Radiotherapy for Graves’ disease. The possible role of low-dose radiotherapy

Arenas, Meritxell; Sabater, S.; Jiménez, P.C. Lara; Rovirosa, Á.; Biete, Albert; Linares, Victòria; Bellés, Montserrat; Panés, J

doi:10.1016/j.rpor.2016.02.001

Cited by 5 publications

(3 citation statements)

References 55 publications

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“…The response to LD-RT is regulated by a sequence of interactions between leukocytes and the endothelium. The mechanisms governing this response include decreased leukocyte-endothelial cell adhesion, induction of cell death by inflammatory infiltration, and decreased expression of adhesion molecules (P-, L-, E-selectins, ICAM-1, VCAM-1) [32–34].…”

Section: Discussionmentioning

confidence: 99%

Human placenta-derived mesenchymal stem cells ameliorate orbital adipogenesis in female mice models of Graves’ ophthalmopathy

et al. 2019

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Background: Graves' ophthalmopathy (GO) is a complication of Graves' disease (GD), in which orbital connective tissues become inflamed and increase in volume and orbital fibroblasts within the orbital fat and extraocular muscles differentiate into adipocytes in vitro when stimulated by hormones, several cytokines, and growth factors including TSH, IGF-1, IL-1, interferon γ, and platelet-derived growth factor. Human placental mesenchymal stem cells (hPMSCs) have immunomodulatory effects in disease pathogenesis. Although a number of studies have reported that hPMSCs can elicit therapeutic effects, these are not sufficient. Therefore, we constructed a GO animal model in order to find out the hPMSCs recovery effect. Methods: We investigated their anti-adipogenic effects in in vitro cultures of orbital fibroblasts established from GO patients. Primary orbital fibroblasts were exposed to differentiation medium for 10 days. After being co-cultured with hPMSCs, the characteristics of orbital fibroblast were determined by Oil Red O stain and real-time PCR. Then, we explored the in vivo regulatory effects of hPMSCs in an experimental mouse model of GO. We developed the GO mouse model using immunization by leg muscle electroporation of pTriEx1.1Neo-hTSHR A-subunit plasmid. Human PMSC injection was performed into the left orbit. We also analyzed the effects of hPMSCs in the GO animal model. Result: We found that hPMSCs inhibited a lipid accumulation and activated factors, such as ADIPONECTIN, PPARγ, C/EBPα, and TGFβ2 genes in adipogenesis-induced primary orbital fibroblasts from GO patients. Moreover, hPMSCs were highly effective at ameliorating adipogenesis in the orbital tissue of the model. Conclusion: These data indicate that hPMSCs recover pathogenic activation of orbital fibroblasts in animals undergoing experimental GO and confirm the feasibility of applying hPMSCs as a novel treatment for GO patients.

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Section: Discussionmentioning

confidence: 99%

Human placenta-derived mesenchymal stem cells ameliorate orbital adipogenesis in female mice models of Graves’ ophthalmopathy

et al. 2019

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“…In group A, the intermittent group, the cells were irradiated in 10 fractions with a dose of 30 mGy each time. The time interval between two irradiations was 24 h [38][39][40]. After that, the cells were irradiated with 2 Gy high-dose ionizing radiation (HDIR).…”

Section: Ldir Strategymentioning

confidence: 99%

Effect of intermittent low-dose irradiation on the radiotherapy efficiency for MDA-MB-231 human breast adenocarcinoma cell line

et al. 2019

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Introduction Despite the fact that high-dose radiotherapy is a main therapeutic modality in cancer treatment, recent evidence suggests that it might confer radioresistance. Hyper-radiosensitivity (HRS) is one of the important biological effects of low-dose ionizing radiation (LDIR) in mammalian cell lines. LDIR is considered as a promising assistant method of clinical cancer therapy. The purpose of this study was to evaluate the efficiency of intermittent LDIR followed by a high-dose radiation therapeutic approach compared with the conventional high-dose radiotherapy in the breast cancer MDA-MB-231 cell line. Materials and methods MDA-MB-231 cells were divided into four experimental groups-intermittent LDIR group: cells were irradiated for 10 fractions with a dose of 30 mGy at each time (interval 24 h) followed by 2 Gy, single LDIR group: cells have accepted a dose of 300 mGy LDIR and after 24 h a high dose of 2 Gy, high-dose ionizing radiation (HDIR) group: cells were exposed to a single high dose of 2 Gy, and control group. Results MTT and flow cytometry assay were used for cell proliferation and apoptosis after 24 h of the last irradiation dose (2 Gy). Also, we examined p21 and cespase3 gene expression by RT-qPCR. We observed that intermittent LDIR significantly increased the killing effect of radiotherapy (viability, 71.95 + 1.25%) (P < 0.01). The apoptosis is proposed to increase up to 32.55 + 0.07% in the intermittent LDIR that was markedly higher than those of other groups (P < 0.01). Caspase3 gene expression in this group was the highest (5.2-fold), 4.26-fold and 1.42-fold in single LDIR and HDIR, respectively. It was observed that the intermittent LDIR potentially decreases p21 expression in comparison with the challenge dose of 2 Gy (0.681-fold). Conclusion LDIR may result in HRS through a concurrent increase of apoptosis and a significant decrease in cell viability. The therapeutic effects of this approach should be further investigated in animal models.

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“…The rationale for using RT in GO is based on its modulating role of inflammatory response in irradiated tissues. Therefore this could be considering an alternative to systemic anti-inflammatory therapies 7 . Although RT induces the production of pro-inflammatory cytokines and leads to an inflammatory response in irradiated tissues, however, RT administrated at low doses (LD-RT) modulates the inflammatory response, producing an anti-inflammatory effect.…”

Section: Radiotherapymentioning

confidence: 99%

Review of the treatment of Graves’ ophthalmopathy: The role of the new radiation techniques

Miguel

Arenas

Carmona

et al. 2018

Saudi Journal of Ophthalmology

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Graves ophthalmopathy (GO) is an autoimmune disorder and the most frequent extrathyroidal manifestation of Graves' disease. GO is an inflammatory process leading to an increased volume of the extraocular muscles and orbital connective and adipose tissues associated with multiple histopathological changes. Despite recent progress in the understanding of its pathogenesis, GO often remains a major diagnostic and therapeutic challenge. It has become increasingly important to classify patients into categories based on disease severity and activity. Low doses of radiotherapy (RT) have demonstrated a benefit in the treatment of moderate-to-severe GO with very few side effects. New RT techniques deliver a more conformal dose distribution to the target and decrease the dose to normal healthy tissue minimizing the risk of side effects. In this review we briefly analyzed the pathogenesis of GO and discussed the most relevant therapeutic approaches, with particular emphasis in the new RT technics. Appropriately designed and powered clinical studies are necessary to determine the most effective treatment with the lowest risk of side effects.

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Radiotherapy for Graves’ disease. The possible role of low-dose radiotherapy

Cited by 5 publications

References 55 publications

Human placenta-derived mesenchymal stem cells ameliorate orbital adipogenesis in female mice models of Graves’ ophthalmopathy

Human placenta-derived mesenchymal stem cells ameliorate orbital adipogenesis in female mice models of Graves’ ophthalmopathy

Effect of intermittent low-dose irradiation on the radiotherapy efficiency for MDA-MB-231 human breast adenocarcinoma cell line

Review of the treatment of Graves’ ophthalmopathy: The role of the new radiation techniques

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