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Explanation of the Anticancer Mechanism and Clinical Chemotherapy for Hybrid Liposomes

Research Project

Project/Area Number 14350439
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 生物・生体工学
Research InstitutionSOJO University

Principal Investigator

UEOKA Ryuichi  SOJO University, Engineering, Professor, 工学部, 教授 (70099076)

Co-Investigator(Kenkyū-buntansha) MATSUMOTO Yoko  SOJO University, Engineering, Professor, 工学部, 教授 (00133562)
MATSUSHITA Taku  SOJO University, Engineering, Assistant Professor, 工学部, 助教授 (10209538)
KANNO Akihiro  Drug Safety Testing Center, Chief Director, 薬理研究所, 部長
金野 明宏  (株)薬物安全性試験センター薬理研究所, 部長
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2003: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥8,700,000 (Direct Cost: ¥8,700,000)
KeywordsHybrid Liposomes / Anticancer Mechanism / Clinical Chemotherapy / Dimyristoylphosphatidylcholine / No Side Effect / Caspases / Apoptosis / Life Prolongation / 担がんマウス / 肝臓がん / 膜融合 / 悪性黒色腫
Research Abstract

Hybrid liposomes can be prepared by simply ultrasonicating a mixture of vesicular and micellar molecules in a buffer solution. The physical properties of these liposomes, such as size, membrane fluidity phase transition temperature, and hydrophobicity can be controlled by changing the composition. In the course of our study, remarkably high inhibitory effects of hybrid liposomes on tumor growth in vitro without drugs have been obtained. No toxicity of the hybrid liposomes was observed in normal cells in vitro and in normal rats in vivo without any side effect.
In this study, we report on the uniform and stable hybrid liposomes composed of dimyristoylphosphatidylcholine (DMPC) and polyoxyethylenealkyl ether (C_<12>(EO)n; n=10-25) having inhibitory effects on the growth of tumor cells in vitro, in vivo and clinical chemotherapy.
Asummary of the noteworthy aspects of this study is as follows : (a) the uniform and stable structure of hybrid liposomes composed of DMPC and C_<12>(EO)_n was obtained. (b) Highly inhibitory effects of hybrid liposomes were obtained on the growth of many kinds of tumor cells in vitro. (c) Induction of apoptosis by hybrid liposomes through activation of death domains and some kind of caspases was verified for the first time. (d) Significantly prolonged survival was obtained in mice inoculated tumor cells after the treatment with hybrid liposomes without any side effect. (e) In clinical application, the prolonged survival was attained in patient with lymphoma and other tumors after the intravenous injection of hybrid liposomes without drugs and the remarkable reduction of solid tumor was obtained after the local administration of hybrid liposomes.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (49 results)

All 2005 2004 2003 2002 Other

All Journal Article (25 results) Book (10 results) Patent(Industrial Property Rights) (3 results) Publications (11 results)

  • [Journal Article] Induction of Apoptosis of Human Lung Carcinoma Cells by Hybrid Liposomes Containing Polyoxyethylenedodecyl Ether2005

    • Author(s)
      Y.Iwamoto
    • Journal Title

      International Journal of Pharmaceutics 292

      Pages: 231-239

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Novel Mechanism of Hybrid Liposomes-Induced Apoptosis in Human Tumor Cell2005

    • Author(s)
      Y.Matsumoto
    • Journal Title

      International Journal of Cancer 115

      Pages: 377-382

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Induction of Apoptosis of Human Lung Carcinoma Cells by Hybrid Liposomes Containing Polyoxyethylenedodecyl Ether2005

    • Author(s)
      Y.Iwamoto
    • Journal Title

      International Journal of Pharmaceutics 115

      Pages: 377-382

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Induction of Apoptosis of Human Lung Carcinoma Cells by Hybrid Liposomes Containing Polyoxyethylenedodecyl Ether2005

    • Author(s)
      Yasunori Iwamoto
    • Journal Title

      International Journal of Pharmaceutics 292・1-2

      Pages: 231-239

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A Novel Mechanism of Hybrid Liposomes-induced Apoptosis in Human Tumor Cells2005

    • Author(s)
      Yoko Matsumoto
    • Journal Title

      International Journal of Cancer 115

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Enzymatic and Hyperglycemia Stability of Chemically Modified Insulins with Hydrophobic Acyl Groups2004

    • Author(s)
      K.Nakashima
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters 14

      Pages: 481-483

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 糖尿病モデルラットを用いたインシュリン含有複合脂質膜の経口治療に関する基礎的研究2004

    • Author(s)
      中島 健太郎
    • Journal Title

      薬学雑誌 124

      Pages: 231-235

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Inhibitory Effects of Extract from Peels of Citrus natsudaidai Encapsulate in Hybrid Liposomes on the Growth of Tumor Cells in Vitro2004

