Log-term effects of proton irradiation on DNA methylation and metabolomic pathways in the hippocampus and heart.
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE132588 | GEO | 2019/06/13
REPOSITORIES: GEO
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Project description:Log-term effects of proton irradiation on DNA methylation and metabolomic pathways in the hippocampus and heart.
| PRJNA548511 | ENA
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 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:Novel particle therapy was implemented into standard-of-care for cancer patients during the last years. However, experimental studies investigating cellular and molecular mechanisms are lacking although prognostic biomarker are urgently needed. The cancer stem cell (CSC)-related marker aldehyde dehydrogenase (ALDH) is known to impact on prostate cancer radiosensitivity through affecting defense against reactive oxygen species (ROS), reducing DNA damage repair and increasing cell survival. Surprisingly, we could show in a previous study that ionizing radiation itself enriches for ALDH-positive CSCs in a time- and dose-dependent manner through alteration in histone methylation. Within the present study, we investigated CSC marker dynamics upon proton beam irradiation and hypothesized that this novel particle therapy may have increased CSC targeting potential due to its increased ionization potential compared to conventional photon irradiation. However, we found that proton irradiation is affecting cellular dynamics and escape from cell death.
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Project description:Proton (PT) therapy represents an alternative to conventional X-ray therapy, and its clinical application for cancer treatment is on the rise due to associated dose deposit advantages. However, our knowledge of biological responses to PT, in comparison to X-ray, remains in its infancy. Identification of PT specific molecular signals is an important opportunity for the discovery of biomarkers and synergistic drugs. We have profiled the transcriptome regulation of lymphoma cells exposed to clinical sources of PT and X-ray radiation, respectively. Subsequent analysis demonstrated both common and radiation-specific deregulation of gene expression. Gene set enrichment discovered pathways unique to PT \ that contribute to the unfolded protein response (UPR) and mitochondrial transport.
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Project description:Novel particle therapy was implemented into standard-of-care for cancer patients during the last years. However, experimental studies investigating cellular and molecular mechanisms are lacking although prognostic biomarker are urgently needed. The cancer stem cell (CSC)-related marker aldehyde dehydrogenase (ALDH) is known to impact on prostate cancer radiosensitivity through affecting defense against reactive oxygen species (ROS), reducing DNA damage repair and increasing cell survival. Surprisingly, we could show in a previous study that ionizing radiation itself enriches for ALDH-positive CSCs in a time- and dose-dependent manner through alteration in histone methylation. Within the present study, we investigated CSC marker dynamics upon proton beam irradiation and hypothesized that this novel particle therapy may have increased CSC targeting potential due to its increased ionization potential compared to conventional photon irradiation. However, we found that proton irradiation is affecting cellular dynamics and escape from cell death.
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Project description:Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH), the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the severe human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of severe PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH in its later stage, which may differ from the earlier stage of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH. Global profiles were determined in human lung tissue and compared across 11 normal and 12 severe pulmonary arterial hypertension patients. Using a combination of microarray and high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the severe human PAH lung.
2014-11-14 | E-GEOD-53408 | biostudies-arrayexpress
Project description:The aim of the study is to disclose the distinct alteration of biological characteristics of gene expression features in pancreas cancer cell, MIAPaCa-2, irradiated by proton and x-ray. The survived MIAPaCa-2 cells after irradiation with proton and x-ray were isolated and gene expression profiles were analyzed.
2017-12-30 | GSE107443 | GEO
Project description:The aim of the study is to disclose the distinct alteration of biological characteristics of gene expression features in pancreas cancer cell, MIAPaCa-2, irradiated by proton and x-ray. The survived MIAPaCa-2 cells after irradiation with proton and x-ray were isolated and gene expression profiles were analyzed.
2017-12-30 | GSE107442 | GEO
Project description:The aim of the study is to disclose the distinct alteration of biological characteristics of gene expression features in pancreas cancer cell, MIAPaCa-2, irradiated by proton and x-ray. The survived MIAPaCa-2 cells after irradiation with proton and x-ray were isolated and gene expression profiles were analyzed.
2017-12-30 | GSE107440 | GEO