Activation of the Fanconi anemia/BRCA pathway at low doses of ionization radiation

Bosch, Pau Castillo; Bogliolo, Massimo; Surrallés, Jordi

doi:10.1016/j.mrgentox.2015.06.010

Cited by 4 publications

(2 citation statements)

References 25 publications

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“…Fanconi anemia is an autosomal recessive or X-linked genetic disorder characterized by chromosome fragility, congenital malformations, and cancer susceptibility. FA patients are usually extremely sensitive to irradiation and radiotherapy 46 . Tropomyosin gene silencing was associated with radioresistance of glioma cells 47 ; higher MKNK2 expression was detected in glioblastoma cells, compared with other brain tumor cell subtypes 48 .…”

Section: Discussionmentioning

confidence: 99%

Association between microRNAs 10b/21/34a and acute toxicity in glioblastoma patients treated with radiotherapy and temozolomide

Stepanović

Nikitović

Stanojković

et al. 2022

Sci Rep

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A personalized approach to chemoradiation is important in reducing its potential side effects and identifying a group of patients prone to toxicity. MicroRNAs have been shown to have a predictive potential for radiotoxicity. The goal of the study was to test if levels of miRNA in peripheral blood mononuclear cells of glioblastoma patients are associated with toxicity and to identify the peak time point for toxicity. MicroRNA-10b/21/34a levels were measured in 43 patients with and without toxicity, at baseline, at the 15th, and at the 30th fraction by Real-Time quantitative Polymerase Chain Reaction. MicroRNA-10b/21 levels increased with toxicity grade (p = 0.014; p = 0.013); miR-21/34a levels were significantly different between patients with and without toxicity at the 15th fraction (p = 0.030; p = 0.045), while miR-34a levels significantly changed during treatment (p < 0.001). All three miRNAs showed a significantly high positive correlation with one another. MiR-34a might be considered as a predictive factor for toxicity due to its changes during treatment, and differences between the groups with and without toxicity; miR-10b might be used to predict toxicity; miR-10b/21 might be used for predicting the grade of toxicity in GB patients.

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Section: Discussionmentioning

confidence: 99%

Association between microRNAs 10b/21/34a and acute toxicity in glioblastoma patients treated with radiotherapy and temozolomide

Stepanović

Nikitović

Stanojković

et al. 2022

Sci Rep

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“…Predictably, recipient cells represented a dominant fraction in transplanted animals and indicate the intended loss of irradiated carrier cells as well as vector delivery to endogenous targets in the bone marrow. To further boost the percentage of phenotypically corrected Fancc –/– HSPCs, we used serial low doses of post-transplant ionizing radiation [24]. Remarkably, the 2° TD Fancc –/– KO animals showed a consistently expanding population of GFP-FANCC expressing cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

Phenotypic correction of Fanconi anemia cells in the murine bone marrow after carrier cell mediated delivery of lentiviral vector

2016

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Fanconi anemia (FA) is an autosomal-recessive disorder associated with hematopoietic failure and it is a candidate for hematopoietic stem cell (HSC)-directed gene therapy. However, the characteristically reduced HSC numbers found in FA patients, their ineffective mobilization from the marrow, and re-oxygenation damage during ex vivo manipulation have precluded clinical success using conventional in vitro approaches. We previously demonstrated that lentiviral vector (LV) particles reversibly attach to the cell surface where they gain protection from serum complement neutralization. We reasoned that cellular delivery of LV to the bone marrow niche could avoid detrimental losses during FA HSC mobilization and in vitro modification. Here, we demonstrate that a VSV-G pseudotyped lentivector, carrying the FANCC transgene, can be transmitted from carrier to bystander cells. In cell culture and transplantation models of FA, we further demonstrate that LV carrier cells migrate along SDF-1α gradients and transfer vector particles that stably integrate and phenotypically correct the characteristic DNA alkylator sensitivity in murine and human FA-deficient target bystander cells. Altogether, we demonstrate that cellular homing mechanisms can be harnessed for the functional phenotype correction in murine FA hematopoietic cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0431-z) contains supplementary material, which is available to authorized users.

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Compromised repair of radiation-induced DNA double-strand breaks in Fanconi anemia fibroblasts in G2

et al. 2020

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Activation of the Fanconi anemia/BRCA pathway at low doses of ionization radiation

Cited by 4 publications

References 25 publications

Association between microRNAs 10b/21/34a and acute toxicity in glioblastoma patients treated with radiotherapy and temozolomide

Association between microRNAs 10b/21/34a and acute toxicity in glioblastoma patients treated with radiotherapy and temozolomide

Phenotypic correction of Fanconi anemia cells in the murine bone marrow after carrier cell mediated delivery of lentiviral vector

Compromised repair of radiation-induced DNA double-strand breaks in Fanconi anemia fibroblasts in G2

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