遺伝子組換えHGFレセプターアンタゴニストによる癌細胞の浸潤・転移抑制剤の開発

• 研究課題/領域番号: 07557199
• 研究種目: 基盤研究(A)
• 配分区分: 補助金
• 応募区分: 展開研究
• 研究分野: 病体医化学
• 研究機関: 大阪大学
• 研究代表者: 中村 敏一 大阪大学, 医学部, 教授 (00049397)
• 研究分担者: 河田 純男 大阪大学, 医学部, 助教授 (90183285) ; 門田 守人 大阪大学, 医学部, 教授 (00127309) ; 船越 洋 大阪大学, 医学部, 助手 (40273685) ; 松本 邦夫 大阪大学, 医学部, 助教授 (90201780) ; 根本 康夫 大阪大学, 医学部, 助手 (30250088)
• 研究期間 (年度): 1995 – 1997
• 研究課題ステータス: 完了 (1997年度)
• 配分額: 6,500千円 (直接経費: 6,500千円); 1997年度: 2,400千円 (直接経費: 2,400千円); 1996年度: 4,100千円 (直接経費: 4,100千円)
• キーワード: HGF / HGFアンタゴニスト / c-Met / 腫瘍・癌 / 癌-間質相互作用 / 浸潤 / 転移 / 癌治療 / NK4 / 浸潤・転移 / 血管新生 / 浸潤・転移抑制剤 / 基底膜浸潤 / コラーゲンゲル内浸潤 / c-met / 癌細胞 / 腫瘍 / 癌浸潤・転移 / 増殖因子 / サイトカイン / レセプター

研究概要

癌細胞の浸潤・転移能といった悪性形質は癌細胞とそれを取り囲む宿主間質細胞との相互作用によって付与されていることが知られている.HGFならびにそのレセプターであるc-Metを中心に癌-間質相互作用を解析した結果,HGFならびにHGF誘導因子を介した局所的な癌細胞と間質細胞の相互作用こそが癌-間質相互作用による癌悪性化の分子機構の一端を担っていることを私たちは明らかにしてきた.この様な観点からHGFの作用を特異的にブロックするアンタゴニスト分子の創製は新しい浸潤・転移抑制剤開発の可能性を開く有意義な研究テーマである.
まず私たちはリコンビナントHGFのエラスターゼ限定分解産物よりHGFのc-Metレセプターへの結合を競合的に阻害し,その生物活性をほぼ完全にブロックするアンタゴニスト分子の精製に成功し,HGF/NK4と名付けた.in vitroにおいて様々な癌細胞がHGF刺激に応じてマトリゲルやコラーゲンゲルへの浸潤能を獲得することが知られているが,HGF/NK4はその浸潤活性をほぼ完全にブロックすることができた.さらにin vivoの実験系においてHGF/NK4の癌悪性化に対する効果を検討した.ヒト胆嚢癌由来細胞GB-dlをヌードマウスの皮下に移植し,腫瘍組織近傍にHGF/NK4の持続投与を行なった結果,HGF/NK4投与群では腫瘍の成長が著しく抑制され,宿主の正常間質組織への浸潤もほとんど認められなかった.さらにがん転移モデルとして汎用されるLewis肺癌その他の癌細胞を用いて同様の実験を行なったところ,やはり腫瘍の成長を顕著に抑制し,その肺・肝転移をほぼ完全に抑制するこに成功した.以上の結果はHGF/NK4が癌浸潤・転移抑制剤としてきわめて効果的であることを示しており,新しい制癌剤としての可能性を示唆するものである.