    • Author(s)
      Y.Kadota
    • Journal Title

      Biological & Pharmaceutical Bulletin 27

      Pages: 1465-1467

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hybrid Liposomes as a Drug Carrier for the Oral Administration of Insulin in Diabetic Rats2004

    • Author(s)
      K.Nakashima
    • Journal Title

      Yakugakuzasshi 124

      Pages: 231-235

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 糖尿病モデルラットを用いたインシュリン含有複合脂質膜の経口治療に関する基礎的研究2004

    • Author(s)
      中島 健太郎
    • Journal Title

      薬学雑誌 124・4

      Pages: 231-235

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Inhibitory Effects of Extracts from Peels of Citrus natsudaidai Encapsulated in Hybrid Liposomes on the Growth of Tumor Cells in Vitro2004

    • Author(s)
      Yutaka Kadota
    • Journal Title

      Biological & Pharmaceutical Bulletin 27・9

      Pages: 1465-1467

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 抗がん剤を含まないハイブリッド型リポソームのみによるin vivoでのがん化学療法2003

    • Author(s)
      市原 英明
    • Journal Title

      薬学雑誌 123

      Pages: 25-34

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Steric-Control for the Enantioselective Hydrolysis of Amino Acid Esters in Hybrid Membrane Systems2003

    • Author(s)
      O.Tanoue
    • Journal Title

      Chemical & Pharmaceutical Bulletin 51

      Pages: 224-226

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Fairly Marked Enantioselectivity for the Hydrolysis of Amino Acid Esters by Chemically Modified Enzymes2003

    • Author(s)
      Y.Yano
    • Journal Title

      Journal of Organic Chemistry 68

      Pages: 1314-1318

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Induction of Apoptosis by Hybrid Liposomes without Antitumor Drug toward Human Breast Tumor Cells2003

    • Author(s)
      H.Nagami
    • Journal Title

      Journal of Chemical Engineering of Japan 36

      Pages: 1127-1129

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Chemotherapy with Hybrid Liposome without any Drug in vivo2003

    • Author(s)
      H.Ichihara
    • Journal Title

      Yakugakuzasshi 123

      Pages: 25-34

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Sterie-Control for the Enantioselective Hydrolysis of Amino Acid Esters in Hybrid Membrane Systems2003

    • Author(s)
      O.Tanoue
    • Journal Title

      Chemical & Pharmaceutical Bulletin 51

      Pages: 224-226

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Steric-Control for the Enantioselective Hydrolysis of Amino Acid Esters in Hybrid Membrane Systems2003

    • Author(s)
      Yoshihiro Yano
    • Journal Title

      The Journal of Organic Chemistry 68・4

      Pages: 1314-1418

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Induction of Apoptosis by Hybrid Liposomes without Antitumor Drugs toward Human Breast Tumor Cells2003

    • Author(s)
      Hideaki Nagami
    • Journal Title

      Journal of Chemical Engineering of Japan 36・9

      Pages: 1127-1129

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Enzymatic and Hyperglycemia Stability of Chemically Modified Insulins with Hydrophobic Acyl Groups2003

    • Author(s)
      Kentaro Nakashima
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters 14・4

      Pages: 481-483

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Specific Accumulation and Growth Inhibitory Effects of Hybrid Liposomes to Hepatoma Cells in Vitro2002

    • Author(s)
      K.Nakano
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters 12

      Pages: 3251-3254

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] レクチンの認識機能を有するハイブリッド型リポソームの調製2002

    • Author(s)
      通阪 栄一
    • Journal Title

      膜 27

      Pages: 202-208

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Enhanced Inhibitory Effects of Extracts from Ginkgo Biloba L.Leaves Encapsulated in Hybrid Liposomes on the Growth of Tumor Cells in vitro2002

    • Author(s)
      S.Yamamoto
    • Journal Title

      Biochemical Engineering Journal 12

      Pages: 125-130

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Preparation of Hybrid Liposomes Recognizing Lectin2002

    • Author(s)
      E.Toorisaka
    • Journal Title

      Membrane 27

      Pages: 202-208

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Enhanced Inhibitory Effects of Extracts from Ginkgo Biloba L. Leaves Encapsulated in Hybrid Liposomes on the Growth of Tumor Cells in vitro2002

    • Author(s)
      S.Yamamoto
    • Journal Title

      Biochemical Engineering Journal 12

      Pages: 125-130

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] ケミカルエンジニアリング 特集 先端治療システム開発の最前線「リポソームによるがん治療と診断」2004

    • Author(s)
      上岡 龍一
    • Total Pages
      7
    • Publisher
      化学工業社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Liposome ni yoru gan-chiryo to shindan (Chemical-engineering)2004

    • Author(s)
      R.Ueoka
    • Total Pages
      7
    • Publisher
      Kagakukogyosya
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] リポソームによるがん治療と診断2004

