1996 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)
Co-Investigator(Kenkyū-buntansha)	BLACKBURN Je 米国, シェフィールド大学, 教授 GRASBY Jane 米国, シェフィールド大学, 講師 RAMANATHAN M 米国, ニューヨーク州立大学, 助教授 STRAUBINGER ロバートエム米国, ニューヨーク州立大学, 助教授 FUNG HoーLeun 米国, ニューヨーク州立大学, 教授横山邦彦金沢大学, 医学部附属病院, 助手 (60230661) 米村豊金沢大学, 医学部附属病院, 講師 (20167042) 中島恵美金沢大学, 医学部附属病院, 助教授 (90115254) 市村藤雄金沢大学, 医学部附属病院, 教授 (40143911) 原田真市金沢大学, 医学部, 助手 (90272955) 米倉秀人金沢大学, 医学部, 助教授 (80240373)
Keywords	アンチセンス / がん / 血管新生 / 薬剤耐性リポソーム / リポソーム / 修飾オリゴヌクレオチド
Research Abstract	本共同研究は、金沢大学と米国・ニューヨーク州立大学バッファロ-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目的で遂行された。本年度研究は、当初計画通り順調に進行し、以下の成果を得た。 1.日本側分担者は、培養細胞を用いた試験管内アッセイで(1)がん増殖・浸潤と(2)血管新生さらには(3)薬剤耐性の阻止に有効なホスホロチオエ-ト型アンチセンス分子をスクリーニングし、各々(1)c-met遺伝子、AMFR遺伝子、(2)VEGF遺伝子、(3)mdr-1遺伝子の発現阻止に有効なアンチセンスDNA標品を得た。 2.米国側分担者は、リポソームや多価陽イオン化担体を用いてアンチセンスDNAを効率よく細胞内に移入させる方法を確立した。 3.英国側分担者は、加水分解抵抗性のホスホネート修飾オリゴヌクレオチドの開発に成功した。 4.平成8年7月には日本側分担者(中島)が米国を訪問し、アンチセンス薬品の動態に関する調査研究を行った。 5.平成9年3月には英国側分担者(Blackburn)が来日し、アンチセンスDNA/RNAの化学・生物学に関するセミナーと研究打ち合わせを行った。

Research Products
(36 results)

All Other

All Publications (36 results)

