Year of publication
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- In Silico Analysis of Cell Cycle Synchronisation Effects in Radiotherapy of Tumour Spheroids (2013)
- Abstract: Tumour cells show a varying susceptibility to radiation damage as a function of the current cell cycle phase. While this sensitivity is averaged out in an unperturbed tumour due to unsynchronised cell cycle progression, external stimuli such as radiation or drug doses can induce a resynchronisation of the cell cycle and consequently induce a collective development of radiosensitivity in tumours. Although this effect has been regularly described in experiments it is currently not exploited in clinical practice and thus a large potential for optimisation is missed. We present an agent-based model for three-dimensional tumour spheroid growth which has been combined with an irradiation damage and kinetics model. We predict the dynamic response of the overall tumour radiosensitivity to delivered radiation doses and describe corresponding time windows of increased or decreased radiation sensitivity. The degree of cell cycle resynchronisation in response to radiation delivery was identified as a main determinant of the transient periods of low and high radiosensitivity enhancement. A range of selected clinical fractionation schemes is examined and new triggered schedules are tested which aim to maximise the effect of the radiation-induced sensitivity enhancement. We find that the cell cycle resynchronisation can yield a strong increase in therapy effectiveness, if employed correctly. While the individual timing of sensitive periods will depend on the exact cell and radiation types, enhancement is a universal effect which is present in every tumour and accordingly should be the target of experimental investigation. Experimental observables which can be assessed non-invasively and with high spatio-temporal resolution have to be connected to the radiosensitivity enhancement in order to allow for a possible tumour-specific design of highly efficient treatment schedules based on induced cell cycle synchronisation. Author Summary: The sensitivity of a cell to a dose of radiation is largely affected by its current position within the cell cycle. While under normal circumstances progression through the cell cycle will be asynchronous in a tumour mass, external influences such as chemo- or radiotherapy can induce a synchronisation. Such a common progression of the inner clock of the cancer cells results in the critical dependence on the effectiveness of any drug or radiation dose on a suitable timing for its administration. We analyse the exact evolution of the radiosensitivity of a sample tumour spheroid in a computer model, which enables us to predict time windows of decreased or increased radiosensitivity. Fractionated radiotherapy schedules can be tailored in order to avoid periods of high resistance and exploit the induced radiosensitivity for an increase in therapy efficiency. We show that the cell cycle effects can drastically alter the outcome of fractionated irradiation schedules in a spheroid cell system. By using the correct observables and continuous monitoring, the cell cycle sensitivity effects have the potential to be integrated into treatment planing of the future and thus to be employed for a better outcome in clinical cancer therapies.
- Nanolesions induced by heavy ions in human tissues: experimental and theoretical studies (2012)
- The biological effects of energetic heavy ions are attracting increasing interest for their applications in cancer therapy and protection against space radiation. The cascade of events leading to cell death or late effects starts from stochastic energy deposition on the nanometer scale and the corresponding lesions in biological molecules, primarily DNA. We have developed experimental techniques to visualize DNA nanolesions induced by heavy ions. Nanolesions appear in cells as “streaks” which can be visualized by using different DNA repair markers. We have studied the kinetics of repair of these “streaks” also with respect to the chromatin conformation. Initial steps in the modeling of the energy deposition patterns at the micrometer and nanometer scale were made with MCHIT and TRAX models, respectively.
- Implications on the collision dynamics via azimuthal sensitive HBT from UrQMD : the Seventh Workshop on Particle Correlations and Femtoscopy, September 20 - 24 2011, University of Tokyo, Japan (2011)
- We explore the shape and orientation of the freezeout region of non-central heavy ion collisions. For this we fit the freezeout distribution with a tilted ellipsoid. The resulting tilt angle is compared to the same tilt angle extracted via an azimuthally sensitive HBT analysis. This allows to access the tilt angle experimentally, which is not possible directly from the freezeout distribution. We also show a systematic study on the system decoupling time dependence on dNch/dh, using HBT results from the UrQMD transport model. In this study we found that the decoupling time scales with (dNch/dh)1/3 within each energy, but the scaling is broken across energies.
- Multi-particle interactions within the UrQMD approach (2011)
- A mechanism for locally density-dependent dynamic parton rearrangement and fusion has been implemented into the Ultrarelativistic Quantum Molecular Dynamics (UrQMD) approach. The same mechanism has been previously built in the Quark Gluon String Model (QGSM). This rearrangement and fusion approach based on parton coalescence ideas enables the description of multi-particle interactions, namely 3 -> 3 and 3 -> 2, between (pre)hadronic states in addition to standard binary interactions. The UrQMD model (v2.3) extended by these additional processes allows to investigate implications of multi-particle interactions on the reaction dynamics of ultrarelativistic heavy ion collisions. The mechanism, its implementation and first results of this investigation are presented and discussed.
