著者

檜山 英三 原田 隆範 兒島 正人

出版者

一般社団法人 日本質量分析学会

雑誌

Journal of the Mass Spectrometry Society of Japan (ISSN:13408097)

巻号頁・発行日

vol.68, no.2, pp.33-37, 2020-04-01 (Released:2020-04-15)

参考文献数

2

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Circulating tumor cell (CTC) has improved the study of cancer disease as it represents a noninvasive biopsy that can be used as prognostic and prediction biomarkers as well as for future molecular diagnosis as an accurate selection of molecular targets and effective drugs. As tumor heterogeneity exists in neuroblastoma (NBL), we aimed to evaluate lipid-metabolomic molecular profile as well as genetic profiles at the single cell level of CTC for better understanding the heterogeneity and malignant grade of NBL. For attempt of CTC analysis in NBL patients, we have isolated single-CTCs and then performed direct trapping of a single cell within a nanospray tip followed by super-sonication after the addition of ionization solvent for metabolomics analysis. And we also performed genomic aberrations and expressions using next-generation sequencing after whole genome/transcriptome amplifications (WGA/WTA). In the NBL-CTCs, metabolomic analysis detected catechol amine metabolites, which are specific to NBL, and drugs included in the patient’s course of therapy in addition to vital molecules such as amino acids. In genomic analysis, the average amount of amplified DNA was 19.0 µg, and the percentage of reads mapped to any targeted region relative to all reads mapped to the reference was 66.5–98.9%. The concordance rates of CTC and tumor mutations were 49–80%. The genomic expression analysis in CTC showed the activation of cancer metastatic, neurogenic, stem cell signaling pathway genes. This “direct single-cell analysis method” seems to be useful for direct and wide range genomic and molecular marker detection in NBL-CTC, for evaluating heterogeneity of NBL tumor at diagnosis as well as during treatments. This method will be applicable for selection of effective drugs and evaluation of treatment efficacy in future.

著者

升島 努 津山 尚宏 水野 初 原田 隆範

出版者

広島大学

雑誌

基盤研究(S)

巻号頁・発行日

2008

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細胞1ヶ生きた様子を見ながら、変化の瞬間、その細胞1ヶの中見たい所を吸引し、10分以内にその分子群を質量分析で網羅的に検出する事に世界で初めて成功した。本手法をアレルギー細胞の細胞質と小器官の一つ顆粒内の分子分布・代謝解析、神経分化細胞の分化時の分子変化、植物の光応答や機能分子生成、薬物の肝臓細胞での代謝直接分析、その超微量性を生かして、汗腺一滴の分子分析に応用し、その豊かな可能性を検証した。