[Publications] Yamagishi,S.: "Advanced glycation endproducts-driven angiogenesis in vitro." J.Biol.Chem.272. 8723-8730 (1997)
[Publications] Hayashi,Y.: "Induction of various blood-brain barrier properties in non-neural endothelial cells by close apposition to co-cultured astrocytes." Glia. 19. 13-26 (1997)
[Publications] Yamagishi,S.: "Advanced glycosylation end products stimulate the growth but inhibit the prostacyclin-producing ability of endothelial cells through interactions with their receptors." FEBS Letters. 384. 103-106 (1996)
[Publications] Yamamoto,Y.: "Advanced glycation endproducts-receptor interactions stimulate the growth of human pancreatic cancer cells through the induction of platelet-derived growth factor-B." Biochem.Biophys.Res.Commun.222. 700-705 (1996)
[Publications] Kaji,M.: "Participation of c-met in the progression of human gastric cancers;anti-c-met oligonucleotides inhibit proliferation or invasiveness of gastric cancer cells." Cancer Gene Therapy. 3. 393-404 (1996)
[Publications] Yamamoto,H.: "Vascular VEGF:The expression and roles in hypoxia-driven angiogenesis." Journal of Vascular Research. 33. 110 (1996)
[Publications] Yamagishi,S.: "Advanced glycation endproducts can promote angiogenesis through autocrine vascular endothelial growth factors." Journal of Vascular Research. 33. 110 (1996)
[Publications] Hayashi,Y.: "Astrocytes can transdifferentiate non-neural endothelial cells into the neural type through endfeet-mediated contacts." Journal of Vascular Research. 33. 33 (1996)
[Publications] Hatakeyama,H.: "The expression of steroidogenic enzyme genes in human vascular cells." Biochem.Mol.Biol.Int.40. 639-645 (1996)
[Publications] Hirono,Y.: "Expression of autocrine motility factor receptor correlates with disease progression in human gastric cancer." British Journal of Cancer. 74. 2003-2007 (1996)
[Publications] Ronan,Paul: "Effect of low frequency magnetic fields and induced current on DNA digestion." Proc.of Australian University Power Engineering Conference. 259-262 (1996)
[Publications] Nafalski,A.: "Measurement of magnetic fields in urban environment." Proc.of Australian University Power Engineering Conference. 247-252 (1996)
[Publications] Nata,K.: "Human gene encoding(ADP-ribosyl cyaclase/cyclic ADP-ribose hydrolase):organization,nucleotide sequences and alternative splicing." Gene. (in press). (1997)
[Publications] Noguchi,N.: "Cyclic ADP-ribose binds to FK506-binding protein 12.6 to release Ca^<2+> from islet microsomes." J.Biol.Chem.272. 3133-3136 (1997)
[Publications] Tohgo,A.: "Lysine 129 of CD38(ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase)participates in the binding of ATPto inhibit the cyclic ADP-ribose hydrolase." J.Biol.Chem.272. 3879-3882 (1997)
[Publications] Okamoto,H.: "Synthesis and hydrolysis of cyclic ADP-ribose by human leukocyte antigen CD38:Inhibition of hydrolysis by ATP and the physiological significance." 280(in press). (1997)
[Publications] Ichimura,F.: "Contribution of lysosomes to the subcellular distribution of basic drugs in the rat liver." Phamaceul.Res.13. 902-906 (1996)
[Publications] Kuno,K.: "Molecular cloning of a gene encoding a new type of metalloproteinase-disintegrin family protein with thrombosypondia motifs as an inflammation associated gene." J.Biol.Chem.(in press). (1996)
[Publications] Nakashima,E.: "A candidate for cancer gene therapy:MIP-1α gene transfer to an adenocarcinoma cell line reduced tumorigenicity and induced protective immunity in immunocompetent mice." Phamaceul.Res.13. 1895-1900 (1996)
[Publications] Yonemura,Y.: "Correlation between overexpression of c-met gene and the progression of gastric cancer." Int.J.Oncology. 8. 555-560 (1996)
[Publications] Yonemura,Y.: "Effects of intraoperative chemo-hyperthemia in patients with gastric cancer with peritoneal dissenmination." Surgery. 119. 437-443 (1996)
[Publications] Yonemura,Y.: "Correlation of the histological effects and survival after neoadjuvant chemotherapy on gastric cancer patients." Hepato-Gastroenterology. 43. 1260-1272 (1996)
[Publications] Fujimura,T.: "Cytoreductive surgery and sandwich therapy with chemo-hyperthemic peritoneal perfusion and intra-aortic chemotherapy for peritoneal dissemination in gastric cancer." Oncology Reports. 3. 513-517 (1996)
[Publications] Yokoyama,K.: "Is radioimmunotherapy using l-131 truley effective for micro and occult metastases?" 37. 44-44 (1996)
[Publications] Kinuya,S: "Effect of induced hypertension with angiotensin II infusion on biodistribution of ^<11>In-labeled monclonal antibody." Nucl.Med.Biol.23. 137-140 (1996)
[Publications] J.P.Balthasar: "Pharmacokinetic and pharmacodynamic optimization of intraperitoneal chemotherapy." Life Sci.58. 535-543 (1996)
[Publications] M.Ramanathan: "A pharmacokinetic approach for evaluating cytokine binding macromolecules as antagonists." Pharm.Res.13. 84-90 (1996)
[Publications] M.J.Rogers: "Bisphosphonates are incorporated into adenine nucleotides by human aminoacyl-tRNA synthetase enzymes." Biochem.Biophys.Res.Commun.224. 863-869 (1996)
[Publications] P.Wentworth: "Toward antibody-directed “abzyme" prodrug therapy,ADAPT:carbamate prodrug activation by a catalytic antibody and its in vitro application to human tumor cell killing." Proc.Natl.Acad.Sci.USA. 93. 799-803 (1996)
[Publications] 山本博: "医学のための基礎分子細胞生物学細胞の基本構造、老化、遺伝病(1)、遺伝病(2)、血管新生" 南山堂(印刷中), (1997)
[Publications] 山本博: "VEGF、動脈硬化+高脂血症研究ストラテジー" 秀潤社, 464 (1996)
[Publications] 山本博: "KEY WORD 1996-'97 炎症・免疫系" 先端医学社, 191 (1996)
[Publications] 山岸昌一: "周皮細胞、血管新生のメカニズムと疾患" 医薬ジャーナル社, 287 (1996)
[Publications] 米倉秀人: "医学のための基礎分子細胞生物学インスリン、グルカゴン、血管作動性物質" 南山堂(印刷中), (1997)
[Publications] Yonemura,Y.: "Contemporary approaches toward cure of gastric cancer" Maeda Shoten Co.,Ltd., 197 (1996)
[Publications] 米村豊: "腹膜播種(Peritoneal Dissemination)" へるす出版, 134 (1996)