    • Author(s)
      上岡龍一
    • Publisher
      化学工業社
    • Related Report
      2004 Annual Research Report
  • [Book] 蛋白質 核酸 酵素 増刊号 科学と生物学の接点がつくるNEWバイオテクノロジー「アポトーシス誘導ハイブリッドリポソームのがん治療効果」2003

    • Author(s)
      松本 陽子
    • Total Pages
      7
    • Publisher
      共立出版
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 生体内の高分子 機能材料開発と医療への新展開「リポソームによる癌治療」2003

    • Author(s)
      上岡 龍一
    • Total Pages
      20
    • Publisher
      エヌ・ティー・エス
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Chemotherapy with Drug-Free Hybrid Liposomes along with Induction of Apoptosis (Protein, Nucleic, acid Enzyme, Special issue number)2003

    • Author(s)
      Y.Matsumoto
    • Total Pages
      7
    • Publisher
      Kyoritsu syuppan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Liposome ni yoru gan-chiryo (Seitainai no kobunshi, Kinozairyoukaihatsu to iryo heno shintenkai)2003

    • Author(s)
      R.Ueoka
    • Total Pages
      20
    • Publisher
      NTS
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] アポトーシス誘導ハイブリッドリポソームの癌治療効果2003

    • Author(s)
      松本陽子
    • Publisher
      共立出版
    • Related Report
      2004 Annual Research Report
  • [Book] 複合脂質膜の制がんメカニズムと臨床への応用2002

    • Author(s)
      松本 陽子
    • Total Pages
      6
    • Publisher
      財団法人バイオインダストリー協会
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] The Novel Mechanism of Drug-Free Hybrid Liposomes for Inhibition of Tumor Growth and Clinical Application2002

    • Author(s)
      Y.Matsumoto
    • Total Pages
      6
    • Publisher
      Bio-Industry kyokai
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 抗腫瘍剤,健康食品及び味噌のエタノール抽出物2003

    • Inventor(s)
      上岡 龍一
    • Industrial Property Rights Holder
      上岡 龍一
    • Patent Publication Number
      2004-244413
    • Filing Date
      2003-10-31
    • Acquisition Date
      2004-09-02
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 抗腫瘍剤、健康食品及び味噌のエタノール抽出物2003

    • Inventor(s)
      上岡 龍一
    • Industrial Property Rights Holder
      上岡 龍一, 株式会社山内本店
    • Industrial Property Number
      2003-373242
    • Filing Date
      2003-10-31
    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] 癌細胞の検出剤2002

    • Inventor(s)
      上岡 龍一
    • Industrial Property Rights Holder
      上岡 龍一
    • Patent Publication Number
      2004-077326
    • Filing Date
      2002-08-20
    • Acquisition Date
      2004-03-11
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Yoshihiro Yano: "Steric-Control for the Enantioselective Hydrolysis of Amino Acid Esters in Hybrid Membrane Systems"The Journal of Organic Chemistry. 68・4. 1314-1418 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hideaki Nagami: "Induction of Apoptosis by Hybrid Liposomes without Antitumor Drugs toward Human Breast Tumor Cells"Journal of Chemical Engineering of Japan. 36・9. 1127-1129 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kentaro Nakashima: "Enzymatic and Hyperglycemia Stability of Chemically Modified Insulins with Hydrophobic Acyl Groups"Bioorganic & Medicinal Chemistry Letters. 14・4. 481-483 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 中島 健太郎: "糖尿病モデルラットを用いたインシュリン含有複合脂質膜の経口治療に関する基礎的研究"薬学雑誌. 124・4. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 松本陽子: "アポトーシス誘導ハイブリッドリポソームの癌治療効果"共立出版. (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Koji Nakano: "Specific Accumulation and Growth Inhibitory Effects of Hybrid Liposomes to Hepatoma Cells In Vitro"Bioorganic & Medicinal Chemistry Letters. 12・22. 3251-3254 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 通阪 栄一: "レクチンの認識機能を有するハイブリッド型リポソームの調製"膜. 27・4. 202-208 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shinjiro Yamamoto: "Enhanced Inhibitory Effects of Extracts from Ginkgo Biloba L.Leaves Encapsulated in Hybrid Liposomes on the Growth of Tumor Cells In Vitro"Biochemical Engineering Journal. 12・2. 125-130 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 市原 英明: "抗がん剤を含まないハイブリッド型リポソームによるin vivoでのがん化学療法"薬学雑誌. 123・1. 25-34 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Osamu Tanoue: "Steric-Control for the Enantioselective Hydrolysis of Amino Acid Esters in Hybrid Membrane Systems"Chemical & Pharmaceutical Bulletin. 51・2. 224-226 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 松本 陽子: "複合脂質膜の制がんメカニズムと臨床への応用"バイオインダストリー協会. 71 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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