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Gene Transfer-applied Cancer Boron Neutron Capture Therapy : Expansion of therapeutic applicability

Research Project

Project/Area Number 09470189
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionKobe University

Principal Investigator

MISHIMA Yutaka  Kobe Univ., School of Medicine, Honorary Professor, 医学部, 名誉教授 (10073743)

Co-Investigator(Kenkyū-buntansha) FUKUMORI Yoshinobu  Faculty of Pharmaceutical Science, Kobe Gakuin Univ., Professor, 薬学部, 教授 (60102927)
YOSHINO Kazuo  Shinshu Univ., Faculty of Science, Assistant Professor, 理学部, 助教授 (70143964)
ONO Koji  Research Reactor Institute, Kyoto Univ., Professor, 原子炉実験所, 教授 (90122407)
SHIBAHARA Shigeki  Tohoku Univ., School of Medicine, Professor, 医学部, 教授 (70206142)
TAMAKI Norihiko  Kobe Univ., School of Medicine, Professor, 医学部, 教授 (10030941)
新津 洋司郎  札幌医科大学, 医学部, 教授 (10045502)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 1998: ¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 1997: ¥6,800,000 (Direct Cost: ¥6,800,000)
Keywordscancer boron neutron capture therapy / in vivo gene-transfer / malignant melanoma / BPA / transferrin-conjugate gene vector / electroporation / isoform of MITF / melanin monomer complex / キトサンナノパーティクル / 遺伝子導入
Research Abstract

During the term of project, April 1997 - March 1999 following research results have been obtained.
I.Basic studies
(1) Enhancement of therapeutic effect for the melanoma BNCT : Transfer of melanogenic gene, TRP-2 into less melanotic (pheomelanotic) human melanoma cells has enhanced their uptake of ^<10>B-BPA (Boronophenylalanine). Further, transfer of tyrosilase gene into fibroblast increased their uptake of ^<10>B-BPA.
(2) Isolation and identification of novel-isoform for MITF gene which can regulate the expression of melanogenic genes. Identification of SRF which may regulate the expression of TRP-2.
(3) Concerning mechanism of selective ^<10>B-BPA uptake into melanoma, we have found the formation of chemical complex between ^<10>B-BPA and melanin monomer/dimer, releasing lOB-boric acid which can be integrated melanin polymer formation.
II.Development of devices and methods for gene and ^<10>B-BPA delivery.
(1) Establishment of methodology to form transferrin-conjugate gene vector.
(2) Form … More ulation method for nano-particle device as ^<10>B-BPA delivery carriers has proven its enhancing therapeutic effects in vovo.
(3) Electroporation method has enhanced uptake of ^<10>B-compounds by target cells in vitro and in vivo.
III.Therapeutic experiment using cancer-bearing animals.
(1) After the tyrosinase-transfer into amelanotic melanoma cells in culture with subsequent subcutaneous transplantation of these cells into mouse, we have found the markedly enhanced killing effect of ^<10>B-BPA BNCT experiment.
(2) After the in vivo tyrosinase gene-transfer into amelanotic melanoma proliferating in hamster skin by intra-tumor injection, we have found enhanced killing effect of ^<10>B-BPA BNCT in preliminary experiment.
(3) Using i.v. injection of transfenin-conjugate of HSV-tk gene to tumor bearing mice, we have found its dstinct enhanced therapeutic effect prolonging their survival period.
(4) After establishment of experimental model for amelanotic melanoma cells proliferating in brain, we have found increased ^<10>B-BPA uptake by these amelanotic melanoma cells, which were previously transfected with tyrosinase-gene, using ^<18>F-PET. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (59 results)

All Other

All Publications (59 results)

