1998 Fiscal Year Annual Research Report

アンチセンスDNAを用いた新しい診断・治療法開発に関する日米英共同研究

Research Project

Project/Area Number	08045063
Research Institution	Kanazawa University
Principal Investigator	山本博金沢大学, 医学部, 教授 (00115198)
Keywords	antisense / antisense display / nucleoside / ribozyme / liposome / aptamer
Research Abstract	(目的) 本研究は、金沢大学と米国・ニューヨーク州立大学バッファロー校、英国・シェフィールド大学との学術交流協定に基づき、3大学が擁する国際的にも屈指のアンチセンスDNA研究陣を結集して、アンチセンスDNAの有機化学・生化学・薬理学・薬剤動態学に関する学際研究を格段に発展させ、特異的メッセンジャーRNAを標的とした各種疾病の新しい診断・治療原理を開発することを目的とする。平成10年度研究は当初計画通り順調に進行し、以下の成果を得た。 (平成10年度) (1) 日本側分担者は、新しい機能性遺伝子スクリーニング法として前年度に考案したAntisense Display法を培養ヒト血管内皮細胞を用いたスクリーニングに応用し、内皮細胞で発現が高く血管新生制御に関与すると考えられる新規遺伝子の分離に成功した。 (2) 米国側分担者は、各種修飾リポソームを用いた核酸薬品の高効率デリバリー法の開発に成功するとともに、前年度見い出された抗インターフェロンDNAはインターフェロンの高次構造を変化させることでアプタマー効果を発揮することを明らかにした。 (3) 英国側分担者は、Mn^<++>要求性新規ヘアピン型リボザイムの触媒メカニズムを明らかにした。 (4) 日米英三国の研究分担者と研究協力者が金沢に集い、アンチセンスDNA/RNAおよびその応用に関する公開ジョイント・セミナーを開催した。

Research Products
(43 results)

All Other

All Publications (43 results)

