1999 Fiscal Year Annual Research Report

血管新生に及ぼすプラスミノーゲン分画とその阻害物質の作用機序の解明

Research Project

Project/Area Number	09670041
Research Institution	HAMAMATU UNIVERSITY SCHOOL OF MEDECINE
Principal Investigator	高田明和浜松医科大学, 医学部, 教授 (80092980)
Co-Investigator(Kenkyū-buntansha)	永井信夫浜松医科大学, 医学部, 助手 (90260281) 井原勇人浜松医科大学, 医学部, 助手 (00223298) 浦野哲盟浜松医科大学, 医学部, 助教授 (50193967)
Keywords	アンギオスタチン / 血管新生 / 腫瘍増殖・転移 / プラスミノーゲン
Research Abstract	この研究の目的は、腫瘍の転移・増殖における線溶系因子の関与を解明することにある。本研究に於いて、浸潤、増殖に不可欠な血管新生を抑制するとされる、プラスミノーゲンの蛋白分解分画であるアンギオスタチンの、腫瘍の増殖・転移能に及ぼす影響を検討した。昨年度までの研究において、ヒトプラスミノーゲンを添加し培養したヒト腫瘍細胞の培養上清中にアンギオスタチンが生成されることが確認でき、これが、より強い抗血管新生効果を有するとされるS-S結合が解離したアンギオスタチンであることが示された。報告されているアンギオスタチンはプラスミノーゲンのクリングル1-4であるが、この方法で得られた分画はクリングル1-5である可能性が示された。ヒト大腸癌切除標本の癌組織中のアンギオスタチン量を測定した。癌組織中においてプラスミノーゲンの抗原性を有する低分子量分子画は、同標本の正常部位と比べてより多く存在した。また、またそのS-S結合が解離していることがわかった。本研究において、このようにプラスミノーゲンのクリングル1-5を有し、S-S結合が解離しているアンギオスタチンが、腫瘍細胞上清中や癌組織中に多く存在することが示された。その血管新生阻害作用に伴い、組織中の発現量が転移、浸潤能とどのように関連が或るか検討しその生理的意義を解明する必要がある。

Research Products

(13 results)

All Other

All Publications (13 results)

[Publications] Endo A,et al: "Proteolysis of neuronal cell adhesion molecule by the tissue plasminogen activator-plasmin system after kainate injection in the mouse hippcocampus"Neurosci,Res.. 33. 1-8 (1999)
[Publications] Malyszko,J,S.,et al: "15-deoxypegualin and platelet aggregation in vitro"Nephron. 81. 370-372 (1999)
[Publications] Takada,A.and Takada,Y.: "Cancer and Fibrinolysis"Turk,J.Haematol.. 16(2). 51-64 (1999)
[Publications] Nagai,N.et al: "Neuronal degeneration and a decrease in laminin-like immunoreactivity in assocciated with elevated tissue-type plasminogen activator in the rat hippocampus after kainic acid injection"Neurosci,Res.. 33. 147-154 (1999)
[Publications] Sakata,K.et al: "Differential effects of enalapril and nitrendipine on the fibrinolytic system in essential hypertension"Am.Heart J.. 137(6). 1094-1099 (1999)
[Publications] Endo,A.et al: "The activation of tissue plasminogen activator-plasmin system induced in the mouse hippocampus after injection of trimethyltin : Possible proteolysis of highly polysialated NCAM"Jpn,J.Physiol.. 49. 463-466 (1999)
[Publications] Abe,J.et al: "Larger and more invasive colorectal carcinoma conatains larger amounts of plasminogen activator inhibitor type I and its relative ratio over urokinase receptor correlates well with tumor size"Cancer. 86(12). 2602-2611 (1999)
[Publications] Pawlak,R.et al: "Differential effects of nicotine against stress-induced changes in dopaminergic system in rat striatum and hippocampus"Eur,J.Pharamacol.. 387. 171-177 (2000)
[Publications] Ahaneku,J.E.et al: "Influence of baseline values on lipids,lipoproteins and fibrinolytic parameters during amlodipine treatment of hypertension in Japanese patients"Phamacol,Res.. 41(1). 79-82 (2000)
[Publications] Ahaneku,J.E.et al: "Influence4 of baseline values on lipids,lipoproteins and fibrinolytic parameners during treatment of hypertension with clinidipine"Phamacol,Res.. 41(1). 73-77 (2000)
[Publications] Urano,T.et al: "Coagulation Associated Enhancement of Fibrinolytic Activity Via a Neutralization of PAI-1 Activity"Semin.Thromb.Hemost.. (in press).
[Publications] Urano,T.et al: "The cleavage and inactivation of plasminogen activator inhibitor type 1 and α2-antiplasmin by reptilase,a thrombin-like venom enzyme"Blood Coagulation & Fibrinolysis. (in press).
[Publications] Urano,T.et al: "Soluble therombomodulin quenches thrombin-mediated neutralization of PAI-1 activity and inhibits fibrinolysis through a TAF1 independent mechanism"Fibrinolysis & Proteolysis. (in press).

