| Project/Area Number |
15209058
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatric surgery
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
HIYAMA Eiso Hiroshima University, Natural Science Center for Basic Research and Development, Professor, 自然科学研究支援開発センター, 教授 (00218744)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Norio Hiroshima University, Radiation Effect Research Foundation, Chief of a laboratory, 遺伝学部, 室長(研究職) (40333546)
HIYAMA Keiko Hiroshima University, Research Institute for Radiation Biology and Medicine, Associate Professor, 原爆放射線医科学研究所, 助教授 (60253069)
KYO Satoru Kanazawa University, Graduate School of Medical Sciences, Assistant Professor, 大学院・医学系研究科, 講師 (50272969)
YAMAOKA Hiroaki Hiroshima University, Hospital, Research Associate, 病院・助手 (90311810)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥45,500,000 (Direct Cost: ¥35,000,000、Indirect Cost: ¥10,500,000)
Fiscal Year 2004: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
Fiscal Year 2003: ¥34,970,000 (Direct Cost: ¥26,900,000、Indirect Cost: ¥8,070,000)
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| Keywords | neuroblastoma / microarray / CGH array / malignant grade / caspase / methylation / risk assesment / Taylor-made therapy / hTERT / 層別化 |
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| Research Abstract |
Microarray and array-based CGH analyses were examined in 322 human neuroblastoma cases. Array-based CGH array revealed MYCN amplification, aberrations in chromosomes 1,3,4,11,14, and 17. Custom CGH array for detection of these aberrations revealed that chromosome 11q deletion was an independently poor prognosis-associated factor. We also made custom array of 182 prognosis-related genes selected by cDNA microarray, genome-wide oligomicroarray for gene expression, and microsort technology. Expression analysis using this custom array could exhibit high accuracy (95%) to predict the neuroblastoma prognosis. We also made custom microarray for detecting DNA methylation in the promoter regions of hTERT, caspases 8 and 9. It revealed that only 2 methylated loci of caspase 8 were correlated with poor prognosis. In 9 cases with intratumoral heterogeneity, 30 tumors resected after chemotherapy, 11 multifocal tumors, and 8 recurrent tumors, 6 tumors which consequently regressed or matured, tumor c
… More
ells were isolated using microdissection to compare the gene expression profiling with each primary tumor. All 12 tumors whose expression profilings were extremely altered showed poor outcome, while no tumor in multifocal tumors or regressing/maturing tumors showed remarkable alteration of gene expression even if DNA ploidy patterns were different.
Telomerase inhibitor or silencing of hTERT by small interfering RNA in 12 neuroblastoma cell lines resulted that 5 or 7 cell lines showed apoptosis and growth inhibition, respectively. In these cell lines, gene expression analysis revealed reduction of cell growth signals and activation of apoptosis related genes. Moreover, 3 cell lines which are induced differentiation by retinoic acid showed decrease of MYCN expression and telomerase expression and increase of apoptosis related signals and neuronal differentiation.
This custom array with CGH analysis is useful to evaluate characteristics in each neuroblastoma. Moreover, it may be also a useful tool to choice the chemotherapeutic regimen and differentiation therapy. Less
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