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

抗尿激酶单克隆抗体靶向化疗的基础研究。

• 批准号: 01570752
• 负责人: AOKI Katsunori
• 金额: $ 1.34万
• 依托单位: Hamamatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01570752/
• 关键词: Plasminogen Activator; Urokinase-type PA; Tissue type PA; PA Inhibitor 1 (PAI-1); PA Inhibitor 2 (PAI-2); Cancer of digestive organs; Metastasis of cancer; Invasion of cancer; Targeting chemotherapy; 胃癌

(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

(1)本文测定了消化道恶性肿瘤患者血浆、尿液和组织中尿激酶型纤溶酶原激活物（u-PA）抗原和组织型纤溶酶原激活物（t-PA）抗原的含量。肿瘤患者尿u-PA水平升高，而t-PA水平无明显变化，手术切除肿瘤后尿u-PA水平普遍下降。尿u-PA水平在肿瘤复发、肝转移或腹膜转移患者中持续升高。癌症患者血浆t-PA水平下降，但u-PA水平没有下降。比较癌组织和癌旁正常粘膜组织中尿激酶的含量，发现癌组织中u-PA的含量总是较高，而t-PA的含量在癌组织和正常粘膜组织中是相同的。结果提示消化道肿瘤纤溶酶原激活物的类型为u-PA型。(2)癌细胞纤溶酶原激活物与消化道肿瘤转移的关系 ...更多信息 被查免疫组化显示u-PA和纤溶酶原激活物抑制剂1（派-1）在肿瘤细胞中呈强阳性表达，尤以主瘤的进展期为主。胃癌及转移淋巴结组织u-PA水平明显高于正常胃组织及淋巴结组织。胃癌组织中u-PA含量与正常胃组织相比无显著性差异，转移淋巴结中t-PA含量明显降低。在肿瘤深度大于暴露深度的病例中，即使大体上无腹膜转移，腹膜中U-PA水平也较高，而t-PA水平较低。派-1高表达的胃主要肿瘤有较高的淋巴结转移倾向。消化道恶性肿瘤患者血浆t-PA水平较健康对照组有降低的趋势。推测来源于癌细胞的u-PA的激活和全身t-PA的降低与肿瘤的局部浸润和转移有关。抗u-PA单克隆抗体靶向化疗可能是预防肿瘤转移的有效方法之一。少

项目成果

西野 暢彦,中村 昌樹,青木 克憲,今野 弘之,馬場 正三,高田 明和: "消化器癌転移におけるPlasminogen activatorの役割" 日本消化器外科学会雑誌. 24. 1096-1100 (1991)

Nobuhiko Nishino、Masaki Nakamura、Katsunori Aoki、Hiroyuki Konno、Shozo Baba、Meiwa Takada：“纤溶酶原激活剂在胃肠道癌症转移中的作用”日本胃肠外科杂志 24. 1096-1100 (1991)。

中村 昌樹,他: "胃癌の浸潤、転移におけるPA及びPAIの意義" 血液と循環. 5. 37-40 (1991)

Masaki Nakamura 等人：“PA 和 PAI 在胃癌侵袭和转移中的意义”《血液与循环》，5. 37-40 (1991)。

NISHINO N, NAKAMURA M, AOKI K, KONNNO H, BABA S, TAKADA A.: "The Role of Plasminogen Activator for Metastasis in Cancer of Digestive Organs." The Japanese Journal of Gastroenterological Surgery.24(4). 1096-1100 (1991)

NISHINO N、NAKAMURA M、AOKI K、KONNNO H、BABA S、TAKADA A.：“纤溶酶原激活剂在消化器官癌症转移中的作用。”

西野 暢彦,青木 克憲,中村 昌樹,今野 弘文,馬場 正三: "消化器癌転移におけるプラスミノ-ゲンアクチベ-タ-の役割" 日本消化器外科学会雑誌. 24. (1991)

Nobuhiko Nishino、Katsunori Aoki、Masaki Nakamura、Hirofumi Konno、Shozo Baba：“纤溶酶原激活剂在胃肠道癌症转移中的作用”日本胃肠外科杂志 24。（1991）。

NAKAMURA M, KONNO H, TANAKA T, MARUO Y, NISHINO N, AOKI K, BABA S, SAKAGUCHI S, TAKADA Y, TAKADA A.: "Possible Roles of Plasminogen Activator Inhibitor 2 in the Prevention of the metastasis of gastric cancer tissues." Thrombosis Research.

NAKAMURA M、KONNO H、TANAKA T、MARUO Y、NISHINO N、AOKI K、BABA S、SAKAGUCHI S、TAKADA Y、TAKADA A.：“纤溶酶原激活剂抑制剂 2 在预防胃癌组织转移中的可能作用。