1999 Fiscal Year Annual Research Report

腫瘍特異的遺伝子導入を用いた難治性癌に対する中性子捕捉療法の開発

Research Project

Project/Area Number	11557092
Research Category	Grant-in-Aid for Scientific Research (B)
Research Institution	The University of Tokyo
Principal Investigator	柳衛宏宣東京大学, 医科学研究所, 助手 (30212278)
Co-Investigator(Kenkyū-buntansha)	小倉紘一日本大学, 生産工学部, 教授 (60059681) 小林久夫立教大学, 原子力研究所, 教授 (10062605) 杉山弘高愛知医科大学, 医学部, 講師 (70242112) 小野公二京都大学, 原子炉実験所, 教授 (90122407)
Keywords	中性子捕捉療法 / ドラッグデリバリーシステム / ボロン化合物 / ステルスリポソーム / Qplex / C型肝炎ウイルス細胞障害領域 / アポトーシス / パルス式中性子発生装置
Research Abstract	インテリジェントターゲッティングシステムを用いた遺伝子治療と中性子捕捉療法の併用効果により選択的な癌治療を目指して研究を進めている。 1)Liposomeのstelth化によるDrug delivery systemの開発: 我々は、Liposomeの表面をPolyethyleneglycolで修飾することにより、細網内皮系による捕捉を回避し、血中滞留性が著しく向上するStealth liposomeを開発した。 AsPC-1あるいはColon26担癌マウスに ^<10>B封入Stealth liposomeを静脈注射後、60時間経過しても腫瘍内^<10>Bを40ppm以上保つことをPlasma emmision spectroscopyにて確認し、この濃度は中性子捕捉療法(BNCT)を行うのに十分量であった。さらに、2×10^<12>n/cm^2の熱中性子を照射し、BNCTを行うと、腫瘍特異的にAsPC-1腫瘍の増殖抑制およびColon26腫瘍の消失を認めた。 2)新規Lipoplex(Quarternary complex,Qplex )の開発: 我々は、Cationic liposomeとplasmid DNAとの複合体であるLipoplexにprotamineおよびtransferrin(TF)を添加した4成分からなる複合体(Quarternary complex,Qplex)を開発した。plasmid DNAはβ-galactosidaseをコードしたものを、細胞としてはCOS7、AsPC-1を用いた。LipoplexおよびLipoplexにprotamineまたはTFのみを添加した複合体に比べて、Qplexはいずれの細胞に対しても著しく高い発現を示した。 3)新規癌抑制遺伝子の固定: C型肝炎ウイルスの中に細胞障害を引き起こす領域を同定した。この領域には、アポトーシスを引き起こし肝細胞を死に至らしめる作用と核染色体異常をおこす作用がある事を見いだした。この領域をINES領域と名付けた。細胞内のRanとExportinに作用して、染色体構造を傷害している事が判明した。そして、肝細胞にアポトーシスを引き起こしていた。 4)パルス式中性子発生装置の開発: 熱中性子を獲得するために、安全で効率のよいパルス式中性子発生装置を開発中であり、熱中性子の線量を計測し試作品を検討している。 5)悪性脳腫瘍に対する中性子捕捉療法の医療照射: 京都大学原子炉では、本年度も、悪性脳腫瘍に対し、BSHあるいはBPAを静脈注射後、中性子捕捉療法の医療照射を行い、症例数を増やし治療成績を上げている。

Research Products

(14 results)

All Other

All Publications (14 results)

[Publications] H. Yanagie et al.: "Application of ^<10>B entrapped PEG-liposome to boron neutron-capture theropy for pancreatic cancer model in vivo"Neutron Imaging Methods to Detect Detects in Materials. 709-715 (1999)
[Publications] H. Yanagie et al.: "Neutron capture autoradiographic determination of ^<10>B distributions and concentrations in biological samples for boron neutron capture therapy"Nuclear Instruments and Methods in Physics Research A. 424. 122-128 (1999)
[Publications] O. Ishida, H. Yanagie et al.: "Targeting-chemotherapy to Solid Tumors with Long-Circulating Thermo sensitive Liposomes and Local Hyperthermia"Jpn. J. Cancer Res.. 91. 118-126 (2000)
[Publications] H. Sugiyama, H. Yanagie et al.: "Identification of nuclear export signals in human type C hepatitis virus"FASEB Journal.. 13(7). 1492 (1999)
[Publications] H. Sugiyama, H. Yanagie et al.: "Analysis of hepatitis C virus mediated nuclear deformation"Journal of Virology. (in prss).
[Publications] K. Ono et al.: "The Combined Effect of Boronphenylalanine and Borocaptate in Boron Neutoron Capture Therapy for SCVII Tumors in Mice"Int. J. Radiati Oncol. Biol. Phys.. 43. 431-436 (1999)
[Publications] S. Masunaga, K. Ono. et al.: "Reoxygeneration in quescent and total intratumor cells following thermol neutron irradiation with or without ^<10>B Compound - Compared with that after γ-ray irradiation"Int. J. Radiat. Oncol. Biol. Phys.. 44(2). 391-398 (1999)
[Publications] K. Amemiya, K. Ogura et al.: "Ultra-high resolution radiography using CR-39 solid state track detectors and atomic force microscopy"Nuclear Instruments and Methods in Physics Research B. 159. 75-80 (1999)
[Publications] J. Scvarc, H. Yanagie et al.: "Selective Radiography with etched track detectors"Nuclear Instruments and Methods in Physics Reseach B. 152. 115-121 (1999)
[Publications] H. Kobayashi et al.: "Basic performance of a neutron sensitive photostimulated luminescence device for neutron radiography"Nuclear Instruments and Methods in Physics Reseach A. 424. 1-8 (1999)
[Publications] H. Kobayashi et al.: "A correlated study between effective total macroscopic cross sections and effective energles for neutron beams of continuous spectra"Nuclear Instruments and Methods in Physics Reseach A. 424. 151-157 (1999)
[Publications] H. Kobayashi et al.: "Study for a novel tomography technique using an imaging plate"Nuclear Instruments and Methods in Physics Reseach A. 424. 221-228 (1999)
[Publications] H. Sawamura, K. Nishimura et al.: "Evoluation of long-term irradiation field in geological disposal of high-level radioactive wastes"Proc. of 9th Int'l Conf. on Radiation Shielding. (in press).
[Publications] Y. Suzuki, K. Nishimura et al.: "Radiation Shielding Analysis for JT-60SV"Proc. of 9th Int'l Conf. on Radiation Shielding. (in press).

