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Mechanism for gastric carcinogenesis by H.pylori infection

Research Project

Project/Area Number 09470136
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

CHIBA Tsutomu  Kyoto Univ.Dep.Med.Professor, 医学研究科, 教授 (30188487)

Co-Investigator(Kenkyū-buntansha) OKAZAKI Kazuichi  Kyoto Univ.Dep.Med.Associate Professor, 医学研究科, 助教授 (70145126)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥13,800,000 (Direct Cost: ¥13,800,000)
Fiscal Year 1998: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1997: ¥10,900,000 (Direct Cost: ¥10,900,000)
KeywordsH.pylori / Gastric adenoma / MALT lymphoma / ECL carcinoid / 胃MALTリンパ腫 / 胃癌 / 腸上皮化生 / パイエル板
Research Abstract

We examined mechanisms for development of various neoplastic lesions by H.pylori infection in neonatal thymectomized BALB/c mice. Thymectomy was performed 3 days after birth, and H.pylori was infected orally at 2 months after thymectomy, and following results were obtained :
1. When we infected H.pylori to BALB/c mice, persistent infection did not occur so often, and moreover, we hardly observed mucosal inflammation of the stomach.
2. In contrast, when H.pylori was infected to BALB/c mice thymectomized 3 days after birth, persistent infection developed in all the mice, which was associated with prominent inflammation of the gastric mucosa.
3. In these mice, intestinal metaplasia developed in the antral mucosa at 3 months after the infection.
4.In these thymectomized mice, 10% of them developed gastric adenoma at 6 months after the infection. However, gastric cancer could not be observed even 1 year after the infection.
5. In these thymectomized mice, development of lympho-follicles was obse … More rved 2 months after the infection, and moreover, 70% of them developed gastric MALT lymphoma.
6. In these mice, gastric carcinoid formation was observed at 1 year after the infection in about 30% of all the animals. Serum gastrin concentrations of these mice was 1450 * 96 pg/ml, whchi was significantly higher than that of non-infected mice (116 * 10 pg/ml) and that of the infected mice without carcinoid formation (765 * 56 pg/ ml) (P < 0.01). Moreover, in the infected mice who were treated with a specific gastrin receptor antagonist, AG041R, no carcinoid formation was observed.
7. Gastric MALT lymphoma, gastric adenoma, and gastric carcinoid did not develop concomittantly. Rank orders of the number of H.pylori and serum gastrin level was carcinoid > adenoma > MALT lymphoma, whereas that of gastric acid secretion was MALT lymphoma > adenoma > carcinoid.
8. Host factors such as capacity of acid secretion and hormone secretion, and immunological responses may be important for deciding the occurence of various disease phenotypes. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (65 results)

All Other

All Publications (65 results)

