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1996 Fiscal Year Final Research Report Summary

EFFECTS OF INTERLEUKIN-2 VIA HEPATIC ARTERIAL INFUSION ON HEPATIC EXTRACTION AND IMMUNOPOTENTIATION

Research Project

Project/Area Number 06454390
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKINKI UNIVERSITY,SCHOOL OF MEDICINE

Principal Investigator

OKUNO Kiyotaka  KINKI UNIVERSITY,SCHOOL OF MEDICINE,ASSISTANT PROFESSOR, 医学部, 講師 (30169239)

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)
Project Period (FY) 1994 – 1996
KeywordsINTERLEUKIN-2 / HEPATIC EXTRACTION / LIVER METASTASIS / HEPATIC ARTERIAL INFUSION / IMMUNO-CHEMOTHERAPY / HEPATIC SINUSOIDAL LYMPHOCYTES
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.

  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] K.Okuno, et al.: "Hepatic immunopotentiaton by galactose-entrapped liposomal IL-2 compound in the treatment of liver metastases." Surg Today (Jpn J Surg). (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Okuno, et al.: " Adjuvant hepatic arterial IL-2 and MMC,5-FU after curative resection of colorectal liver metastases." Hepato-Gastroenterol.43. 688-691 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Okuno, et al.: "IL-2 perfusion to the liver augments the hepatic extraction rate of accompanying anticancer drugs." Surg Today (Jpn J Surg). 26. 662-664 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Okuno, et al.: "Interleukin 12 augments the liver-associated immunity and reduces liver metastases." Hepato-Gastroenterol.43. 1196-1202 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] E.Fuse, et al.: "Hepatic extraction ratio of 5-fluorouracil in rats. Doses dependence and effect of uracil and interleukin-2." Biochemical Pharmacology. 52. 561-568 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Okuno, et al.: "Locoregional immuno-chemotherapy in liver carcinoma. -present and future-." Hepato-Gastroenterol.42. 578-586 (1995)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-09  

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