Gene expression profiles of four murine tumors after carbon-ion (C-ion) or gamma irradiation.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE11629 | GEO | 2008/06/09
SECONDARY ACCESSION(S): PRJNA106145
REPOSITORIES: GEO
Similar Datasets
Project description:Gene expression profiling was used to identify genes that display radiation-induced transcriptional change over tumor histopathology. Keywords: mouse squamous cell carcinoma, fibrosarcoma and mammary carcinoma, gamma-irradiation, carbon ion irradiation, resected sample, transplanted tissues C3H/HeMs male mice were irradiated by gamma-rays (30Gy, 50Gy, 70Gy) or carbon ions (30Gy) as local irradiation in single doses to hind legs where each tumor was transplanted. Animals were sacrificed either before irradiation (pre) or 1 day after irradiation (day 1) for expression analysis.
2009-03-20 | E-GEOD-5331 | biostudies-arrayexpress
Project description:To examine whether the local carbon ion radiotherapy affects the characteristics of the metastatic tumors, the expression profiles of the primary tumors and the lung metastases were studied in a mouse squamous cell carcinoma model by applying local radiotherapy with no irradiation (negative control), gamma-ray irradiation (reference beam), and carbon-ion irradiation. Keywords: mouse, squamous cell carcinoma, primary tumor, lung metastases, radiotherapy, carbon ion, gamma ray A highly metastatic mouse squamous cell carcinoma NR-S1 was implanted into the hind leg of synergetic C3H/HeNrs mice and irradiated with 5 Gy of carbon ion beam. 8 Gy of gamma ray was used as a reference beam. At 2 weeks after the irradiation, the lung tissue was sampled. In order to collect samples of primary tumors, the tumors were implanted in other mice and irradiated in the same manner, and the primary tumors were collected at 1 week after the irradiation. The tumor cells of the primary and metastatic tumors were collected by laser microdissection, and oligonucleotide microarray analysis of the irradiated primary tumors and the metastatic tumors were all performed in comparison to the non-irradiated primary tumor by two-color methods.
2009-04-22 | E-GEOD-9305 | biostudies-arrayexpress
Project description:Carbon-ion irradiation is an emerging therapeutic option for several tumor entities including lung cancer. Well oxygenated tumor areas compared to a hypoxic environment favor therapeutic photon irradiation efficiency of solid tumors due to increased amounts of DNA damage. The resistance of hypoxic tumor areas towards photon irradiation is enhanced through increased HIF-1 signaling. Here, we compared the effects of oxygen and HIF 1 after photon and carbon-ion irradiation with biological equivalent doses in a human non-small lung cancer model. In hypoxia compared to normoxia, A549 and H1299 cells displayed improved survival after photon irradiation. Knockdown of HIF-1M-NM-1 combined with photon irradiation synergistically delayed tumor growth in vivo. Photon irradiation induced HIF-1M-NM-1 and several of its target genes such as PDK1, GLUT-1, LDHA, and VEGF with subsequent enhanced tumor angiogenesis in vivo, a signaling cascade that was not targeted by carbon-ion irradiation. We present evidence that photons but not carbon-ions induce HIF-1M-NM-1 via mTOR pathway. Importantly, after carbon-ion irradiation in vivo, we observed substantial downregulation of HIF-1M-NM-1 and a drastically delayed tumor growth indicating a considerable higher relative biological effectiveness (RBE) than anticipated from the cell survival data. In sum, our results demonstrate that carbon-ions mediate an improved therapeutic response of tumor treatment compared to photon irradiation that is independent of cell oxygenation and HIF-1 signaling. 16 independent cell cultures were used. Each culture was split into an irradiated and a control plate, yieldin a total of 16 paired samples. Paired samples were analysed in 16 two-color hybridizations. Factors time (after irradiation) with levels 1h and 4h and factor radiation quality with levels C12 and X-rays were analyzed. Each of the 2x2 combinations was analyzed in 4 independent experiments.