  • [Publications] Chiba T, et al.: "Distribution of prostaglandin E receptors in the rat gastrointestinal tract" Prostaglandins. 53. 199-216 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chiba T, et al.: "Regenerating gene expression in normal gastric mucosa and indomethacin-induced mucosal lesions of the rats." J.Gastroenterology. 32. 12-18 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chiba T, et al.: "Pepsinogen C gene product is a possible growth factor during gastric mucosal healing" Biochem.Biophys.Res.Commun.238. 17-20 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chiba T, et al.: "Cellular localization of mRNAs for the subtypes of prostaglandin E receptor in the mouse gastrointestinal tract" AM.J.Physiol.272. G681-G687 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chiba T, et al.: "Production and activation of hepatocyte growth factor during the healing of rat gastric ulcer" Digestion. 58. 225-231 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chiba T, et al.: "Helicobacter pylori induces proinflammatory cytokines and major histocompatibility complex." J.Lab.Clin.Med.130. 442-449 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chiba T, et al.: "Downregulation of gastric mucin gene expression and its biosynthesis by dexamethasone in the juman" J.Clin.Gastroenterol.27. S91-S96 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chiba T, et al.: "Comparison of the signal transduction pahtways acivated by gastrin in ECL and parietal cells" Gastroenterology. 115. 93-100 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chiba T, et al.: "Reg protein may mediate gastric mucosal proliferation induced by hypergastrinemia in rats" Gastroenterology. 115. 1483-1493 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chiba T, et al.: "Reciprocal changes in progression of gastric MALT lymphoma and pancreatic somatostatinoma" Am.J.Med.105. 539-541 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chiba T, et al.: "Midkine gene expression in the healing process of gastric ulcer" Lab.Clin.Med.in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chiba T, et al.: "Enterochromaffin-like cells, a cellular source of uroguanylin in rat stomach" Endocrinology. in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chiba T, et al.: "Intragastric distribution of NSAID-related ulcers _Study on subjects without collagen disease-" J.Clin.Gastroenterol.25. 592-594 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chiba T, et al.: "Helicobacter pylori-independent chronological change of gastric acid secretion in japanese." Gut. 41. 452-458 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chiba T, et al.: "Expression of protooncogene c-kit and its ligand stem cell factor in gastric carcinoma cell lines" Dig.Dis.Sci.43. 8-14 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chiba T, et al.: "Rat gastric mucosa cells express ICAM-a and proinflammatory cytokines during indomethacin induced gastric lesions" J.Lab.Clin.Med.131. 538-547 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chiba T, et al.: "Increased hepatocyte growth factor content in rat stomach during omeprazole treatment" Digestion. 59. 102-109 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chiba T, et al.: "Gastric MALToma with M proteins in serum and gastric juice" Gastroenterology. 114. 1353-1354 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chiba T, et al.: "Augmentation of water-immersion-stress induced gastric mucosal lesions in BALB/c mice infected with H.pylori" Digestion. 60. 34-40 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chiba T, et al.: "Possible involvement of H.Pylori infection in gastric ulcer formation after the Hansin-Awaji earthquake" Helicobacter. in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chiba T, et al.: "Cloning and characterization of a novel membrane-associated antigenic protein of Helicobacter pylori" Infection and Immunity. 67. 286-293 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Chiba T, et al.: "New p73 variants with altered C-terminal structures have varied transcriptional activities" Oncogene. in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Kishi, Y.Kinoshita, Y.Matsushima, A.Okada, T.Maekawa, C.Kawanami, N.Watanabe, T.Chiba.: "Pepsinogen C gene product is a possible growth factor during gastric mucosal healing." Biochem.Biophys.Res.Commun.238. 17-20 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Maekawa, Y.Kisnoshita, k.Kishi, A.Okada, C.Kawanami, T.Chiba.: "Helicobacter pylori induces proinflammatory cytokines and major histocompatibility complex." J.Lab.Clin.Med.130. 442-449 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.-Y.Wang, Y.Kinoshita, S.Hassan, Y.Matsushima, H.Fukui, T.Maekawa, A.Okada, S.Waki, C.Kawanami, K.Kishi, M.Watanabe, S.Maeda, T.Chiba.: "Developmental gene expression of gastrin receptor in rat stomach." Regul.Pep.70. 