2000 Fiscal Year Annual Research Report

固型腫瘍の発育・進展における一酸化窒素・酸素ラジカルの役割についての研究

Research Project

Project/Area Number	12215121
Research Institution	Kumamoto University
Principal Investigator	赤池孝章熊本大学, 医学部, 助教授 (20231798)
Co-Investigator(Kenkyū-buntansha)	澤智裕熊本大学, 医学部, 助手 (30284756) 宮本洋一熊本大学, 医学部, 助手 (20295132) 前田浩熊本大学, 医学部, 教授 (90004613)
Keywords	フリーラジカル / NO / パーオキシナイトライト / マトリックスメタロプロテアーゼ / ヘムオキシゲナーゼ / 血管透過性 / EPR効果
Research Abstract	多くの固型腫瘍では誘導型一酸化窒素(NO)合成酵素(iNOS)の発現による過剰なNOの産生が起こっており、そのNOが癌の増殖、血管新生、転移などに関与すると考えられている。そこで、本研究では、腫瘍の増殖さらには転移に関わる酵素類(ヘムオキシゲナーゼ,HO-1,とマトリックスメタロプロテアーゼ,MMPなど)とそのNOによる制御という観点から固型腫瘍におけるNOの役割について解析した。その結果、各種固型腫瘍モデルではiNOSの発現が亢進し、過剰のNO産生が起こっており、そのNOは腫瘍血流を増大し、腫瘍血管透過性を亢進させ、さらに、NOがパーオキシナイトライトの生成を介してMMPを活性化することにより腫瘍増殖や転移を促進させることが明らかになった。一方、腫瘍細胞より産生される誘導型ヘムオキシゲナーゼは、それら窒素酸化物による酸化ストレスから腫瘍細胞そのものを防御しているものと思われた。以上の知見より、iNOS、HO-1、MMPなどを標的とした新たな癌の予防・治療の開発が可能であることが示唆された。

Research Products
(17 results)

All Other

All Publications (17 results)

[Publications] Akaike,T.,et al.: "Viral mutation accelarated by nitric oxide production during intection in vivo"FASEB J.. 14. 1447-1454 (2000)
[Publications] Akaike,T.: "Mechanisms of biological S-nitrosation and its measurement"Free Rad.Res.. 33. 461-469 (2000)
[Publications] Akaike,T.,and Maeda,H.: "Nitric oxide and virus infection"Immunology. 101. 300-308 (2000)
[Publications] Ikebe,N.,et al.: "Protective effect of S-nitrosylated α_1-protease inhibitor on hepatic ischemia-reperfusion injury"J.Pharmacol.Exp.Therap.. 295. 904-911 (2000)
[Publications] Akizuki,E.,et al.: "Role of nitric oxide and superoxide in acute cardiac allograft rejection in rats"Proc.Soc.Exp.Biol.Med.. 225. 151-159 (2000)
[Publications] Sawa,T.,et al: "Tyrosine nitration by peroxynitrite formed from nitric oxide and superoxide generated by xanthine oxidase"J.Biol.Chem.. 275. 32467-32474 (2000)
[Publications] Miyamoto,Y.,et al.: "Novel functions of human alpha l-protease inhibitor after S-nitrosylation:inhibition of cysteine protease and antibacterial activity"Biochem.Biophys.Res.Commun.. 267. 918-923 (2000)
[Publications] Miyamoto,Y.,et al: "S-nitrosylated human α_1-protease inhibitor"Biochim.biophys.Acta. 1477. 90-97 (2000)
[Publications] Sawa,T.,et al.: "Tumor-targeting chemotherapy by a xanthine oxidase-polymer conjugate that generates oxygen-free radicals in tumor tissue"Cancer Res.. 60. 666-671 (2000)
[Publications] Kuwahara,H.,et al.: "Helicobacter pylori urease suppresses bactericidal activity of peroxynitrite via carbon dioxide production"Infect.Immun.. 68. 4378-4383 (2000)
[Publications] Kanazawa,A.,et al.: "Formation of abasic sites in DNA by t-butyl peroxyl radicals:implication for potent genotoxicity of lipid peroxyl radicals."Cancer Letters. 156. 51-55 (2000)
[Publications] Suga,M.,et al.: "Characteristic elevation of matrixmetalloproteinase activity in idiopathic interstitial pneumonias."Am.J.Respir.Crit.Care Med.. 162. 1949-1956 (2000)
[Publications] Yogo,K.,et al.: "Different vasculoprotective roles of NO synthase isoforms in vascular lesion formation in mice."Arterioscler.Thromb.Vasc.Biol.. 20. E96-E100 (2000)
[Publications] Akaike,T.: "Free Radical in viral pathogenesis and mutation."Rev.Med.Virol.. (in press). (2001)
[Publications] Wu,J.,et al.: "Enhanced vascular permeability in solid tumor involving peroxynitrite and matrix metalloproteinases."Jpn.J.Cancer Res.. (in press). (2001)
[Publications] 赤池孝章: "NOとウイルスゲノムの進化"ウイルス. 50. 73-79 (2000)
[Publications] Akaike,T.,and Maeda,H.: "Nitric Oxide:Biology and Pathobiology,L.J.Ignarro(Ed.)"Academic Press,San Diego. 12 (2000)

