In order to understand in more detail
the dynamics of complex biological systems, we also develop novel approaches
and tools for modelling biological system. In the last decades, knowledge of molecular
aspects of human physiology and pathophysiology has grown enormously. Often,
this knowledge is qualitative. Since cellular signalling pathways are embedded
in a complex dynamic system and interact with many other pathways, it is
difficult to gain quantitative information which can be used to model cellular
systems or organisms. Observing dynamic patterns in silico
and comparing them to experimental data in vitro or in vivo could help us
identify and quantify dynamic processes. Since modellers are faced with a high
degree of complexity of biological systems and often encounter experimental
difficulties (for example when determining kinetic constants), appropriate
concepts of system descriptions are needed. The use of dynamic state variables
is expected to make models applicable to a wider range of the dynamics of
biological systems. This is demonstrated by the Multi-Hit-Repair (MHR-) model
which is based on a transient dose equivalent. The model calculates the
survival of cells irradiated by ionizing radiation and it describes correctly a
large variety of radio-biological observations. In addition, the MHR-model is
bridging the gap between processes at the molecular or cellular level and
tissue dynamics. Actual research focus on the modelling of the synergistic
effect of radiation therapy combined with hyperthermia.
The methodology derived by the running
projects has a high potential for model based data analysis in a broader range
of applications in medicine.
References:
Scheidegger S, Fuchs
HU, Füchslin RM (2014): Computational Methods for Exploring the Dynamics of
Cancer: The Potential of State Variables for Description of Complex Biological
Systems. Proc. NOLTA 2014, 168-171.
Scheidegger S, Fuchs
HU, Zaugg K, Bodis S,
Füchslin RM (2013): Using State Variables to Model the Response of Tumour Cells
to Radiation and Heat: A Novel Multi-Hit-Repair (MHR-) Approach. Computational and Mathematical Methods in
Medicine, 2013, http://dx.doi.org/10.1155/2013/587543
Scheidegger S.,
Füchslin R.M., Lutters G., Bodis S.(2012): Dynamic
modelling of the synergistic effect of hyperthermia and radiotherapy. Radiother. Oncol. 103,
Suppl.1, S360-361.
Scheidegger S.,
Füchslin R.M. (2011): Kinetic model for dose equivalent – an efficient way to
predict systems response of irradiated cells. Proc. of ASIM 2011 (full papers, ISBN 978-3-905745-44-3)
Scheidegger S.,
Lutters G., Bodis S. (2011): A LQ-based kinetic model formulation for exploring
dynamics of treatment response of tumours in patients. Z. Med. Phys. 21,164–173
Lohse I., Lang, S., Hrbacek J., Scheidegger
S., Bodis S., Sanchez-Macedo N., Feng J., Lütolf U.M., Zaugg K. (2011): Effect of high dose
per pulse flattening filter – free beams on cancer cell survival. Radiother. Oncol. 101, 226-232
Füchslin RM, Dumont
E, Flumini D, Fuchs HU, Hauser H, Jaeger C, Scheidegger S, Schönenberger-Deuel
J, Lichtensteiger J, Luchsinger R, Weyland Mathias (2014): Morphological control: a design
principle for applications in space science. JBIS 67, 305-313
Füchslin RM, Dzyakanchuk A, Flumini D, Hauser H, Hunt KJ, Luchsinger RH, Reller B, Scheidegger S, Walker R (2013): Morphological computation
and morphological control: Steps toward a formal theory and applications. Artificial Life 19, 9-34
Spaeth, N., Wyss, M. T.,
Weber, B., Scheidegger, S.,
Lutz, A., Verwey, J., Radovanovic,
I., Pahnke, J., Wild, D., Westera,
G., Weishaupt, D., Hermann, D. M., Kaser-Hotz, B., Aguzzi, A., Buck
A. (2004): Uptake of 18F-Fluorocholin, 18F-Fluoroethyl-L-Tyrosine,
and 18F-FDG in Acute Celebral Radiation
Injury in the Rat: Implications for Separation of the Radiation Necrosis from Tumor Recurrence. J. Nucl. Med., 45,
1931-1938
Scheidegger S, Grosse
N, Füchslin R (2014): Homologous Recombination in the View of the MHR-Model. Proc. of Joint Conference of SSRMP, DGMP and
ÖGMP 2014 (ISBN 987-3-9816508-5-3), 194-195
Scheidegger S, Marder D, Timm O, Bonmarin M, Rhodes S (2014): Measuring skin perfusion after
superficial hyperthermia using IR-cam technology. SSBE Annual Meeting 2014, 20
Scheidegger S,
Bonmarin M, Timm O, Rhodes
S, Datta NR (2014): Estimating radio-sensitisation based on re-oxygenation
after hyperthermia by using dynamic models. Panminerva Medica 56, suppl. 1 (2), 24
Scheidegger S,
Rohrer-Bley C, Bodis S (2013): Impact of variation of
cellular repair, fractionation and timing on synergistic effect of radiotherapy
and hyperthermia. Strahlenther Onkol 12, 1067
Scheidegger S, Lomax
N, Timm O, Datta N, Füchslin RM, Bodis S
(2013):Characterisation of hyperthermia in combination with radiotherapy:
temporal homogeneity and limitations of the CEM-concept. . Proc. of 28th Annual Meeting of the European Society for Hyperthermic Oncology 2013, P131
Datta NR, Uric E,
Lomax N, Scheidegger S, Marder D, Bodis S (2013):
Time-Temperature Areau Under Curve (AUC): A proposal
for a novel thermometric parameter for
clinical hyperthermia in bladder cancer. Proc.
of 28th Annual Meeting of the European Society for Hyperthermic Oncology 2013, P122
Scheidegger S,
Füchslin, RM, Lutters G, Bodis S (2012): The dynamic view to hyperthermia – a
comparison of the CEM43° concept. Strahlenther. Onkol. 188(8), 738
Scheidegger S., Zaugg K., Bodis S. (2011): Induced repair as an unique approach to model apoptotic and non-apoptotic cell
survival. Strahlenther. Onkol. 187, 520
Füchslin R.M., Luchsinger
R.H., Reller B., Hauser H., Scheidegger S. (2011):
Morphological computation: applications on different scales exploiting
classical and statistical mechanics. Proc.
of ICMC 2011, 41 - 43
Scheidegger S.
(2010): A theoretical framework to explore low dose hypersensitivity. Proc. of SSRMP Annual Scientific Meeting
2010, ISBN 3 908 125 52 9, 57-59
Scheidegger, S., Lutters, G. (2010): A novel
biophysical model describing repair modifications and growth inhibition of
irradiated cells. Bulletin
SPG SSP, 27,
41.
Scheidegger, S.,
Lutters, G., Bodis, S. (2010): Computer simulation of oxygenation and growth
inhibition of tumours during fractionated radiotherapy: Exploration of the
dynamic system behaviour. Radiother. Oncol. 95,
Suppl.1, 512.
Scheidegger S.,
Lutters G., Bodis S. (2010): A kinetic LQ – based
model for exploring the tumor response onto radiation including the vascular
system. Strahlenther. Onkol. 186, 731
Scheidegger, S.,
Lutters, G., Bodis, S. (2009): A novel approach for biomathematical
modelling to predict treatment response for combined radiotherapy modalities in
patients. Molecular Radiation Biology / Oncology, 8 (2009), 72
Scheidegger, S.,
Lutters, G., Bodis, S. (2009): Understanding tumour dynamics in vivo: The
potential of kinetic models in radio-oncology. Proc. of SSRMP Annual Scientific Meeting 2009, 18-23.