| Project/Area Number |
14570727
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
ATSUSHI Manabe The University of Tokyo, The Institute of Medical Science, Assistant, 医科学研究所, 助手 (20292849)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Neuroblastoma / Molecular targeted therapy / HER-2 / neu / HER-2 |
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| Research Abstract |
This study aimed at the establishment of molecular targeted therapy for HER-2/neu expressed on the neuroblastoma cells. Recently, the mouse-human chimeric monoclonal antibody (trastuzumab) against HER-2/neu overexpressed on breast cancer cells has been used successfully in adult clinical oncology. I-IER-2/neu was first identified on neumblastoma cells of rats. There were very few reports describing the expression of HER-2/neu in human neumblastoma and there was no report demonstrating the effect of trastuzumab on neuroblastoma. Therefore, we investigated the expression of HER-2/neu on neuroblastoma cells from patients with neuroblastoma.
Bone marrow cells were obtained from 11 children diagnosed as having stage 4 neuroblastoma with consents from guardians. Mononuclear cells were separated using a density gradient and cultured in the flasks coated with Engelbreth-Hoim-Swarm Natrix. GD2 (specifically expressed on neuroblastoma cells) disialoganglioside of adherent cells was analyzed using flow cytometry. Then, cytospin preparation of the GD2+ cells were immunostained to detect L-IER-2/neu protein. HER-2/neu was positive only in one case. The cytotoxicity of trastuzumab was investigated using ADCC (antibody-dependent cell-mediated cytotoxicity) assay in this case and the drug had no effect.
It was reported that HER-2/neu was expressed in a majority of samples obtained from patients with neuroblastoma at advanced stages using pathological specimens by the other investigator. However, HER-2/neu was negative in most cases using cultured cells in this study. The method described here using cultured cells has advantages when testing cytotoxicity in vitro. The result suggests that a clinical trial of trastrizumab forneuroblastoma would not be warranted.
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