biopsy specimens were obtained from antrum and four from corpus. The histopathologic evaluation of gastritis was based on Sydney classification of gastritis. All patients were Hp positive based on the [13C] urea breath test (UBT) and the presence of anti-Hp IgG and anti-CagA-antibodies detected by ELISA. The patients were then eradicated with triple therapy consiting of omeprazol (2 × 20 mg), amoxycillin (2 × 1 g) and clarithromycin (2 × 500 mg) for seven days and vitamin C 1 g/day for three months. In gastric mucosal samples obtained from the antrum and corpus before and after eradication, the mRNA expression for ODC, COX-2, and gastrin was assessed by reverse-transcription polymerase chain reaction (RT-PCR). In all patients the gastric secretory analysis was performed by measuring gastric acid output and serum gastrin levels. After triple therapy the successful eradication assessed by UBT was observed in 95% of patients. In 45% of patients the infection with CagA-positive Hp strain was observed. Three months after eradication a significant reduction in the gastric activity (neutrophilic infiltrate) and severity (mononuclear infiltrate) of gastritis was observed. The atrophy score improved in both antrum and corpus after eradication. The expression of COX-2 and ODC was significantly up-regulated in the gastric mucosa of patients with atrophic gastritis and significantly reduced after eradication therapy. In all successfully eradicated patients with atrophic gastritis a significant increase in gastric acid secretion and decrease in serum gastrin were observed. We conclude that: (1) Hp eradication leads to the decrease in ODC and COX-2 gene expression in the gastric mucosa, and this may be relevant for the prevention of the Hp-associated gastric carcinogenesis. (2) gastric atrophy ameliorates upon successful Hp eradication therapy.

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REFERENCES

  1. Marshall BJ, Warren JR: Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1:1311-1315, 1984

    Google Scholar 

  2. Peterson WL: Helicobacter pylori and peptic ulcer disease. N Engl J Med 324:1043-1048, 1991

    Google Scholar 

  3. Huang JQ, Sridhar S, Chen Y, Hunt RH: Meta-analysis of the relationship between Helicobacter pylori seropositivity and gastric cancer. Gastroneterology 114:1169-1179, 1999

    Google Scholar 

  4. Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, Taniyama K, Sasaki N, Schlemper RJ: Helicobacter pylori and the development of gastric cancer. N Engl J Med 345:784-789, 2001

    Google Scholar 

  5. Stolte M: H. pylori and gastric MALT lymphoma. Lancet 339:745-746, 1992

    Google Scholar 

  6. Correa P: Human gastric carcinogenesis: a multistep and multifactorial process-First American Society Award Lecture on Cancer Epidemiology and Prevention. Cancer Res 52:6735-6740, 1992

    Google Scholar 

  7. Kuipers EJ, Grool TA: The dynamics of gastritis. Curr Gastroenterol Rep 3:509-515, 2001

    Google Scholar 

  8. Heby O: Role of polyamines in the control of cell proliferation and differentiation. Differentiation 9:1-20, 1981

    Google Scholar 

  9. Patchett SE, Alstead EM, Butruk L, Przytulski K, Farthing MJ: Ornithine decarboxylase as a marker for premalignancy in the stomach. Gut 37:13-16, 1995

    Google Scholar 

  10. Patchett SE, Katelaris PH, Zhang ZW, Alstead EM, Domizio P, Farthing MJ: Ornithine decarboxylase activity is a marker of premalignany in longstanding Helicobactr pylori infection. Gut 39:807-810, 1996

    Google Scholar 

  11. Hirasawa R, Tatsuta M, Iishi H, Yano H, Baba M, Uedo N, Sakai N: Increase in apoptosis and decrease in ornithine decarboxylase activity of the gastric mucosa in patients with atrophic gastritis and gastric ulcer after successful eradication of Helicobacter pylori. Am J Gastroenterol 94:2398-2402, 1999