研究成果

• [文献書誌] K.Takai et al.: "Hepatocyte growth factor is constitutively produced by human bone marrow stromal cells and promotes erythropoiesis." Blood. 89. 1560-1565 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
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  • 説明: 「研究成果報告書概要(和文)」より
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  • 説明: 「研究成果報告書概要(和文)」より
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  • 説明: 「研究成果報告書概要(和文)」より
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  • 説明: 「研究成果報告書概要(和文)」より
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  • 説明: 「研究成果報告書概要(和文)」より
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  • 説明: 「研究成果報告書概要(和文)」より
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  • 説明: 「研究成果報告書概要(和文)」より
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  • 説明: 「研究成果報告書概要(和文)」より
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  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] T.Nakamura et al.: "Induction of hepatocyte growth factor in fibroblasts by tumor-derived factors affects invasive growth of tumor cells:In vitro analysis of tumor-stromal interaction." Cancer Res.57. 3305-3313 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] T.Imai et al.: "Sparse distribution of hepatocyte growth factor-producing cells inside hepatocellular foci in rats treated with hepatocarcinogens." Jpn.J.Cancer Res.88. 615-618 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
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  • 説明: 「研究成果報告書概要(和文)」より
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  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] R.Morishita et al.: "Role of hepatocyte growth factor in endothelial regulation:Prevention of high D-gluxinduced endothelia lcell death by prostglandins and phosphodiesterase type 3 inhibiton" Diabetologia. 40. 1053-1061 (1997)
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  • 説明: 「研究成果報告書概要(和文)」より
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  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] S.Wakitani et al.: "Hepatocyte growth factor faulitates Cartilage repair:full thickness articular cartilage defect studied in rabbit knee." Acta Orthop.Stand.68. 474-480 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] T.Adachi et al.: "Possible involvement of pertussis toxin-sensitive G protein in hepatocyte growth factor(HGF)-induced signal transduction in cultured rat hepatocytes." Hepatology.26. 295-300 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] V.R.Wallenius et al.: "Chromosomal localization of rat hepatocyte growth factor(Hgf)and HGF receptor(Met)and chractrization of HGF receptor cDNA." Mammalian Genome. 8. 661-667 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
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  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] K.Date et al.: "HGF/NK4 is a specific antagonist for pleiotrophic actions of hepatocyte growth factor." FEBS Lett.420. 1-6 (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] A.Schmassman et al.: "Role of antagotensin II in the reguration of a novel vascular modulator,hepatocyte growth factor(HGF),in experimental hypertensive rats." Gastroenterolgy. 113. 1858-1872 (1997)
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  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] K.Takai et. al.: "Hepatocyte growth factor is constitutively produced human bone marrow stromal cells and promotes erythropoiesis." Blood. 89. 1560-1565 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] R.Morishita et al.: "Potential role of endothelium-specific growth factorhepatocyte growth factor on endothelial damage in diabetes militus." Diabetes. 46. 138-142 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] I.S.Weimar et al.: "Hepatocyte growth factor/scatter factor (HGF/SF) promotes adhesion of lymphoma cells to extra-cellular matrix molecules via a4b, and a5b, integrens." Blood. 89. 990-1000 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] N.Kawakami-Kimura et al.: "Involvement of hepatocyte growth factor in increased integrin expression on Hep G2 cells triggered by adhesion to endothelial cells." Br.J.Cancer. 75. 47-53 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] T.Sakai et al.: "Hepatocyte growth factor in bronchoalveolar kvage fluid and cells in patients with in flammatory chest diseases of the lower respitatory tract : Defection by RIA and in situ hybridization." Am.J.Respir.Cell Mole Biol.16. 