1986 年度実績報告書

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

研究課題

研究課題/領域番号	61010051
研究機関	神戸大学
研究代表者	三島豊神戸大, 医学部, 教授 (10073743)
研究分担者	玉置憲一東海大学, 医学部, 教授 (50055860) 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)
キーワード	単クローン抗体 / 熱中性子捕捉療法 / 原子炉療法
研究概要	本研究の特色は癌細胞表面にある多種の坑原エピトープに夫々特異結合する多種類の単クローン抗体(MoAb)を作成し、これを【^(10)B】担体とした【^(10)B】MoAbを合成投与して熱中性子捕捉療法を行う点にある。単独でも有効であるが、今迄開発して来た代謝活性利用の方法(例えばp-borono-phenylalanine塩酸塩【^10B-1】-BPA・HCl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。下記の業績も両者に跨っている。1.NaHをNa・【^10B-12】【H_(11)】N【H_3】に働かせ【H_3】を【Na_3】に置換後Cl【CH_2】COO【CH_3】と反応、水解。Na・【^10B-12】【H_(11)】C【H_2】COOHと推定される生成物をcarbodiimide法でpoly-D,L-lysineに付加。【^(10)B】含量は高いが水に不溶。水溶化して抗体へ結合の予定。2.肺癌患者リンパ球とマウス骨髄腫の融合株より得た単クローン抗体4G12はIgM入型で、組織染色で広い悪性腫瘍特異性を示す。良性腫瘍に無反応。ヒト肺癌ヌードマウスに投与した【^(12G)I】標識4G12の腫瘍/筋肉濃度比は高く42。3.Top【II】の阻害剤novobiocinは遅い(S-)PLD修復も阻害する。抗癌剤mAMSA,VP16,VM26も亦Top【II】を阻害するので3者のS-PLD修復阻害の有無、PLD修復とTop【II】の関係を研究中。4.【^nB-1】・BPA・HClをcarboxymethy 1-cellulose含有生理食塩水に溶解、中和して得た懸濁液を用い、ラット腹腔内と皮下投与で急性毒性(【LD_(50)】)3,000mg/kg)、1日1回28日間ラット皮下投与で亜急性毒性(0,300,700,1500mg/kgで体重・摂食・摂水量)試験。副作用無。5.鉛製コリメータを製作し、患部以外の被曝を低下。細胞内【^(10)B】濃度分布を考慮した吸収線量計算から見た細胞生残率データの評価。生体内重水濃度を高めて深部照射する可能性を検討。6.【B_1】-BPA・HCl水溶液はpH1の強酸性、中和すれば沈澱生じ静注不適。糖との錯体形成を利用しこの難点を解決。例えばpH8のfructose液100mlは【B_1】-BPA 3gを溶解。7.ICR/NFS4元交配のMCH(AF)ヌードマウスにヒト・マウス黒色腫を移植した実験系で【^10B-1】-BPA投与+中性子照射群は中性子単独群に較べ有意に増殖抑制。

研究成果

(33件)

すべてその他

すべて文献書誌 (33件)

