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@ARTICLE{Gatzweiler:182157,
author = {C. Gatzweiler$^*$ and J. Ridinger$^*$ and S. Ayhan$^*$ and
S. Najafi$^*$ and H. Peterziel$^*$ and O. Witt$^*$ and I.
Oehme$^*$},
title = {{E}valuation of {A}ntitumor and {O}n-{T}arget {A}ctivity of
{HDAC} {I}nhibitors with the {Z}ebrafish {E}mbryo
{X}enograft {M}odel.},
journal = {Methods in molecular biology},
volume = {2589},
issn = {1064-3745},
address = {[Heidelberg]},
publisher = {[Springer]},
reportid = {DKFZ-2022-02468},
isbn = {978-1-0716-2787-7 (print)},
pages = {75-85},
year = {2023},
note = {#EA:B310#LA:B310#},
abstract = {Reliable preclinical drug testing models for cancer
research are urgently needed with zebrafish embryo models
emerging as a powerful vertebrate model for
xenotransplantation studies. Here, we describe the
evaluation of toxicity, efficacy, and on-target activity of
histone deacetylase (HDAC) inhibitors in a zebrafish embryo
yolk sac xenotransplantation model of medulloblastoma and
neuroblastoma cells. For this, we performed toxicity assays
with our zebrafish drug library consisting of 28 clinically
relevant targeted as well as chemotherapeutic drugs with
zebrafish embryos. We further engrafted zebrafish embryos
with fluorescently labeled pediatric tumor cells
(SK-N-BE(2)-C, HD-MB03, or MED8A) and monitored the
progression after HDAC inhibitor treatment of
xenotransplanted tumors through tumor volume measurements
with high-content confocal microscopy in a multi-well
format. The on-target activity of HDAC inhibitors was
verified through immunohistochemistry staining on
paraffin-embedded early larvae. Overall, the zebrafish
embryo xenotransplantation model allows for fast and
cost-efficient in vivo evaluation of targeted drug toxicity,
efficacy, and on-target activity in the field of precision
oncology.},
keywords = {Functional precision medicine (Other) / Pediatric oncology
(Other) / Targeted therapy (Other) / zPDX (Other)},
cin = {B310 / HD01},
ddc = {570},
cid = {I:(DE-He78)B310-20160331 / I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)3 / PUB:(DE-HGF)16},
pubmed = {pmid:36255618},
doi = {10.1007/978-1-0716-2788-4_5},
url = {https://inrepo02.dkfz.de/record/182157},
}