388-397 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] T.Takahashi et al.: "Xenopus LIM motif-containing protein kinase, XLIMK,is expressed in the developing head structure of the embryo." Develop.Dyn.209. 196-205 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] S.Aoki et al.: "Activation of Met tyrosine kinase by hepatocyte growth factor is essential for internal ganogenesis in Xenopus embryo." Biochem.Biophys.Res.Commun.234. 8-14 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Y.Ikeda et al.: "Bile ductular proliferation in the granulation tissue of rat liver. : Histological and serial reconstruction studies." Biomed.Res.18. 113-127 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Y.Matsuda et al.: "Prevential and therapeutic effects in rats of hepatocyte growth factor infusion on liver fibrosis/cirrhosis." Hepatology. 26. 81-89 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] K.Furugori et al.: "Level of Hepatocyte growth factor and its messenger ribonucleic acid in uncomplecated pregnancies and those complicated by preeclamptia." J.Clin.Endocrinol. & Metabo.82. 2726-2730 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] T.Nakamura et al.: "Induction of hepatocyte growth factor in fibroblasts by tumor-derived factors affects invasive growth of tumor cells : In vitro analysis of tumor-stromal interaction." Cancer Res.57. 3305-3313 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] T.Imai et al.: "Sparse distribution of hepatocyte growth factor-producing cells inside hepatocellular foci in rats treated with hepatocarcinogens." Jpn.J.Cancer Res.88. 615-618 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] T.Kaido et al.: "Continous hepatocyte growth factor supply prevents lipopolysacharide-induced liver injury in rats." FEBS Lett.411. 378-382 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] S.E.Hiscox et al.: "Exprssion of the HGF/SF receptor c-met, and its ligand in human colon cancers." Cancer Investigations. 15. 513-521 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] R.Morishita et al.: "Role of hepatocyte growth factor in endothelial regulation : Prevention of highD-glucose induced endothelia lcell death by prostglandins and phosphodiesterase type 3 inhibitor." Diabetologia. 40. 1053-1061 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] H.Li et al.: "Hepatocyte growth factor stimuolates invasion of gallbladder carcinoma cell lines in vitro." Clin.Exp.Metastasis.15. 484-493 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] K.Liu et al.: "Existence of two nonliner elimination mechanisms for hepatocyte growth factor in rats." Am.J.Physiol. 273. E891-E897 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] S.Wakitani et al.: "Hepatocyte growth factor faulitates Cartilage repair : full thickness articular cartilage defect studies in rabbit knee." Acta Orthop.Stand.68. 474-480 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] T.Adachi: "Possible involvement of pertussis toxin-sensitive G protein in hepatocyte growth factor (HGF)-induced signal transduction in cultured rat hepatocytes." Hepatology.26. 295-300 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] V.R.Wallenius et al.: "Chromosomal localization of rat hepatocyte growth factor (Hgf) and HGF receptor (Met) and chractrization of HGF receptor cDNA." Mammalian Genome. 8. 661-667 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] N.Nakano et al.: "Role of antagotensin II in the reguration of a novel vascular modulator hepatocyte growth factor (HGF), in experimental hypertensive rats." Hypertension. 30. 1448-1454 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] K.Date et al.: "HGF/NK4 is a specific antagonist for pleiotrophic actions of hepatocyte growth factor." FEBS Lett.420. 1-6 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] A.Schmassman et al.: "Roles of hepatocyte growth factor and its receptor c-met during gastric ulcer healing in rats." Gastroenterolgy. 113. 1858-1872 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] U.Koshimizu et al.: "cDNA cloning, genomic organization and chromosomal localization of the mouse Lim motif-containing kinase, Limk 2 gene." Biochem.Biophys.Res.Commun.241. 243-250 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] M.Yaekashiwa et al.: "Both simultaneous and delayd administration of hepatocyte growth factor (HGF) repress the fibrotic changes in murine lung injury injuced by bleomycin." Am.J.Resp. & Clin.Care Med.156. 