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Mairani, A.

Publications and source records attributed to Mairani, A..

4 recordsLinked to original sources
bioRxiv2025

High LET Radiation: A Novel Strategy to Overcome Tumor Microtubes -Mediated Radioresistance in Glioblastoma

PurposeTumor cell networks formed by tumor microtubes (TMs) are thought to drive therapy resistance in glioblastoma (GB). X-ray irradiation enhances TM formation, thereby increasing radioresistance. We hypothesize that high linear energy transfer (LET) particle radiotherapy is less affected by TM-mediated resistance due to its reduced reliance on indirect DNA damage. This study explores the impact of LET-induced DNA damage on TMs formation and GB survival Material and MethodsFormation of TMs was investigated in the primary patient derived glioblastoma stem-like cell lines (S24 and T269) irradiated with different LET, ranging from 3 - 107 keV/{micro}m, across dose series (1, 2, 4, 6 Gy) of clinical proton, helium, and carbon ion beams. TM networks and DNA damage patterns, specifically {gamma}H2AX foci, were visualized using fluorescence microscopy. Cell survival was evaluated through clonogenic survival assays. ResultsThe formation of TMs, radiation-induced nuclear DNA damage repair foci, and GB cell survival were correlated with a gradual increase in LET. Consistent with conventional photon/X-rays, low-LET proton irradiation promoted TMs formation in a dose-dependent manner. In contrast, an anti-correlation between LET and TMs induction was found, i.e., a decreased network connectivity with gradual increase of LET and formation of complex DNA damage. Consequently, LET increase correlated with reduced cell survival, with the most pronounced cell killing observed after high-LET carbon irradiation. Moreover, the inverse correlation between LET and TMs density was further confirmed for a broad range of LET modulated within the carbon ion irradiation. ConclusionThis is the first report on the relevance of LET as a novel mean to overcome TMs network-mediated radioresistance in GB, with ramifications for the clinical translation of high-LET particle radiotherapy to further improve outcome in this still devastating disease.

cancer biology↗
bioRxiv2024

Ultra-High Dose Rate Helium Ion Beams: First In Vivo Evidence for Neuroprotective FLASH Effect

Ultra-high dose rate radiotherapy with electrons and protons has shown potential for cancer treatment by effectively targeting tumors while sparing healthy tissues (FLASH effect). This study aimed to investigate the potential FLASH sparing effect of ultra-high-dose rate helium ion irradiation, focusing on acute brain injury and subcutaneous tumor response in a preclinical in vivo setting. Raster-scanned helium ion beams were used to compare the effects of standard dose rate (SDR at 0.2 Gy/s) and FLASH (at 141 Gy/s) radiotherapy on healthy brain tissue. Irradiation-induced brain injury was studied in C57BL/6 mice via DNA damage response, using nuclear {gamma}H2AX as a marker for double-strand breaks (DSB). The integrity of neurovascular and immune compartments was assessed through CD31+ microvascular density and activation of microglia/macrophages. Iba1+ ramified and CD68+ phagocytic microglia/macrophages were quantified, along with the expression of inducible nitric oxide synthetase (iNOS). Tumor response to SDR (0.2 Gy/s) and FLASH (250 Gy/s) radiotherapy was evaluated in A549 carcinoma model, using tumor volume and Kaplan-Meier survival as endpoints. The results showed that helium FLASH radiotherapy significantly reduced acute brain tissue injury compared to SDR, evidenced by lower levels of DSB and preserved neurovascular endothelium. Additionally, FLASH radiotherapy reduced neuroinflammatory signals compared to SDR, as indicated by fewer CD68+ iNOS+ microglia/macrophages. FLASH radiotherapy achieved tumor control comparable to that of SDR radiotherapy. This study is the first to report the FLASH sparing effect of raster scanning helium ion radiotherapy in vivo, highlighting its potential for neuroprotection and effective tumor control.

cell biology↗
bioRxiv2020

Carbon ion dosimetry on a fluorescent nuclear track detector using widefield microscopy

Fluorescent nuclear track detectors (FNTD) are solid-state dosimeters used in a wide range of dosimetric and biomedical applications in research worldwide. FNTDs are a core but currently underutilized dosimetry tool in the field of radiation biology which are inherently capable of visualizing the tracks of ions used in hadron therapy. The ions that traverse the FNTD deposit their energy according to their linear energy transfer (LET) and transform colour centres to form trackspots around their trajectory. These trackspots have fluorescent properties which can be visualized by fluorescence microscopy enabling a well-defined dosimetric readout with a spatial component indicating the trajectory of individual ions. The current method used to analyse the FNTDs is laser scanning confocal microscopy (LSM). LSM enables a precise localization of track spots in x, y and z however due to the scanning of the laser spot across the sample, requires a long time for large samples. This body of work conclusively shows for the first time that the readout of the trackspots present after 0.5 Gy carbon ion irradiation in the FNTD can be captured with a widefield microscope (WF). The WF readout of the FNTD is a factor [~]10 faster, for an area 2.97 times the size making the method nearly a factor 19 faster in track acquisition than LSM. The dramatic decrease in image acquisition time in WF presents an alternative to LSM in FNTD workflows which are limited by time, such as biomedical sensors which combine FNTDs with live cell imaging.

biophysics↗