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Low-LET Proton Irradiation of A549 Non-small Cell Lung Adenocarcinoma Cells: Dose Response and RBE Determination

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TLDR
Comparisons with X ray results indicate that proton irradiation at 10 keV/μm enhanced the tumor radiosensitivity with a significant dose-dependent decrease in the survival fraction.
Abstract
Since 1957, broad proton beam radiotherapy with a spread out Bragg peak has been used for cancer treatment. More recently, studies on the use of proton therapy in the treatment of non-small cell lung cancer (NSCLC) were performed and although the benefit of using protons for the treatment of NSCLC is recognized, more work is needed to gather additional data for the understanding of cell response. Human A549 cell survival was evaluated by colony forming assay 11 days after 10 keV/μm proton beam irradiation at 0.1 and 1 Gy/min. The residual energy of the proton beam at the location of the irradiated cells was 3.9 MeV. In parallel, early effects on the cell viability and DNA damage were assessed and DNA synthesis was measured. The survival curve obtained was fitted with both the linear and the induced-repair models, as a hyper-radiosensitivity was evidenced at very low doses. Above 0.5 Gy, a linear shape was observed with the α parameter equal to 0.824 ± 0.029 Gy−1. In addition, early cell death and cell pro...

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Journal ArticleDOI

Relative biological effectiveness (RBE) values for proton beam therapy. Variations as a function of biological endpoint, dose, and linear energy transfer

TL;DR: This review can serve as a source for defining input parameters for applying or refining biophysical models and to identify endpoints where additional radiobiological data are needed in order to reduce the uncertainties in proton RBE values to clinically acceptable levels.
Journal ArticleDOI

New challenges in high-energy particle radiobiology

TL;DR: Particle radiobiology is now entering into a new phase, where beyond RBE, the tissue response is considered, and these results may open new applications for both cancer therapy and protection in deep space.
Journal ArticleDOI

Multiscale approach predictions for biological outcomes in ion-beam cancer therapy

TL;DR: It is demonstrated that the phenomenon-based MultiScale Approach to the assessment of radiation damage with ions gives a positive answer to the question whether it is possible to quantitatively predict macroscopic biological effects caused by ion radiation on the basis of physical and chemical effects related to the ion-medium interactions on a nanometre scale.
Journal ArticleDOI

A phenomenological biological dose model for proton therapy based on linear energy transfer spectra.

TL;DR: Analysis indicated that non‐linear models could give a better representation of the RBE‐LET relationship, as differences between the models were observed for the SOBP scenario, and both non‐ linear LET spectrum‐ and linear LETd based models should be further evaluated in clinically realistic scenarios.
Journal ArticleDOI

Effect of proton and gamma irradiation on human lung carcinoma cells: Gene expression, cell cycle, cell death, epithelial-mesenchymal transition and cancer-stem cell trait as biological end points.

TL;DR: The effect of proton- and gamma- irradiation on cell cycle, death, epithelial-mesenchymal transition (EMT) and "stemness" in human non-small cell lung carcinoma cells (A549) is investigated.
References
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Journal Article

Low-dose radiation hypersensitivity is associated with p53-dependent apoptosis.

TL;DR: Low-dose hypersensitivity is associated with p53-dependent apoptosis, and the influence of low-dose radiation on cell cycle status and apoptosis by assays for active caspase-3 and phosphatidylserine translocation (Annexin V binding) is examined.
Journal ArticleDOI

Relationship between clonogenic radiosensitivity, radiation-induced apoptosis and DNA damage/repair in human colon cancer cells

TL;DR: The relationship between surviving fraction at 2 Gy (SF2) and the percentage of apoptotic cells 24 h after the same dose was complex, but apoptosis accurately predicted the order of radiosensitivities as measured by SF2.
Journal ArticleDOI

Low-Dose Hypersensitivity in Chinese Hamster V79 Cells Targeted with Counted Protons Using a Charged-Particle Microbeam

TL;DR: The data are well fitted by a model that supports the hypothesis that radioresistance is induced by low-dose hypersensitivity, and demonstrate the potential of the microbeam for performing studies of the effects of single charged particles on cells in vitro.
Journal ArticleDOI

Survival of tumor cells after proton irradiation with ultra-high dose rates.

TL;DR: 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, and the RBE of the pulsed and the (conventional) continuous irradiation mode do not differ significantly.
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