Transcriptomic analysis after proton and neutron therapy
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ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE266475 | GEO | 2025/05/01
REPOSITORIES: GEO
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Project description:Transcriptomic analysis after proton and neutron therapy
| PRJNA1107258 | ENA
Project description:The objective of this investigation was to characterize, at individual level, the transcriptional response and the onset of regenerative processes in mouse skin irradiated with different doses of fast neutrons. We performed a high-throughput gene expression analysis, by DNA oligonucleotide microarray on 24 three months old C57Bl/6 mice irradiated with 0, 0,2 and 1 Gy of mono-energetic 14 MeV neutron. The results, partially validated by quantitative real time RT-PCR, showed an up-regulation of a sub-class of keratin and keratin associated proteins, and of components of the S100 family of Ca2+-binding proteins which was limited to the lower dose. We conclude that the dose-dependent differential gene expression, reminiscent of the onset of re-epithelialization and wound healing, depends upon the proportion of cells carrying multiple lesions at chromosomal level post-irradiation, and it represents an in vivo evidence of a skin regenerative program exerted independently from DNA repair-associated pathways. Four condition experiment: 6h and 24h from 0.2 Gy neutron irradiation; 6h and 24 from 1 Gy neutron irradiation. One replicate for each condition
2010-11-16 | E-GEOD-25343 | biostudies-arrayexpress
Project description:To investigate DNA copy number changes in rat mammary carcinomas induced by neutron or gamma-ray irradiation.
2020-10-29 | GSE160418 | GEO
Project description:Literature data report the helpful role of specific molecularly based signatures to predict response to treatment in cancer, including breast cancer (BC) disease. As known, BC is a heterogeneous disease presenting distinct subtypes with different clinical outcomes. Thus, the choice of a unique treatment plan for all BC patients, including radiation therapy (RT), may be not the best option. Technological advances in RT are evolving with the use of proton beams, which reduce the dose administered to the heart compared to conventional RT. However, limitate data regarding proton-induced molecular changes are currently available. The aim of this study was therefore to study gene expression profiles induced by proton irradiation with 0.5, 2 and 9 Gy of Ionizing radiation (IR) doses in breast cells. The great amount of data here collected, represent an useful tool to better understand the molecular mechanisms elicited by proton irradiation, thereby filling the existing lack of data in the literature.
2019-07-29 | GSE116325 | GEO
Project description:Proton irradiation is touted for its improved tumor targeting due to the physical advantages of ion beams for radiotherapy. Recent studies from our laboratory have shown that, in addition to targeting advantages, proton irradiation can inhibit angiogenic and immune factors and thereby modulate tumor progression. High-energy protons also constitute a principal component of the galactic cosmic rays to which astronauts are exposed. Increased understanding of the biological effects of proton exposure would thus contribute to both improved cancer therapy and carcinogenesis risk assessment for space travel. In addition, age plays a major role in tumor incidence and is a critical consideration for estimating cancer risk. We investigated the effects of host age and proton exposure on tumor progression. Tumor lag time and growth dynamics were tracked following injection of murine Lewis lung carcinoma (LLC) cells into young (68 day) versus old (736 day) mice with or without coincident irradiation. Tumor progression was suppressed in old compared to young mice. Differences in progression were further modulated by proton irradiation (1GeV), with increased inhibition evident in old mice. Through global transcriptome analysis, TGFβ1 and TGFβ2 were determined to be key players that contributed to the tumor dynamics observed. These findings point to older hosts providing decreased systemic tumor support, which can be further inhibited by proton irradiation.
2014-01-01 | GSE45609 | GEO
Project description:Proton irradiation: 2, 6 and 9 Gy + untreated controls Times after irradiation: 3 and 10 days Associated pubblication: Sala, C.; Tarozzi, M.; Simonetti, G.; Pazzaglia, M.; Cammarata, F.P.; Russo, G.; Acquaviva, R.; Cirrone, G.A.P.; Petringa, G.; Catalano, R.; et al. Impact on the Transcriptome of Proton Beam Irradiation Targeted at Healthy Cardiac Tissue of Mice. Cancers 2024.
2024-04-30 | E-MTAB-14006 | biostudies-arrayexpress
Project description:Background: Radiation exposure due to the detonation of an improvised nuclear device remains a major security concern. Radiation from such a device involves a combination of photons and neutrons. Although photons will make the greater contribution to the total dose, neutrons will certainly have an impact on the severity of the exposure as they have high relative biological effectiveness. Results: We investigated the gene expression signatures in the blood of mice exposed to 3 Gy x-rays, 0.75 Gy of neutrons, or to mixed field photon/neutron with the neutron fraction contributing 5%, 15%, or 25% of a total 3 Gy radiation dose. Gene ontology and pathway analysis revealed that genes involved in protein ubiquitination pathways were significantly overrepresented in all radiation doses and qualities. On the other hand, eukaryotic initiation factor 2 (EIF2) signaling pathway was identified as one of the top 10 ranked canonical pathways in neutron, but not pure x-ray, exposures. In addition, the related mTOR and regulation of EIF4/p70S6K pathways were also significantly underrepresented in the exposures with a neutron component, but not in x-ray radiation. The majority of the changed genes in these pathways belonged to the ribosome biogenesis and translation machinery and included several translation initiation factors (e.g. Eif2ak4, Eif3f), as well as 40S and 60S ribosomal subunits (e.g. Rsp19, Rpl19, Rpl27). Many of the differentially downregulated ribosomal genes (e.g. RPS19, RPS28) have been causally associated with human bone marrow failure syndromes and hematologic malignancies. We also observed downregulation of transfer RNA processes, in the neutron-only exposure (p < 0.005). Ingenuity Pathway Analysis (p < 0.05) of differentially expressed genes predicted significantly suppressed activity of the upstream regulators c-Myc and Mycn, transcription factors known to control ribosome biogenesis. Conclusions: We describe the gene expression profile of mouse blood following exposure to mixed field neutron/x-ray irradiation. We have discovered that pathways related to protein translation are significantly underrepresented in the exposures containing a neutron component. Our results highlight the significance of neutron exposures that even the smallest percentage can have profound biological effects that will affect medical management and treatment decisions in case of a radiological emergency.
