Investigation of 'de novo' type colorectal carcinogenesis
| Project/Area Number |
11671254
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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 |
Digestive surgery
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| Research Institution | Kumamoto University |
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Principal Investigator |
SHIMADA Shinya Kumamoto University School of Medicine, Department of Surgery, Assistant Professor, 医学部, 助手 (10284746)
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| Co-Investigator(Kenkyū-buntansha) |
OGAWA Michio Kumamoto UniversitySchool of Medicine, Department of Surgery, Professor and Chairman, 医学部, 教授 (30028691)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1999: ¥3,100,000 (Direct Cost: ¥3,100,000)
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| Keywords | colorectal carcinoma / 'de novo' type carcinogenesis / glycogen phosphorylase / adenoma-carcinoma sequence / K-ras / APC / p53 / tumor genes / 発癌 / 'de novo'型癌 / 'de novo'型大腸癌 |
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| Research Abstract |
The brain (fetal)-type glycogen phosphorylase (BGP) visualized by immunohistochemistry was commonly present in colorectal carcinoma (83.3 %). The expression of this molecule during adenoma carcinoma sequence (ACS) showed excellent correlation with the increased dysplasia and was found prior to p53 overexpression, whereas no BGP expression was seen in the normal human large intestine remote from the cancer foci. Positive BGP staining in transitional mucosa (BGP foci) was observed mainly around carcinomas without any adenoma component. The distribution of brain (fetal)-type glycogen phosphorylase (BGP) positive foci in transitional mucosa has a close relationship with the location of 'de novo' carcinoma. Further investigations to examine the proliferating cell nuclear antigen (PCNA)-labeling index, and the p53 and the codon 12 of K-ras mutation using the polymerase chain reaction-single strand conformation polymorphism were performed in the BGP foci, BGP negative mucosa and carcinoma. The BGP foci were observed sporadically in the transitional mucosa adjacent to the carcinoma in all cases. The PCNA labeling index in the BGP foci was significantly higher than that in the BGP negative mucosa (p<0.001). p53 mutations were observed in 8 carcinomas, but no K-ras mutation was detected. Interestingly, although none of the overexpressions of p53 protein was detected immunohistochemically in the BGP positive foci, the p53 gene frequently (41.2 % of the BGP foci tested) mutated in spite of no K-ras mutation. The present study demonstrates potentially premalignant foci in the colorectal transitional mucosa with frequent p53 gene mutation. It is suggested that BGP foci are promising candidates for the further investigation of 'de novo' colorectal carcinogenesis.
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Report
(3 results)
Research Products
(19 results)
