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1998 Fiscal Year Final Research Report Summary

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
KeywordsH.pylori / Gastric adenoma / MALT lymphoma / ECL carcinoid
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

  • Research Products

    (48 results)

All Other

All Publications (48 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 1999-12-08  

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