2014-04-20 | E-GEOD-45403 | biostudies-arrayexpress
Project description:Linear energy transfer (LET) is an important factor affecting several aspects of the irradiation effect, e.g. cell survival and mutation frequency, making the heavy-ion beam an effective mutagen. To study the mechanisms behind LET-dependent effects, expression profiling was performed after heavy-ion beam irradiation of imbibed rice seeds. Array-based experiments at three time points (0.5, 1, 2 h after the irradiation) revealed that the number of up- or down-regulated genes was highest 2 h after irradiation. Array-based experiments with four different LETs at 2 h after irradiation identified LET-independent regulated genes that were up/down-regulated regardless of the value of LET; LET-dependently regulated genes, whose expression level increased with the rise of LET value, were also identified. Oryza sativa L. 'Nipponbare' seeds were imbibed for 3 days. The seeds were irradiated with 22.5 or 50 keV/μm C-ion at a dose of 15 Gy. Gene expressions of irradiated and unirradiated embryos were measured at 0.5, 1, and 2 hours after irradiation. Three independent experiments were performed at each time and LET.
2016-07-01 | E-GEOD-78997 | biostudies-arrayexpress
Project description:Linear energy transfer (LET) is an important factor affecting several aspects of the irradiation effect, e.g. cell survival and mutation frequency, making the heavy-ion beam an effective mutagen. To study the mechanisms behind LET-dependent effects, expression profiling was performed after heavy-ion beam irradiation of imbibed rice seeds. Array-based experiments at three time points (0.5, 1, 2 h after the irradiation) revealed that the number of up- or down-regulated genes was highest 2 h after irradiation. Array-based experiments with four different LETs at 2 h after irradiation identified LET-independent regulated genes that were up/down-regulated regardless of the value of LET; LET-dependently regulated genes, whose expression level increased with the rise of LET value, were also identified. Oryza sativa L. 'Nipponbare' seeds were imbibed for 3 days. The seeds were irradiated with 22.5 or 50 keV/μm C-ion or 63 or 80 keV/μm Ne-ion at a dose of 15 Gy. Gene expressions of irradiated and unirradiated embryos were measured at 2 hours after irradiation. Three independent experiments were performed at each time and LET.
2016-07-01 | E-GEOD-78994 | biostudies-arrayexpress
Project description:To examine whether the local carbon ion radiotherapy affects the characteristics of the metastatic tumors, the expression profiles of the primary tumors and the lung metastases were studied in a mouse squamous cell carcinoma model by applying local radiotherapy with no irradiation (negative control), gamma-ray irradiation (reference beam), and carbon-ion irradiation. Keywords: mouse, squamous cell carcinoma, primary tumor, lung metastases, radiotherapy, carbon ion, gamma ray
2009-04-23 | GSE9305 | GEO
Project description:The aim of our research is to clarify the mechanisms generating heterogeneity in response to C-ion irradiation that arise from individual genetic variations in humans. In this study, we performed whole lung C-ion irradiation using three different strains of mice to examine whether strain-dependent differences in radiation effects occur in high-LET C-ion thoracic irradiation. Murine strain-variance was evaluated by histopathological examination of intra-alveolar hemorrhage that is likely to occur during the early phase after irradiation, and of lung fibrosis during the late phase, occurring more than three months after irradiation. We also performed microarray analysis to identify the key genes that are differentially regulated in different mouse strains after C-ion irradiation and to determine the mechanism of strain-dependent pulmonary damage after high-LET C-ion irradiation. Eight-week old female inbred C3H/He Slc, C57BL/6J Jms Slc and A/J Jms Slc mice (3 kinds of mice) were used. The whole thorax of three mice was locally irradiated at 10 Gy with C-ion beams, with a reference beam, 137Cs gamma-rays (2 kinds of beam). Three mice of each strain (3 mice) were sacrificed, and immediately dissected for lung extraction at 6 h (6h sample). Lungs for three mice of each strain without irradiation were extracted at the same time as control samples (control sample). Hybridization to microarrays (Whole Mouse Genome 4x44K OligoMicroarray Kit, single color, Cyamine 3-CTP) consisting of 44,000 total spots was conducted using an Agilent Gene Expression hybridization kit. The arrays from three independent replicates for each sample (3 arrays) were scanned on an Agilent dual-laser Microarray Scanner (all from Agilent Technologies) following the manufacturer's instructions. A total of 108 samples were analyzed. 3 replicate arrays x 3 mice x 3 strains x 2 timing for sampling x 2 kinds of beam.
