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1999 Fiscal Year Final Research Report Summary

Basic Research on gene transfer using gene-gun against malignant gliomas

Research Project

Project/Area Number 10470285
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionThe University of Tokyo

Principal Investigator

ASAI Akio  The University of Tokyo Hospital, Neurosurgery, Assistant Professor, 医学部・附属病院, 講師 (50231858)

Project Period (FY) 1998 – 1999
Keywordsgene therapy / gene-gun / glioma / adenovirus
Research Abstract

(1) Ex vivo gene transfer with gene-gun
We evaluated gene-gun-mediated ex vivo gene transfer using subcuateous tumor-bearing rat model. First we transplanted 9L glioma cells into F344 syngeneic rats subcutaneously and surgically removed formed tumors 20 days after transplantation. Lac Z expression vector was transduced by gene-guun at shooting pressure (psi) 100, 200, 400, and 600 (max) or Lca Z expressing adenovirus was incubated with the tumor at MOI 20, 40, and 100 for 24 hours. The tumors were then re-transplanted subcutaneously and gene expression was evaluated 7 days after the re-transplantation. The highest gene-gun-mediated gene transfer rate ranged from 3 to 9 % along with shooting pressure whereas that by adenovirus ranged from 5.5 to 15.9% along with MOI which are statistically different.
(2) In vivo gene transfer with gene-gun
Next, we estimated gene-gun mediated in vivo gene transfer using the same animal model as (1). We surgically opened the skin over the subcutaneously formed tumors and shot Lac Z expression vector at the same psi as (1) or injected Lac Z expression adenovirus at the same MOIs as (1). After the treatments, the wounds were closed and gene expression was examined 7 days after the treatments. The highest gene-gun-mediated gene transfer rate ranged from 3.6 to 9.5 % along with shooting pressure whereas that by adenovirus ranged from 5.8 to 13.2 % along with MOI which are statistically different.
In conclusion, although gene transfer with gene-gun is less effective than adenovirus-mediated gene transfer against gliomas, gene-gun-mediated gene transfer is still a good tool to transduce genes in vivo or ex vivo.

