Non-targeted radiation effects in vivo: A critical glance of the future in radiobiology

Hatzi, Vasiliki I.; Laskaratou, Danae A.; Mavragani, Ifigeneia V.; Nikitaki, Zacharenia; Mangelis, Anastasios; Panayiotidis, Mihalis Ι.; Pantelias, Gabriel E.; Terzoudi, Georgia I.; Georgakilas, Alexandros G.

doi:10.1016/j.canlet.2013.11.018

Cited by 59 publications

(32 citation statements)

References 90 publications

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“…Recently, a growing interest in bystander effect in the field of radiation therapy can be observed, due to emerging studies showing that bystander effect can cause potentiation of the local tumor response, as well as the increase in normal tissue damage (Baskar 2010;Hatzi et al 2015). If we compare these findings in radiation therapy with electroporation-based therapies, we can speculate on the implication of bystander effect on the therapeutic effectiveness of electrochemotherapy, irreversible electroporation and on gene electrotransfer.…”

Section: Discussionmentioning

confidence: 94%

“…In radiation therapy, bystander effect is gaining increasing attention, due to its spatial potentiation of the local tumor response, as well as the increase in normal tissue damage (Baskar 2010;Hatzi et al 2015). Furthermore, it may indirectly (by the involvement of the immune response) negatively influence the growth of distant tumors (Marín et al 2015;Deng et al 2016).…”

Section: Introductionmentioning

confidence: 98%

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Bystander Effect Induced by Electroporation is Possibly Mediated by Microvesicles and Dependent on Pulse Amplitude, Repetition Frequency and Cell Type

et al. 2016

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Bystander effect, a known phenomenon in radiation biology, where irradiated cells release signals which cause damage to nearby, unirradiated cells, has not been explored in electroporated cells yet. Therefore, our aim was to determine whether bystander effect is present in electroporated melanoma cells in vitro, by determining viability of non-electroporated cells exposed to medium from electroporated cells and by the release of microvesicles as potential indicators of the bystander effect. Here, we demonstrated that electroporation of cells induces bystander effect: Cells exposed to electric pulses mediated their damage to the non-electroporated cells, thus decreasing cell viability. We have shown that shedding microvesicles may be one of the ways used by the cells to mediate the death signals to the neighboring cells. The murine melanoma B16F1 cell line was found to be more electrosensitive and thus more prone to bystander effect than the canine melanoma CMeC-1 cell line. In B16F1 cell line, bystander effect was present above the level of electropermeabilization of the cells, with the threshold at 800 V/cm. Furthermore, with increasing electric field intensities and the number of pulses, the bystander effect also increased. In conclusion, electroporation can induce bystander effect which may be mediated by microvesicles, and depends on pulse amplitude, repetition frequency and cell type.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 98%

Bystander Effect Induced by Electroporation is Possibly Mediated by Microvesicles and Dependent on Pulse Amplitude, Repetition Frequency and Cell Type

et al. 2016

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“…These bystander induced effects can include chromosome alterations, altered gene expression, apoptosis, increased radiation resistance or sensitivity and neoplastic transformation [13]. The exact underlying mechanism of the bystander effect has been difficult to elucidate in patients but may be due in part to an immune mediated response.…”

Section: Introductionmentioning

confidence: 99%

Immune modulation in advanced radiotherapies: Targeting out-of-field effects

2015

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By virtue of being a localized treatment modality, radiotherapy is unable to deliver a tumoricidal radiation dose to tissues outside of the irradiated field. Nevertheless, ionizing radiation may result in radiation damage mediated by a bystander like effect away from the irradiated field, but this response is likely to be modest when radiotherapy is the sole treatment modality. Over the last decade there has been a re-emergence of immune modulating therapies as anti-cancer treatment modalities. Clinical trials on vaccines have on the whole been largely disappointing, but greater response rates have been observed from the immune checkpoint modulators. A clinical benefit of using such agents has been shown in disease sites such as melanoma and non-small cell lung cancer. There is growing pre-clinical data and a number of case reports which suggest the presence of abscopal effects when radiotherapy is co-administered with immune checkpoint inhibitors, suggesting that this combination may lead to an enhanced tumour response outside of the primary treatment field. In this review, the mechanisms of such an enhanced out-of-field tumour response, the potential clinical utilities, the optimal radiotherapy delivery and considerations for clinical follow-up following treatment are discussed.

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“…The published results are often controversial and the mechanisms of RIBE both in vivo and in vitro still remain incompletely characterized. 6 Of note is the complexity of the experimental framework and how it can be interpreted as a function of dose/radiation quality. 58 It is likely that different multifactorial pathways are implicated in signaling the response from an irradiated cell to a non-irradiated cell.…”

Section: Introductionmentioning

confidence: 99%

“…The findings also point to the induction of more complex effects, the so-called 'non-targeted effects' (NTE), in cells that do not directly interact with radiation as described above. [1][2][3][4][5][6][7] A range of evidence that has emerged thus far supports that IR induces complex, global cellular responses, such as radiation-induced bystander effects (RIBE), 4,[8][9][10][11] radioadaptive response [12][13][14][15][16][17][18][19] and genomic instability. 3,[20][21][22][23][24][25] The effects have been observed not only in irradiated, but also in nonirradiated bystander cells that receive molecular signals emitted by the irradiated cells.…”

Section: Introductionmentioning

confidence: 99%

Key mechanisms involved in ionizing radiation-induced systemic effects. A current review

Mavragani

Laskaratou

Frey

et al. 2015

Toxicology Research

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Non-targeted radiation effects in vivo: A critical glance of the future in radiobiology

Cited by 59 publications

References 90 publications

Bystander Effect Induced by Electroporation is Possibly Mediated by Microvesicles and Dependent on Pulse Amplitude, Repetition Frequency and Cell Type

Bystander Effect Induced by Electroporation is Possibly Mediated by Microvesicles and Dependent on Pulse Amplitude, Repetition Frequency and Cell Type

Immune modulation in advanced radiotherapies: Targeting out-of-field effects

Key mechanisms involved in ionizing radiation-induced systemic effects. A current review

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