  • [Publications] Mishima Y.: "In vivo diagnosis of human malignant melanoma with pasitron emission tomography using specific melanoma-seeking ^<18>F-DOPA analogue." J.Neuro-Oncology. 33. 163-169 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsuboi,T.: "Enhanced Melanogenesis induced by tyrosinase gene-transfer increases boron-uptake and killing effect of boron neutron capture therapy for amelanotic melanoma." Pigment Cell Res.11・5. 275-282 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Amae,S.: "Identification of a novel isoform of microphthalmia-associated transcription factor that is enriched in retinal pigment epithelium" Biochem.Biophys.Res.Commun.247. 710-715 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ono,K.: "The combined effect of boronopehnylalanine and borocaptate in boron neutron capture therapy for SCCVII tumors is mice." Int.J.Rad.Oncol.Biol.Phys.in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fukuda,H.: "Pharmacokinetics of ^<10>B-p-boronophenylalanine in tumours, skin and blood of melanoma patients:A study of boron neutron capture therapy for malignant melanoma." Melanoma Res.in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Miyamoto,M.: "Preparation of gadlinium-containing emulsion stabilized with phosphatidylcholine-surfactant mixture for neutron-capture therapy." Chem.Pharm.Bull.47・2. 203-208 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mishima,Y.: "“Advances in Neutron Capture Therapy"Proc.7th Internat.Society for Neutron Capture Therapy,Vol.I,Medicine and Physics,Excerpta Medica,ICS 1132(eds.Larsson.B.H.,et al.)(Melanoma and non-melanoma neutron capture therapy using gene therapy:Overview.)" Elsevier Science B.V.,Amsterdam, 583 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ono,K.: "(Boron neutron capture therapy for malignant glioma at Kyoto University Reactor.)ibid." Elsevier Science B.V.,Amsterdam, 583 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Honda,C.: "“Advances in Neutron Capture Therapy"Proc.7th Internat.Society for Neutron Capture Therapy,Vol.II,Chemistry and Biology,Excerpta Medica,ICS 1132(eds.Larsson,B.H.,et al.)(Neutron capture therapy using ^<10>B-BPA and Gd-DTPA in combination for hamster melanoma..)" Elsevier Science B.V.,Amsterdam, 701 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hirathuka,J.: "(Tumor killing effect of BNCT after administration of o-,m-,p-boronophenylalanine..)ibid." Elsevier Science B.V.,Amsterdam, 701 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshino,K.: "(Capture of p-boronophenylalanine in malignant melanoma cells by complex formation with melanin monomers,DOPA,DHI and DHICA.)ibid." Elsevier Science B.V.,Amsterdam, 701 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshino,K.: "(Determination of released boric acid in-vivo after p-boronophenylalanine administration into melanoma-bearing subjects.)ibid." Elsevier Science B.V.,Amsterdam, 701 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shibahara,S.: "“The Pigmentary System, Physiology and Pathophysiology"(eds.Mordlund,J.J.,et al.)(Genetic regulation of the pigment cell.)" Oxford University Press,New York, 1025 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mishima,Y.: "“Frontiers in Neutron Capture Therapy"proc.8th Intnl.Symp.on Neutron Capture Therapy for Cancer(eds.Hawthorne,M.F.,et al.)(Current clinical paradigms in melanoma BNCT:Leading to cell modulation era teamed with passive and active ^<10>B-biodelivery systems)" Plenum Press,New York, (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshino,K.: "(A further mechanism study of boron accumulation to and release from melanoma with p-boronophenylalanine)" Plenum Press,New York, (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kitazawa,M.: "(Structure determination of p-boronophenylalanine-fructose complex using ^1J_<CC> coupling constants) ibid." Plenum Press,New York, (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 三嶋,豊(編集): "遺伝子導入によるがん熱中性子捕捉療法の適応拡大 Kyoto University Research Reactor Institute-Technical Report-427)" 京都大学原子炉実験所, 190 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mishima, Y., et al.: "In vivo diagnosis of human malignant melanoma with positron emission tomography using specific melanoma-seeking ^<18>F-DOPA analogue." J.Neuro-Oncology. 33. 163-169 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsuboi, T., et al.: "Enhanced melanogenesis induced by tyrosinase gene-transfer increases boron-uptake and killing effect of boron neutron capture therapy for amelanotic melanoma." Pigment Cell Res.11. 275-282 (5) (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Amae, S., et al.: "Identification of a novel isoform of microphthalmia-associated transcription factor that is enriched in retinal pigment epithelium." Biochem.Biophys.Res.Commun.247. 710-715 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ono, K., et al.: "The combined effect of boronopehnylalanine and borocaptate in boron neutron capture therapy for SCCVII tumors in mice." Int.J.Rad.Oncol.Biol.Phys.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fukuda, H., et al.: "Pharmacokinetics of ^<10>B-p-boronophenylalanine in tumours, skin and blood of melanoma patients : A study of boron neutron capture therapy for malignant melanoma." Melanoma Res.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Miyamoto, M., et al.: "Preparation of gadlinium-containing emulsion stabilized with phosphatidylcholine-surfactant mixture for neutron-capture therapy." Chem.Pharm.Bull.47. 203-208 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mishima, Y.: Melanoma and non-melanoma neutron capture therapy using gene therapy : Overview. "Advances in Neutron Capture Therapy" Proc.7th Intnl.Symp.on Neutron Capture Therapy for Cancer, Vol.I,Excerpta Medica, JCS 1132 (eds.Larsson, B., et al.). Elsevier Science B.V., Amsterdam, 10-25 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ono, K., et al.: Boron neutron capture therapy for malignant glioma at Kyoto University Reactor.ibid., 39-45

