Mucosal remodeling and genetic instability of stromal cells in ulcerative colitis-associated tumorigenesis
| Project/Area Number |
16590293
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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 |
Human pathology
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| Research Institution | KITASATO UNIVERSITY |
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Principal Investigator |
OKAYASU Isao Kitasato University, School of Medicine, Professor, 医学部, 教授 (20014342)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Tsutomu Kitasato University, School of Medicine, Assistant Professor, 医学部, 講師 (90316943)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | ulcerative colitis / carcinogenesis / genetic instability / stromal cells / colorectal cancer / colorectal adenoma / chronic inflammation / remodeling / 発がん / 大腸がん / マイクロダイセクション |
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| Research Abstract |
In order to clarify both epithelial and stromal genetic instability in colorectal tumorigenesis in patients of ulcerative colitis (UC), the laser-captured microdissection-PCR-GeneScan method was applied to investigate genetic instability in both epithelial and stromal elements of early UC-associated lesions (regenerative mucosa and dysplasia) and carcinomas using multiple microsatellite markers, chiefly close to NCI-recommended standard markers, chromosome 17 (Chr.17) markers and tumor suppressor genes (TSG). In epithelium, although loss of heterozygosity (LOH) for Chr.17 markers increased along with histological progression, the frequencies of LOH or microsatellite instability (MSI) for TSG markers were found to be almost constantly elevated in both stromal and epithelial components of all lesion types. On the other hand, genetic instability of NCI-recommended standard markers was not found to be significantly correlated with UC-associated tumorigenesis and no frame shift mutations were detected using seven mononucleotide repeat markers.
In comparison, sporadic colorectal adenomas and carcinomas were analyzed with the same method as UC-associated lesions. Frequencies of epithelial alterations showed a step-up increase in tumor progression from adenoma with low-grade dysplasia and adenoma with high-grade dysplasia to carcinoma. Frequencies of stromal LOH or MSI were almost constant in adenomas and invasive carcinomas.
In conclusion, the results indicate the presence of genetic alterations in stroma from an early stage of carcinogenesis, accompanied by stepwise increasing genetic instability of epithelia with progression to carcinoma. In particular, genetic instability in the stroma, especially regarding TSG markers, may play an important role in early phase UC-associated tumorigenesis.
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Report
(3 results)
Research Products
(21 results)