[Publications] Yamagishi,S.: "Advanced glycation endproducts inhibit prostacyclin production and induce plasminogen activator inhibilor-1 in human microvascular endothelial cells." Diabetologia. 41(12). 1435-1441 (1998)
[Publications] Takamura,T.: "Transgenic mice overexpressing type 2 nitric oxide synthase in pancreatic β cells develop insulin-dependent diabetes without insulitis." J.Biol.Chem.273. 2493-2496 (1998)
[Publications] Ogawa,H.: "Functional properties of the unc-64 gene encoding a Caenorhabditis elegans syntaxin." J.Biol.Chem.273(4). 2192-2198 (1998)
[Publications] Nomura,M.: "Placenta growth factor(PIGF)mRNA expression in brain tumors." Journal of Neuro-oncology. 40(2). 123-130 (1998)
[Publications] Taniguchi,K.: "The relation between the growth patterns of fastric carcinoma and the expression of hepatocyte growth factor receptor(c-met),autocrime motility factror receptor,and urokinase-type plasminogen activator receptor." Cancer. 82(11). 2112-2122 (1998)
[Publications] Yamagishi,S.: "AGE and endothelial cells." Journal of Atherosclerosis and Thrombosis. 4(4). 141-143 (1998)
[Publications] Segawa,Y.: "Upregulation of retinal vascular endothelial growth factor mRNAs in spontaneously diabetic rats without ophthalmoscopic retinopathy." Ophthalmic Res. 30. 333-339 (1998)
[Publications] Ishizaki,J.: "Characteristic Subcellular Distribution,in Brain,Heart and Lung,of Biperiden,Trihexyphenidyl,and(-)-Quinuclidinyl Benzylate in Rats." Biol.Pharm.Bull.21. 67-71 (1998)
[Publications] Ishizaki,J.: "Effect of Sequence of Adiministraton on the Pharmacokinetic Interaction between the Anticholinergic Drug Biperiden and[^3H]Quinuclidinyl Benzylate or[3H]N-Methylscopolamine in Rats." J.Pharm.Pharmacol.50. 189-196 (1998)
[Publications] Ishizaki,J.: "Influence of Ammonium Chloride on the Tissue Distribution of Anticholinergic Drugs in Rats." J.Pharm.Pharmacol.50. 761-766 (1998)
[Publications] Ishizaki,J.: "Uptake of Basic Drugs into Rat Lung Granule Fraction in Vitro." Biol.Pharm.Bull.21. 858-861 (1998)
[Publications] Yonemura,Y.: "Prognostic significance of c-erbB-2 gene expression in the poorly differentiated type of adenocarcinoma of the stomach." Cancer Detection and Prevention. 22(2). 139-146 (1998)
[Publications] Nazaki,S.: "Immunohistochemical localization of a urokinase-type plasrninogen activator system in squamoous cell carcinoma of the oral cavity:association with mode of invasion and lymph node metastasis." Eur.J.Cancer. 34(1). 58-62 (1998)
[Publications] Fujimura,T.: "Trypsinogen expression and early detection for peritoneal dissemination in gastric cancer." J.Surg.Oncol.69(2). 71-75 (1998)
[Publications] Bando,E.: "Immunohistochemical study of MT-MMP tissus status in gastric carcinoma and correlation with survival analyzed by univariate and multivariate analysis." Oncol.Rep.5(6). 1483-1488 (1998)
[Publications] Kinuya,S.: "Rhenium-186-mercaptoacethyltriglycine labeled monoclonal antibody for radioimmunotherapy:In vitro assessment,in vivokinetics and dosimetry in tumor-bearing nude mice" Jpn J Cancer Res. 89. 870-878 (1998)
[Publications] Watanabe,N.: "Radiotoxicity after iodine-131 therapy for thyroid cancer using the micronucleus assay." J.Nucl.Med.38. 436-440 (1998)
[Publications] Watanabe,N.: J.Nucl.Med.39. 2077-2079 (1998)
[Publications] Booth BP: "Regulation of in vivo whole blood aggregation in rats by calcitonin gene related peptide." Can J Physiol Pharmacol. 76(7-8). 811-813 (998)
[Publications] Tabrizi-Fard MA: "Effects of nitro-L-arginine on blood pressure and cardiac index in anesthetized rats:a pharmacokinetic-pharmacodynamic analysis." Pharm Res. 15(7). 1063-1068 (1998)
[Publications] Booth BP: "Contribution of vascular tissue to the antiplatelet activity of sodium nitroprusside." J Cardovasc Pharmacol. 32(1). 129-133 (1998)
[Publications] Edgerton M.: "Candidacidal activity of salivary histatins.Identificaiton of a histatin 5-binding protein on Candida albicans." J Biol Chem. 273(32). 20438-20447 (1998)
[Publications] Balasubramanian V.: "Interferon-gamma-inhibitory oligodeoxynucleotidesalter the conformation of interferon-gamma." Mol pharmacol. 53(5). 926-932 (1998)
[Publications] Ramanathan M: "Analysis of intracellular Th1 cytokine secretion data using parametric methodology." Cytometry. 32(2). 147-156 (1998)
[Publications] Williams DM: "Synthesis and binding of stable bisubstrate ligands for phosphoglycerate kinase." Bioorg Med Chem Lett. 8(18). 2603-2608 (1998)
[Publications] Caplan NA: "Novel bisphosphonate inhibitors of phosphoglyceratekinase." Bioorg Med Chem Lett. 8(5). 515-520 (1998)
[Publications] Jakeman DL: "Highly potent bisphosphonate ligands for phosphoglycerate kinse." J Med Chem. 41(23). 4439-4452 (1998)
[Publications] Blackburn GM: "Two hydrolase resistant analogues of diadenosine 5′5″′-P1,P3-triphosphate for studies with Fhit,the human fragile histidine triad protein." Nucleosides Necleotides. 17(1-3). 301-308 (1998)
[Publications] Bemstein BE: "A bisubstrate analog induces unexpected conformational changes in phosphoglycerate kinase from Trypanosoma brucei." J Mol Biol. 279(5). 1137-1148 (1998)
[Publications] Pace HC: "Genetic,biochemical,and crystallographic characterization of Fhit-substrate complexes as the active signaling form of Fhit." Proc Natl Acd Sci USA. 95(10). 5484-5489 (1998)
[Publications] Yamagishi,S.: "Vascular endothelial growth factor acts as pericyte mitogen under hypoxia." Laboratory Investigation. 79(4)(in press). (1999)
[Publications] Yamagishi,S.: "Insulin stimulates the growth and tube formation of human microvascular endothelial cells through autocrine vascular endothelial growth factor." Microvasc Res. (in press). (1999)
[Publications] Yonekura,H.: "Antisense display-a method for functional gene screening:evaluation in a cell-free system and isolation of angiogenesis-related genes." Nucleic Acids Res.(in press). (1999)
[Publications] Kinuya,S.: "Eary response of tumour to radiotherapy should be assessed by both uptake and retention of single photon tracers: in vitro analysis with 201TI chloride,99mTc-sestamibi and 99mTc-tetrofosmin." Nucl.Med.Com.(in press). (1999)
[Publications] Kinuya,S.: "Persistent distension and enhanced diffusive extravasation of tumor vessels improved uniform tumor targeting of radioimmunoconjugate in mice administered with angiotensin II and kininase inhibitor." Oncol.Res.(in Press). (1999)
[Publications] Kinuya,S.: "Combination radioimmunotherapy with local hyperthermia: increased delivery or radioimmunoconjugate by vascular effect and its retention by increased antigen expression in colon cancer xenografts." Cancer Lett.(in press). (1999)
[Publications] 山岸昌一: "実験医学「血管の分子医学その最前線」糖尿病性網膜症の血管生物学" 羊土社, 208 (1998)
[Publications] 藤森英希: "「血管と内皮」特集:内皮のストレスとその応答 AGEと内皮応答" メディカルレビュー社, 100 (1998)
[Publications] 米倉秀人: "「KEY WORD 1998-2000 高血圧症・動脈硬化」:3章血管新生" 先端医学社(斎藤康、萩原俊男、馬渕宏編), 207 (1998)
[Publications] 山本靖彦: "「現代医療」:糖尿病-AGE受容体" 現代医療社, 344 (1998)
[Publications] Yonemura,Y.: "Peritoneal Dissemenation -Molecular mechanisms and the latest therapy-" Maeds Shoten Kanazawa(Japan), (1998)
[Publications] 山岸昌一: "「メビオ」:糖尿病と網膜血管障害" (株)メジカルビュー社(in press), (1999)
[Publications] 山岸昌一: "「組織培養工学」:糖尿病と血管新生" ニューサイエンス社(in press), (1999)