183-189 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] I.Shoji, H.Aizaki, H.Tani, K.Ishii, T.Chiba, I.Saito, T.Miyamura Y.Tastuura.: "Efficient gene transfer into various mammalian cells including non-hepatic cells by baculovirous vectors." J.Gen.Virol.78. 1657-1664 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Kinoshita, C.Kawanami, K.Kishi, H.Nakata, Y.Seino, T.Chiba.: "Helicobacter pylori-independent chronological change of gastric acid secretion in Japanese." Gut. 41. 452-458 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Hassan, Y.Kinoshita, C.Kawanami, K.Kishi, Y.Matsushima, A.Ohashi, Y.Funasaka, A.Okada, T.Maekawa, Wang He-Yao, T.Chiba.: "Expression of protooncogene c-kit and its ligand stem cell factor(SCF)in gastric carcinoma cell lines." Dig.Dis.Sci.43. 8-14 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] A.Okada, Y.Kinoshita, S.Waki, H.Fukui, T.Maekawa, Y.Matsushima, C.Kawanami, K.Kishi, H.Nakata, He-Yao Wang, S.Hassan, T.Chiba: "Rat gastric mucosa cells express ICAM-1 and proinflammatory cytokines during indomethacin induced mucosal injury." J.Lab.Clin.Med.131. 538-547 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] N.Watanabe, T.Nomura, T.Takai, T.Chiba, T.Honjo, T.Tsubata.: "Antigen receptor cross-linking by anti-immunoglobulin antibodies coupled to cell surface membrane induces rapid apoptosis of normal spleen B cells" Scand.J.Immunol. 47. 541-547 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Kinoshita, S.Hassan, M.Kawamura, Y.Matsushima, A.Okada, T.Maekawa, H.Fukui, S.Waki, K.Kishi, T.Chiba.: "Increased hepatocyte growth factor content in rat stomach during omeprazole treatment." Digestion. 59. 102-109 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Waki, Y.Kinoshita, He-Yao Wang, M.Asahara, Y.Matsushima, S.Hassan, A.Okada, T.Maekawa, H.Fukui, C.Kawanami, K.Kishi, T.Chiba.: "Effect of aging on gastrin receptor gene expression in rat stomach." Peptides. 19. 225-229 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] N.Aoyama, Y.Kinoshita, S.Fujimoto, S.Himeno, A.Todo, M.Kasuga, T.Chiba.: "Peptic ulcers after the Hanshin-Awaji earthquake -increased incidence of bleeding gastric ulcers-." Am.J.Gastroenterol.93. 311-316 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Hassan, Y.Kinoshita, A.Okada, H.Fukui, T.Chiba.: "Geranylgeranylacetone(GGA), an antiulcer drug, stimulates hexosamine production in rat gastric mucosal cell line through binding to a specific cytosolic protein." J.Gastoenterol.Hepatol. 13. 809-815 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Kinoshita, T.Fujimori, T.Chiba.: "Gastric MALToma with M proteins in serum and gastric juice." Gastroenterology. 114. 1353-1354 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Okazaki, T.Chiba.K.Hajiro: "Downregulation of gastric mucin gene expression and its biosynthesis by dexamethasone in the human." J.Clin.Gastorenterol.27. S91-S96 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Kinoshita, H.Nakata, K.Kishi, C.Kawanami, M.Sawada, T.Chiba.: "Comparison of the signal transduction pathways activated by gastrin in enterochromaffin-like and parietal cells." Gastoenterology. 115. 93-100 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Kusaka, Y.Sano, J.Arao, K.Ichikawa, Y.Yamamura-Idei, S.Shimizu, K.Tsuchiya, Y.Ueda, T.Chiba and T.Fujimori.: "A huge polypoid type early gastric neuroendocrine cell carcinoma." Digestive Endoscopy. 10. 236-239 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] H.Fukui, Y.Kinoshita, T.Maekawa, A.Okada, S.Waki, MD S.Hassan, H.Okamoto, T.Chiba.: "Reg protein may mediate gastric mucosal proliferation induced by hypergastrinemia in rats" Gastroenterology. 115. 1483-1493 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Watanabe, S.Tomita, M.Kudo, M.Kurokawa, A.Orino, A.Todo, T.Chiba.: "Detection of Helicobacter pylori gene by means of immunomagnetic separation-based polymerase chain reaction in feces." Scand.J.Gastroenterol. 33. 1140-1143 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Maekawa, Y.Kinoshita, S.Hirota, K.Chihara, T.Fujimori, T.Chiba.: "Reciprocal changes in progression of gastric MALT lymphoma and pancreatic somatostatinoma." Am.J.Med.105. 539-541 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Matsushima, Y.Kinoshita, M.Watanabe, S.Hassan, H.Fukui, T.Maekawa, A.Okada, C.Kawanami, K.Kishi, N.Watanabe, M.Nakao, T.Chiba.: "Augmentation of water -immersion-stress induced gastric mucosal lesions in BALB/c mice infected with Helicobacter felis." Digestion. 60. 534-540 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] M.Yoshida, Y.Wakatsuki, Y.Kobayashi, T.Itoh, K.Murakami, T.Usui, T.Chiba, T.Kita.: "Cloning and characterization of a novel membrane-associated antigenic protein of Helicobacter pylori." Infection and Immunity. 