1937-1944 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Y.Yo et al.: "Actions of hepatocyte growth factor as a local modulator in the kidney : Potential role in pathogenesis of renal disease." Kindney Intern.53. 50-58 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] D.Schuppan et al.: "Collagens in the liver extracellular matrix hepatocyte growth factor." Gastroenterology.114. 139-152 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] M.Lyon et al.: "Hepatocyte growth factor/scatter factor binds with high affinity to dermatan sulphate." J.Biol.Chem.273. 271-278 (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] U.Koshimizu et al.: "Hepatotrophic activities of HGF in liver regeneration after injury and the clinical potentiality for liver diseases." Narosa-Elsevier Verlag. 220-229 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] K.Matsumoto et al.: "HGF : its organotrophic role and therapeutic potential." Ciba Foundation Symposium. 212. 198-214 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] K.Matsumoto et al.: "Hepatocyte growth factor (HGF) as a tissue organizer for organogenesis and regeneration." Biochem.Biophys.Res.Commun.(Mini-Review). 239. 639-644 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] R.Morishita: "Potential role of a novel vascular modulator, hepatocyte growth factor (HGF), in cardiovascular disease : characterization and regulation of local HGF system." J.Atherosclerosis and Thrombosis. 4. 12-19 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] K.Matsumoto et al.: "Pathophysiological aspects and therapeutic potential of hepatocyte growth factor in liver disease." Internal Medicine and Endocrinology : Pathophysiological and clinical interactions. 95-106 (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] K.Liu et al.: "Change in hepatic handling of hepatocyte growth factor during liver regeneration in rats." Am J.Physiol.269 (in press). (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] M.T.Donato et al.: "Human hepatocyte growth factor down regulated the expression of cytochrome P450 isozymes in human hepatocytes in primaoy culture." J.Pharmacl Exp.Therap.(in press). (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] K.Liu et al.: "Protamine enhances the proliferative activity of hepatocyte growth factor in rats." Am.J.Physiol.(in press). (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] R.Gal-Levi et al.: "Hepatocyte growth factor as a potent regulator of skeletal muscle satellite cell proliferation and differentiation." Biochem.Biophys.Acta. (in press). (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] T.Miyazawa et al.: "Protection of hippocampal neurons from ischemia-induced delayd neuronal death by hepatocyte growth factor : A novel neurotrophic factor." J.Celebral Blood Flow Metabolism.(in press). (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] W.G.Jiang et al.: "Hepatocyte growth factor/scatter factor, its molecular, cellular and impacts in cancer." Crit, Rev.Oncolo.Hematol.clinical. (in press). (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] S.Mizuno et al.: "Hepatocyte growth factor prevents renal fibrosis and dysfunction in mouse model of chronio renal disease." j.Clin.Invest. (in press). (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] H.Ohmichi et al.: "Hepatocyte growth factor (HGF) acts as a mesenchymal-derived morphogenic factor during fetal lung development." Development. (in press). (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] K.Kosai et al.: "Hepatocyte growth factor abrogates Fas-induced lethal liver apoptosis in mice." Biochem.Biophys.Res.Commun.(in press). (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] F.Tamura et al.: "FK506 promotes liver regeneration by suppressing natural killer cell activity." J.Gastroenterol.and Hepatol.(in press). (1998)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] K.Takai et al.: "Hepatocyte growth factor is constitutively produced by human bone marrow stromal cells and promotes erythropoiesis." Blood. 89. 1560-1565 (1997)
• [文献書誌] R.Morishita et al.: "Potential role of endothelium-specific growth factor hepatocyte growth factor,on endothelial damage in diabetes militus." Diabetes. 46. 138-142 (1997)
