Influence of chronic hypoxia and radiation quality on cell survival

Ma, Ningyi; Tinganelli, Walter; Maier, Andreas; Durante, Marco; Kraft-Weyrather, W.

doi:10.1093/jrr/rrs135

Cited by 47 publications

(69 citation statements)

References 28 publications

(27 reference statements)

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“…Based on experimental data, it has also been suggested that chronically hypoxic cells might be more sensitive than acutely hypoxic cells [38–40]. The present study, however, does not take into account the difference in sensitivity between the two types of hypoxic cells, since they cannot yet be distinguished in vivo .…”

Section: Discussionmentioning

confidence: 86%

Clinical oxygen enhancement ratio of tumors in carbon ion radiotherapy: the influence of local oxygenation changes

Antonovic

Lindblom

Daşu

et al. 2014

Journal of Radiation Research

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The effect of carbon ion radiotherapy on hypoxic tumors has recently been questioned because of low linear energy transfer (LET) values in the spread-out Bragg peak (SOBP). The aim of this study was to investigate the role of hypoxia and local oxygenation changes (LOCs) in fractionated carbon ion radiotherapy. Three-dimensional tumors with hypoxic subvolumes were simulated assuming interfraction LOCs. Different fractionations were applied using a clinically relevant treatment plan with a known LET distribution. The surviving fraction was calculated, taking oxygen tension, dose and LET into account, using the repairable–conditionally repairable (RCR) damage model with parameters for human salivary gland tumor cells. The clinical oxygen enhancement ratio (OER) was defined as the ratio of doses required for a tumor control probability of 50% for hypoxic and well-oxygenated tumors. The resulting OER was well above unity for all fractionations. For the hypoxic tumor, the tumor control probability was considerably higher if LOCs were assumed, rather than static oxygenation. The beneficial effect of LOCs increased with the number of fractions. However, for very low fraction doses, the improvement related to LOCs did not compensate for the increase in total dose required for tumor control. In conclusion, our results suggest that hypoxia can influence the outcome of carbon ion radiotherapy because of the non-negligible oxygen effect at the low LETs in the SOBP. However, if LOCs occur, a relatively high level of tumor control probability is achievable with a large range of fractionation schedules for tumors with hypoxic subvolumes, but both hyperfractionation and hypofractionation should be pursued with caution.

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Section: Discussionmentioning

confidence: 86%

Clinical oxygen enhancement ratio of tumors in carbon ion radiotherapy: the influence of local oxygenation changes

Antonovic

Lindblom

Daşu

et al. 2014

Journal of Radiation Research

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“…Asynchronously growing cells showed for low doses an OER similar to that in G1 which increased with decreasing survival levels to a value near that of S-phase cells. The slightly different behavior of our two measured cell lines may then be due to differences in the cell cycle distribution: RAT-1 cells had an averaged cell cycle distribution of 58% G1, 22% S and 20% G2/M, while CHO were 34% in G1, 50% in S and 16% in G2/M [33]. The higher number of S-phase cells could thus explain the greater difference in OER values for CHO cells.…”

Section: Discussionmentioning

confidence: 99%

Influence of acute hypoxia and radiation quality on cell survival

Tinganelli

Neubeck

et al. 2013

Journal of Radiation Research

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To measure the effect of acute oxygen depletion on cell survival for different types of radiation, experiments have been performed using Chinese hamster ovary (CHO) cells and RAT-1 rat prostate cancer cells. A special chamber has been developed to perform irradiations under different levels of oxygenation. The oxygen concentrations used were normoxia (air), hypoxia (94.5% N2, 5% CO2, 0.5% O2) and anoxia (95% N2, 5% CO2). Cells were exposed to X-rays and to C-, N- or O-ions with linear energy transfer (LET) values ranging from 100–160 keV/µm. The oxygen enhancement ratio (OER) and relative biological effectiveness (RBE) values have been calculated from the measured clonogenic survival curves. For both cell lines, the X-ray OER depended on the survival level. For particle irradiation, OER was not dependent on the survival level but decreased with increasing LET. The RBE of CHO cells under oxic conditions reached a plateau for LET values above 100 keV/µm, while it was still increasing under anoxia. In conclusion, the results demonstrated that our chamber could be used to measure radiosensitivity under intermediate hypoxia. Measurements suggest that ions heavier than carbon could be of additional advantage in the irradiation, especially of radioresistant hypoxic tumor regions.

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“…Multiple realms of research have unveiled a few signaling pathways that contribute to resistance to IR. Among them, hypoxia pathway was one of the most extensively studied pathways, due to its intimate association with ionizing conditions [26][27][28]. Here, we demonstrated that quercetin could sensitize keloid fibroblasts to IR treatment, and the effect was associated with expression of HIF-1α, a critical component of radioresistance related hypoxia pathway.…”

Section: Discussionmentioning

confidence: 68%

Radiation Sensitization of Keloid Firboblasts by Quercetin through PI3K/Akt Pathway Dependent Regulation of HIF-1α

Si¹,

Han²,

Long³

et al. 2017

J Clin Exp Dermatol Res

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Objective: Keloid is a benign tumor in the derma, which is generally treated by surgical excision and radiation in clinic. However, recurrence has been an intricate problem in treatment of keloid. Therefore, it is imperative to develop novel interfering means to increase the sensitivity of keloid to radiation. Quercetin is a natural compound, which has been shown to sensitize some tumors to radiation. We tested the potential of quercetin in sensitizing keloid fibroblast to radiation and identified its downstream pathways. Methods: Keloid fibroblast cells were challenged by radiation with or without the presence of quercetin. Cellular response was detected by flow cytometry, western blot, qRT-PCR and immunofluorescence staining. HIF-1α was down-regulated by siRNA transfection. Results: In this study, we firstly demonstrate that keloid fibroblasts acquire resistance after IR treatment, and this can be relieved by treating with quercetin. Further, we showed that hypoxia-inducible factor 1 (HIF-1), a prognostic marker used in clinical practice after radiation therapy, was associated with stronger radioresistance in keloid fibroblast, which was downregulated after quercetin treatment. The inhibition on HIF-1 expression by quercetin was found to depend on phosphatidylinositol-3-kinase (PI3K)/Akt pathway and quercetin also reduce phosphorylation of Akt. Conclusion: Taken together, we revealed a mechanism underlying the suppression on radioresistance by quercetin, which involves the regulation of HIF-1α by PI3K/Akt pathway. Our study provides molecular interpretation for the application quercetin in sensitizing radiation in keloid treatment.

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Influence of chronic hypoxia and radiation quality on cell survival

Cited by 47 publications

References 28 publications

Clinical oxygen enhancement ratio of tumors in carbon ion radiotherapy: the influence of local oxygenation changes

Clinical oxygen enhancement ratio of tumors in carbon ion radiotherapy: the influence of local oxygenation changes

Influence of acute hypoxia and radiation quality on cell survival

Radiation Sensitization of Keloid Firboblasts by Quercetin through PI3K/Akt Pathway Dependent Regulation of HIF-1α

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