1999 Fiscal Year Annual Research Report

腫瘍特異的遺伝子導入を用いた難治性癌に対する中性子捕捉療法の開発

Principal Investigator

柳衛 宏宣 東京大学, 医科学研究所, 助手 (30212278)

Research Products

[Publications] H. Yanagie et al.: "Application of ^<10>B entrapped PEG-liposome to boron neutron-capture theropy for pancreatic cancer model in vivo"Neutron Imaging Methods to Detect Detects in Materials. 709-715 (1999)

[Publications] H. Yanagie et al.: "Neutron capture autoradiographic determination of ^<10>B distributions and concentrations in biological samples for boron neutron capture therapy"Nuclear Instruments and Methods in Physics Research A. 424. 122-128 (1999)

[Publications] O. Ishida, H. Yanagie et al.: "Targeting-chemotherapy to Solid Tumors with Long-Circulating Thermo sensitive Liposomes and Local Hyperthermia"Jpn. J. Cancer Res.. 91. 118-126 (2000)

[Publications] H. Sugiyama, H. Yanagie et al.: "Identification of nuclear export signals in human type C hepatitis virus"FASEB Journal.. 13(7). 1492 (1999)

[Publications] H. Sugiyama, H. Yanagie et al.: "Analysis of hepatitis C virus mediated nuclear deformation"Journal of Virology. (in prss).

[Publications] K. Ono et al.: "The Combined Effect of Boronphenylalanine and Borocaptate in Boron Neutoron Capture Therapy for SCVII Tumors in Mice"Int. J. Radiati Oncol. Biol. Phys.. 43. 431-436 (1999)

[Publications] S. Masunaga, K. Ono. et al.: "Reoxygeneration in quescent and total intratumor cells following thermol neutron irradiation with or without ^<10>B Compound - Compared with that after γ-ray irradiation"Int. J. Radiat. Oncol. Biol. Phys.. 44(2). 391-398 (1999)

[Publications] K. Amemiya, K. Ogura et al.: "Ultra-high resolution radiography using CR-39 solid state track detectors and atomic force microscopy"Nuclear Instruments and Methods in Physics Research B. 159. 75-80 (1999)

[Publications] J. Scvarc, H. Yanagie et al.: "Selective Radiography with etched track detectors"Nuclear Instruments and Methods in Physics Reseach B. 152. 115-121 (1999)

[Publications] H. Kobayashi et al.: "Basic performance of a neutron sensitive photostimulated luminescence device for neutron radiography"Nuclear Instruments and Methods in Physics Reseach A. 424. 1-8 (1999)

[Publications] H. Kobayashi et al.: "A correlated study between effective total macroscopic cross sections and effective energles for neutron beams of continuous spectra"Nuclear Instruments and Methods in Physics Reseach A. 424. 151-157 (1999)

[Publications] H. Kobayashi et al.: "Study for a novel tomography technique using an imaging plate"Nuclear Instruments and Methods in Physics Reseach A. 424. 221-228 (1999)

[Publications] H. Sawamura, K. Nishimura et al.: "Evoluation of long-term irradiation field in geological disposal of high-level radioactive wastes"Proc. of 9th Int'l Conf. on Radiation Shielding. (in press).

[Publications] Y. Suzuki, K. Nishimura et al.: "Radiation Shielding Analysis for JT-60SV"Proc. of 9th Int'l Conf. on Radiation Shielding. (in press).

柳衛宏宣東京大学, 医科学研究所, 助手 (30212278)