Dose- and time-dependent gene expression alterations in prostate and colon cancer cells after in vitro exposure to carbon ion and X-irradiation

Suetens, Annelies; Moreels, Marjan; Quintens, Roel; Soors, Els; Buset, Jasmine; Chiriotti, S.; Tabury, Kevin; Grégoire, Vincent; Baatout, Sarah

doi:10.1093/jrr/rru070

Cited by 36 publications

(40 citation statements)

References 46 publications

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“…In a next step, we further investigated the changes of genes involved in motility processes. Our results showed that the magnitude of expression of these genes was time- and dose-dependent for both PC3 and Caco-2 cells, although a cell-type-specific response to X- and carbon ion irradiation was observed ( 29 ). With regard to the changes in cell cycle-related gene sets, we further aimed to investigate the acute cellular responses induced by different radiation qualities.…”

Section: Introductionmentioning

confidence: 72%

Higher Initial DNA Damage and Persistent Cell Cycle Arrest after Carbon Ion Irradiation Compared to X-irradiation in Prostate and Colon Cancer Cells

et al. 2016

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The use of charged-particle beams, such as carbon ions, is becoming a more and more attractive treatment option for cancer therapy. Given the precise absorbed dose-localization and an increased biological effectiveness, this form of therapy is much more advantageous compared to conventional radiotherapy, and is currently being used for treatment of specific cancer types. The high ballistic accuracy of particle beams deposits the maximal dose to the tumor, while damage to the surrounding healthy tissue is limited. In order to better understand the underlying mechanisms responsible for the increased biological effectiveness, we investigated the DNA damage and repair kinetics and cell cycle progression in two p53 mutant cell lines, more specifically a prostate (PC3) and colon (Caco-2) cancer cell line, after exposure to different radiation qualities. Cells were irradiated with various absorbed doses (0, 0.5, and 2 Gy) of accelerated 13C-ions at the Grand Accélérateur National d’Ions Lourds facility (Caen, France) or with X-rays (0, 0.1, 0.5, 1, 2, and 5 Gy). Microscopic analysis of DNA double-strand breaks showed dose-dependent increases in γ-H2AX foci numbers and foci occupancy after exposure to both types of irradiation, in both cell lines. However, 24 h after exposure, residual damage was more pronounced after lower doses of carbon ion irradiation compared to X-irradiation. Flow cytometric analysis showed that carbon ion irradiation induced a permanent G2/M arrest in PC3 cells at lower doses (2 Gy) compared to X-rays (5 Gy), while in Caco-2 cells the G2/M arrest was transient after irradiation with X-rays (2 and 5 Gy) but persistent after exposure to carbon ions (2 Gy).

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Section: Introductionmentioning

confidence: 72%

Higher Initial DNA Damage and Persistent Cell Cycle Arrest after Carbon Ion Irradiation Compared to X-irradiation in Prostate and Colon Cancer Cells

et al. 2016

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“…In addition to anchorage-dependent signaling and morphologic changes adherent cells undergo during detachment, enzymatic detachment solutions, such as trypsin, cleave membrane-bound adhesion molecules that function as major signalers in cellular stress responses, including apoptosis 26 27 28 29 . Post-irradiation cell detachment can further confound determination of RBE because photons and ions have different effects on cell adhesion and motility 30 31 32 . As such, immediate post-irradiation plating readouts involve coupling the effect of the radiation treatment with cellular reattachment, except in the plating efficiency control used to determine overall SF levels.…”

Section: Discussionmentioning

confidence: 99%

Spatial mapping of the biologic effectiveness of scanned particle beams: towards biologically optimized particle therapy

Guan

Bronk

Titt

et al. 2015

Sci Rep

131

176

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The physical properties of particles used in radiation therapy, such as protons, have been well characterized, and their dose distributions are superior to photon-based treatments. However, proton therapy may also have inherent biologic advantages that have not been capitalized on. Unlike photon beams, the linear energy transfer (LET) and hence biologic effectiveness of particle beams varies along the beam path. Selective placement of areas of high effectiveness could enhance tumor cell kill and simultaneously spare normal tissues. However, previous methods for mapping spatial variations in biologic effectiveness are time-consuming and often yield inconsistent results with large uncertainties. Thus the data needed to accurately model relative biological effectiveness to guide novel treatment planning approaches are limited. We used Monte Carlo modeling and high-content automated clonogenic survival assays to spatially map the biologic effectiveness of scanned proton beams with high accuracy and throughput while minimizing biological uncertainties. We found that the relationship between cell kill, dose, and LET, is complex and non-unique. Measured biologic effects were substantially greater than in most previous reports, and non-linear surviving fraction response was observed even for the highest LET values. Extension of this approach could generate data needed to optimize proton therapy plans incorporating variable RBE.

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“…As mentioned above, carbon ions have a higher RBE and thus greater cell killing effectiveness (19,20). This can overcome radioresistance of hypoxic tumor regions, reduce the effect of fractionation and decrease cell cycle dependence of the radiation response (21).…”

Section: Introductionmentioning

confidence: 99%

Combination Therapy With Charged Particles and Molecular Targeting: A Promising Avenue to Overcome Radioresistance

et al. 2020

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Radiotherapy plays a central role in the treatment of cancer patients. Over the past decades, remarkable technological progress has been made in the field of conventional radiotherapy. In addition, the use of charged particles (e.g., protons and carbon ions) makes it possible to further improve dose deposition to the tumor, while sparing the surrounding healthy tissues. Despite these improvements, radioresistance and tumor recurrence are still observed. Although the mechanisms underlying resistance to conventional radiotherapy are well-studied, scientific evidence on the impact of charged particle therapy on cancer cell radioresistance is restricted. The purpose of this review is to discuss the potential role that charged particles could play to overcome radioresistance. This review will focus on hypoxia, cancer stem cells, and specific signaling pathways of EGFR, NFκB, and Hedgehog as well as DNA damage signaling involving PARP, as mechanisms of radioresistance for which pharmacological targets have been identified. Finally, new lines of future research will be proposed, with a focus on novel molecular inhibitors that could be used in combination with charged particle therapy as a novel treatment option for radioresistant tumors.

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Dose- and time-dependent gene expression alterations in prostate and colon cancer cells after in vitro exposure to carbon ion and X-irradiation

Cited by 36 publications

References 46 publications

Higher Initial DNA Damage and Persistent Cell Cycle Arrest after Carbon Ion Irradiation Compared to X-irradiation in Prostate and Colon Cancer Cells

Higher Initial DNA Damage and Persistent Cell Cycle Arrest after Carbon Ion Irradiation Compared to X-irradiation in Prostate and Colon Cancer Cells

Spatial mapping of the biologic effectiveness of scanned particle beams: towards biologically optimized particle therapy

Combination Therapy With Charged Particles and Molecular Targeting: A Promising Avenue to Overcome Radioresistance

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