  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Sano T, Asai A, Mishima K, Fujimaki T, Kirino T: "Telomerase activity in 144 brain tumors"Br J Cancer. 77. 1633-1637 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinoura N, Yoshida Y, Sadata A, Hanada K, Yamamoto S, Kirino T, Asai A, Hamada H: "Apoptosis by retrovirus- and adenovirus-mediated gene transfer of Fas ligand to glioma cells: Implication for gene therapy"Hum Gene Ther. 9. 1983-1993 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinoura N, Ohashi M, Yoshida Y, Asai A, Kirino T, Saito I, Hamada H: "Construction, propagation, and titer estimation of recombinant adenoviruses carrying proapoptotic genes"Hum Gene Ther. 9. 2683-2689 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chi S, Kitanaka C, Noguchi K, Mochizuki T, Nagashima Y, Shirouzu M, Fujita H, Yoshida M, Chen W, Asai A, Himeno M, Yokoyama S, Kuchino: "Oncogenic Ras triggers cell suicide through the activation of a caspase-independent cell death program in human cancer cells"Oncogene. 18. 2281-2290 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakaguchi H, Fujimaki T, Matsuno A, Matsuura R, Asai A, Suzuki I, Sasaki T, Kirino T: "Postoperative residual tumor growth of meningioma can be predicted by MIB-1 immunohistochemistry"Cancer. 85. 2249-2254 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinoura N, Yoshida Y, Tsunoda R, Ohashi M, Zhang W, Asai A, Kirino T, Hamada H: "Highly augmented cytopathic effect of a fiber-mutant EIB-defective adenovirus for gene therapy of gliomas"Cancer Res. 59. 3411-3416 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wenbin C, Asai A, Teramoto A, Sanno N, Kirino T: "Mutations of the MEN1 tumor suppressor gene in sporadic pituitary tumors"Cancer Lett. 142. 43-47 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinoura N, Yoshida Y, Nishimura M, Muramatsu Y, Asai A, Kirino T, Hamada H: "Expression level of Bcl-2 determines anti- or proapoptotic function"Cancer Res. 59. 4119-4128 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinoura N, Yoshida Y, Asai A, Kirino T, Hamada H: "Relative level of expression of Bax and Bcl-XL determines the cellular fate of apoptosis/necrosis induced by the overexpression of Bax"Oncogene. 18. 5703-5713 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinoura N, Muramatsu Y, Nishimura M, Yoshida Y, Saito A, Yokoyama T, Furukawa T, Horii A, Hashimoto M, Arai A, Kirino T, Hamada H: "Adenovirus-mediated transfer of p33ING1 with p53 drastically augments apoptosis in gliomas"Cancer Res. 59. 5521-5528 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Asai A, Qiu J-h, Narita Y, Chi S, Saito N, Shinoura N, Hamada H, Kuchino Y, Kirino T: "High-level calcineurin activity predisposes neuronal cells to apoptosis"J Biol Chem. 274. 34450-34458 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nagane M, Asai A, Shibui S, Oyama H, Nomura K, Kuchino Y: "Expression pattern of chemoresistance-related genes in human malignant brain tumors: a working knowledge for proper selection of anticancer drugs"Jpn J Clin Oncol. 29. 527-534 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ueki K, Chen W-B, Narita Y, Asai A, Kirino T: "Tight association of loss of merlin expression with loss of heterozygosity at chromosome 22q in sporadic meningiomas"Cancer Res. 59. 5995-5998 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sano T, Asai A, Mishima K, Fujimaki T, Kirino T: "Telomerase activity in l44 brain tumors."Br J Cancer. 77. 1633-1637 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinoura N, Yoshida Y, Sadata A, Hanada K, Yamamoto S, Kirino T, Asai A, Hamada H: "Apoptosis by retrovirus- and adenovirus-mediated gene transfer of Fas ligand to glioma cells : Implication for gene therapy."Hum Gene Ther. 9. 1983-1993 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinoura N, Ohashi M, Yoshida Y, Asai A, Kirino T, Saito I, Hamada H: "Construction, propagation, and titer estimation of recombinant adenoviruses carrying proapoptotic genes."Hum Gene Ther. 9. 2683-2689 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chi S, Kitanaka C, Noguchi K, Mochizuki T, Nagashima Y, Shirouzu M, Fujita H, Yoshida M, Chen W, Asai A, Himeno M, Yokoyama S, Kuchino Y: "Oncogenic Ras trigger cell suicide through the activation of a caspase-independent cell death program in human cancer cells."Oncogene. 18. 2281-2290 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakaguchi H, Fujimaki T, Matsuno A, Matsuura R, Asai A, Suzuki I, Sasaki T, Kirino T: "Postoperative residual tumor growth of meningioma can be predicted by MIB-1 immunohistochemistry."Cancer. 85. 2249-2254 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinoura N, Yoshida Y, Tsunoda R, Ohashi M, Zhang W, Asai A, Kihno T, Hamada H: "Highly augmented cytopathic effect of a fiber-mutant E1B-defective adenovirus for gene therapy of gliomas."Cancer Res. 59. 3411-3416 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wenbin C, Asai A, Teramoto A, Sanno N, Kirino T: "Mutations of the MEN1 tumor suppressor gene in sporadic pituitary tumors."Cancer Lett. 142. 43-47 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinoura N, Yoshida Y, Nishimura M, Muramatsu Y, Asai A, Kirino T, Hamada H: "Expression level of Bcl-2 determines anti- or proapoptotic function."Cancer Res. 59. 4119-4128 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinoura N, Yoshida Y, Asai A, Kirino T, Hamada H: "Relative level of expression of Bax and Bcl-XィイD2LィエD2 determines the cellular fate of apoptosis/necrosis induced by the overexpression of Bax."Oncogene. 18. 5703-5713 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinoura N, Muramatsu Y, Nishimura M, Yoshida Y, Saito A, Yokoyama T, Furukawa T, Horii A, Hashimoto M, Asai A, Kirino T, Hamada H: "Adenovirus-mediated transfer of p33ィイD1ING1ィエD1 with p53 drastically augments apoptosis in gliomas."Cancer Res. 59. 5521-5528 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Asai A, Qiu J-h, Narita Y, Chi S, Saito N, Shinoura N, Hamada H, Kuchino Y, Kirino T: "High-level calcineurin activity predisposes neuronal cells to apoptosis."J Biol Chem. 274. 34450-34458 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nagane M, Asai A, Shibui S, Oyama H, Nomura K, Kuchino Y: "Expression pattern of chemoresistance-related genes in human malignant brain tumors : a working knowledge for proper selection of anticancer drugs."Jpn J Clin Oncol. 29. 527-534 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ueki K, Chen W-B, Narita Y, Asai A, Kirino T: "Tight association of loss of merlin expression with loss of heterozygosity at chromosome 22q in sporadic meningioma."Cancer Res. 59. 5995-5998 (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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