Project/Area Number |
13480287
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Biomedical engineering/Biological material science
|
Research Institution | University of Tsukuba |
Principal Investigator |
OHSHIMA Norio University of Tsukuba, Institute of Basic Medical Sciences, Professor, 基礎医学系, 教授 (50015971)
|
Project Period (FY) |
2001 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 2002: ¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 2001: ¥7,700,000 (Direct Cost: ¥7,700,000)
|
Keywords | tumor microcirculation / hemodynamics / angiogenesis / nitric oxide / confocal laser-scanning microscope / intravital microscope / leukocyte |
Research Abstract |
Using an experimental tumor model developed by the authors, intravital microscopic observations of the angiogenic processes in the mesenteric microvasculature and the hemodynamics of the newly formed microvessels were performed. In this model, tumor growth accompanying a marked angiogenesis was microscopically observable for up to 10 days. The length of the microvessels showed a significant increase in the tumor-bearing mesentery. In the newly formed tumor vessels, rolling and adherence of leukocytes in venules were both attenuated as compared with those in the normal mesenteric venules. To elucidate the mechanisms of these altered behavior of hemodynamics, the role of nitric oxide (NO) in regulating leukocyte dynamics in the tumor microcirculation was examined. Reduction of the baseline levels of leukocyte-endothelial cell interactions observed in the tumor venules were markedly increased by inhibition of NO synthase (NOS). These increases were neither found in the tumor-free rats nor in normal microvessels of the tumor-bearing rats. These results suggest that an excessive production of NO in the tumor tissues creates the tumor-specific microenvironment, thereby modulating leukocyte behavior in the angiogenic tumor vessels.
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