• [文献書誌] I.S.Weimar et al.: "Hepatocyte growth factor/scatter factor(HGF/SF)promotes adhesion of lymphoma cells to extra-cellular matrix molecules via a4b,and a5b,integrens." Blood. 89. 990-1000 (1997)
• [文献書誌] N.Kawakami-Kimura et al.: "Involvement of hepatocyte growth factor in increased integrin expression on Hep G2 cells triggered by adhesion to endothelial cells." Br.J.Cancer. 75. 47-53 (1997)
• [文献書誌] T.Sakai et al.: "Hepatocyte growth factor in bronchoalveolar lavage fluid and cells in patients with in flammatory chest diseases of the lower respitatory tract:Defection by RIA and in situ hybridization." Am.J.Respir.Cell Mole Biol.16. 388-397 (1997)
• [文献書誌] T.Takahashi et al.: "Xenopus LIM motif-containing protein kinase,XLIMK,is expressed in the developing head structure of the embryo." Develop.Dyn.209. 196-205 (1997)
• [文献書誌] S.Aoki et al.: "Activation of Met tyrosine kinase by hepatocyte growth factor is essential for internal ganogenesis in Xenopus embryo." Biochem.Biophys.Res.Commun.234. 8-14 (1997)
• [文献書誌] Y.Ikeda et al.: "Bile ductular proliferation in the granulation tissue of rat liver.:Histological and serial reconstruction studies." Biomed.Res.18. 113-127 (1997)
• [文献書誌] Y.Matsuda et al.: "Prevential and therapeutic effects in rats of hepatocyte growth factor infusion on liver fibrosis/cirrhosis." Hepatology. 26. 81-89 (1997)
• [文献書誌] K.Furugori et al.: "Level of Hepatocyte growth factor and its messenger ribonucleic acid in uncomplecated pregnancies and those complicated by preeclamptia." J.Clin.Endocrinol.& Metabo.82. 2726-2730 (1997)
• [文献書誌] T.Nakamura et al.: "Induction of hepatocyte growth factor in fibroblasts by tumor-derived factors affects invasive growth of tumor cells:In vitro analysis of tumor-stromal interaction." Cancer Res.57. 3305-3313 (1997)
• [文献書誌] T.Imai et al.: "Sparse distribution of hepatocyte growth factor-producing cells inside hepatocellular foci in rats treated with hepatocarcinogens." Jpn.J.Cancer Res.88. 615-618 (1997)
• [文献書誌] T.Kaido et al.: "Continous hepatocyte growth factor supply prevents lipopolysacharide-induced liver injury in rats." FEBS Lett.411. 378-382 (1997)
• [文献書誌] S.E.Hiscox et al.: "Expression of the HGF/SF receptor c-met,and its ligand in human colon cancers." Cancer Investigations. 15. 513-521 (1997)
• [文献書誌] R.Morishita et al.: "Role of hepatocyte growth factor in endothelial regulation:Prevention of high D-glucose induced endothelia lcell death by prostglandins and phosphodiesterase type 3 inhibitor." Diabetologia. 40. 1053-1061 (1997)
• [文献書誌] H.Li et al.: "Hepatocyte growht factor stimuolates invasion of gallbladder carcinoma cell lines in vitro." Clin.Exp.Metastasis.15. 484-493 (1997)
• [文献書誌] K.Liu et al.: "Existence of two nonliner elimination mechanisms for hepatocyte growth factor in rats." Am.J.physiol.273. E891-E897 (1997)
• [文献書誌] S.Wakitani et al.: "Hepatocyte growth factor faulitates Cartilage repair:full thickness articular cartilage defect studied in rabbit knee." Acta Orthop.Stand.68. 474-480 (1997)
• [文献書誌] T.Adachi et al.: "Possible involvement of pertussis toxin-sensitive G protein in hepatocyte growth factor(HGF)-induced signal transduction in cultured rat hepatocytes." Hepatology.26. 295-300 (1997)
• [文献書誌] V.R.Wallenius et al.: "Chromosomal localization of rat hepatocyte growth factor(Hgf)and HGF receptor(Met)and chractrization of HGF receptor cDNA." Mammalian Genome. 8. 661-667 (1997)
• [文献書誌] N.Nakano et al.: "Role of antagotensin II in the reguration of a novel vascular modulator,hepatocyte growth factor(HGF),in experimental hypertensive rats." Hypertension. 30. 1448-1454 (1997)
• [文献書誌] K.Date et al.: "HGF/NK4 is a specific antagonist for pleiotrophic actions of hepatocyte growth factor." FEBS Lett.420. 1-6 (1997)
• [文献書誌] A.Schmassman et al.: "Role of antagotensin II in the reguration of a novel vascular modulator,hepatocyte growth factor(HGF),in experimental hypertensive rats." Gastroenterolgy. 113. 1858-1872 (1997)
• [文献書誌] U.Koshimizu et al.: "cDNA cloning,genomic organization and chromosomal localization of the mouse Lim motif-containing kinase,Limk 2 gene." Biochem.Biophys.Res.Commun.241. 243-250 (1997)
• [文献書誌] M.Yaekashiwa et al.: "Both simultaneous and delayed administration of hepatocyte growth factor(HGF)repress the fibrotic changes in murine lung injury induced by bleomycin." Am.J.Resp.& Clin.Care Med.156. 1937-1944 (1997)
• [文献書誌] R.Morishita et al.: "Potential role of a novel vascular modulator,hepatocyte growth factor(HGF),in cardiovascular disease:characterization and regulation of local HGF system." J.Atherosclerosis and Thrombosis. 4. 12-19 (1997)
