| Project/Area Number |
09670201
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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 | DOKKYO UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
FUJIMORI Takahiro Dokkyo University School of Medicine Department of pathology, Professer, 医学部, 教授 (30095385)
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| Co-Investigator(Kenkyū-buntansha) |
ONO Yuko Dokkyo University School of Medicine Department of pathology, Lecturer, 医学部, 講師 (90254961)
HIRABAYASHI Kaoru Dokkyo University School of Medicine Department of pathology, Lecturer, 医学部, 講師 (50189859)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | flat cancer / Pit pattern / honeycomb units / K-ras / Cathepsin D / Adhesion molecules / DCC / experimental research / 表面型大腸癌 / 大腸腺腫 / p53 / NF1 / NSAIDs / 炎症性発がんモデル / 表面型大腸がん / 実体顕微鏡観察 / P53 / DOP-PCR |
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| Research Abstract |
The multistep model of colorectal carcinogenesis proposed by Vogelstein et al. is based on adenoma-carcinoma sequence ; the most important events of tumor evolution are recognized to be the activation of oncogenes (i.e., ras gene mutation) and collagenolytic factors, the loss of function of tumor suppressor genes (i.e., p53, apc, dcc) and dysfunction of adhesion molecules. The activations of the k-ras genes and cox-2 are correlated with increased tumor atypia and tumor size, and are thought to be involved at a relatively early stage in colorectal carcinogenesis. These data were based mainly on the analysis of polypoid adenoma and cancer. However, our reports show that flat or depressed tumors have no or few k-ras mutation and no overexpression of cox-2 in tumor cells. These suggest that there are some different genetic pathways for the development of colorectal tumors. Flat type carcinoma with the honeycomb-like type surface might be a new carcinoma which develops via a different pathway than carcinomas with sulciform or intermediate type surface, and might be a candidate of de novo carcinogenesis. In this immunohistochemistry of colorectal carcinomas, the presence of high levels of p53 protein and the decrease of the expression of adhesion molecules are detected in correlation with tumor invasiveness. Increased expression of cathepsin D was also a feature of easily invasive colorectal carcinoma. We concluded in this study that the genetic analysis may help morphologic diagnosis and the correlation between the dissecting microscopic observation of the surface structure of colorectal tumor and the analysis of genetic background may be useful for connection with assessment of their growth and progression. We confirmed these results using experimental models.
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