2000 Fiscal Year Annual Research Report

固型腫瘍の発育・進展における一酸化窒素・酸素ラジカルの役割についての研究

Principal Investigator

赤池 孝章 熊本大学, 医学部, 助教授 (20231798)

Research Products

[Publications] Akaike,T.,et al.: "Viral mutation accelarated by nitric oxide production during intection in vivo"FASEB J.. 14. 1447-1454 (2000)

[Publications] Akaike,T.: "Mechanisms of biological S-nitrosation and its measurement"Free Rad.Res.. 33. 461-469 (2000)

[Publications] Akaike,T.,and Maeda,H.: "Nitric oxide and virus infection"Immunology. 101. 300-308 (2000)

[Publications] Ikebe,N.,et al.: "Protective effect of S-nitrosylated α_1-protease inhibitor on hepatic ischemia-reperfusion injury"J.Pharmacol.Exp.Therap.. 295. 904-911 (2000)

[Publications] Akizuki,E.,et al.: "Role of nitric oxide and superoxide in acute cardiac allograft rejection in rats"Proc.Soc.Exp.Biol.Med.. 225. 151-159 (2000)

[Publications] Sawa,T.,et al: "Tyrosine nitration by peroxynitrite formed from nitric oxide and superoxide generated by xanthine oxidase"J.Biol.Chem.. 275. 32467-32474 (2000)

[Publications] Miyamoto,Y.,et al.: "Novel functions of human alpha l-protease inhibitor after S-nitrosylation:inhibition of cysteine protease and antibacterial activity"Biochem.Biophys.Res.Commun.. 267. 918-923 (2000)

[Publications] Miyamoto,Y.,et al: "S-nitrosylated human α_1-protease inhibitor"Biochim.biophys.Acta. 1477. 90-97 (2000)

[Publications] Sawa,T.,et al.: "Tumor-targeting chemotherapy by a xanthine oxidase-polymer conjugate that generates oxygen-free radicals in tumor tissue"Cancer Res.. 60. 666-671 (2000)

[Publications] Kuwahara,H.,et al.: "Helicobacter pylori urease suppresses bactericidal activity of peroxynitrite via carbon dioxide production"Infect.Immun.. 68. 4378-4383 (2000)

[Publications] Kanazawa,A.,et al.: "Formation of abasic sites in DNA by t-butyl peroxyl radicals:implication for potent genotoxicity of lipid peroxyl radicals."Cancer Letters. 156. 51-55 (2000)

[Publications] Suga,M.,et al.: "Characteristic elevation of matrixmetalloproteinase activity in idiopathic interstitial pneumonias."Am.J.Respir.Crit.Care Med.. 162. 1949-1956 (2000)

[Publications] Yogo,K.,et al.: "Different vasculoprotective roles of NO synthase isoforms in vascular lesion formation in mice."Arterioscler.Thromb.Vasc.Biol.. 20. E96-E100 (2000)

[Publications] Akaike,T.: "Free Radical in viral pathogenesis and mutation."Rev.Med.Virol.. (in press). (2001)

[Publications] Wu,J.,et al.: "Enhanced vascular permeability in solid tumor involving peroxynitrite and matrix metalloproteinases."Jpn.J.Cancer Res.. (in press). (2001)

[Publications] 赤池孝章: "NOとウイルスゲノムの進化"ウイルス. 50. 73-79 (2000)

[Publications] Akaike,T.,and Maeda,H.: "Nitric Oxide:Biology and Pathobiology,L.J.Ignarro(Ed.)"Academic Press,San Diego. 12 (2000)

赤池孝章熊本大学, 医学部, 助教授 (20231798)