| Project/Area Number |
06454390
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | KINKI UNIVERSITY,SCHOOL OF MEDICINE |
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Principal Investigator |
OKUNO Kiyotaka KINKI UNIVERSITY,SCHOOL OF MEDICINE,ASSISTANT PROFESSOR, 医学部, 講師 (30169239)
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| Co-Investigator(Kenkyū-buntansha) |
SHIGEOKA Hironori KINKI UNIVERSITY,SCHOOL OF MEDICINE,SENIOR FELLOW, 医学部, 助手 (70247998)
HIROHATA Takeshi KINKI UNIVERSITY,SCHOOL OF MEDICINE,ASSISTANT PROFESSOR, 医学部, 講師 (60228848)
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| Project Period (FY) |
1994 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | INTERLEUKIN-2 / HEPATIC EXTRACTION / LIVER METASTASIS / HEPATIC ARTERIAL INFUSION / IMMUNO-CHEMOTHERAPY / HEPATIC SINUSOIDAL LYMPHOCYTES |
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| Research Abstract |
A pilot study we conducted on hepatic infusion chemotherapy (MMC,5-FU) combined with interleukin-2 (IL-2) for metastatic liver malignancies revealed very encouraging results which indicate that this treatment modality is more effective than either of the anti-cancer drugs used alone. To clarify the mechanisms underlying the synergism of these modalities, the pharmacokinetics of anti-cancer drugs and immunopotentiating effects in the presence of IL-2 were examined in a rat model. Adult rats were given chemotherapy combined with various doses of IL-2 for the measurement of hepatic extraction rates (HER) and hepatic anti-cancer activity using ^<51>Cr release assay. The HER or 5-FU was significantly increased (p<0.01) in combination with IL-2 in a dose-dependent fashion while that of MMC also showed a tendency to increase. Thus, it is conceivable that the increase of vascular permeability by IL-2 results in the augmentation of the HER of associated anti-cancer drugs. This effect may improve the delivery of anti-cancer drugs to the liver and alleviate the general toxicity by reducing the amount of circulating anti-cancer agents. Immunological assessment of hepatic infusion of IL-2 have shown to increase the number of hepatic sinusoidal lymphocytes and the cytolytic activity against tumor target cells in a dose-dependent fashion. Associated chemotherapy did not interfere the cytotoxic activity of HSL under this regimen.
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