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- Langen, Britta, et al.
(författare)
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Non-targeted transcriptomic effects upon thyroid irradiation: similarity between in-field and out-of-field responses varies with tissue type
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Non-targeted effects can induce responses in tissues that have not been exposed to ionizing radiation. Despite their relevance for risk assessment, few studies have investigated these effects in vivo. In particular, these effects have not been studied in context with thyroid exposure, which can occur e.g. during irradiation of head and neck tumors. To determine the similarity between in-field and out-offield responses in normal tissue, we used a partial body irradiation setup with female mice where the thyroid region, the thorax and abdomen, or all three regions were irradiated. After 24h, transcriptional regulation in the kidney cortex, kidney medulla, liver, lungs, spleen, and thyroid was analyzed using microarray technology. Thyroid irradiation resulted in transcriptional regulation in the kidney medulla and liver that resembled regulation upon direct exposure of these tissues regarding both strength of response and associated biological function. The kidney cortex showed fewer similarities between the setups, while the lungs and spleen showed little similarity between in-field and out-of-field responses. Interestingly, effects were generally not found to be additive. Future studies are needed to identify the molecular mechanisms that mediate these systemic effects, so that they may be used as targets to minimize detrimental side effects in radiotherapy.
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- Langen, Britta, et al.
(författare)
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Thyroid irradiation and non-targeted effects: in-field and out-of-field responses on the transcriptomic level show tissue-specific similarity
- 2016
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Ingår i: SweRays Workshop, Stockholm, Sweden, Aug 25-26.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Radiation exposure can result in non-targeted effects that strongly influence cellular responses in non-irradiated tissues. However, radiotherapy planning does not consider out-of-field effects in current risk assessment, because knowledge of these effects is still scarce. Non-targeted effects from the thyroid are of particular concern, since it is a major regulatory gland and often subject to exposure during irradiation of e.g. head and neck, lung and breast tumors. The aim of this study was to characterize in-field and out-of-field responses on the transcriptomic level in vivo after thyroid irradiation. Methods: Anaesthetized female BALB/c nude mice were irradiated with 2 Gy from 4 MV photon beams in a partial body irradiation setup: the thyroid region, the thorax and abdomen, or all three regions combined (n=3/group). Control mice (n=5) were anaesthetized but not irradiated. Mice were killed after 24h and the kidneys, liver, lungs, spleen, and thyroid were sampled. Expression microarray analysis was performed on total RNA extracted from tissue samples. Results: Thyroid irradiation induced complex gene regulation responses in kidney medulla and liver that were highly similar to direct exposure of these tissues. In contrast, kidney cortex showed a lesser degree of similarity between setups, while lungs and spleen exhibited only marginal out-of-field responses. Interestingly, non-targeted effects and in-field responses did not appear to show simple additive behavior. Conclusions: Thyroid exposure can induce significant responses in other tissues similar to direct irradiation, but these non-targeted effects show tissue-specificity. The underlying mechanisms may yield molecular targets for minimizing systemic side-effects in radiotherapy.
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- Sandblom, Viktor, 1987, et al.
(författare)
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Combination therapy of medullary thyroid cancer using radiation and vandetanib
- 2017
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. Annual Congress of the European Association of Nuclear Medicine October 21 – 25, 2017 Vienna, Austria. Vol. 44, Suppl. 2. EP-0792. - : Springer. - 1619-7070 .- 1619-7089.
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Konferensbidrag (refereegranskat)abstract
- INTRODUCTION Most patients diagnosed with medullary thyroid cancer (MTC) present with metastatic disease. MTC are rare neuroendocrine tumours that occur either sporadically or in a hereditary form. Surgical resection of the thyroid gland followed by external beam radiotherapy (EBRT) or the use of tyrosine kinase inhibitors are current clinical methods for management of MTC. Unfortunately, the 10-year survival for patients with metastatic disease is only about 40%. However, many MTC tumours overexpress somatostatin receptors as molecular targets. Therefore, one option for patients with MTC is systemic treatment with radiolabelled somatostatin analogues (e.g. 177Lu-octreotate) that bind with high affinity and specificity to somatostatin receptors on the tumour cells. In addition, the tyrosine kinase inhibitor vandetanib has recently been approved for single-agent treatment of MTC by the U.S. Food and Drug Administration (FDA). The aim of this study was to investigate the potential synergistic effect of combining irradiation and vandetanib for treatment of MTC. SUBJECTS & METHODS BALB/c nude mice were transplanted with patient-derived MTC cells (GOT2). When developed tumours reached a volume of about 500 mm3, the mice were treated with EBRT, vandetanib or a combination of both. The radiation dose and the amount of vandetanib were chosen to give moderate effect as single treatment to enable detection of any increased effect from the combination. Tumour volume was followed and compared with that in untreated mice. RESULTS We found that the largest treatment effect over time was seen for the animals receiving a combination of both EBRT and vandetanib. Given as single-agent treatment, EBRT and vandetanib resulted in a reduction in tumour size or in tumour growth arrest. For example, at two weeks after start of treatment, the tumour volume was reduced by 64%, 52%, and 73% compared with the untreated control group, for the animals treated with single EBRT, single vandetanib, and the combination, respectively. CONCLUSION The results indicate that an additive or even synergistic effect could be achieved when combining irradiation with vandetanib for treatment of patients with MTC. Further studies are needed to investigate the possibility of using 177Lu-octreotate for treatment of MTC, both as single-agent treatment or in combination with vandetanib.
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