Systems Biology Modeling of the Radiation Sensitivity Network: A Biomarker Discovery Platform

Eschrich, Steven; Zhang, Hongling; Zhao, Hang; Boulware, David; Lee, Ji‐Hyun; Bloom, Gregory; Torres-Roca, Javier F.

doi:10.1016/j.ijrobp.2009.05.056

Cited by 241 publications

(239 citation statements)

References 43 publications

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“…88 In a molecular regulatory network model based on mRNA expression profiles, it has been possible to identify 10 hubs of interactions associated to radiosensitivity. 89 It is not clear whether these patterns can be used for all cancers, or they are tissuespecific. Individual NSCLC patients' responses to chemotherapy are highly variable, 90 and similar spread is measured irradiating NSCLC cell lines.…”

Section: Tumour Tissuementioning

confidence: 99%

New challenges in high-energy particle radiobiology

Durante

2014

BJR

125

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Densely ionizing radiation has always been a main topic in radiobiology. In fact, a-particles and neutrons are sources of radiation exposure for the general population and workers in nuclear power plants. More recently, high-energy protons and heavy ions attracted a large interest for two applications: hadrontherapy in oncology and space radiation protection in manned space missions. For many years, studies concentrated on measurements of the relative biological effectiveness (RBE) of the energetic particles for different end points, especially cell killing (for radiotherapy) and carcinogenesis (for late effects). Although more recently, it has been shown that densely ionizing radiation elicits signalling pathways quite distinct from those involved in the cell and tissue response to photons. The response of the microenvironment to charged particles is therefore under scrutiny, and both the damage in the target and non-target tissues are relevant. The role of individual susceptibility in therapy and risk is obviously a major topic in radiation research in general, and for ion radiobiology as well. Particle radiobiology is therefore now entering into a new phase, where beyond RBE, the tissue response is considered. These results may open new applications for both cancer therapy and protection in deep space.Biological effects of densely ionizing radiation have been studied since the beginning of radiobiology. As a matter of fact, a-particles deliver the main contribution to the background radiation dose on Earth, owing to inhalation of the indoor radon.1 Neutrons have also been extensively studied because of protection of workers in nuclear power plants; use of fast neutrons in radiotherapy; and of the exposure of the survivors of the atomic bomb in Hiroshima and Nagasaki, where a neutron component was added to g-rays. Bacq and Alexander 2 already elegantly described the radiobiology of a-particles and neutrons in their 1955 seminal book.More recently, radiobiology research has focused on highenergy protons and heavy ions, mostly for two reasons: charged particle therapy (CPT) in oncology and radiation protection in manned space missions. In both cases, charged particles at energies .100 MeV n 21 are involved. The characteristic depth-dose distribution with the sharp Bragg peak at the end of the range can be exploited for killing tumours; on the other hand, densely ionizing radiation can effectively delay tissue morbidity. Notwithstanding the many differences in exposure conditions, CPT and space radiation protection share several research topics, including individual sensitivity, non-targeted effects, late stochastic effects and so forth.3 Research in these fields requires large high-energy accelerators and is often performed by the same research groups with a common interest in particle radiobiology. Research is rapidly moving forward owing to the diffusion of CPT centres in the USA, Europe, and Asia 4 and to the growing interest in manned space exploration, now a priority for all space agencies, 5 but wi...

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Section: Tumour Tissuementioning

confidence: 99%

New challenges in high-energy particle radiobiology

Durante

2014

BJR

125

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“…25 NF-kB is also the most important mediator in radioresistance. 26 Sandur et al concluded that NF-kB dependent cell survival pathway was crucial for radio-resistance in CRC cell lines and that suppression of inducible NF-kB led to radio-sensitivity. 27 We found a decrease in NF-kB p65 expression after single DHA or EPA treatment.…”

Section: Early Apoptosis (%)mentioning

confidence: 99%

Interaction of ω-3 polyunsaturated fatty acids with radiation therapy in two different colorectal cancer cell lines

et al. 2014

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Methods: LS174T and HT-29 cells were treated with 20 or 50 mmol/L EPA or DHA followed by single X-ray RT of 0, 2 or 4 Gy, to evaluate cell survival, apoptosis, peroxide and malondialdehyde productions. Inflammation-and apoptosis-related proteins were analyzed by Western Blot. ANOVAs were used for statistical analysis. Results: LS174T was more sensitive to RT than HT-29. DHA and to a lesser extent EPA increased cell death, apoptosis and peroxide production after RT in LS174T and to a lesser extent in HT-29 (p < 0.05). This was associated with increased expression of heat shock protein 70, decreased expression of NF-kB p65, COX-2 and Bcl-2 proteins. Conclusions: The effect of RT combination with DHA and to a lesser extent EPA was synergistic in the radio-sensitive LS174T cells, but additive in the radio-resistant HT-29 cells. This enhanced cytotoxicity was provoked at least partly by lipid peroxidation, which consequently modulated inflammatory response and induced apoptosis.

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“…Nevertheless, some investigations have demonstrated the involvement of several genes, including HDAC1, MDM2, c-Jun, PKC-β, c-Abl and CDK1, in cellular responses to radiation (79)(80)(81). Some of these genes have been studied as potential targets for radiosensitizer development.…”

Section: Targeting Network Flexibilitymentioning

confidence: 99%