1999 Fiscal Year Annual Research Report

血管新生に及ぼすプラスミノーゲン分画とその阻害物質の作用機序の解明

Principal Investigator

高田 明和 浜松医科大学, 医学部, 教授 (80092980)

Research Products

[Publications] Endo A,et al: "Proteolysis of neuronal cell adhesion molecule by the tissue plasminogen activator-plasmin system after kainate injection in the mouse hippcocampus"Neurosci,Res.. 33. 1-8 (1999)

[Publications] Malyszko,J,S.,et al: "15-deoxypegualin and platelet aggregation in vitro"Nephron. 81. 370-372 (1999)

[Publications] Takada,A.and Takada,Y.: "Cancer and Fibrinolysis"Turk,J.Haematol.. 16(2). 51-64 (1999)

[Publications] Nagai,N.et al: "Neuronal degeneration and a decrease in laminin-like immunoreactivity in assocciated with elevated tissue-type plasminogen activator in the rat hippocampus after kainic acid injection"Neurosci,Res.. 33. 147-154 (1999)

[Publications] Sakata,K.et al: "Differential effects of enalapril and nitrendipine on the fibrinolytic system in essential hypertension"Am.Heart J.. 137(6). 1094-1099 (1999)

[Publications] Endo,A.et al: "The activation of tissue plasminogen activator-plasmin system induced in the mouse hippocampus after injection of trimethyltin : Possible proteolysis of highly polysialated NCAM"Jpn,J.Physiol.. 49. 463-466 (1999)

[Publications] Abe,J.et al: "Larger and more invasive colorectal carcinoma conatains larger amounts of plasminogen activator inhibitor type I and its relative ratio over urokinase receptor correlates well with tumor size"Cancer. 86(12). 2602-2611 (1999)

[Publications] Pawlak,R.et al: "Differential effects of nicotine against stress-induced changes in dopaminergic system in rat striatum and hippocampus"Eur,J.Pharamacol.. 387. 171-177 (2000)

[Publications] Ahaneku,J.E.et al: "Influence of baseline values on lipids,lipoproteins and fibrinolytic parameters during amlodipine treatment of hypertension in Japanese patients"Phamacol,Res.. 41(1). 79-82 (2000)

[Publications] Ahaneku,J.E.et al: "Influence4 of baseline values on lipids,lipoproteins and fibrinolytic parameners during treatment of hypertension with clinidipine"Phamacol,Res.. 41(1). 73-77 (2000)

[Publications] Urano,T.et al: "Coagulation Associated Enhancement of Fibrinolytic Activity Via a Neutralization of PAI-1 Activity"Semin.Thromb.Hemost.. (in press).

[Publications] Urano,T.et al: "The cleavage and inactivation of plasminogen activator inhibitor type 1 and α2-antiplasmin by reptilase,a thrombin-like venom enzyme"Blood Coagulation & Fibrinolysis. (in press).

[Publications] Urano,T.et al: "Soluble therombomodulin quenches thrombin-mediated neutralization of PAI-1 activity and inhibits fibrinolysis through a TAF1 independent mechanism"Fibrinolysis & Proteolysis. (in press).

高田明和浜松医科大学, 医学部, 教授 (80092980)