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DEVELOPMENT OF A NEW IMMUNOTHERAPY FOR GLIOMA PATIENTS USING MOLECULER BIOTHCHNOLOGICAL TECHNIQUES

Research Project

Project/Area Number 04454356
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Cerebral neurosurgery
Research InstitutionNIIGATA UNIVERSITY

Principal Investigator

TAMURA Tetsuro (1993)  NIIGATA UNIVERSITY, MEDICAL HOSPITAL, ASSISTANT, 医学部・附属病院, 助手 (40221402)

吉田 誠一 (1992)  新潟大学, 医学部附属病院, 助手 (50174933)

Co-Investigator(Kenkyū-buntansha) TANAKA Ryuichi  NIIGATA UNIVERSITY, BRAIN RES.INST., PROFESSOR, 脳研究所, 教授 (30018816)
田村 哲郎  新潟大学, 医学部附属病院, 助手 (40221402)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1993: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1992: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsLAK CELLS / EGF-R / GLIOMA CELLS / ANTISENSE CLIGOMER / GROWTH FACTOR / TGF ALPHA / アンチセンス療法 / オートクライン機構 / TGF alpha / オリゴマー / neu / erbB2 / 悪性グリオーマ / T細胞レセプター / LAK療法 / サイトカイン産生能 / ICAM-1
Research Abstract

To promote the efficiency of LAK therapy, at first, we investigated the possibility of the combination of LAK cells with the anti-EGF-R monoclonal antibody by the avidin-biotin method. By this method, we could enhance the LAK activity of lymphocytes from glioma patients about 1.2 times. We could also produce sufficient LAK cells from patients'helper T cell by theis procedure. From this result, it was suggested that LAK therapy for glioma patients might be promoted by the combined use of LAK cells with the anti-EGF-R antibody. Secondaly, we examined the effect of 18-bp oligodeoxynucleotides complementary to the sense mRNA of erbB2, TGF alpha, c-fos, and c-myc upon glioma cell growth. We investigated the expression of these genes within cultured human glioma cell lines by using ploymerase chain reaction. We could detct mRNA transcripts of TGF alpha in 4 out of 7 glioma cell lines. The antisense oligonucleotieds complementary to TGF alpha mRNA were efficiently incorporated into glioma cells in vitro and the kinetic study showed thast maximum uptake occurred within 48 hours of incubation with antisense oligomers. Exposure of human glioma cell lines to antisense oligodeoxylnucleotides targeted against first initiation codon inhibited cell proliferation in a time and dose dependent fashion. The addition of 1microM TGF alpha-specific antisense primer to the human glioma cell line SNB-19 resulted in an 80% inhibition in glioma growth. This effect was saturable and specific. Antisense primers directed to another sites of this mRNA were not effective in suppressing glioma growth Neither antisense or sense primers inhibited the growth of our glioma cells. In contrast to this, the corresponding sense oligomers inhibited neither syntheses of TGF-alpha protein nor glioma cell growth. Other antisense oligonucleotides could not affect glioma cells. Taken together, these results clearly support a role of TGF-alpha protein in the proliferation process and show that inducivle protein

