Sparing effects of FLASH irradiation in patient-derived lung tissue
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PROVIDER: PRJNA1097629 | ENA |
REPOSITORIES: ENA
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Project description:This study aims to assess the effect of conventional radiotherapy compared to FLASH radiotherapy on healthy human lung tissue. FLASH radiotherapy, characterized by ultra-high dose rates, is hypothesized to spare healthy tissue from radiation-induced damage while maintaining efficacy against tumors. To achieve this goal and better characterize this sparing effect, bulk RNA sequencing analysis was conducted on 3 patients to study the molecular and cellular responses of lung tissue to both types of radiotherapy. The main objectives are to evaluate if FLASH radiotherapy effectively spares healthy lung tissue from radiation-induced damage and to understand the underlying molecular mechanisms behind this potential protective effect.
2025-09-08 | GSE263484 | GEO
Project description:We performed single-cell RNA sequencing to analyze murine lung tissues exposed to either conventional dose rate (CONV) or FLASH radiation therapy (FLASH-RT). This approach elucidated distinct early immune responses in radiation-induced lung injury and revealed protective mechanisms specific to FLASH irradiation. Systematic characterization of over 135,000 cells within the pulmonary microenvironment uncovered critical immune and stromal cell dynamics that differentiate CONV and FLASH-RT responses. These findings provide mechanistic insights into FLASH-RT's biological effects and its potential clinical applications in thoracic oncology.
2025-06-06 | GSE298566 | GEO
Project description:Purpose: Tumor hypoxia is a major cause of treatment resistance, especially to radiation therapy at conventional dose rate (CONV), and we wanted to assess whether hypoxia does alter tumor sensitivity to FLASH. Methods and materials: We engrafted several tumor types (glioblastoma [GBM], head and neck cancer, and lung adenocarcinoma) subcutaneously in mice to provide a reliable and rigorous way to modulate oxygen supply via vascular clamping or carbogen breathing. We irradiated tumors using a single 20-Gy fraction at either CONV or FLASH, measured oxygen tension, monitored tumor growth, and sampled tumors for bulk RNAseq and pimonidazole analysis. Next, we inhibited glycolysis with trametinib in GBM tumors to enhance FLASH efficacy. Results: Using various subcutaneous tumor models, and in contrast to CONV, FLASH retained antitumor efficacy under acute hypoxia. These findings show that in addition to normal tissue sparing, FLASH could overcome hypoxia-mediated tumor resistance. Follow-up molecular analysis using RNAseq profiling uncovered a FLASH-specific profile in human GBM that involved cell-cycle arrest, decreased ribosomal biogenesis, and a switch from oxidative phosphorylation to glycolysis. Glycolysis inhibition by trametinib enhanced FLASH efficacy in both normal and clamped conditions. Conclusions: These data provide new and specific insights showing the efficacy of FLASH in a radiation-resistant context, proving an additional benefit of FLASH over CONV.
2024-01-24 | GSE223607 | GEO
Project description:FLASH Irradiation Modulates Immune Responses and Accelerates Lung Recovery: A Single-Cell Perspective
| PRJNA1269944 | ENA
Project description:Thoracic radiation therapy is limited by the development of acute (i.e. pneumonitis) and late (i.e. pulmonary fibrosis) side-effects. The goal of this study is to analyze, at the single cell level, the molecular impact of two radiation treatments : a conventional/clinical (CONV) modality vs. FLASH, a new radiation method that spares healthy tissue from late radiation-induced toxicities (Science Translational Medicine 6: 245ra293, 2014). We analyzed by single cell RNA sequencing (scRNAseq) dissociated lung cells from a non-irradiated control mouse (NI), a mouse 4 days after CONV thoracic irradiation (CONV) and a mouse 4 days after FLASH irradiation (FLASH). We identify transcriptional alterations induced in the distinct lung cell types after irradiation and show that FLASH irradiated lung cells present a reduced pro-inflammatory phenotype as well as a diminished activation of epithelial lung progenitor cells. In line with previous report (Radiother Oncol 124: 365-9, 2017), this study indicates that FLASH radiation therapy limits inflammation and preserves the regenerative capcity of the lung.
