ESTRO 36 Abstract Book

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S979 ESTRO 36 2017
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Consequently, hiPSC-derived chondrocytes did not easily
undergo apoptosis as hiPSCs. Nevertheless, the hiPSC-
derived chondrocytes also reveal increased level of cells
undergoing senescence.
Conclusion
The genetic integrity of pluripotent SCs and their
derivatives is very relevant due to the unavoidable
exposure of SCs to genotoxic and cytotoxic agents during
diagnostic procedures, as well as during anti-cancer
therapies. For that reason, further studies concerning the
safety of stem and stem-derived cells treated with IR are
required.
Funding:
National Science Centre (2012/E/NZ3/01819)
Greater Poland Cancer Centre
(19/02/2016/PRB/WCO/010)
EP-1809 Effect of thalidomide on radiation-induced
urinary bladder dysfunction
J. Kowaliuk1, E. Bozsaky2 , S. Sarsarshahi1, P. Kuess3, W.
Dörr2
1 Medical University of Vienna, Department of
Radiotherapy- ATRAB - Applied and Translational
Radiobiology, Vienna, Austria
2 Medical University of Vienna, Department of
Radiotherapy- ATRAB - Applied and Translational
Radiobiology and Christian Doppler Laboratory for
Medical Radiation Research for Radiation Oncology,
Vienna, Austria
3 Medical University of Vienna, Department of
Radiotherapy - Christian Doppler Laboratory for Medical
Radiation Physics for Radiation Oncology, Vienna,
Austria
Purpose or Objective
The urinary bladder represents an important organ at risk
during of radiotherapy pelvic tumors. Exposure to
significant radiation doses results in the impairment of the
biological function, presenting as a decrease in bladder
capacity. Patients suffer from dysuria, urgency,
incontinence, and increased micturition frequency,
including nocturia. The radiation response occurs in three
distinct phases: a reversible, biphasic early response, a
symptom-free latent phase and an irreversible late phase
eventually resulting in fibrosis. Local inflammatory
processes are significantly involved in the pathogenesis of
radiation response, with a potentially central role of the
transcription factor NF-κB. Therefore, thalidomide, a
potent NF-κB inhibitor, is studied in a mouse model for its
potential to prevent or alleviate bladder dysfunction.
Material and Methods
This preclinical study was performed in a well-established
mouse model. Groups of female mice of the C3H/Neu
strain were subjected to local single dose irradiation of
the urinary bladder with graded doses in order to generate
complete dose-effect curves. Bladder compliance was
determined by transurethral cystotonometry - defining the
bladder capacity at an intravesical pressure of 10 mm Hg
- in 3-day intervals in the early response phase (day 0-30
p. irr) and subsequently at 4-week intervals until day 360.
The “mouse toilet”, designed to record individual
urinations of the mice for analyses of micturition
frequency and volume per micturition, was used on a
monthly basis. Thalidomide was applied intraperitoneally,
at a daily dose of 100 mg/kg over various time intervals in
early and latent phase.
Results
Preliminary results demonstrate that thalidomide clearly
reduces radiation- induced functional urinary bladder
changes. Daily administration from day 0 – day 15 or day
15 – day 30 significantly reduced the number of responding
mice (response: >50 % reduction in bladder capacity).
Furthermore, the maximum reduction in bladder capacity
was less pronounced in thalidomide treated vs. only
irradiated untreated mice.
Conclusion
The preliminary data indicate that thalidomide has a clear
potential to alleviate radiation-induced urinary bladder
function impairment in the early phase. This illustrated
the crucial involvement of NF-κB in the pathogenesis of
the early changes. This will further be confirmed in
mechanistic, immunohistochemical investigations. The
consequences of the early thalidomide treatment, as well
as of administration in the latent phase, on late effects
are subject to ongoing studies. Data will be presented.
Electronic Poster: Radiobiology track: Radiobiology of
cancer (others)
EP-1810 Both location and complexity of DNA damage
contribute to radiation induced senescence
J. Wang1
1Institute of Modern Physics- Chinese Academy of
Sciences, Biophysics, Lanzhou, China
Purpose or Objective
Cellular senescence was involved in aging by irreversible
loss of proliferative potential. It causes inhibition of cell
growth and reduction of cellular function. However, the
molecular bases of the DNA damage and their contribution
to cellular senescence are not completely clear. The
purpose of this study is to investigate the significant role
of persistent DNA damage response (DDR) in cellular
senescence induced by different kinds of ionizing
radiation.
Material and Methods
By measuring senescence associated-β-galactosidase, cell
proliferation, activity of Ki67, the number of XRCC1 foci
and 53BP1 foci, we identified that heavy ions (including
carbon ions, iron ions) and X-rays irradiation could induce
senescence in human uveal melanoma 92–1 cells.
Results
We found that heavy ions were more effective at inducing
senescence than X-rays. It was observed that with the
repairing of DNA damage, the percentage of 53BP1 foci co-
localized with telomeres continually increased and
reached to 30% for X-rays at the 5th day after irradiation
while the percentage of 53BP1 foci co-localized with
telomeres remained steadily around 15% for carbon ions
irradiation, implying that the persistent DNA damage
induced by X-rays was preferentially associated with
telomeric DNA and the telomere-favored persistent DNA
damage mainly contributed to cellular senescence induced
by X-rays. For heavy ions, less efficient repair of DNA
damage was observed and most of the irreparable damage
was the complex of single strand breaks and double strand
breaks, suggesting that DNA damage induced by heavy ion
was often complex and difficult to repair, thus presented
as persistent DNA damage and pushed the cells into
senescence. In contrast, DNA damage induced by X-rays
was mostly repaired in 24 hours.
Conclusion
In concusion, both location and complexity of DNA damage
contribute to cellular senescence induced by ionizing
radiation. These deepening interpretation of cellular
senescence following exposure to different kinds of
ionizing radiation will provide new insights into the link of
DNA damage and aging which is relevant to radiotheray.
Electronic Poster: RTT track: Patient preparation,
positioning and immobilisation
EP-1811 Aligning the chest with a couch improved
reproducibility in radiotherapy for head and neck
cancers