10 results on '"Greubel, Christoph"'
Search Results
2. The influence of the channel size on the reduction of side effects in microchannel proton therapy.
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Girst, Stefanie, Greubel, Christoph, Reindl, Judith, Siebenwirth, Christian, Zlobinskaya, Olga, Dollinger, Günther, and Schmid, Thomas
- Abstract
The potential of proton microchannel radiotherapy to reduce radiation effects in the healthy tissue but to keep tumor control the same as in conventional proton therapy is further elucidated. The microchannels spread on their way to the tumor tissue resulting in different fractions of the healthy tissue covered with doses larger than the tumor dose, while the tumor gets homogeneously irradiated. The aim of this study was to evaluate the effect of increasing channel width on potential side effects in the normal tissue. A rectangular 180 × 180 µm and two Gaussian-type dose distributions of σ = 260 µm and σ = 520 µm with an interchannel distance of 1.8 mm have been applied by 20-MeV protons to a 3D human skin model in order to simulate the widened channels and to compare the irradiation effects at different endpoints to those of a homogeneous proton irradiation. The number of protons applied was kept constant at all irradiation modes resulting in the same average dose of 2 Gy. All kinds of proton microchannel irradiation lead to higher cell viability and produce significantly less genetic damage than homogeneous proton irradiation, but the reduction is lower for the wider channel sizes. Our findings point toward the application of microchannel irradiation for clinical proton or heavy ion therapy to further reduce damage of normal tissues while maintaining tumor control via a homogeneous dose distribution inside the tumor. [ABSTRACT FROM AUTHOR]
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- 2015
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3. Reduced side effects by proton microchannel radiotherapy: study in a human skin model.
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Zlobinskaya, Olga, Girst, Stefanie, Greubel, Christoph, Hable, Volker, Siebenwirth, Christian, Walsh, Dietrich, Multhoff, Gabriele, Wilkens, Jan, Schmid, Thomas, and Dollinger, Günther
- Abstract
The application of a microchannel proton irradiation was compared to homogeneous irradiation in a three-dimensional human skin model. The goal is to minimize the risk of normal tissue damage by microchannel irradiation, while preserving local tumor control through a homogeneous irradiation of the tumor that is achieved because of beam widening with increasing track length. 20 MeV protons were administered to the skin models in 10- or 50-μm-wide irradiation channels on a quadratic raster with distances of 500 μm between each channel (center to center) applying an average dose of 2 Gy. For comparison, other samples were irradiated homogeneously at the same average dose. Normal tissue viability was significantly enhanced after microchannel proton irradiation compared to homogeneous irradiation. Levels of inflammatory parameters, such as Interleukin-6, TGF-Beta, and Pro-MMP1, were significantly lower in the supernatant of the human skin tissue after microchannel irradiation than after homogeneous irradiation. The genetic damage as determined by the measurement of micronuclei in keratinocytes also differed significantly. This difference was quantified via dose modification factors (DMF) describing the effect of each irradiation mode relative to homogeneous X-ray irradiation, so that the DMF of 1.21 ± 0.20 after homogeneous proton irradiation was reduced to 0.23 ± 0.11 and 0.40 ± 0.12 after microchannel irradiation using 10- and 50-μm-wide channels, respectively. Our data indicate that proton microchannel irradiation maintains cell viability while significantly reducing inflammatory responses and genetic damage compared to homogeneous irradiation, and thus might improve protection of normal tissue after irradiation. [ABSTRACT FROM AUTHOR]
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- 2013
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4. Double-strand break-induced transcriptional silencing is associated with loss of tri-methylation at H3K4.
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Seiler, Doris, Rouquette, Jacques, Schmid, Volker, Strickfaden, Hilmar, Ottmann, Christian, Drexler, Guido, Mazurek, Belinda, Greubel, Christoph, Hable, Volker, Dollinger, Günther, Cremer, Thomas, and Friedl, Anna
- Abstract
Epigenetic alterations induced by ionizing radiation may contribute to radiation carcinogenesis. To detect relative accumulations or losses of constitutive post-translational histone modifications in chromatin regions surrounding DNA double-strand breaks (DSB), we developed a method based on ion microirradiation and correlation of the signal intensities after immunofluorescence detection of the histone modification in question and the DSB marker γ-H2AX. We observed after ionizing irradiation markers for transcriptional silencing, such as accumulation of H3K27me3 and loss of active RNA polymerase II, at chromatin regions labeled by γ-H2AX. Confocal microscopy of whole nuclei and of ultrathin nuclear sections revealed that the histone modification H3K4me3, which labels transcriptionally active regions, is underrepresented in γ-H2AX foci. While some exclusion of H3K4me3 is already evident at the earliest time amenable to this kind of analysis, the anti-correlation apparently increases with time after irradiation, suggesting an active removal process. Focal accumulation of the H3K4me3 demethylase, JARID1A, was observed at damaged regions inflicted by laser irradiation, suggesting involvement of this enzyme in the DNA damage response. Since no accumulation of the repressive mark H3K9me2 was found at damaged sites, we suggest that DSB-induced transcriptional silencing resembles polycomb-mediated silencing rather than heterochromatic silencing. [ABSTRACT FROM AUTHOR]
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- 2011
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5. Scanning irradiation device for mice in vivo with pulsed and continuous proton beams.