1998 Fiscal Year Annual Research Report

アンチセンスDNAを用いた新しい診断・治療法開発に関する日米英共同研究

Principal Investigator

山本 博 金沢大学, 医学部, 教授 (00115198)

Research Products

[Publications] Yamagishi,S.: "Advanced glycation endproducts inhibit prostacyclin production and induce plasminogen activator inhibilor-1 in human microvascular endothelial cells." Diabetologia. 41(12). 1435-1441 (1998)

[Publications] Takamura,T.: "Transgenic mice overexpressing type 2 nitric oxide synthase in pancreatic β cells develop insulin-dependent diabetes without insulitis." J.Biol.Chem.273. 2493-2496 (1998)

[Publications] Ogawa,H.: "Functional properties of the unc-64 gene encoding a Caenorhabditis elegans syntaxin." J.Biol.Chem.273(4). 2192-2198 (1998)

[Publications] Nomura,M.: "Placenta growth factor(PIGF)mRNA expression in brain tumors." Journal of Neuro-oncology. 40(2). 123-130 (1998)

[Publications] Taniguchi,K.: "The relation between the growth patterns of fastric carcinoma and the expression of hepatocyte growth factor receptor(c-met),autocrime motility factror receptor,and urokinase-type plasminogen activator receptor." Cancer. 82(11). 2112-2122 (1998)