• [文献書誌] U.Koshimizu et al.: "Hepatotrophic activities of HGF in liver regeneration after injury and the clinical potentiality for liver diseases." "Liver and Environmental Xenobiotics"Narosa-Elsevier Verlag,. 220-229 (1997)
• [文献書誌] K.Matsumoto et al.: "HGF:its organotrophic role and therapeutic potential." "Plasminogen-Related Growth Factors". 212. 198-214 (1997)
• [文献書誌] K.Matsumoto et al.: "Hepatocyte growth factor(HGF)as a tissue organizer for organogenesis and regeneration." Biochem.Biophys.Res.Commun.(Mini-Review). 239. 639-644 (1997)
• [文献書誌] K.Matsumoto et al.: "Pathophysiological aspects and therapeutic potential of hepatocyte growth factor in liver disease." Internal Medicine and Endocrinology:Pathophysiological and clinical interactions(eds by A.Fabbrini and V.Santiemma.). 95-106 (1997)
• [文献書誌] D.Schuppan et al.: "Collagens in the liver extracellular matrix hepatocyte growth factor." Gastroenterology.114. 139-152 (1998)
• [文献書誌] M.Lyon et al.: "Hepatocyte growth factor/scatter factor binds with high affinity to dematan sulphate." J.Biol.Chem.273. 271-278 (1998)
• [文献書誌] Y.Yo et al.: "Actions of hepatocyte growth factor as a local modulator in the kidney:Potential role in pathogenesis of renal disease." Kindney Intern. 53. 50-58 (1998)
• [文献書誌] K.Liu et al.: "Protamine enhances the proliferactive activity of hapatocyte growth factor in rats." Am.J.Physiol.(in press.). (1997)
• [文献書誌] R.Gal-Levi et al.: "Hepatocyte growth factor as a potent regulator of skeletal muscle satellite cell proliferation and differentiation." Biochem.Biophys.Acta.(in press.). (1997)
• [文献書誌] K.Liu et al.: "Change in hepatic handling of hepatocyte growth factor during liver regeneration in rats." Am.J.Physiol.269(in press). (1998)
• [文献書誌] S.Mizuno et al.: "Hepatocyte growth factor prevents renal fibrosis and dysfunction in mouse model of chronio renal disease." J.Clin.Invest.(in press.). (1998)
• [文献書誌] H.Ohmichi et al.: "Hepatocyte growth factor(HGF)acts as a mesenchymal-derived morphogenic factor during fetal lung develpment." Development.(in press). (1998)
• [文献書誌] T.Miyazawa et al.: "Protection of hippocampal neurons from ischemia-induced delayed neuronal death by hepatocyte growth factor:A novel neurotrophic factor." J.Celebral Blood Flow Metabolism.(in press.). (1998)
• [文献書誌] M.T.Donato et al.: "Human hepatocyte growth factor down regulated the expression of cytochrome P450 isozymes in human hepatocytes in primaoy culture." J.Pharmacl Exp.Therap.(in press.). (1998)
• [文献書誌] K.Kosai et al.: "Hepatocyte growth factor abrogates Fas-induced lethal liver apoptosis in mice." Biochem.Biophys.Res.Commun.(in press.). (1998)
• [文献書誌] F.Tamura et al.: "FK506 promotes liver regeneration by suppressing natural killer cell activity natural killer cell activity." J.Gastroenterol.and Hepatol.(in press.). (1998)
• [文献書誌] W.G.Jiang et al.: "Hepatocyte growth factor/scatter factor,its molecular,cellular and clinical impacts in cancer." Crit.Review Onclo.Hematol.(in press.). (1998)
• [文献書誌] 中村敏一: "標準分子医化学" 医学書院, 843-852 (1997)
• [文献書誌] 中村敏一: "分子生物学プロトコール改訂版 タンパク質の生化学的分析" 南江堂(印刷中), (1997)
• [文献書誌] 中村敏一: "肝臓病-今日の診断と最新の治療" 国際医書出版, 299-310 (1997)
• [文献書誌] 中村敏一: "生命体システムの修復" 講談社サイエンティフィック, 124 (1997)
• [文献書誌] 松本邦夫、中村敏一: "病理学キーワード" 文光社, 40 (1997)
• [文献書誌] N.Nishi: "Changes in gene expression of growth factors and their receptors during castration-induced involusion and androgen-induced regrowth of rat prostate." Prostate. 28. 139-152 (1996)
• [文献書誌] M.Hamanoue: "Neurotrophic effect of hepatocyte growth factor on CNS neurons in vivo." J.Neurosci.Res.43. 554-564 (1996)
• [文献書誌] T.Kaido: "Continous HGF supply from spleen transplanted HGF-expressing fibroblasts prevents CCl_4-induced acute liver injury in rats." Biochem.Biophys.Res.Commun.218. 1-5 (1996)
• [文献書誌] M.Inui: "Enhanced gene expression of transforming growth factor-α and c-met in rat urinary bladder cancer." Urol.Res.24. 55-60 (1996)
• [文献書誌] H.Yamazaki: "Biphasic changes in serum hepatocyte growth factor after transcatheter arterial chemoembolization theraphy for hepatocellular carcinoma." Cytokine. 8. 178-182 (1996)
• [文献書誌] T.Imai: "Expression of hepatocyte growth factor and c-met mRNAs during rat chemically induced hepatocarcinogenesis in the Solt-Farber model." Carcinogenesis. 17. 19-24 (1996)