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Greubel, Christoph, Assmann, Walter, Burgdorf, Christian, Dollinger, Günther, Guanghua Du, Hable, Volker, Hapfelmeier, Alexander, Hertenberger, Ralf, Kneschaurek, Peter, Michalski, Dörte, Molls, Michael, Reinhardt, Sabine, Röper, Barbara, Schell, Stefan, Schmid, Thomas E., Siebenwirth, Christian, Wenzl, Tatiana, Zlobinskaya, Olga, and Wilkens, Jan J.
- Abstract
technical set-up for irradiation of subcutaneous tumours in mice with nanosecond-pulsed proton beams or continuous proton beams is described and was successfully used in a first experiment to explore future potential of laser-driven particle beams, which are pulsed due to the acceleration process, for radiation therapy. The chosen concept uses a microbeam approach. By focusing the beam to approximately 100 × 100 μm, the necessary fluence of 10 protons per cm to deliver a dose of 20 Gy with one-nanosecond shot in the Bragg peak of 23 MeV protons is achieved. Electrical and mechanical beam scanning combines rapid dose delivery with large scan ranges. Aluminium sheets one millimetre in front of the target are used as beam energy degrader, necessary for adjusting the depth-dose profile. The required procedures for treatment planning and dose verification are presented. In a first experiment, 24 tumours in mice were successfully irradiated with 23 MeV protons and a single dose of 20 Gy in pulsed or continuous mode with dose differences between both modes of 10%. So far, no significant difference in tumour growth delay was observed. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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6. Author Correction: DNA damage interactions on both nanometer and micrometer scale determine overall cellular damage.
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Friedrich, Thomas, Ilicic, Katarina, Greubel, Christoph, Girst, Stefanie, Reindl, Judith, Sammer, Matthias, Schwarz, Benjamin, Siebenwirth, Christian, Walsh, Dietrich W. M., Schmid, Thomas E., Scholz, Michael, and Dollinger, Günther
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DNA damage ,NANOSTRUCTURED materials - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]
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- 2020
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7. DNA damage interactions on both nanometer and micrometer scale determine overall cellular damage.
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Friedrich, Thomas, Ilicic, Katarina, Greubel, Christoph, Girst, Stefanie, Reindl, Judith, Sammer, Matthias, Schwarz, Benjamin, Siebenwirth, Christian, Walsh, Dietrich W. M., Schmid, Thomas E., Scholz, Michael, and Dollinger, Günther
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DNA double strand breaks (DSB) play a pivotal role for cellular damage, which is a hazard encountered in toxicology and radiation protection, but also exploited e.g. in eradicating tumors in radiation therapy. It is still debated whether and in how far clustering of such DNA lesions leads to an enhanced severity of induced damage. Here we investigate - using focused spots of ionizing radiation as damaging agent - the spatial extension of DNA lesion patterns causing cell inactivation. We find that clustering of DNA damage on both the nm and µm scale leads to enhanced inactivation compared to more homogeneous lesion distributions. A biophysical model interprets these observations in terms of enhanced DSB production and DSB interaction, respectively. We decompose the overall effects quantitatively into contributions from these lesion formation processes, concluding that both processes coexist and need to be considered for determining the resulting damage on the cellular level. [ABSTRACT FROM AUTHOR]
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- 2018
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8. Survival of tumor cells after proton irradiation with ultra-high dose rates
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Auer, Susanne, Hable, Volker, Greubel, Christoph, Drexler, Guido A, Schmid, Thomas E, Belka, Claus, Dollinger, Günther, and Friedl, Anna A
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lcsh:Medical physics. Medical radiology. Nuclear medicine ,Time Factors ,Cell Survival ,lcsh:R895-920 ,Apoptosis ,lcsh:RC254-282 ,laser acceleration ,Neoplasms ,proton therapy ,Humans ,Heavy Ions ,Ions ,Radiotherapy ,Research ,Lasers ,X-Rays ,Cell Cycle ,dose rate effects ,Flow Cytometry ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Microscopy, Fluorescence ,Oncology ,Radiology Nuclear Medicine and imaging ,Particle Accelerators ,Protons ,Relative Biological Effectiveness ,HeLa Cells - Abstract
