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Boron10・モノクローナル抗体による癌の選択的原子炉療法の研究

Research Project

Project/Area Number 62010051
Research Category

Grant-in-Aid for Cancer Research

Allocation TypeSingle-year Grants
Research InstitutionKobe University

Principal Investigator

三島 豊  神戸大学, 医学部, 教授 (10073743)

Co-Investigator(Kenkyū-buntansha) 福田 寛  放射線医学総合研究所, 臨床研究部, 主任研究員 (30125645)
森 芳弘  信州大学, 理学部, 教授 (40020648)
神田 啓治  京都大学, 原子炉実験所, 助教授 (10027419)
田中 千賀子  神戸大学, 医学部, 教授 (20025571)
谷口 克  千葉大学, 医学部, 教授 (80110310)
Project Period (FY) 1987
Project Status Completed (Fiscal Year 1987)
Budget Amount *help
¥12,400,000 (Direct Cost: ¥12,400,000)
Fiscal Year 1987: ¥12,400,000 (Direct Cost: ¥12,400,000)
Keywords単クローン抗体 / 熱中性子捕捉療法 / 原子炉療法 / 悪性黒色腫
Research Abstract

本研究の特色は癌細胞表面上の抗原エピトープに特異結合する単クローン抗体(MoAb)を作成,これに多数の^<10>B原子を付加した^<10>BMoAbを投与して熱中性子捕捉療法を行う点にある. 単独でも有効だが,今迄開発して来た代謝活性利用の方法(例えばpーboronoーphenylalanine,^<10>B_1ーBPA投与下で同療法を行う黒色腫治療)を併用すれば相加相乗効果が期待できる. 下記業績も両者に跨っている.
1.Na^<10>B_<12>H_1NH_<3-n>(CH_2COOH)_n(n=1〜3)と推定される新化合物を合成,n=2のものとCH_3O(CH_2CH_2O)_m_<CH>2をavidin(糖蛋白)に化合させて水溶性ホウ素化avidinを得た。
2.(1)Biotin付加した抗黒色腫MoAbを培養黒色腫細胞に作用後,上記ホウ素化avidinで処理,(2)ハプテンとしてDNPを導入したMoAbを黒色腫細胞に作用,biotin付加の抗ハプテン抗体,ホウ素化avidin処理,の2系に熱中性子照射し細胞致死を証明.
3.^<10>B_1ーBPA共存下で熱中性子捕捉処理したBー16黒色腫細胞の速型PLD修復は不生起,遅型PLD修復は極僅.
4.^nBBPAの中性懸濁液の亜急性毒性をラット皮下投与で検討. 治療有効量で毒性無.
5.^<10>BーBPAなど難水溶性B薬物の静注液作成の目的でcyclodextrinとの包接化合物につき研究開始.
6.本研究班で開発して来た即発Г線による生体内^<10>B濃度測定をヒト患者に実施し,治療照射条件の設定に資した(10参照).
7.(1)^<10>B_1ーBPAと単糖類間の錯形成定数を測定,目的濃度のBPA溶液調製に便利な糖量表作成. (2)経口投与^<10>B_1ーBPAの組織内B濃度時間変化を追究.
8.ヒト黒色腫培養IHARA株はヌードマウス皮下で発育速く,継代率80%. 中性子照射時の発熱を防止できれば治療モデルに適す.
9.各種濃度の^<10>BーBPA,^<10>Bホウ酸で処理した細胞を熱中性子照射,生残曲線より^<10>B(n,α)^7Li反応のRBE,^<10>BーBPAのメラノーマ集積性究明.
10.昭和62・7・11治療実施のヒト黒色腫第1症例は10月以後も順調で再発・転移の徴候なく,完治期待. 63・3・2実施の第2例も経過良好. 観察続行中.

Report

(1 results)
  • 1987 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Jukuda,H.: Int.J.Radiat.Biol.51. 167-175 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 三島 豊: 病理と臨床. 5. (19871044-1055)

    • Related Report
      1987 Annual Research Report
  • [Publications] 市橋正光: 放射線生物研究. 22. (198773-102)

    • Related Report
      1987 Annual Research Report
  • [Publications] 平塚純一: 川崎医学会誌. 13. 308-314 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 笹瀬晃弘: Skin Cancer. 2. 101-106 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Utsumi,H.: Carcinogenesis. 8. 1439-1444 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Mishima,Y.(Alan R Liss,Inc,New York): Pigment Cell Res.2. (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Matsumoto,T.(Alan R Liss,Inc,New York): Pigment Cell Res.2. (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Taniguchi,M.(Alan R Liss,Inc,New York): Pigment Cell Res.2. (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Komura,A(Alan R Liss,Inc,New York): Pigment Cell Res.2. (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Mori,Y.(Alan R Liss,Inc,New York): Pigment Cell Res.2. (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Yoshino,K.(Alan R Liss,Inc,New York): Pigment Cell Res.2. (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Taniyama,K.(Alan R Liss,Inc,New York): Pigment Cell Res.2. (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Brown,K.(Alan R Liss,Inc,New York): Pigment Cell Res.2. (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Ichihashi,M.(Alan R Liss,Inc,New York): Pigment Cell Res.2. (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Fukuda,H.(Alan R Liss,Inc,New York): Pigment Cell Res.2. (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Utsumi,H.(Alan R liss,Inc,New York): Pigment Cell Res.2. (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Tamaoki,N.(Alan R Liss,Inc,New York): Pigment Cell Res.2. (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Barkla,D.H.(Alan R Liss,Inc,New York): Pigment Cell Res.2. (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Shirakawa,J.(Alan R Liss,Inc,New York): Pigment Cell Res.2. (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Hiratsuka,J.(Alan R Liss,Inc,New York): Pigment Cell Res.2. (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Fukuda,H.(Alan R Liss,Inc,New York): Pigment Cell Res.2. (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Mishima,Y.: "Cutaneous Melanoma(Selective eradication of malignant melanoma by thermal neutron capture therapy using melanomaーseeking ^<10>Bーcompounds" Academic Press Inc.Ltd.,London, 693 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Mishima,Y.: "Cutaneous Melanoma(Glycosylation and melanogenesis)" Academic Press Inc.Ltd.,London, 693 (1987)

    • Related Report
      1987 Annual Research Report

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Published: 1987-04-01   Modified: 2016-04-21  

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