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] 吉田 誠一 他: "悪性グリオーマ患者の腫瘍内浸潤リンパ球のT細胞抗原レセプターのV領域遺伝子の発現" 神経免疫研究. 5. 18-25 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 吉田 誠一 他: "アンチセンスオリゴマーを用いたグリオーマへのアプローチ" 第52回日本癌学会総会抄録集. 256 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 山中 龍也 他: "悪性グリオーマのサイトカインネットワークの解析" 神経免疫研究. 15. 111-114 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ryuya YAMANAKA et.al: "Effects of Irradiation on Cytokine Production in Glioma Cell Lines" Neurologia medico-chiruugica. 33. 744-748 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ryuya YAMANAKA et al: "Effects of Irradiation on the Expression of the adhesion Molecules(NCAM,ICAM-1)by Glioma Cell Lines" Neurologia medico-chiruugica. 33. 749-752 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Saxna A, Ali I U: "Increased expression of gnes from growth factor signaling pathways in glioblastoma cell lines" Oncogene. 7(2). 243-247 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Torp SH, Helseth E, Ryan L et al.: "Amplification of the epidermal growth factor receptor gene in Human gliomas." Anticancer Res. 11(6). 2095-2098 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Mashiyama S, Murakami Y, Yoshimoto T et al.: "Detection of p53 gene mutations in human brain tumors by single-strand conformation polymorphism analysis of polymerase chain reaction products." Oncogene. 6(8). 1313-1318 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Berdel WE, de Vos S, Maurer J et al.: "Oberberg-D ; Recombinant human stem cell factor stimulates growth of a human glioblastoma cell line expressing c-kit protooncogene." Cancer Res. 52(12). 3498-3502 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Alama A, Barbieri F, Bottini F et al.: "The use of antisense oligodeoxynucleotides (aODNs) for the therapy of cancer." Drugs Exp Clin Res. 17(12). 575-579 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Akhtar S, Kole R, Juliano RL: "Stability of antisense DNA oligodeoxynucleotide analogs in cellulr extracts and sera." Life Sci. 49(24). 1793-1801 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hsieh SY, Taylor J: "Regulation of polyadenylation of hepatitis delta virus antigenomic RNA." J Virol. 65(12). 6438-6446 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Genevee C, Diu A, Nierat J et al.: "An experimentally validated panel of subfamily specific oligonucleotide primers for the study oof human T cell receptor variable V gene segment usage by polymerase chain reaction." Eur J Immunol. 22. 1261-1269 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Belldegrun A, Kasid A, Uppenkamp M et al.: "Human tumor infiltrating lymphocytes : Analysis of lymphokine mRNA expression and relevance to cancer immunotherapy." J Immunol. 142. 4520-4526 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Fuller GN, Bigner SH: "Amplified cellular oncogenes in neoplasms of human central nervous system." Mutat Res. 276(3). 299-306 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 吉田誠一 他: "悪性グリオーマ患者の腫瘍内浸潤リンパ球のT細胞抗原レセプターのV領域遺伝子の発現" 神経免疫研究. 5. 18-25 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] 吉田誠一 他: "アンチセンスオリゴマーを用いたグリオーマへのアプローチ" 第52回日本癌学会総会抄録集. 256 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 山中龍也 他: "悪性グリオーマのサイトカインネットワークの解析" 神経免疫研究. 5. 111-114 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ryuya YAMANAKA et al: "Effects of Irradiation on Cytokine Production in Glioma Cell Lines" Neurologia medico-chiruugica. 33. 744-748 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ryuya YAMANAKA et al: "Effects of Irradiation on the Expression of the adhesion Molecules(NCAM,ICAM-1)by Glima Cell Lines" Neurologia medico-chiruugica. 33. 749-752 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 吉田 誠一: "LAK療法を中心とした免疫療法の現状" 脳神経外科ジャーナル. 2. 110-115 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 吉田 誠一: "悪性グリオーマ患者リンパ球の細胞傷害能とT細胞レセプターレパトアの養子免疫療法に伴う変動" 日本免疫学会抄録集. 22. 296- (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] S.Yoshida: "Overexpression of multiple oncogenes related to histological grade of astrocytic glioma" Br.J.Cancer. 66. 106-112 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] R.Yamanaka: "Effects of ACNU and Cranial Irradiation on the Mouse Immune System" Neurologia medico-chirrurgica. 33. 65-70 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] 森 宏: "悪性脳腫瘍患者末梢リンパ球サブセット動態におよぼす集学的治療の効果" 新潟医学会雑誌. 106. 536-542 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] S.Yoshida: "Expression of MHC classII antigens on human glioma cells modulated by transfection with genes encoding these antigens" Neurologia medico-chirrurgica. 31. 623-628 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] 吉田 誠一: "脳腫瘍の免疫と分子生物学" 金芳堂, 8 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] S.Yoshida: "Biological Aspects of Brain Tumors" Springer-Verlag, 5 (1991)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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