    Google Scholar 

  12. Wang TC, Daugler CA, Chen D, Goldenring JR, Koh T, Raychowdhurry R, Coffey RJ, Ito S, Varro A, Dockray GJ, Fox JG: Synergistic interaction between hypergastrinemia and Helicobacter infection in mouse model of gastric cancer. Gastroenterology 118:36-41, 2000

    Google Scholar 

  13. Van Rees BP, Ristimäki BP: Cyclooxygenase-2 in carcinogenesis of the gastrointestinal tract. Scand J Gastroenterol 9:897-901, 2001

    Google Scholar 

  14. Sung JJ, Leung WK, Go MY, To KF, Cheng AS, Ng EK, Chan FK: Cyclooxygenase-2 expression in Helicobacter pylori-associated premalignant and malignant gastric lesions. Am J Pathol 157:729-735, 2000

    Google Scholar 

  15. Dixon MF, Genta RM, Yardley JH: Classification and grading of gastritis. The Updated Sydney System. Am J Surg Pathol 20:1161-1181, 1996

    Google Scholar 

  16. Konturek PC, Konturek SJ, Sulekova Z, Meixner H, Bielanski W, Starzynska T, Karczewska E, Marlicz K, Stachura J, Hahn EG: Expression of hepatocyte growth factor, transforming growth factor alpha, apoptosis related proteins Bax and Bcl-2, and gastrin in human gastric cancer. Aliment Pharmacol Ther 15:989-999, 2001

    Google Scholar 

  17. Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156-159, 1987

    Google Scholar 

  18. Konturek JW, Gutwinska-Konturek M, Gabrylewicz A, Konturek SJ, Domschke W: Cholecystokinin in the control of gastric acid secretion in humans. J Clin Gastroenterol 19 (suppl 1):S40-S45, 1993

    Google Scholar 

  19. Konturek PC, Bielanski W, Konturek SJ, Hartwich A, Rehfeld JF: Progastrin and cyclooxygenases-2 in colorectal cancer. Dig Dis Sci (in press)

  20. Bielanski W, Konturek SJ: New approach to 13C-urea breath test; capsule-based modification of low dose 13C-urea in the diadnosis of Helicobacter pylori infection. J Physiol Pharmacol 47:545-553, 1996

    Google Scholar 

  21. Konturek JW, BielanskiW, Konturek SJ: Eradication of Helicobacter pylori and gastrin-somatostatin link in duodenal ulcer patients. J Physiol Pharmacol 47:161-176, 1996

    Google Scholar 

  22. Sung JJ, Lin SR, Ching JY, Zhou LY, To KF, Wang RT, Leung WK, Ng EK, Lau JY, Lee YT, Yeung CK, Chao W, Chung SC: Atrophy and intestinal metaplasia one year after cure of H. pylori infection: a prospective, randomized study. Gastroneterology 119:7-14, 2000

    Google Scholar 

  23. Ohkusa T, Fujiki K, Takashimizu I, Kumagai J, Tanizawa T, Eishi Y, Yokoyama T, Watanabe M: Improvement in atrophic gastritis and intestinal metaplasia in patients in whom Helicobacter pylori was eradicated. Ann Intern Med 134:380-386, 2001

    Google Scholar 

  24. Annibale B, Aprile MR, D'ambra G, Caruna P, Bordi C, Delle Fave G: Cure of H. pylori infection in atrophic body gastritis patients does not improve mucosal atrophy but reduces hypergastrinemia and its related effects on body ECL-cell hyperplasia. Aliment Pharmacol Ther 14:625-634, 2000

    Google Scholar 

  25. Satoh K, Kimura K, Takimoto T, Kihira K: A follow-up study of atrophic gastritis and intestinal metaplasia after eradication of Helicobacter pylori. Helicobacter 3:236-240, 1998

    Google Scholar 

  26. Auvinen M, Paasinen A, Anderson LC, Höltta E: Ornithine decarboxylase activity is critical for cell transformation. Nature 360:355-358, 1992