1996 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-driven angiogenesis in vitro." J.Biol.Chem.272. 8723-8730 (1997)

[Publications] Hayashi,Y.: "Induction of various blood-brain barrier properties in non-neural endothelial cells by close apposition to co-cultured astrocytes." Glia. 19. 13-26 (1997)

[Publications] Yamagishi,S.: "Advanced glycosylation end products stimulate the growth but inhibit the prostacyclin-producing ability of endothelial cells through interactions with their receptors." FEBS Letters. 384. 103-106 (1996)

[Publications] Yamamoto,Y.: "Advanced glycation endproducts-receptor interactions stimulate the growth of human pancreatic cancer cells through the induction of platelet-derived growth factor-B." Biochem.Biophys.Res.Commun.222. 700-705 (1996)

[Publications] Kaji,M.: "Participation of c-met in the progression of human gastric cancers;anti-c-met oligonucleotides inhibit proliferation or invasiveness of gastric cancer cells." Cancer Gene Therapy. 3. 393-404 (1996)

[Publications] Yamamoto,H.: "Vascular VEGF:The expression and roles in hypoxia-driven angiogenesis." Journal of Vascular Research. 33. 110 (1996)

[Publications] Yamagishi,S.: "Advanced glycation endproducts can promote angiogenesis through autocrine vascular endothelial growth factors." Journal of Vascular Research. 33. 110 (1996)

[Publications] Hayashi,Y.: "Astrocytes can transdifferentiate non-neural endothelial cells into the neural type through endfeet-mediated contacts." Journal of Vascular Research. 33. 33 (1996)

[Publications] Hatakeyama,H.: "The expression of steroidogenic enzyme genes in human vascular cells." Biochem.Mol.Biol.Int.40. 639-645 (1996)

[Publications] Hirono,Y.: "Expression of autocrine motility factor receptor correlates with disease progression in human gastric cancer." British Journal of Cancer. 74. 2003-2007 (1996)

[Publications] Ronan,Paul: "Effect of low frequency magnetic fields and induced current on DNA digestion." Proc.of Australian University Power Engineering Conference. 259-262 (1996)

[Publications] Nafalski,A.: "Measurement of magnetic fields in urban environment." Proc.of Australian University Power Engineering Conference. 247-252 (1996)

[Publications] Nata,K.: "Human gene encoding(ADP-ribosyl cyaclase/cyclic ADP-ribose hydrolase):organization,nucleotide sequences and alternative splicing." Gene. (in press). (1997)

[Publications] Noguchi,N.: "Cyclic ADP-ribose binds to FK506-binding protein 12.6 to release Ca^<2+> from islet microsomes." J.Biol.Chem.272. 3133-3136 (1997)

[Publications] Tohgo,A.: "Lysine 129 of CD38(ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase)participates in the binding of ATPto inhibit the cyclic ADP-ribose hydrolase." J.Biol.Chem.272. 3879-3882 (1997)

[Publications] Okamoto,H.: "Synthesis and hydrolysis of cyclic ADP-ribose by human leukocyte antigen CD38:Inhibition of hydrolysis by ATP and the physiological significance." 280(in press). (1997)