- HBT radii from the UrQMD transport approach at different energies (2011)
- We present results on Hanbury Brown-Twiss (HBT) radii extracted from the Ultra-relativistic Molecular Dynamics (UrQMD) approach to relativistic heavy ion collisions. The present investigation provides a comparison of results from pure hadronic transport calculations to a Boltzmann + Hydrodynamic hybrid approach with an intermediate hydrodynamic phase. For the hydrodynamic phase different Equations of State (EoS) have been employed, i.e. bag model, hadron resonance gas and a chiral EoS. The influence of various freeze-out scenarios has been investigated and shown to be negligible if hadronic rescatterings after the hydrodynamic evolution are included. Furthermore, first results of the source tilt from azimuthal sensitive HBT and the direct extraction from the transport model are presented and exhibit a very good agreement with E895 data at AGS.
- Hybrid approaches to heavy ion collisions and future perspectives (2011)
- We present the current status of hybrid approaches to describe heavy ion collisions and their future challenges and perspectives. First we present a hybrid model combining a Boltzmann transport model of hadronic degrees of freedom in the initial and final state with an optional hydrodynamic evolution during the dense and hot phase. Second, we present a recent extension of the hydrodynamical model to include fluctuations near the phase transition by coupling a chiral field to the hydrodynamic evolution.
- Direct photon emission in heavy ion collisions from microscopic transport theory and fluid dynamics : XLVIII International Winter Meeting on Nuclear Physics, BORMIO2010, January 25 - 29, 2010, Bormio, Italy (2010)
- Direct photon emission in heavy-ion collisions is calculated within a relativistic micro+macro hybrid model and compared to the microscopic transport model UrQMD. In the hybrid approach, the high-density part of the collision is calculated by an ideal 3+1-dimensional hydrodynamic calculation, while the early (pre-equilibrium-) and late (rescattering-) phase are calculated with the transport model. Different scenarios of the transition from the macroscopic description to the transport model description and their effects are studied. The calculations are compared to measurements by the WA98-collaboration and predictions for the future CBM-experiment are made.
- Parton recombination and fluctuations of conserved charges (2007)
- We study various fluctuation and correlation signals of the deconfined state using a dynamical recombination approach (quark Molecular Dynamics, qMD). We analyse charge ratio fluctuations, charge transfer fluctuations and baryon-strangeness correlations as a function of the center of mass energy with a set of central Pb+Pb/Au+Au events from AGS energies on (Elab = 4 AGeV) up to the highest RHIC energy available (V sNN = 200 GeV) and as a function of time with a set of central Au+Au qMD events at V sNN = 200 GeV with and without applying our hadronization procedure. For all studied quantities, the results start from values compatible with a weakly coupled QGP in the early stage and end with values compatible with the hadronic result in the final state. We show that the loss of the signal occurs at the same time as hadronization and trace it back to the dynamical recombination process implemented in our model.
- An introduction to mini black holes at LHC (2007)
- Relying on the existing estimates for the production cross sections of mini black holes in models with large extra dimensions, we review strategies for identifying those objects at collider experiments. We further consider a possible stable final state of such black holes and discuss their characteristic signatures. Keywords: Black holes
- Longitudinal flow and onset of deconfinement (2006)
- The effects of the onset of deconfinement on longitudinal and transverse flow are studied. First, we analyze longitudinal pion spectra from Elab = 2A GeV to √sNN = 200 GeV within Landau’s hydrodynamical model and the UrQMD transport approach. From the measured data on the widths of the pion rapidity spectra, we extract the sound velocity c2s in the early stage of the reactions. It is found that the sound velocity has a local minimum (indicating a softest point in the equation of state, EoS) at Ebeam = 30A GeV. This softening of the EoS is compatible with the assumption of the formation of a mixed phase at the onset of deconfinement. Furthermore, the energy excitation function of elliptic flow (v2) from Ebeam = 90A MeV to √sNN = 200 GeV is explored within the UrQMD framework and discussed in the context of the available data. The transverse flow should also be sensitive to changes in the equation of state. Therefore, the underestimation of elliptic flow by the UrQMD model calculation above Elab = 30A GeV might also be explained by assuming a phase transition from a hadron gas to the quark gluon plasma around this energy. This would be consistent with the model calculations, indicating a transition from hadronic matter to “string matter” in this energy range.