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Honda, C., et al.: Neutron capture therapy using ^<10>B_1-BPA and Gd-DTPA in combination for hamster melanoma. "Advances in Neutron Capture Therapy" Proc.7th Intnl.Symp.on Neutron Capture Therapy for Cancer, Vol.II,Excerpta Medica, ICS 1132 (eds.Larsson, B., et al.). Elsevier Science B.V., Amsterdam, 484-487 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hiratsuka, J., et al.: Tumor-killing effect of BNCT after administration of o-, m-, p-boronophenylalanine.ibid., 512-515

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshino, K., et al.: Capture of p-boronophenylalanine in malignant melanoma cells by complex formation with melanin monomers, DOPA,DHI and DHICA.ibid., 234-238

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshino, K., et al.: Determination of released boric acid in-vivo after p-borono-phenylalanine administration into melanoma-bearing subject.ibid., 334-338

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shibahara, S., et al.: Genetic regulation of the pigment cell. "The Pigmentary System, Physiology and Pathophysiology" (eds.Nordlund, J.J., et al.). Oxford University Press, New York, 251-273 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mishima, Y., et al.: Current clinical paradigms in melanoma BNCT : Leading to cell modulation era teamed with passive and active ^<10>B-biodelivery systems. "Frontiers in Neutron Capture Therapy" Proc.8th Intnl.Symp.on Neutron Capture Therapy for Cancer (eds.Hawthorne, M.F., et al.). Plenum Press, New York (in press),

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshino, K., et al.: A further mechanism study of boron accumulation to and release from melanoma with p-boronophenylalanine.ibid.,

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kitazawa, M., et al.: Structure determination of p-boronophenylalanine-fructose complex using ^1J_<cc> coupling constants.ibid.,

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Mishima, Y.(ed.): Gene Transfer-applied Cancer Boron Neutron Capture Therapy Kyoto University Research Reactor Institute-Technical Report-427. 1-190 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tsuboi,T.: "Enhanced Melanogenesis induced by tyrosinase gene-transfer increases boron-うptake and killing effect of boron neutron capture therapy for amelanotic melanoma." Pigment Cell Res.11・5. 275-282 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fukuda,H.: "Pharmacokinetics of ^<10>B-p-boronophenylalanine in tumours,skin and blood of melanoma patients : A study of boron neutron capture therapy for malignant melanoma." Melanoma Res.(in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Amae,S.: "Identification of a novel isoform of microphthalmia-associated transcription factor that is enriched in retinal pigment epithelium" Biochem.Biophys.Res.Commun.247. 710-715 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yasumoto,K.: "A big gene linked to small eyes encodes multiple MITF isoforms : Many promoters make light work." Pigment Cell Res.11・6. 329-336 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ono,K.: "The combined effect of boronopehnylalanine and borocaptate in boron neutron capture therapy for SCCVII tumors in mice." Int.J.Rad.Oncol.Biol.Phys.(in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Miyamoto,M.: "Preparation of gadlinium-containing emulsion stabilized with phosphatidylcholine-surfactant mixture for neutron-capture therapy." Chem.Pharm.Bull.47・2. 203-208 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mishima,Y.: "“Frontiers in Neutron Capture Therapy"Proc.8th Intnl.Symp.on Neutron Capture Therapy for Cancer (eds.Hawthorne,M.F.,et al) (Current clinical paradigms in melanoma BNCT : Leading to cell modulation era teamed with passive and active B-biodelivery systems)" Plenum Press,New York (in press),