[Publications] Yamagishi,S.: "AGE and endothelial cells." Journal of Atherosclerosis and Thrombosis. 4(4). 141-143 (1998)

[Publications] Segawa,Y.: "Upregulation of retinal vascular endothelial growth factor mRNAs in spontaneously diabetic rats without ophthalmoscopic retinopathy." Ophthalmic Res. 30. 333-339 (1998)

[Publications] Ishizaki,J.: "Characteristic Subcellular Distribution,in Brain,Heart and Lung,of Biperiden,Trihexyphenidyl,and(-)-Quinuclidinyl Benzylate in Rats." Biol.Pharm.Bull.21. 67-71 (1998)

[Publications] Ishizaki,J.: "Effect of Sequence of Adiministraton on the Pharmacokinetic Interaction between the Anticholinergic Drug Biperiden and[^3H]Quinuclidinyl Benzylate or[3H]N-Methylscopolamine in Rats." J.Pharm.Pharmacol.50. 189-196 (1998)

[Publications] Ishizaki,J.: "Influence of Ammonium Chloride on the Tissue Distribution of Anticholinergic Drugs in Rats." J.Pharm.Pharmacol.50. 761-766 (1998)

[Publications] Ishizaki,J.: "Uptake of Basic Drugs into Rat Lung Granule Fraction in Vitro." Biol.Pharm.Bull.21. 858-861 (1998)

[Publications] Yonemura,Y.: "Prognostic significance of c-erbB-2 gene expression in the poorly differentiated type of adenocarcinoma of the stomach." Cancer Detection and Prevention. 22(2). 139-146 (1998)

[Publications] Nazaki,S.: "Immunohistochemical localization of a urokinase-type plasrninogen activator system in squamoous cell carcinoma of the oral cavity:association with mode of invasion and lymph node metastasis." Eur.J.Cancer. 34(1). 58-62 (1998)

[Publications] Fujimura,T.: "Trypsinogen expression and early detection for peritoneal dissemination in gastric cancer." J.Surg.Oncol.69(2). 71-75 (1998)

[Publications] Bando,E.: "Immunohistochemical study of MT-MMP tissus status in gastric carcinoma and correlation with survival analyzed by univariate and multivariate analysis." Oncol.Rep.5(6). 1483-1488 (1998)

[Publications] Kinuya,S.: "Rhenium-186-mercaptoacethyltriglycine labeled monoclonal antibody for radioimmunotherapy:In vitro assessment,in vivokinetics and dosimetry in tumor-bearing nude mice" Jpn J Cancer Res. 89. 870-878 (1998)

[Publications] Watanabe,N.: "Radiotoxicity after iodine-131 therapy for thyroid cancer using the micronucleus assay." J.Nucl.Med.38. 436-440 (1998)

[Publications] Watanabe,N.: J.Nucl.Med.39. 2077-2079 (1998)

[Publications] Booth BP: "Regulation of in vivo whole blood aggregation in rats by calcitonin gene related peptide." Can J Physiol Pharmacol. 76(7-8). 811-813 (998)

[Publications] Tabrizi-Fard MA: "Effects of nitro-L-arginine on blood pressure and cardiac index in anesthetized rats:a pharmacokinetic-pharmacodynamic analysis." Pharm Res. 15(7). 1063-1068 (1998)

[Publications] Booth BP: "Contribution of vascular tissue to the antiplatelet activity of sodium nitroprusside." J Cardovasc Pharmacol. 32(1). 129-133 (1998)

[Publications] Edgerton M.: "Candidacidal activity of salivary histatins.Identificaiton of a histatin 5-binding protein on Candida albicans." J Biol Chem. 273(32). 20438-20447 (1998)

[Publications] Balasubramanian V.: "Interferon-gamma-inhibitory oligodeoxynucleotidesalter the conformation of interferon-gamma." Mol pharmacol. 53(5). 926-932 (1998)

[Publications] Ramanathan M: "Analysis of intracellular Th1 cytokine secretion data using parametric methodology." Cytometry. 32(2). 147-156 (1998)

