Changes in oxygen metabolism in solid tumors by administration of artificial oxygen carriers

人工氧载体给药改变实体瘤中的氧代谢

• 批准号: 15390422
• 负责人: KOBAYASHI Koichi
• 金额: $ 8.19万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390422/
• 关键词: tumor oxygenation; tumor perfusion; artificial oxygen carrier; tumor irradiation; ラット; LY-80; 酸素代謝; 腫瘍の酸素化; 腎腫瘍

Establishment of isolated renal tumor model : In rats, LY80 tumor was inoculated in the subcapsule space of the left kidney. Wrapping with Parafilm prevented tumor infiltration into the surrounding tissue. After 6 days, the left renal vein and the abdominal aorta was cannulated. Right renal artery, and the aorta was ligated proximal to the bifurcation of left renal artery. In this way, the circulation of the left renal tumor was isolated. We observed an increase in tumor tissue oxygen tension, when the tumor was perfused with oxygenated artificial oxygen carrier. By sampling arterial and venous blood, we will be able to estimate the oxygen consumption within tumor tissue. The model needs to be further refined in order to achieve this objective.Oxygenation of tumor tissue by intraarterial infusion of rHSA-FecycP : Tumor tissue oxygen tension started to rise 5 minutes after the start of infusion, and remained elevated for 15 minutes. Based on this finding, since it takes at least 15 minutes to irradiate 20Gy using our irradiator, we decided to start irradiation and infusion simultaneously.Combination of rHSA-FecycP with radiation : Local tumor control was superior in the combination group compared with radiation alone. It was questionable whether tumor oxygenation was the only mechanism for this synergy. The impact on survival needs further evaluations.

肾肿瘤模型的建立：在大鼠左肾包膜下接种LY 80肿瘤。用石蜡膜包裹防止肿瘤浸润到周围组织中。6天后，左肾静脉和腹主动脉插管。右肾动脉，左肾动脉分叉近端结扎主动脉。通过这种方式，左肾肿瘤的循环被隔离。我们观察到肿瘤组织氧张力的增加，当肿瘤灌注含氧人工氧载体。通过对动脉和静脉血进行采样，我们将能够估计肿瘤组织内的耗氧量。通过动脉内输注rHSA-FEVcP的肿瘤组织氧合：肿瘤组织氧分压在输注开始后5分钟开始升高，并保持升高15分钟。基于这一发现，由于使用我们的照射器照射20 Gy至少需要15分钟，因此我们决定同时开始照射和输注。rHSA-FcP与放射的组合：与单独放射相比，组合组的局部肿瘤控制上级。肿瘤氧合是否是这种协同作用的唯一机制还值得怀疑。对生存的影响需要进一步评估。