| Co-Investigator(Kenkyū-buntansha) |
YAMAUCHI Tokuko Keio University, School of Medicine, Instructor, 医学部, 助手 (30306732)
WATANABE Masazumi Keio University, School of Medicine, Instructor, 医学部, 助手 (90201227)
KOBAYASHI Koichi Keio University, School of Medicine, Professor, 医学部, 教授 (80051704)
YAMAMOTO Manabu Keio University, School of Medicine, Instructor, 医学部, 助手 (10317159)
IWAMARU Arifumi Keio University, School of Medicine, Instructor, 医学部, 助手 (00296592)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
The environment of metastatic tumor in the lung is much different in terms of oxygen supply and microcirculation compare to those metastatic tumors in other organs. To investigate the establishment of microcirculation of metastatic lung tumor, we have to establish syngenic model of lung metastasis.
To observe lung microcirculation, we implanted a crystal window chamber in the chest wall of a rat. Through this window, we could observe pulmonary arteriole, alveolar capillary, and pulmonary vein using laser confocal microscope and fluorescent dye. The images were recorded in VCR and analyzed afterwards. Inner diameter of vasculature could be measured and blood flow could be evaluated in capillary area. More sophistication was necessary to measure the blood flow in pulmonary arteriole because flow was fast enough to capture individual fluorescent labeled red blood cells. To establish lung metastasis, we evaluated 5 models using LY80 which is ascitis hepatoma in Donryu rat. Examined modaliti
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es were as follows, intraperitoneal tumor cell injection, subcutaneous implantation of tumor cells, implantation of tumor cells to the lung directly by thoracotomy, tail vein infusion of tumor cells, and tail vein infusion of small tissue suspension taken from subcutaneous implanted tumor. Among these modalities, tail vein infusion of small tissue suspension taken form subcutaneous implanted tumor gave us the most reliable and stable results. After 15 to 17 days after infusion, we could evaluate the pulmonary metastatic tumor.
To evaluate the reactivity of tumor microvasculature, we used oxyhemoglobin solution and HbV suspension. Oxyhemoglobin solution is a strong potential of contraction of microvasculature, while HbV (liposome encapsulated hemoglobin), which is originally developed as an artificial oxygen carrier, is thought to have little effect on microvasculature. In normal animals, pulmonary arterioles contract after injection of Oxyhemoglobin while transient contraction was observed after HbV injection. There are little change of diameter, flow in alveolar capillary. However, pulmonary arteriole react these challenges revealing that Nitric Oxide is one of major modulator in determining the tone of pulmonary vasculature.
In tumor burden animals, especially in current model, alveolar capillary was dilated. But we could not observe any changes in arteriole and/or venule area. The effect of oxyhemoglobin and HbV in this model is similar to those observed in intact animals. We have to improve the model to analyze the event in microcirculation of metastatic lung tumor. Less
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