67. 286-293 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Maekawa, S.Waki, A.Okada, H.Fukui, Y.Kinoshita, T.Chiba.: "Midkine gene expression in the healig process of gastric ulcer" J.Lab.Clin.Med.(in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Date, M.Nakazato, H.Yamaguchi, K.Kanagawa, Y.Kinoshita, T.Chiba, Y.Ueta, H.Yamashita, S.Matsukura.: "Enterochromaffin-like cells, a cellular source of uroguanylin in rat stomach." Endocrinology. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Matsushima, H.Fukuda, Y.Kinoshita, N.Aoyama, T.Todo, S.Himeno, S.Fujimoto, M.Kasuga, T.Chiba.: "Possible involvement of Helicobacter pylori infection in gastric ulcer fomation after the Hanshin-Awaji earthquake -A case control study of Helicobacter pylori infection and stress-induced gastric ulcers-." Helicobacter. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Chiba, Y.Kinoshita, M.Sawada, K.Kishi, A.Baba, E.Hoshino.: "The role of endogenous gastrin in the development of enterochromaffin-like(ECL)cell carcinoid tumors in Mastomys natalensis -A study with the specific gastrin receptor antagonist AG-041R-." Yale J.Biol.Med.(in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Y.Ueda, M.Hijikata, S.Takagi, T.Chiba, K.Shimotohno.: "New p73 variants with altered C-terminal structures have varied transcriptional activaties." Oncogene. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hassan S,et al.: "Expression of protooncogene c-kit and its ligand stem cell factor in gastric carcinoma cell lines" Dig.Dis.Sci.43. 8-14 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Okada A.et al.: "Rat gasric mucosa cells express ICAM-1 and proinflammatory cytokines during indomethacin induced mucosal damage" J.Lab.Clin.Med.131. 538-547 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Oshima C,et al.: "An animal model of chronic follicular gastritis with MALT using neonatal thymectomized mice" Gut. 43. A26 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Chiba T,et al: "The role of endogenous gastrin in the development of ECL cell carcinoid tumors in Mastomys natalensis" Yale J.Biol.Med.in press (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kinoshita Y.et al: "Comparison of the signal transduction pathways activated by gastrin in ECl and parietal cells" Gastroenterology. 115. 93-100 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kinoshita Y,et al.: "Gastric MALToma with M proteins in serum and gastric juice" Gastroenterology. 114. 1353-1354 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Maekawa T,et al: "Reciprocal changes in progression of gastric MALT lymphoma and pancreatic somatostatinoma" Am.J.Med.105. 539-541 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Matsushima Y,et al.: "Possible involvement of Helicobacter phlori infection in gastric ulcer formation after the Hanshin-Awaji earthquake" Helicobacter. in press (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fukui H,et al.: "Reg protein may mediate gastric mucosal proliferation induced by hypergastrinemia in rats" Gastroenterology. 115. 1483-1493 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Matsushima Y,et al.: "Augmentation of water-immersion stress induced gastric mucosal lesions in BALB/c mice infected with Helicobacter felis" Digestion. 60. 34-40 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yoshida M,et al: "Cloning and characterization of a novel membrane-associated antigenic protein of Helicobacter polori" Infect.Immun.67. 286-293 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kinoshita Y, et al.: "Helicobacter pylori-independent chronological changes of gastric acid secretion in Japanese" Gut. 41. 452-458 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Maekawa T, et al.: "Helicobacter pylori induces proinflammatory cytokins and major histocompatibility complex" J.Lab.Clin.Med.130. 442-449 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kishi K, et al.: "Pepsinogen C gene product is a possible growth factor during gastric mucosal healing" Biochem.Biophys.Res.Commun.238. 17-20 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Okada A, et al.: "Rat gastric mucosa cells express ICAM-1 and proinflammatory cytokins during mucosal healing" J.Lab.Clin.Med.(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kinoshita Y, et al.: "Gastric lymphoma of mucosa-asociated lymphoid tissue(MALT) with monoclonal immunoglobulins in serum" Gastroenterology. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kinoshita Y, et al.: "Comparison of the signal transduction pathways activated by gastrin in ECL and parietal cells of Mastomys" Gastroenterology. (in press). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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