1991 Fiscal Year Final Research Report Summary
Basic research on targeting chemotherapy using anti-urokinase monoclonal antibody.
| Project/Area Number |
01570752
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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 | Hamamatsu University School of Medicine |
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Principal Investigator |
AOKI Katsunori Hamamatsu Univ., Sch. Med, Dep. of Emergency Medicine, Assistant Professor, 医学部付属病院・救急部, 助教授 (20124927)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Masaki Hamamatsu Univ., Sch. Med, Second Department of Surgery, Assistant., 医学部付属病院第2外科, 医員
NISHINO Nobuhiko Hamamatsu Univ., Sch. Med, Second Department of Surgery, Assistant., 医学部外科学第2講座, 助手 (80228197)
KONNNO Hiroyuki Hamamatsu Univ., Sch. Med, Second Department of Surgery, Lecturer., 医学部付属病院第2外科, 講師 (00138033)
TAKADA Akikazu Hamamatsu Univ., Sch. Med, Second Department of Physiology, Professor., 医学部・生理学第2講座, 教授 (80092980)
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| Project Period (FY) |
1989 – 1991
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| Keywords | 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 |
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| Research Abstract |
(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
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