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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 ArticleDOI

Relative biological effectiveness (RBE) values for proton beam therapy.

TL;DR: There is too much uncertainty in the RBE value for any human tissue to propose RBE values specific for tissue, dose/fraction, proton energy, etc, and experimental in vivo and clinical data indicate that continued employment of a generic RBEvalue is reasonable.
Journal ArticleDOI

Low-dose hypersensitivity : Current status and possible mechanisms

TL;DR: This paper proposes possible mechanisms to explain the phenomenon in which cells die from excessive sensitivity to small single doses of ionizing radiation but remain more resistant (per unit dose) to larger single doses.
Journal ArticleDOI

Intrinsic radiosensitivity of human cell lines is correlated with radioresponsiveness of human tumors: analysis of 101 published survival curves.

TL;DR: It was found that cells from tumors with low radioresponsiveness (melanomas and glioblastomas) are the less radiosensitive, and the range of survival at a dose of 2 Gy is broad enough to account, in large measure, for observed differences in clinical tumor radiore sponsorship.
Journal ArticleDOI

Proton beam therapy

TL;DR: Proton beam radiotherapy, one form of charged particle therapy, allows for excellent dose distributions, with the added benefit of no exit dose, which makes this form of radiotherapy an excellent choice for the treatment of tumours located next to critical structures such as the spinal cord, eyes, and brain.
Journal ArticleDOI

Induction of replicative senescence biomarkers by sublethal oxidative stresses in normal human fibroblast

TL;DR: Sublethal oxidative stresses lead HDFs to a state close to replicative senescence, and the common 4977 bp mitochondrial DNA deletion was detected in WI-38 HDFs at late C PDs and at early CPDs after t-BHP stresses.
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