1999 Fiscal Year Final Research Report Summary
Helicobacter pylori infection augments telomerase activity in gastric cancer and noncancerous tissues
| Project/Area Number |
10670490
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Sapporo Medical University School of Medicine |
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Principal Investigator |
WATANABE Naoki Dept. Of Laboratory Diagnosis, Prof., 医学部, 教授 (10158644)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Daisuke Dept. Of Laboratory Diagnosis, Instructor, 医学部, 助手 (50295359)
YAGIHASHI Atsuhito Dept. Of Laboratory Diagnosis, Assistant Prof., 医学部, 講師 (40260757)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Helicobacter pylori / telomere / telomerase / gastric cancer / intestinal metaplasia / atrophic gastritis / TRAP / human telomerase associated molecules |
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| Research Abstract |
Telomerase adds hexameric repeats of 5'TTAGGG-3 to the ends of chromosomal DNA (telemeter), Telomerase has been implicated in cell immortalization and cellular senescence. The aim of this study was to quantitatively measure telomerase activity and telomerase associated molecules content in gastric cancer and to examine the relation between these values and hisologic factors including Helicobacter pylori as a risk factor for gastric cancer. In cancerous and non-cancerous tissues (intestinal metaplasia, chronic gastritis, and normal mucosa) from 31 gastric cancer patients, telomerase activity was measured by a modified telomeric repeat amplification protocol, expression of telomerase associated molecules (hTR, TEP1 and hTERT) RNA was examined by quantitative reverse transcriptase polymerase chain teaction using fluorescent probes. Telomerase activity in intestinal metaplasia (16.7) and chronic gastritis (10.6) was higher than in normal mucosa (3.5). The expression of telomerase associated molecules RNA was not correlated with telomerase activity.
In patients with intestinal type gastric cancer, telomerase activity in intestinal metaplasia with Helicobacter pylori infection was higher than without infection. Therefore, we elucidated whether Helicobacter pylori infection can induce telomerase activity in gastric mucosa using the Mongolian gerbil model system. Seven-week-old male Mongolian gerbils (MGS/Sea) and Helicobacter pylori ATCC 43504 were used in this study. Helicobacter pylori (1.5 × 10ィイD18ィエD1 CFUs/animal) was orally inoculated into each gerbil in the test group.
Six months after the inoculation, Helicobacter pylori and intestinal metaplasia were found in all the same samples in the treated group. In the control samples, there were no histopathologic changes or Helicobacter pylori organisms detected. The mean telomerase activity in the treated group was 40.2±28.5, versus 10.3±9.8 in the control group. This intergroup difference was significant (P<0.05).
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