Background Laser acceleration of protons and heavy ions may in the future be used in radiation therapy. Laser-driven particle beams are pulsed and ultra high dose rates of >109 Gy s-1may be achieved. Here we compare the radiobiological effects of pulsed and continuous proton beams. Methods The ion microbeam SNAKE at the Munich tandem accelerator was used to directly compare a pulsed and a continuous 20 MeV proton beam, which delivered a dose of 3 Gy to a HeLa cell monolayer within < 1 ns or 100 ms, respectively. Investigated endpoints were G2 phase cell cycle arrest, apoptosis, and colony formation. Results At 10 h after pulsed irradiation, the fraction of G2 cells was significantly lower than after irradiation with the continuous beam, while all other endpoints including colony formation were not significantly different. We determined the relative biological effectiveness (RBE) for pulsed and continuous proton beams relative to x-irradiation as 0.91 ± 0.26 and 0.86 ± 0.33 (mean and SD), respectively. Conclusions At the dose rates investigated here, which are expected to correspond to those in radiation therapy using laser-driven particles, the RBE of the pulsed and the (conventional) continuous irradiation mode do not differ significantly.
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9. Live cell imaging of mitochondria following targeted irradiation in situ reveals rapid and highly localized loss of membrane potential.
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Walsh, Dietrich W. M., Siebenwirth, Christian, Greubel, Christoph, Ilicic, Katarina, Reindl, Judith, Girst, Stefanie, Muggiolu, Giovanna, Simon, Marina, Barberet, Philippe, Seznec, Hervé, Zischka, Hans, Multhoff, Gabriele, Schmid, Thomas E., and Dollinger, Guenther
- Abstract
The reliance of all cell types on the mitochondrial function for survival makes mitochondria an interesting target when trying to understand their role in the cellular response to ionizing radiation. By harnessing highly focused carbon ions and protons using microbeams, we have performed in situ live cell imaging of the targeted irradiation of individual mitochondria stained with Tetramethyl rhodamine ethyl ester (TMRE), a cationic fluorophore which accumulates electrophoretically in polarized mitochondria. Targeted irradiation with both carbon ions and protons down to beam spots of <1 μm induced a near instant loss of mitochondrial TMRE fluorescence signal in the targeted area. The loss of TMRE after targeted irradiation represents a radiation induced change in mitochondrial membrane potential. This is the first time such mitochondrial responses have been documented in situ after targeted microbeam irradiation. The methods developed and the results obtained have the ability to shed new light on not just mitochondria's response to radiation but to further elucidate a putative mechanism of radiation induced depolarization and mitochondrial response. [ABSTRACT FROM AUTHOR]
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- 2017
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10. Chromatin organization revealed by nanostructure of irradiation induced γH2AX, 53BP1 and Rad51 foci.
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Reindl, Judith, Girst, Stefanie, Walsh, Dietrich W. M., Greubel, Christoph, Schwarz, Benjamin, Siebenwirth, Christian, Drexler, Guido A., Friedl, Anna A., and Dollinger, Günther
- Abstract
The spatial distribution of DSB repair factors γH2AX, 53BP1 and Rad51 in ionizing radiation induced foci (IRIF) in HeLa cells using super resolution STED nanoscopy after low and high linear energy transfer (LET) irradiation was investigated. 53BP1 and γH2AX form IRIF with same mean size of (540 ± 40) nm after high LET irradiation while the size after low LET irradiation is significantly smaller. The IRIF of both repair factors show nanostructures with partial anti-correlation. These structures are related to domains formed within the chromatin territories marked by γH2AX while 53BP1 is mainly situated in the perichromatin region. The nanostructures have a mean size of (129 ± 6) nm and are found to be irrespective of the applied LET and the labelled damage marker. In contrast, Rad51 shows no nanostructure and a mean size of (143 ± 13) nm independent of LET. Although Rad51 is surrounded by 53BP1 it strongly anti-correlates meaning an exclusion of 53BP1 next to DSB when decision for homologous DSB repair happened. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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