2018-06-15 | GSE113509 | GEO
Project description:Proton irradiation is touted for its improved tumor targeting due to the physical advantages of ion beams for radiotherapy. Recent studies from our laboratory have shown that, in addition to targeting advantages, proton irradiation can inhibit angiogenic and immune factors and thereby modulate tumor progression. High-energy protons also constitute a principal component of the galactic cosmic rays to which astronauts are exposed. Increased understanding of the biological effects of proton exposure would thus contribute to both improved cancer therapy and carcinogenesis risk assessment for space travel. In addition, age plays a major role in tumor incidence and is a critical consideration for estimating cancer risk. We investigated the effects of host age and proton exposure on tumor progression. Tumor lag time and growth dynamics were tracked following injection of murine Lewis lung carcinoma (LLC) cells into young (68 day) versus old (736 day) mice with or without coincident irradiation. Tumor progression was suppressed in old compared to young mice. Differences in progression were further modulated by proton irradiation (1GeV), with increased inhibition evident in old mice. Through global transcriptome analysis, TGFβ1 and TGFβ2 were determined to be key players that contributed to the tumor dynamics observed. These findings point to older hosts providing decreased systemic tumor support, which can be further inhibited by proton irradiation. For genome-wide expression profiling of tumor tissue, Mouse WG-6 BeadArray chips (Illumina, San Diego, CA) were used. Total RNA was amplified with the Ambion Illumina TotalPrep Amplification Kit (Ambion, Austin, TX) and labeled from all replicate biological samples for each condition. For tumor replicates, thirty tumor samples from adolescent and thirty tumor samples from old mice, for a total of 60 tumor samples, were used. All replicate samples were run individually. For each age group, ten tumor samples had received proton irradiation while twenty tumor samples were from unirradiated mice (as described above). Total RNA was isolated and purified using TRIzol (Invitrogen) and quantified using an Agilent Bioanalyzer. Samples were deemed suitable for amplification and hybridization if they had 28s/18s = 2:1, RIN >7. Total RNA of 500ng per sample was amplified using AmbionTotalPrep, and 1.5ug of the product was loaded onto the chips. Following hybridization at 55C, the chips were washed and then scanned using the Illumina iScan System. The data was checked with GenomeStudio (Illumina) for quality control. In GenomeStudio, data was background subtracted and rank invariant normalization was applied. Data was imported into MultiExperiment Viewer, MeV, for statistical analysis. The statistically significant genes were determined using MeV by applying a one-way ANOVA analysis with standard Bonferroni correction with a FDR <0.05 that resulted in a list of significant genes. Average gene expression signals <10 were filtered out due to signal being
2014-01-01 | E-GEOD-45609 | biostudies-arrayexpress
Project description:Age plays a crucial role in the interplay between tumor and host; with further perturbations induced by irradiation. Proton irradiation on tumors induces biological modulations including inhibition of angiogenic and immune factors critical to “hallmark” processes impacting tumor development, in addition to physical targeting advantages. These advantages have provided promising results for proton therapy in cancer. Additionally, protons have implications for carcinogenesis risk of space travel (due to the high proportion of high energy protons in space radiation). Through a systems biology approach, we investigated how host tissue (i.e. splenic tissue) of tumor-bearing mice is altered with age, with or without whole-body proton exposure. Transcriptome analysis was performed on splenic tissue from adolescent (68 day) versus old (736 day) C57BL/6 male mice injected with Lewis lung carcinoma cells with or without three fractionations of 0.5Gy (1GeV) proton irradiation. Global transcriptome analysis indicated that proton irradiation of adolescent hosts caused significant signaling changes within splenic tissues that support carcinogenesis within the mice, as compared to old subjects. Increases in cell cycling and immunosuppression in irradiated adolescent hosts with CDK2, MCM7, CD74, and RUVBL2 as the key players were involved in the regulatory changes in host environment response (i.e. spleen). These results suggest a significant biological component to proton irradiation, operative through host age, that would indicate a modulation of host’s ability to support carcinogenesis in adolescence and the bestowal of resistance to immunosuppression, carcinogenesis, and genetic perturbation by old age.
2015-06-22 | GSE67243 | GEO
Project description:CGH was used to compare induced structural variation among soybean fast neutron lines, developed in background M92-220. 114 different soybean fast neutron lines were hybridized against the parental reference genotype M92-220. The soybean tiling array consists of 700k probes, spaced at approximately 1.1 kb intervals.
2011-08-01 | E-GEOD-31038 | biostudies-arrayexpress