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

2004 Fiscal Year Final Research Report Summary

• Project/Area Number: 15390422
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Keio University
• Principal Investigator: KOBAYASHI Koichi Keio University, Department of Surgery, Professor, 医学部, 教授 (80051704)
• Co-Investigator(Kenkyū-buntansha): HORINOUCHI Hirohisa Keio University, Department of Surgery, Associate Professor, 医学部, 講師 (60173647) ; KAWAMURA Masafumi Keio University, Department of Surgery, Associate Professor, 医学部, 講師 (70169770) ; WATANABE Masazumi Keio University, Department of Surgery, Instructor, 医学部, 助手 (90201227) ; IZUMI Yotaro Keio University, Department of Surgery, Instructor, 医学部, 助手 (90245506) ; FUJIMOTO Hiroyuki Keio University, Department of Surgery, Instructor, 医学部, 助手 (20338073)
• Project Period (FY): 2003 – 2004
• Keywords: tumor oxygenation / tumor perfusion / artificial oxygen carrier / tumor irradiation

Research Abstract

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.