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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Agreement on the assessment of metastatic spine instability is moderate. The SINS can help improve communication among clinicians in oncology care.

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BackgroundLung cancer remains one of the most prevalent forms of cancer. Radiotherapy, with or without other therapeutic modalities, is an effective treatment. Our objective was to report on the use of radiotherapy for lung cancer, its variability in our region, and to compare our results with the previous study done in 2004 (VARA-I) in our region and with other published data.MethodsWe reviewed the clinical records and radiotherapy treatment sheets of all patients undergoing radiotherapy for lung cancer during 2007 in the 12 public hospitals in Andalusia, an autonomous region of Spain. Data were gathered on hospital, patient type and histological type, radiotherapy treatment characteristics, and tumor stage.Results610 patients underwent initial radiotherapy. 37% of cases had stage III squamous cell lung cancer and were treated with radical therapy. 81% of patients with non-small and small cell lung cancer were treated with concomitant chemo-radiotherapy and the administered total dose was ≥ 60 Gy and ≥ 45 Gy respectively. The most common regimen for patients treated with palliative intent (44.6%) was 30 Gy. The total irradiation rate was 19.6% with significant differences among provinces (range, 8.5-25.6%; p < 0.001). These differences were significantly correlated with the geographical distribution of radiation oncologists (r = 0.78; p = 0.02). Our results were similar to other published data and previous study VARA-I.ConclusionsOur results shows no differences according to the other published data and data gathered in the study VARA-I. There is still wide variability in the application of radiotherapy for lung cancer in our setting that significantly correlates with the geographical distribution of radiation oncologists.

There is a need to evidence the cost of genetic testing and know their profitability in order to establish criteria for priorizing access to genetic testing for these diseases. We determinated the cost per positive genotyping in 234 index cases with diagnosis of hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), long-QT syndrome (LQTS), or Brugada syndrome (BS). The genetic tests of the most prevalent genes and the estimation of the costs of periodical screening in wildtype relatives (WT) were calculated. A total of 738 individuals (517 HCM, 76 ARVC, 71 LQTS and 74 BS) from 234 probands were genotyped. The savings made by not having to perform the clinical testing of WT relatives exceeded the cost of genotyping for HCM families € +220,710, ARVC families € +9405 and LQTS families € +8362. The balance in BS was negative (€ –25,112). Our data suggests that individuals with conclusive clinical diagnostic of HCM should have a priority to access genetic testing. A positive overall benefit was also demonstrated in ARVC and LQTS

We aim to study the SCN5A gene in a cohort of Brugada syndrome (BS) patients and evaluate the genotype-phenotype correlation. BS is caused by mutations in up to 10 different genes, SCN5A being the most frequently involved. Large genomic rearrangements in SCN5A have been associated with conduction disease, but its prevalence in BS is unknown. Seventy-six non-related patients with BS were studied. Clinical characteristics and family risk profile were recorded. Direct sequencing and multiplex ligation-dependent probe amplification (MLPA) of the SCN5A gene for identification of mutations and larger rearrangements were performed, respectively. Eight patients (10.5%) had point mutations (R27H, E901K, G1743R (detected in three families), V728I, N1443S and E1152X). Patients with mutations had a trend toward a higher proportion of spontaneous type I Brugada electrocardiogram (ECG) (87.5% vs 52.9%, p = 0.06) and had evidence of familial disease (62.5%, vs 23.5%, p = 0.03). The symptoms and risk profile of the carriers were not different from wild-type probands. There were non-significant differences in the prevalence of type I ECG, syncope and history of arrhythmia in carriers of selected polymorphisms. None of the patients had any deletion/duplication in the SCN5A gene. In conclusion, 10.5% of our patients had mutations in the SCN5A gene. Patients with mutations seemed to have more spontaneous type I ECG, but no differences in syncope or arrhythmic events compared with patients without mutations. Larger studies are needed to evaluate the role of polymorphisms in the SCN5A in the expression of the phenotype and prognosis. Large rearrangements were not identified in the SCN5A gene using the MLPA technique.

The observed underuse of radiotherapy in lung cancer in our region should be a matter of concern, given its negative and measurable impact on the survival of the patients.