MZT(株)ゼブラフィッシュ創薬研究所

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最近の記事

2024/08/06
Validation of a new protocol for a zebrafish MEFL (malformation or embryo-fetal lethality) test method that conforms to the ICH S5 (R3) guideline.
2024/05/21
In vivo assessment of individual and total proteinuria in zebrafish larvae using the solvatochromic compound ZMB741
2021/10/31
Generation of a Transgenic Zebrafish Line for In Vivo Assessment of Hepatic Apoptosis
2021/08/19
Patient-Derived Cancer Xenograft Zebrafish Model (PDXZ) for Drug Discovery Screening and Personalized Medicine
2021/07/09
Establishment of a Quality Control Protocol for Zebrafish Developmental Toxicity Studies
2020/10/13
Gap junction protein beta 4 plays an important role in cardiac function in humans, rodents, and zebrafish
2020/05/28
A novel orexin antagonist from a natural plant was discovered using zebrafish behavioural analysis
2019/10/15
C3orf70 Is Involved in Neural and Neurobehavioral Development
2019/09/22
Generation of a Triple-Transgenic Zebrafish Line for Assessment of Developmental Neurotoxicity during Neuronal Differentiation
2019/07/17
Aging-associated microstructural deterioration of vertebra in zebrafish

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2015/03/24
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In vivo selective imaging and inhibition of leukemia stem-like cells using the fluorescent carbocyanine derivative, DiOC5(3)

Beibei Zhanga, Yasuhito Shimada, Junya Kuroyanagia, Michiko Ariyoshia, Tsuyoshi Nomotof, Taichi Shintouf, Noriko Umemotoa, b, Yuhei Nishimura, Takeshi Miyazakif, Toshio Tanaka
doi:10.1016/j.biomaterials.2015.02.009 Volume 52, June 2015, Pages 14-25

Abstract
Elimination of leukemia stem cells (LSCs) is necessary for the destruction of malignant cell populations. Owing to the very small number of LSCs in leukemia cells, xenotransplantation studies are difficult in terms of functionally and pathophysiologically replicating clinical conditions of cell culture experiments. There is currently a limited number of lead compounds that target LSCs. Using the LSC-xenograft zebrafish screening method we previously developed, we found that the fluorescent compound 3,3′-dipentyloxacarbocyanine iodide (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.

関連リンク

  • Biomaterials