| Research Abstract |
Post-operative recurrence is frequent in cases of curative resection of pancreatic cancer, and liver metastasis is the most important factor for prognosis. Then, attempting to establish intraoperative chemotherapy with lower side-effect and higher anti-cancer effect, we have studied the targeting chemotherapy using liposome against pancreatic cancer cells. Adriamycin (ADM) was used as anti-cancer agent to be encapsulated, and purified-anti-CA 19-9 as an antibody to be conjugated. In vitro, the human pancreatic cancer cell line, PK-1, established by us, and in vivo, its subcutaneous graft to nude mice were used. In vitro, at each concentration of 1, 0.1 and 0.01 mu g/ml of ADM, the antibody-conjugated liposome showed a stronger growth-inhibitory effect after two hours contact than free ADM, and especially at 0.01 mu g/ml, only the antibody-conjugated liposome showed a significant difference from the control. In vivo, in group of antibody-conjugated liposome the highest concentration of ADM in tumor tissue and the highest growth inhibitory effect were obtained. The distribution of liposome was examined on dogs. As compared with free ADM, ADM-encapsulated liposome showed over three times accumulation in the liver without accompanying any significant dysfunction. The detailed distribution is not clear, but longer retention of a higher level of ADM near tumor cells is probable Accordingly, the transportal administration of mono- clonal antibody-conjugated liposome is considered to be an effective measure against liver metastasis in cases of curative resection of pancreatic cancer.
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