| Project/Area Number |
01570809
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Osaka University |
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Principal Investigator |
SHIMIZU Keiji Osaka Univ., Dept of Neurosurg, Assistant Prof, 医学部, 助手 (50162699)
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| Co-Investigator(Kenkyū-buntansha) |
HAYAKAWA Toru Osaka Univ., Dept of Neurosurg. Prof., Chairman, 医学部, 教授 (20135700)
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| Project Period (FY) |
1989 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1990: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1989: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Medulloblastoma / Brain neoplasms / Major Histo-compatibility Complex (MHC) / Immuno-therapy / Antibodies, monoclonal / Lymphokine-activated killer (LAK) Cells / Interferons / 髄芽種 |
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| Research Abstract |
Medulloblastoma are among the most common malignant brain tumors in children. It suggested that the precursors of these tumors consisted of immature bipotential cells which could differentiate into neuronal and glial cells. We established two human medulloblastoma cell lines in order to investigate their characterization and cell differentiation. One was derived from a 2-year-old girl with a cerebellar tumor (designated as ONS-76 cells), and another was from a 9-year-old girl with a metastatic tumor in the right lower frontal lobe from her posterior fossa (designated as ONS-81 cells). The in vitro population-doubling times were 18.6 and 19.2 hours, respectively. These cells were transplantable into the nude mice subcutaneously and intrathecally. Experimental models with meningeal dissemination were produced by intracisternal inoculation of ONS-76 cells into the nude mice. All mice were dead within 65 days after 1x107 tumor cells were inoculated intracisternally. Their median survival t
… More
ime (MST) was 56 days.
Immunohistochemical studies showed that both cells possessed neurofilament protein (NFP) (Mr 145 K and 200K) and neuron-specific enolase (NSE), without glial fibrillar acidic protein (GFAP) or S-100 protein. These cell lines also had epidermal growth factor (EGF) receptor (R), Transferrin-R, and lnsulinーR. These cells could grow in the growth medium without fetal calf serum (FCS). Most these cells possessed class I major histocompatibility complex (MHC) antigens, and these class I antigens were able to be enhanced by human interferon-g (IFN-g). Both cell lines didn't have class II MHC antigen, but these antigens could be induced by human IFN-g. ONS-76 and ONS-81 cells expressed proto-oncogene (N-myc and c-src) products. These cells showed drug-induced differentiation under 50-100 mM of dibutyryl cyclic-adenosine 3', 5'-monophosphate (dbt-cAMP). Fluorescence-activated cell sorter (FACScan) analysis also showed that these both cell lines increased expression of pp60^<c-src> products and NFP (145 K and 200 K). A monoclonal antibody (mAb) (ONS-M-1.0) of lgG2 isotype was raised against medulloblastoma by immunization of mice with ONS--76 cells. This mAb bound these two human medulloblastoma (ONS-76 and -81) cells selectively. Natural killer cells were demonstrated a little ONS-M-1.0 antigens. Biochemical analysis showed that these antigens were sensitive to trypsin but not to neuraminidase, and that they were heat-stable. The high specificity of this antibody^* on medullobalstoma cells might be contributory to the diagnostic and therapeutic strategies for medulloblastoma. Less
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