2019-12-07 | GSE133992 | GEO
Project description:Total body irradiation (TBI) of mice using two dose rates, conventional dose rate (CDR) versus flash dose rate (FLASH), induced transient decrease of number of LT-HScs in bone marrow and a total recovery of these cells 15 days after TBI We used microarrays to detail the global programme of gene expression underlying the recovery of LT-HSCs and identified distinct classes of up or down- regulated genes according the modality of irradiation
2015-01-01 | GSE54526 | GEO
Project description:Radiotherapy (RT) is a cornerstone treatment for nearly 50% of cancer patients, yet its efficacy remains limited by cumulative damage to healthy tissues over time. Delivering RT at ultra-high dose rates (FLASH-RT) represents a transformative strategy, as it appears to maintain tumor control, while sparing the surrounding normal tissue—a phenomenon termed FLASH effect. Here, we compared electron FLASH-RT and conventional RT (CONV-RT) on skin and muscle tissue of naïve mice assessing tissue integrity and gene expression. Bulk RNA sequencing revealed striking differences: FLASH induced minimal transcriptional disruption in skin and muscle, whereas CONV-RT triggered thousands of differentially expressed genes, including massive activation of fibrosis, inflammation, cell death-related pathways in skin, and broad dysregulation of genes linked to muscle function, remodeling and the unfolded protein response. Histological and ultrastructural analyses corroborated the findings, showing reduced immune infiltration in the skin and preserved tissue architecture both in skin and muscle following FLASH. In conclusion our study not only confirms the protective nature of FLASH but also provides novel mechanistic insights into the cascade linking local injury to systemic dysfunction under CONV-RT, reinforcing the translational potential of FLASH to expand the therapeutic window of radiotherapy.
2025-09-15 | GSE307570 | GEO
Project description:Numerous studies have demonstrated the normal tissue-sparing effects of ultra-high dose rate 'FLASH' irradiation in vivo, with an associated reduction in damage burden being reported in vitro. Towards this, two key radiochemical mechanisms have been proposed: radical-radical recombination (RRR) and transient oxygen depletion (TOD), with both being proposed to lead to reduced levels of induced damage. Previously, we reported that FLASH induces lower levels of DNA strand break damage in whole-blood peripheral blood lymphocytes (WB-PBL) ex vivo, but our study failed to distinguish the mechanism(s) involved. A potential outcome of RRR is the formation of crosslink damage (particularly, if any organic radicals recombine), whilst a possible outcome of TOD is a more anoxic profile of induced damage resulting from FLASH. Therefore, the aim of the current study was to profile FLASH-induced damage via the Comet assay, assessing any DNA crosslink formation as a putative marker of RRR and/or anoxic DNA damage formation as an indicative marker of TOD, to determine the extent to which either mechanism contributes to the "FLASH effect". Following FLASH irradiation, we see no evidence of any crosslink formation; however, FLASH irradiation induces a more anoxic profile of induced damage, supporting the TOD mechanism. Furthermore, treatment of WB-PBLs pre-irradiation with BSO abrogates the reduced strand break damage burden mediated by FLASH exposures. In summary, we do not see any experimental evidence to support the RRR mechanism contributing to the reduced damage burden induced by FLASH. However, the observation of a greater anoxic profile of damage following FLASH irradiation, together with the BSO abrogation of the reduced strand break damage burden mediated by FLASH, lends further support to TOD being a driver of the reduced damage burden plus a change in the damage profile mediated by FLASH.
| S-EPMC10138874 | biostudies-literature
Project description:Female BALB/c nude mice (n=3/group) were subjected to partial body irradiation under anesthesia using 2 Gy external photon (4 MV, nominal) irradiation. In group A, the collum (i.e. the thyroid) was irradiated; in group B, thorax+abdomen were irradiated, and in group C, collum+thorax+abdomen were irradiated. The control group (n=5) was anesthetized but not irradiated. At 24 h after treatment, the kidneys, liver, lungs, spleen, and thyroid were excised, flash-frozen, and stored at -80°C. Total RNA was extracted from homogenized tissue samples (kidney cortex and kidney medulla were treated separately) and subjected to expression analysis using RNA microarray technology.
2016-03-31 | GSE66372 | GEO
Project description:Transcriptomic profiling of normal mouse tissue following 131I irradiation.
2012-05-18 | GSE32014 | GEO