| Project/Area Number |
63570646
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | Nagoya City University |
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Principal Investigator |
YURA Jiro Nagoya City University Medical School, Professor, 医学部, 教授 (90079997)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUNO Isamu Nagoya City University Medical School, Lecturer, 医学部, 講師 (20157506)
YOTSUYANAGI Toshihisa Faculty of Pharmaceutical Sciences, Nagaya City University, Assistant Professor, 薬学部, 助教授 (40080189)
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| Project Period (FY) |
1988 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1990: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1989: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1988: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Liposome / VX2 tumor / Liposome-entrapped adrimycin / Liver metastasis / Portal vein administration / 経門脈投与 / Liposome-Adriamycin / 組織cytotoxicity / liposome / liposome-adriamycin / 家兎VX2腫瘍 |
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| Research Abstract |
We examined the tissue distributions and antitumor effect of freeze-dried liposome-entrapped adriamycin (Lipo-ADM) administered via the portal vein to rabbits bearing VX2 tumors. Liposomes composed of egg phosphatidylcholine (cholesterol 50 mol%) were used as drug carriers. Liver concentration of ADM increased after delivery and cardiac uptake decreased compared with free drug treatment. The in vivo antitumor effect of Lipo-ADM was determined in rabbits inoculated VX2 tumor. Repeated injections via the portal vein, prolonged the life-spans of tumor-bearing rabbits. Lipo-ADM treatment further prolonged those compared with the control group and the free ADM group. Histological examination revealed that the damage caused by Lipo-ADM administered via the portal vein did not differ from that observed in animals treated with free ADM. These results indicate that portal vein administration of Lipo-ADM may be more effective in dealing with liver metastases than treatment with free ADM and may
… More
be therapeutically useful without toxic side effects. Considering these results we have studied the effect of Lipo-ADM administered via the portal vein and the clinical application of this treatment in the therapy and inhibition of the liver metastases. In clinical evaluations, chemotherapy via the portal vein was performed using a subcutaneously implanted reservoir. 10 patients were treated via the portal vein with Lipo-ADM (20-30 mg/2 weeks) and the clinical effects evaluated. No liver dysfunction, bone narrow suppression or other side effects were noted when Lipo-ADM was administered via the portal vein. The postoperative mean survival time was 141 days for 9 patients treated previously with free ADM and MTX-5FU therapy. In contrast, the mean survival time was 439 days for 10 patients treated with Lipo-ADM therapy ; moreover, 3 cases of gastric cancer and one case of uterine cancer survived for 468 days postoperatively, and 2 cases have survived for more 600 days. This study demonstrates that chemotherapy using Lipo-ADM via the portal vein in inoperable metastatic liver cancer markedly improves the survival time. Less
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