Synchrotron radiation-based experimental determination of the optimal energy for cell radiotoxicity enhancement following photoelectric effect on stable iodinated compounds

This study was designed to experimentally evaluate the optimal X-ray energy for increasing the radiation energy absorbed in tumours loaded with iodinated compounds, using the photoelectric effect. SQ20B human cells were irradiated with synchrotron monochromatic beam tuned at 32.8, 33.5, 50 and 70 keV. Two cell treatments were compared to the control: cells suspended in 10 mg ml1 of iodine radiological contrast agent or cells pre-exposed with 10 mM of iodo-desoxyuridine (IUdR) for 48 h. Our radiobiological end point was clonogenic cell survival. Cells irradiated with both iodine compounds exhibited a radiation sensitisation enhancement. Moreover, it was energy dependent, with a maximum at 50 keV. At this energy, the sensitisation calculated at 10% survival was equal to 2.03 for cells suspended in iodinated contrast agent and 2.60 for IUdR. Cells pretreated with IUdR had higher sensitisation factors over the energy range than for those suspended in iodine contrast agent. Also, their survival curves presented no shoulder, suggesting complex lethal damages from Auger electrons. Our results confirm the existence of the 50 keV energy optimum for a binary therapeutic irradiation based on the presence of stable iodine in tumours and an external irradiation. Monochromatic synchrotron radiotherapy concept is hence proposed for increasing the differential effect between healthy and cancerous tissue irradiation

Validation of distinct pathogenic patterns in a cohort of membranoproliferative glomerulonephritis patients by cluster analysis

Background: A novel data-driven cluster analysis identified distinct pathogenic patterns in C3-glomerulopathies and immune complex-mediated membranoproliferative glomerulonephritis. Our aim was to replicate these observations in an independent cohort and elucidate disease pathophysiology with detailed analysis of functional complement markers. ----- Methods: A total of 92 patients with clinical, histological, complement and genetic data were involved in the study, and hierarchical cluster analysis was done by Ward method, where four clusters were generated. ----- Results: High levels of sC5b-9 (soluble membrane attack complex), low serum C3 levels and young age at onset (13 years) were characteristic for Cluster 1 with a high prevalence of likely pathogenic variations (LPVs) and C3 nephritic factor, whereas for Cluster 2-which is not reliable because of the small number of cases-strong immunoglobulin G staining, low C3 levels and high prevalence of nephritic syndrome at disease onset were observed. Low plasma sC5b-9 levels, decreased C3 levels and high prevalence of LPV and sclerotic glomeruli were present in Cluster 3, and patients with late onset of the disease (median: 39.5 years) and near-normal C3 levels in Cluster 4. A significant difference was observed in the incidence of end-stage renal disease during follow-up between the different clusters. Patients in Clusters 3-4 had worse renal survival than patients in Clusters 1-2. ----- Conclusions: Our results confirm the main findings of the original cluster analysis and indicate that the observed, distinct pathogenic patterns are replicated in our cohort. Further investigations are necessary to analyse the distinct biological and pathogenic processes in these patient groups

C4 nephritic factor in patients with immune-complex-mediated membranoproliferative glomerulonephritis and C3-glomerulopathy

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