Neurotoxicity from Old and New Radiation Treatments for Brain Tumors

Soffietti, Riccardo; Pellerino, Alessia; Bruno, Francesco; Mauro, Alessandro; Rudà, Roberta

doi:10.3390/ijms241310669

Cited by 6 publications

(6 citation statements)

References 134 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are several hypotheses covering the mechanisms behind radiation-induced damage in the brain ( 7 , 19 ). Neuro-inflammation takes place following irradiation, and depending on the dosage and fractionation, this may lead to chronically elevated oxidative stress ( 7 ). Mature neurons might survive irradiation, but still undergo a change in their transmitting abilities.…”

Section: Discussionmentioning

confidence: 99%

“…Mature neurons might survive irradiation, but still undergo a change in their transmitting abilities. In the hippocampus, irradiation can lead to long-term loss of dendritic spines ( 7 ). Furthermore, irradiation induced damage to the blood-brain barrier, due to alterations of the microvasculature, can lead to ischemia and neuro-toxicity ( 7 ).…”

Section: Discussionmentioning

confidence: 99%

“…It would be beneficial to optimize radiotherapy against glioblastoma. Firstly, tumor control could potentially be increased if the total dose could be increased without severe side effects ( 7 ). Secondly, it seems like radiotherapy can elicit an immunologically mediated anti-tumor response ( 5 , 8 , 9 ), but the dose per fraction needs to be altered in order to elicit a more effective immunological response ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Comparable survival in rats with intracranial glioblastoma irradiated with single-fraction conventional radiotherapy or FLASH radiotherapy

Liljedahl,

Konradsson,

Linderfalk

et al. 2024

Front. Oncol.

View full text Add to dashboard Cite

BackgroundRadiotherapy increases survival in patients with glioblastoma. However, the prescribed dose is limited by unwanted side effects on normal tissue. Previous experimental studies have shown that FLASH radiotherapy (FLASH-RT) can reduce these side effects. Still, it is important to establish an equal anti-tumor efficacy comparing FLASH-RT to conventional radiotherapy (CONV-RT).MethodsFully immunocompetent Fischer 344 rats with the GFP-positive NS1 intracranial glioblastoma model were irradiated with CONV-RT or FLASH-RT in one fraction of 20 Gy, 25 Gy or 30 Gy. Animals were monitored for survival and acute dermal side effects. The brains were harvested upon euthanasia and tumors were examined post mortem.ResultsSurvival was significantly increased in animals irradiated with CONV-RT and FLASH-RT at 20 Gy and 25 Gy compared to control animals. The longest survival was reached in animals irradiated with FLASH-RT and CONV-RT at 25 Gy. Irradiation at 30 Gy did not lead to increased survival, despite smaller tumors. Tumor size correlated inversely with irradiation dose, both in animals treated with CONV-RT and FLASH-RT. Acute dermal side effects were mild, but only a small proportion of the animals were alive for evaluation of those side effects.ConclusionThe dose response was similar for CONV-RT and FLASH-RT in the present model. Tumor size upon the time of euthanasia correlated inversely with the irradiation dose.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Comparable survival in rats with intracranial glioblastoma irradiated with single-fraction conventional radiotherapy or FLASH radiotherapy

Liljedahl,

Konradsson,

Linderfalk

et al. 2024

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…The early identification of neurocognitive complications post-SRS treatment as well as an improved ability to predict who might develop neurocognitive effects is therefore a key research priority. 15 , 16 …”

Section: The Need For a Better Biomarkermentioning

confidence: 99%

A brain metastasis liquid biopsy: Where are we now?

