1993 Fiscal Year Final Research Report Summary
DEVELOPMENT OF A NEW IMMUNOTHERAPY FOR GLIOMA PATIENTS USING MOLECULER BIOTHCHNOLOGICAL TECHNIQUES
| Project/Area Number |
04454356
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | NIIGATA UNIVERSITY |
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Principal Investigator |
TAMURA Tetsuro NIIGATA UNIVERSITY, MEDICAL HOSPITAL, ASSISTANT, 医学部・附属病院, 助手 (40221402)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Ryuichi NIIGATA UNIVERSITY, BRAIN RES.INST., PROFESSOR, 脳研究所, 教授 (30018816)
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| Project Period (FY) |
1992 – 1993
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| Keywords | LAK CELLS / EGF-R / GLIOMA CELLS / ANTISENSE CLIGOMER / GROWTH FACTOR / TGF ALPHA |
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| 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
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