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@ARTICLE{Roohani:277077,
author = {S. Roohani$^*$ and J. Loskutov and J. Heufelder and F.
Ehret$^*$ and L. Wedeken and M. Regenbrecht and R. Sauer and
D. Zips$^*$ and A. Denker and A. M. Joussen and C. R. A.
Regenbrecht and D. Kaul$^*$},
title = {{P}hoton and {P}roton irradiation in {P}atient-derived,
{T}hree-{D}imensional {S}oft {T}issue {S}arcoma {M}odels.},
journal = {BMC cancer},
volume = {23},
number = {1},
issn = {1471-2407},
address = {Heidelberg},
publisher = {Springer},
reportid = {DKFZ-2023-01261},
pages = {577},
year = {2023},
abstract = {Despite their heterogeneity, the current standard
preoperative radiotherapy regimen for localized high-grade
soft tissue sarcoma (STS) follows a one fits all approach
for all STS subtypes. Sarcoma patient-derived
three-dimensional cell culture models represent an
innovative tool to overcome challenges in clinical research
enabling reproducible subtype-specific research on STS. In
this pilot study, we present our methodology and preliminary
results using STS patient-derived 3D cell cultures that were
exposed to different doses of photon and proton radiation.
Our aim was: (i) to establish a reproducible method for
irradiation of STS patient-derived 3D cell cultures and (ii)
to explore the differences in tumor cell viability of two
different STS subtypes exposed to increasing doses of photon
and proton radiation at different time points.Two
patient-derived cell cultures of untreated localized
high-grade STS (an undifferentiated pleomorphic sarcoma
(UPS) and a pleomorphic liposarcoma (PLS)) were exposed to a
single fraction of photon or proton irradiation using doses
of 0 Gy (sham irradiation), 2 Gy, 4 Gy, 8 Gy and 16 Gy. Cell
viability was measured and compared to sham irradiation at
two different time points (four and eight days after
irradiation).The proportion of viable tumor cells four days
after photon irradiation for UPS vs. PLS were significantly
different with $85\%$ vs. $65\%$ (4 Gy), $80\%$ vs. $50\%$
(8 Gy) and $70\%$ vs. $35\%$ (16 Gy). Proton irradiation led
to similar diverging viability curves between UPS vs. PLS
four days after irradiation with $90\%$ vs. $75\%$ (4 Gy),
$85\%$ vs. $45\%$ (8 Gy) and $80\%$ vs. $35\%$ (16 Gy).
Photon and proton radiation displayed only minor differences
in cell-killing properties within each cell culture (UPS and
PLS). The cell-killing effect of radiation sustained at
eight days after irradiation in both cell
cultures.Pronounced differences in radiosensitivity are
evident among UPS and PLS 3D patient-derived sarcoma cell
cultures which may reflect the clinical heterogeneity.
Photon and proton radiation showed similar dose-dependent
cell-killing effectiveness in both 3D cell cultures.
Patient-derived 3D STS cell cultures may represent a
valuable tool to enable translational studies towards
individualized subtype-specific radiotherapy in patients
with STS.},
keywords = {Organoid (Other) / Patient-derived (Other) / Photon (Other)
/ Proton (Other) / Radiotherapy (Other) / Sarcoma, 3D cell
culture (Other) / Soft tissue sarcoma (Other)},
cin = {BE01},
ddc = {610},
cid = {I:(DE-He78)BE01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37349697},
doi = {10.1186/s12885-023-11013-y},
url = {https://inrepo02.dkfz.de/record/277077},
}