@techreport{oai:mie-u.repo.nii.ac.jp:00011751, author = {田中, 利男 and Tanaka, Toshio and 西村, 有平 and Nishimura, Yuhei and 川瀬, 玲子 and Kawase, Reiko}, month = {Jun}, note = {application/pdf, 我々が発見した選択的ヒトがん幹細胞阻害薬の中で、in vitroとin vivoにおいてヒトがん幹細胞に対して最も選択性が高く、かつ蛍光特性のある特徴的新規化合物ZM-B708を中心に、がん幹細胞に選択性の無いimatinib等の臨床分子標的抗がん剤等の作用機序を解析し、ヒトがん幹細胞に対する独自の選択的阻害薬ZM-B708の選択性の分子基盤を解明した。その成果より、独自の選択的ヒトがん幹細胞阻害薬ZM-B708の最大の特徴である蛍光特性を活用し、ヒトがん幹細胞に対する選択性の分子機構を解明し、ヒトがん幹細胞に対するin vitro及びin vivo選択的増殖阻害の分子機構を解明した。, Elimination of leukemia stem cells is necessary for the destruction of malignant cell populations. Using the LSC-xenograft zebrafish screening method we previously developed, we found that the fluorescent compound DiOC5(3) selectively marked LSCs and suppressed their proliferation in vivo and in vitro. DiOC5(3) had no obvious toxicity to human umbilical cord blood CD34+ progenitor cells and normal zebrafish. It accumulated in mitochondria through organic anion transporter polypeptides that are overexpressed in the plasma membrane of LSCs, and induced apoptosis via ROS overproduction. DiOC5(3) also inhibited the nuclear translocation of NF-κB through the downregulation of LSC-selective pathways, as indicated from DNA microarray analysis. In summary, DiOC5(3) is a new type of anti-LSC compound available for diagnostic imaging and therapeutics that has the advantage of being a single fluorescent chemical., 2015年度~2015年度科学研究費補助金(挑戦的萌芽研究)研究成果報告書, 15K15051}, title = {新規蛍光ヒトがん幹細胞阻害薬の発見とin vivo作用機構解明}, year = {2016}, yomi = {タナカ, トシオ and ニシムラ, ユウヘイ and カワセ, レイコ} }