Szereotaktikus sugársebészeti kezelés szövődményeinek és azok csökkentése lehetőségének vizsgálata = Research on neuroprotective agent for radiation injury caused by stereotactic radiosurgery

Klinikai kutatásainkban az agytumorban szenvedő betegek adatait, új kezelési eljárások eredményeit dolgoztuk fel. Kísérleteinkben CT-3D sztereotaktikus, majd még kisebb volumenű fokális patkány-agy besugárzást (RT) végeztünk 10 Gy-vel növelt dózisokkal 30-120 Gy-ig. A RT-tervezés, dozimetriai mérések, a RT minőség-ellenőrzése a humán kezelés magas színvonalán történt. A neuro-funkcionális vizsgálatok, az MR morphológiai és a hisztológiai elváltozások szoros összefüggést mutattak a RT dózisával és a posztirradiációs idővel. Ezen kísérletek alapján (módszer, dózis (40 Gy)) több sugárvédő anyag tesztelését végeztük, melyek közül 3 bizonyult további kutatásra érdemesnek. A Copaxon (eredetileg tervezett), a más agyi kórképekben aktív L-alpha glycerylphosphorylcholine (GPC) és egy bizonyos kinurénsav származék (KSZ). Az egyes szerek neuro-radioprotektív hatása pathomechanizmusának detektálására immunhisztokémiai és molekuláris biológiai vizsgálatokat végeztünk . Így proteomikai és genomikai értékeléssel derítettünk fényt a GPC és KSZ proinflammatorikus aktiváció csökkentő szerepére. A széleskörű interdiszciplináris együttműködésben végzett munka megteremtette hazánkban a terápiához kapcsolódó sugárbiológiai műhely alapjait. Az általunk bevezetett saccharomyces törzsek-, szövettenyészetek-, zebradánó hal-embrió-, és kisállat kísérleti rendszerek hierarchikus kialakítása a sugárhatás-, -sugárhatás-módosítás, ill. új sugárminőségek hatékony preklinikai kutatását teszi lehetővé. | Clinical data and results of new therapeutic approaches were studied in brain tumor patients. In the preclinical work stereotactic foton and focal electron irradiation of the rat brain were performed with dose escalation (10 Gy steps) from 30 to 120Gy using special techniques. The treatment planning, dosimetry, and portal imaging closely followed the QA procedures of human radiotherapy. Postirradiation neurofunctional tests, MRI and histological examination confirmed dose and time dependent radiation brain injury. On that basis the time frame, radiation technique and dose (40Gy) could be defined for reasearch on radiation protectors. Three of the tested drugs warranted further investigation: glatiramer acetate, L-alpha glycerylphosphorylcholine (GPC) and a synthetic kynurenic acid (SK). Research (proteomics, genetics, immunhistochemistry) on the pathomechanism of radiation damage and its modification revealed the reductive effect of proinflammatory activation both by GPC and SK. The wide interdisciplinary and inter-institutionally collaboration established for the current project, provides further the basis for therapy associated extended radiobiological research. The hierarchical organisation of different biological systems (saccharomyces strains, cell cultures, zebrafish embrios, small animals – sensitive examinations and biological end points) provides reliable and effective methods for preclinical investigation on radiation effects, and radiation modifyers

Individual positioning: a comparative study of adjuvant breast radiotherapy in the prone versus supine position

PURPOSE: To study breast radiotherapy in the prone vs. supine positions through dosimetry and clinical implementation. METHODS AND MATERIALS: Conformal radiotherapy plans in 61 patients requiring only breast irradiation were developed for both the prone and supine positions. After evaluation of the of the first 20 plan pairs, the patients were irradiated in the prone or supine position in a randomized fashion. These cases were analyzed for repositioning accuracy and skin reactions related to treatment position and patient characteristics. RESULTS: The planning target volume covered with 47.5-53.5 Gy in the prone vs. the supine position was 85.1% +/- 4.2% vs. 89.2 +/- 2.2%, respectively (p < 0.0001). Radiation exposure of the ipsilateral lung, expressed in terms of the mean lung dose and the V(20Gy), was dramatically lower in the prone vs. supine position (p < 0.0001), but the doses to the heart did not differ. There was no difference in the need to correct positioning during radiotherapy, but the extent of displacement was significantly higher in the prone vs. supine position (p = 0.021). The repositioning accuracy in the prone position exhibited an improvement over time and did not depend on any patient-related parameters. Significantly more radiodermatitis of Grade 1-2 developed following prone vs. supine irradiation (p = 0.025). CONCLUSIONS: Conformal breast radiotherapy is feasible in the prone position. Its primary advantage is the substantially lower radiation dose to the ipsilateral lung. The higher dose inhomogeneity and increased rate of Grade 1-2 skin toxicity, however, may be of concern