• [文献書誌] Y.Kubo: "Hepatocyte proliferation induced in rats by lead nitrate is suppressed by several tumor necrosis factor-α inhibitors." Hepatology. 23. 104-114 (1996)
• [文献書誌] S.Takada: "Serum HGF levels in acute renal rejection after living related renal transplantation." Transplant.Intern.9. 151-154 (1996)
• [文献書誌] M.Joaquin: "Hepatocyte growth factor and transforming growth factor beta regulates 6-phosph of ructo-2-kinase/fructose-2,6-bisphos-phatase gene expression in rat hepatocyte primary cultures." Biochem.J.314. 235-240 (1996)
• [文献書誌] M.Takahashi: "Constitutive expression of hepatocyte growth facotr may maintain the sheet construction of gastric epithelial cells through facilitating actin-myosin contractile system." Biochem.Biophys.Res.Commun.219. 40-46 (1996)
• [文献書誌] M.J.Tabata: "Hepatocyte growth factor is involved in the morphogenesis of tooth gern in murine molars." Development. 122. 1243-1251 (1996)
• [文献書誌] Y.Kobayashi: "Induction of hepatocyte growth by intraportal infusion of hepatocyte growth factor into beagle dogs." Biochem.Biophys.Res.Commun.220. 7-12 (1996)
• [文献書誌] I.Fabregat: "Epidermal growth factor,but not hepatocyte growth factor,suppresses the apoptosis induced by transforming growth factor-beta in fetal hapatocytes in primaty culture." FEBS Lett.384. 14-18 (1996)
• [文献書誌] P.Gines: "Inhibitory actions of cyclic aden osine monophosphate and pertussis toxin define two distinct epidermal growth factor-regulated pathways leading to activation of mitogen-activated protein kinase in rat hapatocytes." Hepatology. 23. 1167-1173 (1996)
• [文献書誌] K.Sugimoto: "Molecular cloning and characterization of a newly identified member of the cadherin family,PB-cadherin." J.Biol.Chem.271. 11548-11556 (1996)
• [文献書誌] S.Takada: "HGF prevent tacrolimus (FK506)-induced nephrotoxicity in SHR rats." Transplant.Proc.28. 1089-1090 (1996)
• [文献書誌] T.Adachi: "Mitogen-activated protein kinase activation in hepatocyte growth factor-stimulated rat hapatocytes : Involvement of protein tyrosine kinase and protein kinase C." Hepatology. 23. 1244-1253 (1996)
• [文献書誌] M.J.Gomez-Lechon: "Cell cycle progression proteins (cyclins),oncogene expression and signal transduction during the proliferative response of human hepatocytes to hapatocyte growth factor." Hepatology. 23. 1012-1019 (1996)
• [文献書誌] S.Hayashi: "Autocrine-paraqrine effects of over-expression of hepatocyte growth factor gene on growth of endothelial cells." Biochem.Biophys.Res.Commun.220. 539-545 (1996)
• [文献書誌] H.Amaike: "Human recombinant HGF prevents lethal side effects of cyclosporin A in mice." Cytokine. 8. 387-394 (1996)
• [文献書誌] R.J.Mason: "Hepatocyte growth factor is a mitogen for alveolar type II cells in rat lavage fluid." Am.J.Physiol. 271. L46-L53 (1996)
• [文献書誌] N.Nakayama: "Hepatocyte growth factor and c-met expression in Long-Evans Cinnamon rats with spontaneous hepatitis and hapatoma." Hepatology. 24. 596-602 (1996)
• [文献書誌] H.Ohmichi: "In vivo mitogenic action of hepatocyte growth factor on branchial epithelial cells : Pulmotrophic role of HGF in lung regeneration." Am.J.Physiol.270. L1031-L1039 (1996)
• [文献書誌] M.I.Guillen: "The hepatocyte growth factor regulates the synthesis of acute-phase proteins in human hepatocytes. Divergent effects on IL-6-stimulated genes." Hepatology. 23. 1345-1352 (1996)
• [文献書誌] K.Matsumoto: "Acquistion of invasive phenotype in gallblader cancer cells via looped interaction of stromal fibroblasts and cancer cells mediated by HGF." Jap.J.Cancer Res.87. 702-710 (1996)
• [文献書誌] T.Nakamura: "Cloning and expression of xenopus HGF-like protein (HLP) and Ron/HLP receptor implicate their involvement in early neural development." Biochem.Biophys.Res.Commun.224. 564-573 (1996)
• [文献書誌] H.G.Chang: "Serum Repatocyte growth facotr concentration in patients with vatious degrees of chronic renal failure." Nephrology. 2. 175-179 (1996)
• [文献書誌] S.Ueno: "Exogenous hapatocyte growth factor markedly stimulates liver regeneration following portal branch ligation in dogs." Cancer Chemoter.and Pharmacol.38. 233-237 (1996)
• [文献書誌] Y.Nakamura: "A.vaschlar modulator,hepatocyte growth facotr (HGF),is associated with systolic blood pressure." Hypertension. 28. 409-413 (1996)
• [文献書誌] E.Ichimura: "Over expression of c-met/HGF receptor in human non small cell lung cancinoma in vitro and in vivo its prognostic significance." Jap.J.Cancer Res.87. 1063-1069 (1996)
