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Analysis of genomic changes in the intestinal metaplastic epithelial cells of the human stomach

Research Project

Project/Area Number 11670202
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionAichi Cancer Center Research Institute

Principal Investigator

INADA Ken-ichi  Aichi Cancer Center Research Institute, Laboratory of Pathology, Senior Researcher, 腫瘍病理学部, 主任研究員 (70246081)

Co-Investigator(Kenkyū-buntansha) IKEHARA Yuzuru  Aichi Cancer Center Research Institute, Laboratory of Pathology, Researcher, 腫瘍病理学部, 研究員 (10311440)
NAKANISHI Hayao  Aichi Cancer Center Research Institute, Laboratory of Pathology, Section head, 腫瘍病理学部, 室長 (20207830)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsintestinal metaplasia / gastric and intestinal mixed-type / intesitnal-type / crypt isolation technique / semi-quantitative RT-PCR / differentiation factor / cdx-1 / cdx-2 / Intestinal metaplasia / intestinal-type / 定量的RT-PCR法
Research Abstract

1) Qie of the most important results of this project is that we couldexploit a very effective method to isolate the smallest target of mtestinalized gastric glands under conditions in which the tissue RNA was well preserved After glands in pyloric mucosa were isolated by a crypt isolation technique, they were fixed in 70 % ethanol in 20-30minutes and then stained by Alcian-blue (AB) staining to identify goblet cells. In addition to definition of morphological characteristics of the isolated glands under phase-contrast microscopy, AB staining allowed us to discriminate between gastric and intestinal type glands. Synthesis of CDNA was successfully from accomplished isolated glands using the RT-PCR method.
2) However, differential display could not be achieved because it was too difficult to synthesize sufficient CDNA from only one isolated gland.
3) Isolated glands of each subtype of intestinal metaplasia (IM), ten were collected and processed for genomic analyses. With the three subtypes … More of isolated glands (IM (-), moderate IM, and severe IM), the expression of mRNAs of homeobox genes, Cdx-1 and Cdx-2, revealedto be important transcriptional factors introducing and maintaining the differentiation of large or small intestinal mucosal epithelial cells in the immature cells of the crypts, were investigated by the semi-quantitative RT-PCR method The expression of β-actin mRNA was also examined as a positive control. The intestinalized gastric glands consistently expressed both Cdx-1 and Cdx-2 mRNAs, levels generally increasing with severity of IM. No obvious differences in mRNA levels between Cdx-1 and Cdx-2 were apparent. Moreover, when mRNA levels of MUC5AQ Pgll, MUC2, villin, defensinS were examined, isolated glands without IM, associated with gastric and intestinal mixed-type IM, and intestinal-type IM showed different expression patterns. Immunohistochemical analyses with antibodies to their gene products demonstrated close correlation between mRNA and protein expression.
4) In conclusion, it is suggested that some genes, which have important roles in differentiation and maintenance of the intestinal mucosal epithelial cells, might control the appearance of IM in gastric mucosa.
5) The interrelationships among these genes are now under investigation. Less