    • Related Report
      1998 Annual Research Report
  • [Publications] Yoshino,K.: "(A further mechanism study of boron accumulation to and release from melanoma with ρ-boronophenylalanine) ibid." Plenum Press,New York (in press),

    • Related Report
      1998 Annual Research Report
  • [Publications] Yoshino,K.: "(Fluorination of ρ-boronophenylalanine) ibid." Plenum Press,New York (in press),

    • Related Report
      1998 Annual Research Report
  • [Publications] Yoshino,K.: "(Simultaneous determination of ρ-boronophenylalanine and boric acid using ^<11>B-NMR) ibid." Plenum Press,New York (in press),

    • Related Report
      1998 Annual Research Report
  • [Publications] Kitazawa,M.: "(Structure determination of ρ-boronophenylalanine-fructose complex using ^1J_<cc> coupling constants) ibid." Plenum Press,New York (in press),

    • Related Report
      1998 Annual Research Report
  • [Publications] 三嶋,豊(編集): "遺伝子導入によるがん熱中性子捕捉療法の適応拡大 Kyoto University Research Reactor Insitute-Technical Report(KURRI-TR427)" 京都大学原子炉実験所, 190 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mishima,Y.: "In vivo diagnosis of human malignant melanoma with positron emission tomography using specific melanoma-seeking ^<18>F-DOPA analogue." J.Neuro-Oncology. 33. 169-169 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsuboi,T.: "Tyrosinase gene-transfer enhances killing effect ofr amelanotic malignant melanoma using boron neutron capture therapy." Pigment Cell Res.(in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Kuga,T: "Fibronection fragment-facilitated retroviral transfer of the glutathione-S-transferase π gene into CD34+ cells to protect them against alkyling agent." Human Gene Ther.8・16. 1901-1908 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sato,T.: "Anapotosis inducing gene therapy for pancreatic cancer with a combination of 55kDa TNF receptor gene transfection and mutein TNF administration." Cancer Res.(in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Yasumoto,K.: "Molecular cloning of a cDNA encoding a human TFEC isoform, a newly identified transcriptional regulator." Biochim.Biophys.Acta. 1353. 23-31 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Masunaga,S.: "Modification of the response of a quiescent cell population within a murine solid tumour to boron nertron capture irradiation : studies with nicotinamide and hyperthermia." Br.J.Radiol.70. 391-398 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mishima,Y.: "“Advances in Neutron Capture Therapy" Proc.7th Internat.Society for Neutron Capture Therapy, VoI.I,Medicine and Physics, Excerpta Medica, ICS1132(eds.B.H.Larsson, et al.)(Melanoma and non-melanoma neutron capture therapy using gene therapy: Overvview.)" Elsevier Science B.V., Amesterdam, 583 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Honda,C.: "“Advances in Neutron Capture Therapy" Proc.7th Internat.Society for Neutron Capture Therapy, Vol.II,Chemistry and Biology Excerta Medica, ICS1132 (eds.B.H.Larsson, et al.)(Neutron capture therapy using ^<10>B_1-BPA and Gd-DTPA in combination for hamster melanoma..)" Elsevier Science B.V., Amsterdam, 701 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shibahara,S.: "“The Pigmentary System, Physiology and Phthophysiology"(eds.J.J.Nordlund, et al.)(Genetic regulation of the pigment cell.)" Oxford University Press, New York, NY.(in press),

    • Related Report
      1997 Annual Research Report
  • [Publications] Hiratsuka,J.: "“Advances in Neutron Capture Therapy" Proc.7th Internat.Society for Neutron Capture Therapy, Vol.II, Chemistry and Biology, Excerpta Medica, ICS1132(eds.B.H.Larsson, et al.)(Tumor killing effect of BNCT after administration of o,m,p-boronophenylalanine..)" Elsevier Science B.V., Amsterdam, 701 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshino,K.: "(Capture of p-boronophenylalanine in malignant melanoma cells by complex formation with melanin monomers, DOPA, DHI and DHICA.)ibid." Elsevier Science B.V., Amsterdam, 701 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshino,K: "(Metabolic study of L-p-boronophenylalanine with L-tyrosine decarboxylase..)ibid." Elsevier Science B.V., Amsterdam, 701 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshino,K.: "(Determination of released boric acid in-vivo after p-boronophenylalanine administration into melanoma-bearing subjet..)ibid." Elsevier Science B.V., Amsterdam, 701 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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