2004 Fiscal Year Final Research Report Summary
ACF as a marker for colon carcinogensis in patients with ulcerative colitis and its gene analysis
| Project/Area Number |
15590666
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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 |
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Principal Investigator |
TAKAYAMA Tetsuji Sapporo Medical University, School of Medicine, Assistant professor, 医学部, 講師 (10284994)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Ulcerative colitis / ACF / Carcinogenesis |
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| Research Abstract |
Aim: we identified aberrant crypt foci (ACF) in patients with ulcerative colitis (IJC), investigated various gene alterations and clarified the significance of ACF as a biomarker in colon carcinogenesis. Methods and Results: (1) Twenty-eight patients with UC were enrolled. We observed rectal area using magnifying endoscopy with the aid of methylene blue staining as previously we described (N Engl J Med, 1998). We found ACF lesions in 27 patients out of 28. ACF in UC patients showed obscure crypt lining as compared to ACF in non-UC patients. The number of ACF in patients with dysplasia was significantly more than that without dysplasia. (2) There were positive correlations between dysplasia and ACF number or duration of disease. (3) Essentially there were no mutations of APC and K-ras in ACF and dysplasia as revealed by In vitro synthesized protein (IVSP) assay and 2-step PCR RFLP respectively. (4) Very low rates of MSI were detected in ACF and dysplasia by PCR SSCP method. (5) There was no p53 mutation in ACF although it was frequently positive in dysplasia and cancer by PCR SSCP method. Immunostaining for p53 also revealed no accumulation of p53 in ACF although it was frequently accumulated in dysplasia and cancer. (6) Hypermethylation of p16 was highly positive in ACF, dysplasia and cancer by bisulfite method. Conclusion: It was demonstrated that ACF are viable marker for detection of dysplasia and subsequent cancer. It was also strongly suggested that ACF develop by p16 hypermethylation and proceed to dysplasia by p53 mutation.
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Research Products
(8 results)
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[Journal Article] Prolonged survival of mice, with multiple liver metastases of human colon cancer by intravenous administration of replicable 1B-55K-deleted adenovirus with ElA expressed by CEA promoter2004
Author(s)
Sagawa T, Takahashi M, Sato Y, Lu Y, Sumiyoshi T, Yamada Y, Iyama S, Fukaura J, Sasaki K, Hamada H, Miyanishi K, Takayama T, Kato J, Niitsu Y.
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Journal Title
Molecular Ther 10
Pages: 1043-50
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Glutathione S-transferase Pl-1 protects aberrant crypt foci from apoptosis induced by deoxycholic acid2004
Author(s)
Nobuoka A, Takayama T, Miyanishi K, Sato T, Hayashi T, Kukitsu T, Takanashi K, Sato Y, Takahashi M, Okamoto T, Matsunaga T, Kato J, Oda M, Azuma T, Niitsu Y.
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Journal Title
Gastroenterology 127
Pages: 428-443
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Augmentation of Antitumor Effects of p53 Gene Therapy by Combination with HDAC Inhibitor
Author(s)
Takimoto R, Kato J, Terui T, Takada K, Kuroiwa G, Wu J, Ohnuma H, Takahari D, Kobune M, Sato Y, Takayama T, Matsunaga T, Niitsu Y.
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Journal Title
Cancer Biol Ther 4(in press)
Description
「研究成果報告書概要(欧文)」より