Robinson,

de Boisanger,

Pearl

et al. 2024

Neuro-Oncology Advances

View full text Add to dashboard Cite

Brain metastases remain a challenging and feared complication for patients with cancer and research in this area has lagged behind research into metastases to other organs. Due to their location and the risks associated with neurosurgical biopsies, the biology underpinning brain metastases response to treatment and evolution over time remains poorly understood. Liquid biopsies are proposed to overcome many of the limitations present with tissue biopsies, providing a better representation of tumour heterogeneity, facilitating repeated sampling, and providing a non-invasive assessment of tumour biology. Several different liquid biopsy approaches have been investigated including circulating tumour cells, circulating tumour DNA, extracellular vesicles, and tumour educated platelets; however, these have generally been less effective in assessing brain metastases compared to metastases to other organs requiring improved techniques to investigate these approaches, studies combining different liquid biopsy approaches and/or novel liquid biopsy approaches. Through this review we highlight the current state of the art and define key unanswered questions related to brain metastases liquid biopsies.

show abstract

“…While CuES may be effective at targeting glioma and glioblastoma cells, the effect it has on the surrounding parenchyma needs to be considered. An ideal treatment would target tumor cells while leaving the surrounding tissue minimally affected, especially in the brain where treatment such as radiation therapy has been linked to oxidative stress and cognitive dysfunction (Soffietti et al, 2023;Yoo et al, 2023). Gliomas are intermixed with neurons and astrocytes-cell types that have previously been shown to be vulnerable to copper toxicity and dyshomeostasis Gromadzka et al, 2020;Hwang et al, 2014;Pal & Prasad, 2014).…”

Section: Introductionmentioning

confidence: 99%

Copper induces neuron‐sparing, ferredoxin 1‐independent astrocyte toxicity mediated by oxidative stress

Gale,

Hartnett‐Scott,

Ross

et al. 2023

Journal of Neurochemistry

View full text Add to dashboard Cite

Copper is an essential enzyme cofactor in oxidative metabolism, anti‐oxidant defenses, and neurotransmitter synthesis. However, intracellular copper, when improperly buffered, can also lead to cell death. Given the growing interest in the use of copper in the presence of the ionophore elesclomol (CuES) for the treatment of gliomas, we investigated the effect of this compound on the surround parenchyma—namely neurons and astrocytes in vitro. Here, we show that astrocytes were highly sensitive to CuES toxicity while neurons were surprisingly resistant, a vulnerability profile that is opposite of what has been described for zinc and other toxins. Bolstering these findings, a human astrocytic cell line was similarly sensitive to CuES. Modifications of cellular metabolic pathways implicated in cuproptosis, a form of copper‐regulated cell death, such as inhibition of mitochondrial respiration or knock‐down of ferredoxin 1 (FDX1), did not block CuES toxicity to astrocytes. CuES toxicity was also unaffected by inhibitors of apoptosis, necrosis or ferroptosis. However, we did detect the presence of lipid peroxidation products in CuES‐treated astrocytes, indicating that oxidative stress is a mediator of CuES‐induced glial toxicity. Indeed, treatment with anti‐oxidants mitigated CuES‐induced cell death in astrocytes indicating that oxidative stress is a mediator of CuES‐induced glial toxicity. Lastly, prior induction of metallothioneins 1 and 2 in astrocytes with zinc plus pyrithione was strikingly protective against CuES toxicity. As neurons express high levels of metallothioneins basally, these results may partially account for their resistance to CuES toxicity. These results demonstrate a unique toxic response to copper in glial cells which contrasts with the cell selectivity profile of zinc, another biologically relevant metal.image

show abstract

Neurotoxicity from Old and New Radiation Treatments for Brain Tumors

Cited by 6 publications

References 134 publications

Comparable survival in rats with intracranial glioblastoma irradiated with single-fraction conventional radiotherapy or FLASH radiotherapy

Comparable survival in rats with intracranial glioblastoma irradiated with single-fraction conventional radiotherapy or FLASH radiotherapy

A brain metastasis liquid biopsy: Where are we now?

Copper induces neuron‐sparing, ferredoxin 1‐independent astrocyte toxicity mediated by oxidative stress

Contact Info

Product

Resources

About