[文献書誌] Mishima,Y.: Transactions of Am.Nucl.Soc.53. 33-34 (1986)
[文献書誌] Mishima,Y.: Exploration of the possibility of high let radiation for non-conventional radiotherapy in cancer. 396. 37-54 (1986)
[文献書誌] Hayashibe,K.: J.Invest.Dermatol.87. 89-94 (1986)
[文献書誌] Hayashibe,K.: Proc.Jpn.Soc.Invest.Dermatol.10. 85-86 (1986)
[文献書誌] Hatta,S.: Proc.Jpn.Soc.Invest.Dermatol.10. 87-88 (1986)
[文献書誌] Fukuda,H.: Int.J.Radiat.Biol.51. 167-175 (1987)
[文献書誌] Natali,P.: J.Invest.Dermatol.85. 340-346 (1985)
[文献書誌] Hirabayashi,Y.: Biochemica et Biophysica Acta. 875. 126-128 (1986)
[文献書誌] Gunji,Y.: Jpn.J.Cancer Prs.77. 595-601 (1986)
[文献書誌] Sakiyama,H.: Cell Struct.Funct.
[文献書誌] Uchiyama,K.: Jpn.J.Cancer Res.
[文献書誌] Saito,H.: Cancer Res.
[文献書誌] Ichihashi,M.: Proc.Jap.Soci.Invest Dermatol.
[文献書誌] Kanda,K.: Trans.Am.Nucl.Soc.53. 26-27 (1986)
[文献書誌] 古林徹: 第21回京都大学原子炉実験所学術講演会要旨集. 67-71 (1987)
[文献書誌] Tada,N.: Immunogenetics. 24. 275-277 (1986)
[文献書誌] 玉置憲一: 医学のあゆみ. 136. 393-399 (1986)
[文献書誌] Hashimoto,K.: Brit.J.Dermatol.115. 205-209 (1986)
[文献書誌] Mishima,Y.: "Boron-Neutron Capture Therapy for Tumors(Experimental treatment of malignant melanomaーClinically and pathologically confirmed cure by neutron capture therapy using melanogenesis-seeking compounds)" Nishimura Co.,Ltd.,Niigata, 463 (1986)
[文献書誌] Mishima,Y.: "Neutron Capture Therapy(Prerequisites of first clinical trial for melanoma selective thermal neutron capture therapy)" Nishimura Co.,Ltd.,Niigata, 449 (1986)
[文献書誌] Ichihashi,M.: "Neutron Capture Therapy(Selective lethal effects of 【^10B-1】-para-boronophenylalaine on mouse and human melanoma cells in thermal neutron capture therapy enhanced by tyrosine and phenylalaine deficiency." Nishimura Co.,Ltd.,Niigata, 449 (1986)
[文献書誌] Hatta,S.: "Neutron Capture Therapy(Selective affinity of 【^10B-1】-paraboronophenylalanine・HCl to malignant melanoma:in relation to thermal neutron capture therapy" Nishimura Co.,Ltd.,Niigata, 449 (1986)
[文献書誌] Hiratsuka,J.: "Neutron Capture Therapy(RBC of thermal neutron capture therapy of malignant melanoma using 【^10B-1】-para-boronophenylalanine(【^(10)B】-BPA)in comparison with 9MeV electron beam irradiation" Nishimura Co.,Ltd.,Niigata, 449 (1986)
[文献書誌] Karashima,H.: "Neutron Capture Therapy(Clinical dosimetry using human phantom with skelton bone for thermal neutron capture therapy)" Nishimura Co.,Ltd.,Niigata, 449 (1986)
[文献書誌] Ichihashi,M.: "Boron-Neutron Capture Therapy for Tumors(Melanoma-specific lethal and potentially lethal damage of 【^10B-1】-para-boronophenylanine in the thermal neutron capture therapy)" Nishimura Co.,Ltd.in Niigata, 463 (1986)
[文献書誌] Utsumi,H.: "Neutron Capture Therapy(Potentially lethal damage repair of B-16 melanoma cells pretreated with 【^10B-1】-para-boronophenylanine after exposure to thermal neutron radiation)" Nishimura Co.,Ltd.in Niigata, 449 (1986)
[文献書誌] Kobayashi,T.: "Neutron Capture Therapy(Measurement of Boron-10 Concentrations and Its Location in Phantom by Prompt Gamma-ray Spectroscopy)" Nishimura Co.,Ltd.in Niigata, 449 (1986)
[文献書誌] Kanda,K.: "Neutron Capture Therapy(Progress in Physics for Boron Neutron Capture Therapy)" Nishimura Co.,Ltd.in Niigata, 449 (1986)
[文献書誌] Aoki,K.: "Neutron Capture Therapy(Fine Neutron Distributions in a Phantom for Beam Neutrons)" Nishimura Co.,Ltd.in Niigata, 449 (1986)
[文献書誌] Ujeno,Y.: "Neutron Capture Therapy(Enhancement of the killing Effect of Thermal Neutron on Cancer Cells by Boron-10 Compound)" Nishimura Co.,Ltd.in Niigata, 449 (1986)
[文献書誌] Yoshino,K.: "Neutron Capture Therapy(Chemical assay of boron and its distribution in melanoma-bearing subjects)" Nishimura Co.,Ltd.in Niigata, 449 (1986)
[文献書誌] 玉置憲一: "免疫科学第3巻免疫担当細胞(免疫担当細胞の種類と分化)" 岩波書店, 309 (1986)
[文献書誌] Jimbow,K.: "Structure and Function of Melanin Vol.3,1986(Ultrastrucural Characteristics and Kinetics of Tyrosinase of Cultured Human Melanocytes" Fuji-Shoin Co.,Ltd.in Sapporo, 122 (1986)

1986 年度 実績報告書

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

研究代表者

三島 豊 神戸大, 医学部, 教授 (10073743)

研究成果

[文献書誌] Mishima,Y.: Transactions of Am.Nucl.Soc.53. 33-34 (1986)

[文献書誌] Mishima,Y.: Exploration of the possibility of high let radiation for non-conventional radiotherapy in cancer. 396. 37-54 (1986)

[文献書誌] Hayashibe,K.: J.Invest.Dermatol.87. 89-94 (1986)

[文献書誌] Hayashibe,K.: Proc.Jpn.Soc.Invest.Dermatol.10. 85-86 (1986)

[文献書誌] Hatta,S.: Proc.Jpn.Soc.Invest.Dermatol.10. 87-88 (1986)

[文献書誌] Fukuda,H.: Int.J.Radiat.Biol.51. 167-175 (1987)

[文献書誌] Natali,P.: J.Invest.Dermatol.85. 340-346 (1985)

[文献書誌] Hirabayashi,Y.: Biochemica et Biophysica Acta. 875. 126-128 (1986)

[文献書誌] Gunji,Y.: Jpn.J.Cancer Prs.77. 595-601 (1986)

[文献書誌] Sakiyama,H.: Cell Struct.Funct.

