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

(1)测定消化道癌患者血浆、尿液和组织中尿激酶型纤溶酶原激活物(u-PA)和组织型纤溶酶原激活物(t-PA)抗原的含量。癌症患者尿u-PA水平升高，而t-PA水平无明显变化，手术切除后尿u-PA水平普遍下降。肿瘤复发或有肝、腹膜转移的患者尿u-PA水平持续升高。癌症患者血浆t-PA水平下降，但不降低u-PA水平。比较癌组织和癌旁正常粘膜中UK的含量，癌组织中u-PA的水平始终较高，而t-PA在肿瘤组织和正常粘膜中的水平相同。结果提示，消化道癌组织中纤溶酶原激活物的类型为u-PA型。(2)癌细胞来源的纤溶酶原激活物与消化系肿瘤转移的关系：…更多的调查正在进行中。免疫组织化学染色显示u-PA和纤溶酶原激活物抑制物-1(PAI-1)在肿瘤细胞，尤其是主瘤的晚期部位有较强的表达。主瘤和转移淋巴结组织中u-PA水平高于正常胃组织和淋巴结组织。与u-PA水平相比，胃肿瘤组织和正常胃组织中t-PA含量无明显差异，而转移淋巴结中t-PA含量降低。在无腹膜转移的情况下，腹膜u-PA水平在主瘤深度大于Se(S暴露)的病例中所占比例较高，而腹膜t-PA水平则低于Se(S暴露)。PAI-1的高水平提示胃主要肿瘤有较高的淋巴结转移倾向。消化道癌患者血浆t-PA水平明显低于健康对照组。推测癌细胞来源的u-PA的激活和t-PA的全身性降低与肿瘤的局部侵袭和转移有关。应用抗u-PA单抗进行靶向化疗可能是预防肿瘤组织转移的有效方法之一。较少

(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