BackgroundWe have recently shown that radiotherapy may not only be a successful local and regional treatment but, when combined with MSCs, may also be a novel systemic cancer therapy. This study aimed to investigate the role of exosomes derived from irradiated MSCs in the delay of tumor growth and metastasis after treatment with MSC + radiotherapy (RT).MethodsWe have measured tumor growth and metastasis formation, of subcutaneous human melanoma A375 xenografts on NOD/SCID-gamma mice, and the response of tumors to treatment with radiotherapy (2 Gy), mesenchymal cells (MSC), mesenchymal cells plus radiotherapy, and without any treatment. Using proteomic analysis, we studied the cargo of the exosomes released by the MSC treated with 2 Gy, compared with the cargo of exosomes released by MSC without treatment.ResultsThe tumor cell loss rates found after treatment with the combination of MSC and RT and for exclusive RT, were: 44.4% % and 12,1%, respectively. Concomitant and adjuvant use of RT and MSC, increased the mice surviving time 22,5% in this group, with regard to the group of mice treated with exclusive RT and in a 45,3% respect control group. Moreover, the number of metastatic foci found in the internal organs of the mice treated with MSC + RT was 60% less than the mice group treated with RT alone. We reasoned that the exosome secreted by the MSC, could be implicated in tumor growth delay and metastasis control after treatment.ConclusionsOur results show that exosomes derived form MSCs, combined with radiotherapy, are determinant in the enhancement of radiation effects observed in the control of metastatic spread of melanoma cells and suggest that exosome-derived factors could be involved in the bystander, and abscopal effects found after treatment of the tumors with RT plus MSC. Radiotherapy itself may not be systemic, although it might contribute to a systemic effect when used in combination with mesenchymal stem cells owing the ability of irradiated MSCs-derived exosomes to increase the control of tumor growth and metastasis.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0867-0) contains supplementary material, which is available to authorized users.

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BACKGROUND: The objective of the present study was to analyse the kinetics of photodegradation of three antibiotics from the tetracycline group (tetracycline (TC), chlortetracycline (CTC) and oxytetracycline (OTC)), and the influence of the operational variables: (1) initial concentration; (2) initial solution pH; (3) addition of hydrogen peroxide; (4) effect of the aqueous matrix (ultrapure water (UW), surface water (SW), groundwater (GW) and waste-water (WW) on these processes. RESULTS:The results obtained show that the photodegradation of the three tetracyclines fits first-order kinetics. The degradation rate depends on initial concentration and pH. Low concentrations of H 2 O 2 markedly increased the efficacy of TC photolysis, with a linear relationship between degradation rate and H 2 O 2 concentration for concentrations of 2 × 10 −2 to 2 × 10 −1 mmol L −1 . The photodegradation rate is higher in real waters than in ultrapure water. The toxicity of oxidation by-products formed during tetracyclines photooxidation process was determined by a bioluminescent test, showing that toxicity increases during the process.CONCLUSIONS: Oxidation of tetracyclines by UV radiation alone is slow due to the low quantum yield determined. The UV/H 2 O 2 process is an interesting alternative to oxidise tetracyclines in aqueous solution, because this process decreases total organic carbon concentration and tetracyclines oxidation by-products toxicity.

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