| Project/Area Number |
16590617
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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 | Osaka City University |
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Principal Investigator |
TOMINAGA Kazunari Osaka City university, Graduate School of Medicine, Department of Gastroenterology, Lecturer, 大学院医学研究科, 講師 (80336768)
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| Co-Investigator(Kenkyū-buntansha) |
HIGUCHI Kazuhide Osaka City university, Graduate School of Medicine, Department of Gastroenterology, Associate professor, 大学院医学研究科, 准教授 (20218697)
FUJIWARA Yasuhiro Osaka City university, Graduate School of Medicine, Department of Gastroenterology, Lectuer, 大学院医学研究科, 講師 (40285292)
WATANABE Toshio Osaka City university, Graduate School of Medicine, Department of Gastroenterology, Lecturer, 大学院医学研究科, 講師 (50336773)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Peritoneal mesothelail cells / Interleukin 10 / gastrointestinal cancer / Gene therapy / Peritoneal dissemination / 腹膜中皮 / interleikin / interleukin / Interleukin(IL)-10 / 細胞増殖 / サイトカイン / COX-2 / VEGF |
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| Research Abstract |
Purpose: Interleukin (IL)-10 is a cytokine which has multiple biological properties such as anti-inflammation and inhibition of proliferation and metastasis on various cancer cells. But it is difficult to keep on high concentration, because its half-life period is very rapid. The aim of this study was to clarify whether IL-10 gene transfer targeting to peritoneal mesothelial cells (PMCs) which abundantly exist in peritoneal cavity can be suitable for maintaining high concentration of IL-10 and its therapeutic effects for peritoneal dissemination of gastric cancer in mice. Experimental design: We assessed the transfection efficacy of adenovirus for primarily isolated PMCs and MKN45 gastric cancer cells. MKN45 cells were intraperitoneally inoculated in BALB/c nude mice, followed by single intraperitoneal injection with adenovirus containing mouse IL-10 gene (Ad-mlL-10) 3 days later. Intraperitoneal IL-10 levels after the treatment were measured by enzyme-linked immunosorbent assay. We evaluated the number of pritoneal nodules, microvascular density, body weight and the survival rate. Results: Transfection efficiency showed about 10-folds higher to PMCs than MKN45 cells. In peritoneal lavage, IL-10 concentration was remarkably elevated for at least 3 weeks in the treated groups. Ad-mlL-10 treatment decreased total number of peritoneal nodules via suppression of intratumor angiogenesis. Furthermore, it improved cachexia and prolonged their survival without any significant adverse effects. Conclusion: IL-10 gene transfer to PMCs could be a new strategy against peritoneal dissemination of gastric cancer since it induces continuous high IL-10 concentration in peritoneal cavity.
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