| Project/Area Number |
14207050
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | Gunma University |
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Principal Investigator |
KUWANO Hiroyuki Gunma University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (90186560)
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| Co-Investigator(Kenkyū-buntansha) |
ASAO Takayuki Gunma University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (40212469)
KATO Hiroyuki , 医学部, 講師 (70224532)
SHIMURA Tatsuo , 医学部, 助手 (00282393)
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| Project Period (FY) |
2002 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥43,420,000 (Direct Cost: ¥33,400,000、Indirect Cost: ¥10,020,000)
Fiscal Year 2005: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2004: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
Fiscal Year 2003: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
Fiscal Year 2002: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
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| Keywords | gastroenteral cancer / epigenetic change / cell-to-cell interaction / metastatic potential / invasive potential / post-genome / 消化器癌 / co-culture / 癌関連遺伝子 / RT-PCR / p53 / HLA-DR / gap junction |
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| Research Abstract |
1.Four kinds of human cancer cell lines and one mouse cancer cell line were inoculated into the subepithelial area of the anorectum of female nude mice. Among the cell lines, two cell lines (KATO III and Lu 135) showed the potential enforcement of atypical changes in the adjacent mouse anorectal epithelium. Moreover, the submucosal invasion of the malignant transformed cells of the mouse epithelium was demonstrated in specimens obtained from three KATO III-inoculated mice. This exciting and novel phenomenon clearly demonstrates the need to change the present general concept of a single-cell origin of cancer tissue. This valuable and novel discovery may change the basis of oncology research while also providing new ideas for projects to investigate the mechanisms of carcinogenesis from several aspects such as molecular biology, cell biology, and pathology. Moreover, the novel experimental design itself is also extremely useful as a simple model for investigating the mechanisms of oncoge
… More
nesis.
2.Although cell density in cultured cells has demonstrated several alterations in the nature of cell kinetics, the changes in the metastatic aggressiveness of cancer lines under different cell densities have not yet been studied. METHODS : In the current study, we investigated the influence of changing the cell density of cultured cancer cells (colon 26 and B16-F10) injected into the tail vein in BALB/c mice on the metastatic activity by evaluating the number of lung metastases, and the possible mechanisms of this phenomenon were discussed based on the basis of the results of an invasion assay and a cell adhesion assay. RESULTS : The number of metastatic nodules was significantly higher in the high-density group than in the low one in colon 26 (p<0.005), however, this phenomenon was not seen in B16-F10. Next, we performed the same experiment by changing the environment to the opposite conditions for the cells in the low- and high-density groups, and the results showed the metastatic activities to be always higher in the high-density group. Moreover, although no difference was seen regarding the invasive activity between the high- and low-density groups, an adhesion assay showed the difference in the adhesion cell rate to be significantly higher in the high-density group especially in early period after coculture with human umbilical vein endothelial cells (HUVEC) (p<0.05). CONCLUSION : In some cell types, the metastatic activity could be altered and reversed by changing the environment, such as the cell density, during a relatively short period. As a result, the epigenetic changes of cancer cells are thus suggested to play a certain role in the malignant potentiality. Less
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