[Publications] Williams DM: "Synthesis and binding of stable bisubstrate ligands for phosphoglycerate kinase." Bioorg Med Chem Lett. 8(18). 2603-2608 (1998)

[Publications] Caplan NA: "Novel bisphosphonate inhibitors of phosphoglyceratekinase." Bioorg Med Chem Lett. 8(5). 515-520 (1998)

[Publications] Jakeman DL: "Highly potent bisphosphonate ligands for phosphoglycerate kinse." J Med Chem. 41(23). 4439-4452 (1998)

[Publications] Blackburn GM: "Two hydrolase resistant analogues of diadenosine 5′5″′-P1,P3-triphosphate for studies with Fhit,the human fragile histidine triad protein." Nucleosides Necleotides. 17(1-3). 301-308 (1998)

[Publications] Bemstein BE: "A bisubstrate analog induces unexpected conformational changes in phosphoglycerate kinase from Trypanosoma brucei." J Mol Biol. 279(5). 1137-1148 (1998)

[Publications] Pace HC: "Genetic,biochemical,and crystallographic characterization of Fhit-substrate complexes as the active signaling form of Fhit." Proc Natl Acd Sci USA. 95(10). 5484-5489 (1998)

[Publications] Yamagishi,S.: "Vascular endothelial growth factor acts as pericyte mitogen under hypoxia." Laboratory Investigation. 79(4)(in press). (1999)

[Publications] Yamagishi,S.: "Insulin stimulates the growth and tube formation of human microvascular endothelial cells through autocrine vascular endothelial growth factor." Microvasc Res. (in press). (1999)

[Publications] Yonekura,H.: "Antisense display-a method for functional gene screening:evaluation in a cell-free system and isolation of angiogenesis-related genes." Nucleic Acids Res.(in press). (1999)

[Publications] Kinuya,S.: "Eary response of tumour to radiotherapy should be assessed by both uptake and retention of single photon tracers: in vitro analysis with 201TI chloride,99mTc-sestamibi and 99mTc-tetrofosmin." Nucl.Med.Com.(in press). (1999)

[Publications] Kinuya,S.: "Persistent distension and enhanced diffusive extravasation of tumor vessels improved uniform tumor targeting of radioimmunoconjugate in mice administered with angiotensin II and kininase inhibitor." Oncol.Res.(in Press). (1999)

[Publications] Kinuya,S.: "Combination radioimmunotherapy with local hyperthermia: increased delivery or radioimmunoconjugate by vascular effect and its retention by increased antigen expression in colon cancer xenografts." Cancer Lett.(in press). (1999)

[Publications] 山岸昌一: "実験医学「血管の分子医学その最前線」糖尿病性網膜症の血管生物学" 羊土社, 208 (1998)

[Publications] 藤森英希: "「血管と内皮」特集:内皮のストレスとその応答 AGEと内皮応答" メディカルレビュー社, 100 (1998)

[Publications] 米倉秀人: "「KEY WORD 1998-2000 高血圧症・動脈硬化」:3章 血管新生" 先端医学社(斎藤 康、萩原俊男、馬渕 宏編), 207 (1998)

[Publications] 山本靖彦: "「現代医療」:糖尿病-AGE受容体" 現代医療社, 344 (1998)

[Publications] Yonemura,Y.: "Peritoneal Dissemenation -Molecular mechanisms and the latest therapy-" Maeds Shoten Kanazawa(Japan), (1998)

[Publications] 山岸昌一: "「メビオ」:糖尿病と網膜血管障害" (株)メジカルビュー社(in press), (1999)

[Publications] 山岸昌一: "「組織培養工学」:糖尿病と血管新生" ニューサイエンス社(in press), (1999)

山本博金沢大学, 医学部, 教授 (00115198)

[Publications] 米倉秀人: "「KEY WORD 1998-2000 高血圧症・動脈硬化」:3章血管新生" 先端医学社(斎藤康、萩原俊男、馬渕宏編), 207 (1998)