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1998 Fiscal Year Final Research Report Summary

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)
Project Period (FY) 1997 – 1998
Keywordscancer boron neutron capture therapy / in vivo gene-transfer / malignant melanoma / BPA / transferrin-conjugate gene vector / electroporation / isoform of MITF / BPA / melanin monomer complex
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

  • Research Products

    (34 results)

All Other

All Publications (34 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 1999-12-08  

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