Report

(4 results)
  • 2001 Final Research Report Summary
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Ikehara, Y.: "A novel glycosyltransferase with polyglutamine repeat ; a new candidate for GD1α synthase (ST6GalNAC V)"FEBS Lett.. 463. 92-96 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ikehara, Y.: "Cloning and expression of a human gene encoding an N-acetylgalactosamine-α2,6-sialyltransferase (ST6GalNAC I) which is a candidate for synthesis of cancer-associated sialyl-Tn antigens"Glycobiology. 9. 1213-1224 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakanishi, H.: "Molecular diagnostic detection of free cancer cells in the peritoneal cavity of patients with gastrointestinal and gynecologic malignancies"Cancer Chemother.Pharmacol.. 43. S32-S36 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakanishi, H.: "Chemosensitivity of micrometastases and circulating tumor cells to uracil and tegafur as evaluated using LacZ gene-tagged Lewis lung carcinoma cell"Cancer Lett.. 142. 31-41 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakanishi, H.: "Induction of apoptosis in metastatic foci from human gastric cancer xenografts in nude mice and reduction of crrculating tumor cells in blood by 5-FU and 1-hexylcarbamoyl-5 fluorouracil"J.Cancer Res.Clin.Oncol.. 125. 660-668 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Inada, K.: "Identification of Paneth cells in pyloric glands associated with gastric and intestinal mixed type intestinal metaplasia of the human stomach"Virchows Arch.. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ikehara, Y. et al: "A novel glycosyltransferase with polyglutamine repeat ; a new candidate for GD1α synthase (ST6GalNAc V)"FEBS Lett.. 463. 92-96 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ikehara, Y. et al: "Cloning and expression of a human gene encoding an N-acetylgalactosamine-α2,6-sialyltransferase (ST6GalNAc I) which is a candidate for synthesis of cancer-associated sialyl-Tn antigens"Glycobiology. 9. 1213-1224 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakanishi, H. et al: "Molecular diagnostic detection of free cancer cells in the peritoneal cavity of patients with gastrointestinal and gynecologic malignancies"Cancer Chemother. Pharmacol.. 43. S32-S36 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakanishi, H. et al: "Chemosensitivity of micro-metastases and circulating tumor cells to uracil and tegafur as evaluated using LacZ gene-tagged Lewis lung carcinoma cell"Cancer Lett.. 142. 31-41 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakanishi, H. et al: "Induction of apoptosis in metastatic foci from human gastric cancer xenografts in nude mice and reduction of circulating tumor cells in blood by 5-FU and 1-hexylcarbamoyl-5-fluorouracil"J. Cancer Res. Clin. Oncol.. 125. 660-668 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Inada, K. et al: "Identification of Paneth cells in pyloric glands associated with gastric and intestinal mixed type intestinal metaplasia of the human stomach"Virchows Arch.. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ikehara,Y.: "A novel glycosyltransferase with polyglutamine repeat ; a new candidate for GD1α synthase (ST6GalNAC V)"FEBS Lett.. 463. 92-96 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ikehara,Y.: "Cloning and expression of a human gene encoding an N-acetylgalactosamine-α2, 6-sialyltransferase (ST6GalNAC I) which is a candidate for synthesis of cancer-associated sialyl-Tnlantigens"Glycobiology. 9. 1213-1224 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakanishi,H.: "Molecular diagnostic detection of free cancer cells in the peritoneal cavity of patients with gastrointestinal and gynecologic malignancies"Cancer Chemother.Pharmacol.. 43. S32-S36 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakanishi,H.: "Chemosensitivity of micrometastases and circulating tumor cells to uracil and tegafur as evaluated using LacZ gene-tagged Lewis lung carcinoma cell"Cancer Lett.. 142. 31-41 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakanishi,H.: "Induction of apoptosis in metastatic fori from human gastric cancer xenografts in nude mice and reduction of circulating tumor cells in blood by 5-FU and 1-hexylcarbamoyl-5 fluorouracil"J.Cancer Res.Clin.Oncol.. 125. 660-668 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Inada,K.: "Identification of Paneth cells in pylonc glands associated with gastric and intestmal mixed type intestinal metaplasia of the human stomach"Virchows Arch.. (in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ikehara, Y.et al.: "A novel glycosyltransferase with polyglutamine repeat ; a new candidate for GDIα synthase (ST6GaINAc V)."FEBS Lett.. 463. 92-96 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ikehara, Y.et al.: "Cloning and expression of a human gene encoding an N-acetylgalactosamine-α2,6-sialyltransferase (ST&GalNAc I) which is a candidate for synthesis of cancer-associated sialyl-Tn antigens."Glycobiology. 9. 1213-1224 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakanishi, H.et al.: "Molecular diagnostic detection of free cancer cells in the peritoneal cavity of patients with gastrointestinal and gynecologic malignancies."Cancer Chemother. Pharmacol.. 43. 32-36 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakanishi, H.et al.: "Chemosensitivity of micrometastases and circulating tumor cells to uracil and tegafur as evaluated using LacZ gene-tagged Lewis lung carcinoma cell."Cancer Lett.. 142. 31-41 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakanishi, H.et al.: "Induction of apoptosis in metastatic foci from human gastric cancer xenografts in nude mice and reduction of circulating tumor cells in blood by 5-FU and 1-hexylcarbamoyl-5-fluorouracil."J.Cancer Res. Clin. Oncol.. 125. 660-668 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Inada, K.et al.: "Identification of Paneth cells in pyloric glands associated with gastric and intestinal mixed type intestinal metaplasia of the human stomach."Virchows Arch.. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ikehara,Y.: "A novel glycosyltransferase with polyglutamine repeat ; a new candidate for GD1_α synthase (ST6GalNAc V)"FEBS Lett.. 463. 92-96 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ikenhara,Y.: "Cloning and expression of a human gene encoding an N-acetylgalactosamine-α2,b-sialyl transferase(ST6GalNAc I) which is a candidate for synthesis cancer-associated sialyl-Tn antigens"Glycobiology. 9. 1213-1224 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakanishi,H.: "Molecular diagnostic detection of free cancer cells in the peritoneal cavity of patients with gastrointestinal and gynecologic malignancies"Cancer Chemother Pharmacol.. 43. S32-S36 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakanishi,H.: "Chemosensitivity of micrometastases and circulating tumor cells to uracil and tegafur as evaluated using LacZ gene-tagged Lewis lung carcinoma cell"Cancer Lett.. 142. 31-41 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakanishi,H.: "Induction of apoptosis in metastatic foci from human gastric cancer xenografts in nude mice and reduction of circulating tumor cells in blood by 5-FU and 1-hexylcorhamoryl 5-fluorouracil"J.CancerRes.Clin.Oncol.. 125. 660-668 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Inada,K.: "Identification of Paneth cells in pyloric glands associated with gastric and Intestinal mixed type intestinal metaplasis of the human stomach."Virchows Arch.. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 稲田健一,塚本徹哉,他: "器官培養法を用いたヒト胃粘膜腸上皮化生腺管の細胞動態-腺管分離法による解析-"消化器癌の発生と進展. 10. 347-350 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ikehara, Y., Shimizu, N. et al.: "A novel glycosyltransterase with polyglutamine repeat ; a new candidate for GD1α synthase (ST6GalNAcV)"FEBS Lett.. 463. 92-96 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shimizu, N., Inada, K. et al.: "Helicobacter pylori infection enhances glandular stomach carcinogenesis in Mongolian gerbils treated with chemical carcinogens"Carcinogenesis. 20・4. 669-676 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoshikawa, A., Inada K. et al.: "Phenotypic shift in human differentiated gastric cancers from gastric to intestinal epithelial cell type during disease progression"Gastric Cancer. 1. 134-141 (1998)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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