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.

建立孤立的肾肿瘤模型：在大鼠中，LY80肿瘤被接种在左肾的囊囊空间中。用parafilm包裹可防止肿瘤浸润到周围的组织中。 6天后，插管了左肾静脉和腹主动脉。右肾动脉，主动脉与左肾动脉分叉的近端相连。这样，分离了左肾肿瘤的循环。我们观察到肿瘤组织氧张力的增加，当肿瘤被氧化的人造氧载体灌注时。通过取样动脉和静脉血，我们将能够估计肿瘤组织内的氧气消耗。为了实现这一目标，需要进一步完善该模型。通过肉毒内输注RHSA-FECYCP对肿瘤组织的氧化：肿瘤组织氧张力在输注开始后5分钟开始上升，并保持升高15分钟。基于这一发现，由于使用辐射器需要至少15分钟的时间来照射20GY，因此我们决定同时启动辐照和输注，以辐射的RHSA-FECYCP进行辐射：组合组的局部肿瘤控制与单独的辐射相比，局部肿瘤的控制率更高。值得怀疑的是，肿瘤氧合是这种协同作用的唯一机制。对生存的影响需要进一步评估。