| Project/Area Number |
08670598
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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 | Yamaguchi University |
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Principal Investigator |
SAKAIDA Isao Yamaguchi University Hospital. Assistant, 医学部附属病院, 助手 (80263763)
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| Co-Investigator(Kenkyū-buntansha) |
OKITA Kiwamu Yamaguchi University School of Medicine, Professor, 医学部, 教授 (70107738)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | Ito cell / Cancer / Fibrosis / Preneoplastic lesion / TGF-beta1 / 肝発癌 / 発癌 |
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| Research Abstract |
Administration of a choline deficient L-amino acid defined (CDAA) diet for 16 weeks led to the development of preneoplastic lesions that were positive for the placental form of glutathione S-transferase (GSTP) and induced hepatocellular carcinoma in 90% of rats after one year. Prolyl 4-hydroxylase inhibitor (HOE 077, 200 ppm) significantly reduced the size and incidence of preneoplastic lesions after 16 weeks and also the incidence of HCC (50%) in rats fed a CDAA diet for one year by the inactivation of Ito cell resulting in the prevention of fibrosis.
Injection of pig serum into rats twice a week for 8 weeks induced.TGF-beta_1 mRNA expression and protein production resulting in liver fibrosis without parenchymal cell injury. Administration of a choline deficient L-amino acid defined (CDAA) diet for 6 weeks with or without pig serum pretreatment led to the development of preneoplastic lesions that were positive for the placental form of glutathione S- transferase (GSTP). Pig serum pretreatment induced more activated stellate cells with increased TGF-beta_1, mRNA expression and protein production in the livers of rats subsequently fed a CDAA diet for 6 weeks compared to rats fed the CDAA diet alone.
These results indicate that pre-existing fibrosis with the activated stellate cells accelerates the development of preneoplastic lesions in a CDAA.diet model and that TGF-beta_1 induced by pig serum treatment failed to prevent the development of preneoplastic lesions in a CDAA-diet model.
Cancer cell seems to prevent the activation of Ito cell in co-culture system but further examinations are necessary.
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