    Google Scholar 

  27. Alam K, Arlow FL, Ma CK, Schubert TT: Decrease in ornithine decarboxylase activity after eradication of Helicobacter pylori. Am J Gastroenterol 89:888-893, 1994

    Google Scholar 

  28. Russo F, Linsalata M, Giorgio I, Caruso ML, Armentano R, Di Leo A: Polyamine levels and ODC activity in intestinal-type and diffusetype gastric carcinoma. Dig Dis Sci 42:576-579, 1997

    Google Scholar 

  29. Parsonnet J, Vandersteen D, Goates J, Sibley RK, Pritikin J, Chang Y: Helicobacter pylori in intestinal-and diffuse-type gastric adenocarcinoma. J Natl Cancer Inst 83:640-643, 2002

    Google Scholar 

  30. Humar B, D'Orazio D, Albrecht C, Bauerfeind P, Muller H, Dobbie Z, Bendik I: Expression of putative anticancer targets in familial adenomatous polyposis and its association with the APC mutation status. Int J Oncol 19:1179-1186, 2001

    Google Scholar 

  31. Ristimäki A, Honkanen N, Jänkälä H, Sipponen P, Härkönen M: Expression of cyclooxygenase-2 in human gastric carcinoma. Cancer Res 57:1276-1280, 2002

    Google Scholar 

  32. Tsuji S, Tsujii M, Kawano S, Hori M: Cyclooxygenase-2 upregulation as a perigenetic change in carcinogenesis. J Exp Clin Cancer Res 20:117-129, 2001

    Google Scholar 

  33. Takahashi S, Fujita T, Yamamoto A: Role of cyclooxygenase-2 in Helicobacter pylori-induced gastritis in Mongolian gerbils. Am J Gastrointest Liver Physiol 279:G791-G798, 2000

    Google Scholar 

  34. McColl KE, El-Omar E, Gillen D: Helicobacter pylori gastritis and gastric physiology. Gastroenterol Clin North Am 29:687-703, 2000

    Google Scholar 

  35. El-Omar EM: The importance of interleukin 1β in Helicobacter pylori associated disease. Gut 48:743-747, 2001

    Google Scholar 

  36. Bukin YV, Draudin-Krylenko VA, Orlov EN, Kuvshinov YP, Paddubny BK, Vorobyeva OV, Shabanov MA. Effect of prolong beta-carotene or DL-alpha-tocopheryl acetate supplementation on ornithine decarboxylase activity in human atrophic stomach mucosa. Cancer Epidemiol Biomarkers Prev 8:865-870, 1995.

    Google Scholar 

  37. Konturek SJ, Konturek PC, Plonka M, Duda A, Sito E, Zuchowicz M, Hahn EG: Implication of gastrin in cyclooxygenase expression in Helicobacter pylori-infected gastric ulceration. Prostaglandins Other Lipid Mediators 66:39-51, 2001

    Google Scholar 

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Authors and Affiliations

  1. Department of Medicine I, University Erlangen-Nuremberg, Erlangen, Germany

    Peter C. Konturek, K. Galuschka & Eckhart G. Hahn

  2. Jagellonian College of Medicine, Krakow, Poland

    Kazimierz Rembiasz & Danuta Karcz

  3. Institute of Pathology, Krakow, Poland

    Stanislaw J. Konturek & Jerzy Stachura

  4. and Department of Surgery, Institute of Physiology, Krakow, Poland

    Wladyslaw Bielanski

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  1. Peter C. Konturek
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  3. Stanislaw J. Konturek
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  6. K. Galuschka
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Konturek, P.C., Rembiasz, K., Konturek, S.J. et al. Gene Expression of Ornithine Decarboxylase, Cyclooxygenase-2, and Gastrin in Atrophic Gastric Mucosa Infected with Helicobacter pylori Before and After Eradication Therapy. Dig Dis Sci 48, 36–46 (2003). https://doi.org/10.1023/A:1021774029089

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