[Publications] Ichimura,F.: "Contribution of lysosomes to the subcellular distribution of basic drugs in the rat liver." Phamaceul.Res.13. 902-906 (1996)

[Publications] Kuno,K.: "Molecular cloning of a gene encoding a new type of metalloproteinase-disintegrin family protein with thrombosypondia motifs as an inflammation associated gene." J.Biol.Chem.(in press). (1996)

[Publications] Nakashima,E.: "A candidate for cancer gene therapy:MIP-1α gene transfer to an adenocarcinoma cell line reduced tumorigenicity and induced protective immunity in immunocompetent mice." Phamaceul.Res.13. 1895-1900 (1996)

[Publications] Yonemura,Y.: "Correlation between overexpression of c-met gene and the progression of gastric cancer." Int.J.Oncology. 8. 555-560 (1996)

[Publications] Yonemura,Y.: "Effects of intraoperative chemo-hyperthemia in patients with gastric cancer with peritoneal dissenmination." Surgery. 119. 437-443 (1996)

[Publications] Yonemura,Y.: "Correlation of the histological effects and survival after neoadjuvant chemotherapy on gastric cancer patients." Hepato-Gastroenterology. 43. 1260-1272 (1996)

[Publications] Fujimura,T.: "Cytoreductive surgery and sandwich therapy with chemo-hyperthemic peritoneal perfusion and intra-aortic chemotherapy for peritoneal dissemination in gastric cancer." Oncology Reports. 3. 513-517 (1996)

[Publications] Yokoyama,K.: "Is radioimmunotherapy using l-131 truley effective for micro and occult metastases?" 37. 44-44 (1996)

[Publications] Kinuya,S: "Effect of induced hypertension with angiotensin II infusion on biodistribution of ^<11>In-labeled monclonal antibody." Nucl.Med.Biol.23. 137-140 (1996)

[Publications] J.P.Balthasar: "Pharmacokinetic and pharmacodynamic optimization of intraperitoneal chemotherapy." Life Sci.58. 535-543 (1996)

[Publications] M.Ramanathan: "A pharmacokinetic approach for evaluating cytokine binding macromolecules as antagonists." Pharm.Res.13. 84-90 (1996)

[Publications] M.J.Rogers: "Bisphosphonates are incorporated into adenine nucleotides by human aminoacyl-tRNA synthetase enzymes." Biochem.Biophys.Res.Commun.224. 863-869 (1996)

[Publications] P.Wentworth: "Toward antibody-directed “abzyme" prodrug therapy,ADAPT:carbamate prodrug activation by a catalytic antibody and its in vitro application to human tumor cell killing." Proc.Natl.Acad.Sci.USA. 93. 799-803 (1996)

[Publications] 山本博: "医学のための基礎分子細胞生物学 細胞の基本構造、老化、遺伝病(1)、遺伝病(2)、血管新生" 南山堂(印刷中), (1997)

[Publications] 山本博: "VEGF、動脈硬化+高脂血症研究ストラテジー" 秀潤社, 464 (1996)

[Publications] 山本博: "KEY WORD 1996-'97 炎症・免疫系" 先端医学社, 191 (1996)

[Publications] 山岸昌一: "周皮細胞、血管新生のメカニズムと疾患" 医薬ジャーナル社, 287 (1996)

[Publications] 米倉秀人: "医学のための基礎分子細胞生物学 インスリン、グルカゴン、血管作動性物質" 南山堂(印刷中), (1997)

[Publications] Yonemura,Y.: "Contemporary approaches toward cure of gastric cancer" Maeda Shoten Co.,Ltd., 197 (1996)

[Publications] 米村豊: "腹膜播種(Peritoneal Dissemination)" へるす出版, 134 (1996)

山本博金沢大学, 医学部, 教授 (00115198)

[Publications] 山本博: "医学のための基礎分子細胞生物学細胞の基本構造、老化、遺伝病(1)、遺伝病(2)、血管新生" 南山堂(印刷中), (1997)

[Publications] 米倉秀人: "医学のための基礎分子細胞生物学インスリン、グルカゴン、血管作動性物質" 南山堂(印刷中), (1997)