[文献書誌] Uchiyama,K.: Jpn.J.Cancer Res.

[文献書誌] Saito,H.: Cancer Res.

[文献書誌] Ichihashi,M.: Proc.Jap.Soci.Invest Dermatol.

[文献書誌] Kanda,K.: Trans.Am.Nucl.Soc.53. 26-27 (1986)

[文献書誌] 古林徹: 第21回京都大学原子炉実験所学術講演会要旨集. 67-71 (1987)

[文献書誌] Tada,N.: Immunogenetics. 24. 275-277 (1986)

[文献書誌] 玉置憲一: 医学のあゆみ. 136. 393-399 (1986)

[文献書誌] Hashimoto,K.: Brit.J.Dermatol.115. 205-209 (1986)

[文献書誌] Mishima,Y.: "Boron-Neutron Capture Therapy for Tumors(Experimental treatment of malignant melanomaーClinically and pathologically confirmed cure by neutron capture therapy using melanogenesis-seeking compounds)" Nishimura Co.,Ltd.,Niigata, 463 (1986)

[文献書誌] Mishima,Y.: "Neutron Capture Therapy(Prerequisites of first clinical trial for melanoma selective thermal neutron capture therapy)" Nishimura Co.,Ltd.,Niigata, 449 (1986)

[文献書誌] Ichihashi,M.: "Neutron Capture Therapy(Selective lethal effects of 【^10B-1】-para-boronophenylalaine on mouse and human melanoma cells in thermal neutron capture therapy enhanced by tyrosine and phenylalaine deficiency." Nishimura Co.,Ltd.,Niigata, 449 (1986)

[文献書誌] Hatta,S.: "Neutron Capture Therapy(Selective affinity of 【^10B-1】-paraboronophenylalanine・HCl to malignant melanoma:in relation to thermal neutron capture therapy" Nishimura Co.,Ltd.,Niigata, 449 (1986)

[文献書誌] Hiratsuka,J.: "Neutron Capture Therapy(RBC of thermal neutron capture therapy of malignant melanoma using 【^10B-1】-para-boronophenylalanine(【^(10)B】-BPA)in comparison with 9MeV electron beam irradiation" Nishimura Co.,Ltd.,Niigata, 449 (1986)

[文献書誌] Karashima,H.: "Neutron Capture Therapy(Clinical dosimetry using human phantom with skelton bone for thermal neutron capture therapy)" Nishimura Co.,Ltd.,Niigata, 449 (1986)

[文献書誌] Ichihashi,M.: "Boron-Neutron Capture Therapy for Tumors(Melanoma-specific lethal and potentially lethal damage of 【^10B-1】-para-boronophenylanine in the thermal neutron capture therapy)" Nishimura Co.,Ltd.in Niigata, 463 (1986)

[文献書誌] Utsumi,H.: "Neutron Capture Therapy(Potentially lethal damage repair of B-16 melanoma cells pretreated with 【^10B-1】-para-boronophenylanine after exposure to thermal neutron radiation)" Nishimura Co.,Ltd.in Niigata, 449 (1986)

[文献書誌] Kobayashi,T.: "Neutron Capture Therapy(Measurement of Boron-10 Concentrations and Its Location in Phantom by Prompt Gamma-ray Spectroscopy)" Nishimura Co.,Ltd.in Niigata, 449 (1986)

[文献書誌] Kanda,K.: "Neutron Capture Therapy(Progress in Physics for Boron Neutron Capture Therapy)" Nishimura Co.,Ltd.in Niigata, 449 (1986)

[文献書誌] Aoki,K.: "Neutron Capture Therapy(Fine Neutron Distributions in a Phantom for Beam Neutrons)" Nishimura Co.,Ltd.in Niigata, 449 (1986)

[文献書誌] Ujeno,Y.: "Neutron Capture Therapy(Enhancement of the killing Effect of Thermal Neutron on Cancer Cells by Boron-10 Compound)" Nishimura Co.,Ltd.in Niigata, 449 (1986)

[文献書誌] Yoshino,K.: "Neutron Capture Therapy(Chemical assay of boron and its distribution in melanoma-bearing subjects)" Nishimura Co.,Ltd.in Niigata, 449 (1986)

[文献書誌] 玉置憲一: "免疫科学第3巻免疫担当細胞(免疫担当細胞の種類と分化)" 岩波書店, 309 (1986)

[文献書誌] Jimbow,K.: "Structure and Function of Melanin Vol.3,1986(Ultrastrucural Characteristics and Kinetics of Tyrosinase of Cultured Human Melanocytes" Fuji-Shoin Co.,Ltd.in Sapporo, 122 (1986)

1986 年度実績報告書

三島豊神戸大, 医学部, 教授 (10073743)