Improved FBX chemical dosimeter system with enhanced radiochemical yield for reference dosimetry in radiobiology and radiotherapy research

Radiation dosimetry plays important role in the reproducibility of radiobiology experiments, in the replicability of results, as well as in the successful and safe use of radiotherapy procedures. The consistency and accuracy of the applied dosimetry methods pre-define the outcomes of these applications. This paper presents a version of the well-known ferrous sulphate – benzoic acid – xylenol orange (FBX) chemical dosimeter with improved sensitivity, accuracy and precision. Sensitivity is increased due to a slight modification in composition and the preparation procedures. We use stock solutions for the preparation of the dosimeter solution, which consists of 1 mM ferrous sulphate and 16 mM benzoic acid with 0.25 mM xylenol orange added post-irradiation. The nonlinear response to the absorbed dose of this system is eliminated by the increased ferrous sulphate concentration, permitting the calculation of the absorbed dose by a linear relationship between the absorbed dose and the optical absorbance of the solution. The measured chemical yield of our dosimeter is 9.08⋅10−6mol/J for 6 MV photon beams and 6.42⋅10−6mol/J for 250 kVp x-rays. This is a 24% enhancement over the original FBX solution, which permits a finer dose resolution. The accuracy and precision of our method is assured by a well-designed and consistently used practice. A custom designed multipurpose PMMA slab phantom was used for irradiation in reference conditions. This phantom can be used for irradiation in reference conditions of dosimetric solutions, dosimetric films and chemical or biological samples. The combined standard uncertainty of this system is 1.12%, which can be improved by using an appropriate temperature correction factor. Furthermore, a working protocol has been established which allows dosimetry measurements using less than 1 mL dosimetric solutions

Application of Lacunarity for Quantification of Single Molecule Localization Microscopy Images

The quantitative analysis of datasets achieved by single molecule localization microscopy is vital for studying the structure of subcellular organizations. Cluster analysis has emerged as a multi-faceted tool in the structural analysis of localization datasets. However, the results it produces greatly depend on the set parameters, and the process can be computationally intensive. Here we present a new approach for structural analysis using lacunarity. Unlike cluster analysis, lacunarity can be calculated quickly while providing definitive information about the structure of the localizations. Using simulated data, we demonstrate how lacunarity results can be interpreted. We use these interpretations to compare our lacunarity analysis with our previous cluster analysis-based results in the field of DNA repair, showing the new algorithm’s efficiency

Lipidomic analysis reveals a radiosensitizing role of gamma-linolenic acid in glioma cells

Previous studies have demonstrated that gamma-linolenic acid (GLA) is effective against glioma cells under both in vitro and in vivo conditions. In the present study we determined how GLA alone or in combination with irradiation alters the fatty acid (FA) and lipid profiles, the lipid droplet (LD) content, the lipid biosynthetic gene expression and the apoptosis of glioma cells. In GLA-treated cells direct correlations were found between the levels of various FAs and the expression of the corresponding FA biosynthetic genes. The total levels of saturated and monosaturated FAs decreased in concert with the down-regulation of FASN and SCD1 gene expression. Similarly, decreased FADS1 gene expression was paralleled by lowered arachidonic acid (20:4 n-6) and eicosapentaenoic acid (20:5 n-3) contents, while the down-regulation of FADS2 expression was accompanied by a diminished docosahexaenoic acid (22:6 n-3) content. Detailed mass spectrometric analyses revealed that individual treatments gave rise to distinct lipidomic fingerprints. Following uptake, GLA was subjected to elongation, resulting in dihomo-gamma-linolenic acid (20:3 n-6, DGLA), which was used for the synthesis of the LD constituent triacylglycerols and cholesteryl esters. Accordingly, an increased number of LDs were observed in response to GLA administration after irradiation. GLA increased the radioresponsiveness of U87 MG cells, as demonstrated by an increase in the number of apoptotic cells determined by FACS analysis. In conclusion, treatment with GLA increased the apoptosis of irradiated glioma cells, and GLA might therefore increase the therapeutic efficacy of irradiation in the treatment of gliomas