• [文献書誌] K.Matsumoto: "Heparin functions as a hepatotrophic factor by inducing production of hepatocyte growth factor." Biochem.Biophys.Res.Commun.227. 455-461 (1996)
• [文献書誌] Y.Nakamura: "Hepatocyte growth facotr (HGF) is a novel member of endothelium-specific growth factors : additive stimulatory effect of HGF with basic fibroblast growth factor,but not vascular endothelial growth factor." J.Hypertens.14. 1067-1072 (1996)
• [文献書誌] T.Mizuguchi: "Recovery of mRNA expression of tryphophan 2,3-dioxygenase and serine dehydratase in long-term cultures of primary rat hapatocytes." J.Biochem.120. 511-517 (1996)
• [文献書誌] A.Uchiyama: "Interleukin 4 inhibits hapatocyte growth factor-induced invasion and migration of colon carcinoma." J.Cell.Biochem.62. 443-453 (1996)
• [文献書誌] M.Dalmau: "Nitric oxide inhibits DNA synthesis and induces activation of poly (ADP-ribose) polymerase in cultured rat hepatocytes." Exp.Cell Res.228. 14-18 (1996)
• [文献書誌] Z.G.Han: "Regulation of motility,invasiveness and growth of lung cancer cell by hepatocyte growth factor/scatter factor." Surg.Res.Commun.18. 217-229 (1996)
• [文献書誌] W.G.Jiang: "Hepatocyte growth factor induces tyrosine phosphorylation of focal adhesion kinase (FAK) adn paxillin and enhances cell matrix interaction." Oncology Reports. 3. 819-823 (1996)
• [文献書誌] S.Aoki: "Molecular cloning of Xenopus c-met/hepatocyte growth factor receptor and its regional expression during early development." J.Biochem.120. 961-968 (1996)
• [文献書誌] T.Iwazawa: "Primary human fibroblasts induce diverse tumor invasiveness -Involvement of HGF as an important paracrine factor." Jap.J.Cancer Res.87. 1134-1142 (1996)
• [文献書誌] S.Kasai: "Hepatocyte growth factor is a paracrine regulator of rat prostate epithelial growth." Biochem.Biophys.Res.Commun.228. 646-652 (1996)
• [文献書誌] M.Takahashi: "Hepatocyte growth factor as a key to modulate anti-ulcer action of prostaglandins in stomach." J.Clin.Invest.98. 2604-2611 (1996)
• [文献書誌] G.Shiota: "Inhibitory effect of hepatocyte growth factor on metastosis of hepatocellular carcinoma in transgenic mice." Res.Commun.Mole.Pahol.Pharmacol.91. 33-39 (1996)
• [文献書誌] T.Adachi: "Phospholipase D activation in hapatocyte growth factor-stimulated rat hapatocytes mediates the expression of c-jun and c-fos : Involvement of protein tyrosine kinase,protein kinase C,and Ca^<2+>." Hepatology. 24. 1274-1281 (1996)
• [文献書誌] K.Lui: "Change in hepatic handling of hepatocyte growth factor during liver regeneration in rats." Am.J.Physiol.269(in press). (1996)
• [文献書誌] N.Torok: "Upregulation of molecular motor encoding genes during HGF-and EGF-induced cell motility." J.Biol.Chem.(in press). (1997)
• [文献書誌] S.Hiscox: "Expression of HGF/SF and its receptor cMET in human colon cancers." Cancer Investigations. (in press). (1997)
• [文献書誌] G.Shiota: "Coexpression of hepatocyte growth factor and its receptor (c-met oncogene) in HGL 4 glioblastoma cells." Lab.Invest. (in press). (1997)
• [文献書誌] K.Takai: "Hepatocyte growth factor is consititutively produced by human bone marrow stromal cells and promotes erythropoiesis." Blood. (in press). (1997)
• [文献書誌] R.Morishita: "Potential role of endothelium-specific growth factor hepatocyte growth factor,on endothelial damage in diabetes militus." Diabetes. (in press). (1997)
• [文献書誌] I.S.Weimar: "Hepatocyte growth factor/scatter factor (HGF/SF) promotes adhesion of lymphoma cells to extra-cellular matrix molecules via α_4β,and α_5β,integrens." Blood. (in press). (1997)
• [文献書誌] T.Sakai: "Hepatocyte growth factor in bronchoalveolar lavage fluid and cells in patients with in flammatory chest diseases of the lower respitatory tract : Defection by RIA and in situ hybridization." Am.J.Resp.Cell Mole Biol.(in press). (1996)
• [文献書誌] Y.Matsuda: "Prevential and therapeutic effects in rats of hepatocyte growth factor on liver fibrosis/cirrhosis." Hepatology. (in press). (1997)
• [文献書誌] T.Takahashi: "Xenopus LIM motif-containing protein kinase 1 XLIMK 1 is expressed mainly in embryonic neural tissues that develop sensoryorgans." Develop.Dyn.(in press). (1997)
• [文献書誌] K.Matsumoto: "Emerging multipotent aspects of hepatocyte growth factor." J.Biochem.119. 591-600 (1996)
• [文献書誌] K.Matsumoto: "HGF in lung morphogenesis and tumor invasion : roles as a mediator in epithelial-mesenchymal and tumor-stromal interactions." Cancer Chemother.and Pharmacol.38. S42-S47 (1996)
• [文献書誌] 立石紀子、中村敏一: "Hepatocyte Growth Factor,HGF" 動脈硬化. 23. 683-688 (1996)
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