Microarray analysis of U87 Glioblastoma Multiforme cell line exposed to proton irradiation during acute hypoxia.
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PROVIDER: PRJNA684139 | ENA |
REPOSITORIES: ENA
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Project description:Glioblastoma multiforme (GBM), is the most malignant and common tumor among glial neoplasms. It is characterized by a peak of incidence between 45 and 70 years and a patient median survival time of 14.6 months. In addition, GBM undergoes malignant progression under hypoxic conditions that contributes to strong radioresistance and chemoresistance; alters the metabolism of the tumor cells; generates a strong genome instability, increases the angiogenesis, vasculogenesis, and contributes to the formation of the Cancer Stem Cells (CSCs) and the infamous Circulating Tumor Cells (CTCs) involved in metastasis formation. Moreover, GBMs have a poor prognosis due to treatment (such as surgical resection, conventional RT and chemotherapy) plan failures. In this sense, since standard GBM treatments are not effective, new promising strategies such as Proton Therapy (PT), are under investigation because supported by encouraging results. Considering these assumptions, the main aim of this study was to analyze GBM response to PT innovative treatment during induced acute hypoxia, by using a whole gene expression analysis. Thus, in this work we have reported in a descriptive way, the most statistically and biologically relevant pathways deregulated in U87 GBM cell line, according to specific PT plans during hypoxia condition, and in addition, some interesting biomarker networks were following discussed.
2021-05-05 | GSE162986 | GEO
Project description:In Glioblastoma Multiforme (GBM), hypoxia is associated with radioresistance and poor prognosis. Since standard GBM treatments are not always effective, new strategies are needed to overcome resistance to therapeutic treatments, including radiotherapy (RT). Our study aims to shed light on the biomarker network involved in a hypoxic (0.2% oxygen) GBM cell line that is radioresistant after proton therapy (PT). For cultivating cells in acute hypoxia, GSI's hypoxic chambers were used. Cells were irradiated in the middle of a spread-out Bragg peak with increasing PT doses to verify the greater radioresistance in hypoxic conditions. Whole-genome cDNA microarray gene expression analyses were performed for samples treated with 2 and 10 Gy to highlight biological processes activated in GBM following PT in the hypoxic condition. We describe cell survival response and significant deregulated pathways responsible for the cell death/survival balance and gene signatures linked to the PT/hypoxia configurations assayed. Highlighting the molecular pathways involved in GBM resistance following hypoxia and ionizing radiation (IR), this work could suggest new molecular targets, allowing the development of targeted drugs to be suggested in association with PT.
| S-EPMC8073933 | biostudies-literature
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: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.
2021-12-31 | GSE192817 | 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.
2022-01-03 | GSE192899 | GEO
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:Cellular plasticity upon proton irradiation determines tumor cell radiosensitivity
| PRJNA793260 | ENA
Project description:The goal of this experiment was to identify methylation and metabolomic pathways the respond to proton irradiation and examine whether these two pathways coregulate biological pathways.
2019-06-13 | GSE132588 | 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 | GSE107443 | GEO