Basic research on targeting chemotherapy using anti-urokinase monoclonal antibody.

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(1) The amounts of urokinase-type plasminogen activator (u-PA) antigen and tissue type plasminogen activator (t-PA) antigen were determined in plasma, urine and tissues of patients with cancer of digestive tracts. Urinary levels of u-PA, but not those of t-PA increased in patients with cancer, and generally decreased after the removal of cancer by operation. Urinary u-PA levels kept increasing in patients with recurrence of cancer or with metastasis into liver or peritoneum. Plasma levels of t-PA, but not those of u-PA decreased in patients with cancer. When the amounts of UK were compared in cancer tissues and their adjacent normal mucosal layer, cancer tissues always had higher levels of u-PA, but t-PA levels were the same between tumor tissues and normal mucosa. The results suggest that the type of plasminogen activator was u-PA type in cancer of digestive tracts.(2) The relationship between plasminogen activator derived from cancer cell and metastasis in cancer of digestive organs … More was investigated. Immunohistochemical staining showed strong stain of u-PA and plasminogen activator inhibitor 1 (PAI-1) in tumor cells, especially advanced site of main tumor. Main tumor and metastatic lymph node showed higher levels of u-PA than normal tissues of stomach and lymph node. In contrast of u-PA levels, the amount of t-PA were not different between tumor tissues and normal tissues in stomach, and decreased in metastatic lymph node. U-PA levels in peritoneum showed higher rate in case which depth of main tumor was deeper than se (s exposed) even though there was no peritoneal metastasis grossly, in contrast t-PA levels in peritoneum were lower in such case. High PAI-1 levels of main gastric tumors showed high tendency of lymph node metastasis. Plasma t-PA levels in patients with cancer of digestive tracts tended to show lower rate than those of healthy controls. It was speculated that activation of u-PA derived from cancer cells and systemic decrease of t-PA related to local invasion and metastasis of cancer. It is likely that targeting chemotherapy using anti-u-PA monoclonal antibody should be one of beneficial methods for prevention of metastasis formation of cancer tissue. Less