2014-02-26 | E-GEOD-20959 | biostudies-arrayexpress
Project description:Radiotherapy can act as in situ vaccine activating preventive tumor-specific immune responses in treated patients. While carbon ion radiotherapy holds superior biophysical properties over conventional photon irradiation, little is known about the immunological effects induced by this radiation type. Multiple strategies combining radiotherapy with immune checkpoint inhibition (radioimmunotherapy) to enhance anti-tumor immunity have been described, however, results on the immune cell composition in tumors following radioimmunotherapy with carbon ions are lacking. Here, we present a bilateral tumor model based on time-shifted transplantation of murine, Her2+ EO771 tumor cells onto the flanks of immune competent mice followed by selective irradiation of the primal tumor. αCTLA4- but not αPD-L1-based radioimmunotherapy induced complete tumor rejection and mediated eradication of even non-irradiated, distant tumors. Cured mice were protected against EO771 rechallenge indicative of long lasting, tumor-specific immunological memory. Single cell RNA-sequencing and flow cytometric analyses of irradiated tumors revealed activation of NK cells and distinct tumor-associated macrophage clusters with upregulated expression of TNF and IL1 responsive genes. Distant tumors of irradiated mice showed higher frequencies of naïve T cells, which were activated upon combination with CTLA4 blockade. Thus, radioimmunotherapy with carbon ions plus CTLA4 inhibition reshapes the tumor-infiltrating immune cell composition and can induce complete rejection even of non-irradiated tumors. Our data suggest to combine radiotherapy approaches with CTLA4 blockade to achieve durable anti-tumor immunity. Furthermore, evaluation of future radioimmunotherapy approaches should not be restricted to immunological impacts at the irradiation site, but should also consider systemic immunological effects on non-irradiated tumors.
2022-09-30 | GSE214524 | GEO
Project description:Carbon-ion irradiation is an emerging therapeutic option for several tumor entities including lung cancer. Well oxygenated tumor areas compared to a hypoxic environment favor therapeutic photon irradiation efficiency of solid tumors due to increased amounts of DNA damage. The resistance of hypoxic tumor areas towards photon irradiation is enhanced through increased HIF-1 signaling. Here, we compared the effects of oxygen and HIF 1 after photon and carbon-ion irradiation with biological equivalent doses in a human non-small lung cancer model. In hypoxia compared to normoxia, A549 and H1299 cells displayed improved survival after photon irradiation. Knockdown of HIF-1α combined with photon irradiation synergistically delayed tumor growth in vivo. Photon irradiation induced HIF-1α and several of its target genes such as PDK1, GLUT-1, LDHA, and VEGF with subsequent enhanced tumor angiogenesis in vivo, a signaling cascade that was not targeted by carbon-ion irradiation. We present evidence that photons but not carbon-ions induce HIF-1α via mTOR pathway. Importantly, after carbon-ion irradiation in vivo, we observed substantial downregulation of HIF-1α and a drastically delayed tumor growth indicating a considerable higher relative biological effectiveness (RBE) than anticipated from the cell survival data. In sum, our results demonstrate that carbon-ions mediate an improved therapeutic response of tumor treatment compared to photon irradiation that is independent of cell oxygenation and HIF-1 signaling.
2014-04-20 | GSE45403 | GEO
Project description:Little is known about molecular mechanism for its effectiveness of C-ions in melanomas. In this study, we examined the cytotoxic effects of C-ions on 6 human malignant melanoma cell lines, and gene expression profiles and cell cycle progression were also examined to reveal the mechanism of the therapeutic effectiveness of C-ions. Equivalent doses of the C-ions were more effective at reducing the survival rates than X-rays, and the relative biological effectiveness (RBE) was > 2.0 in all cell lines. In unsupervised 2D clustering performed for C-ions irradiated groups at 1 h after irradiation, many of the probes were down-regulated among 6 cell lines. We identified probes, such as XKRY, ELA3A, T-STAR, SCN9A, ELA2A, CRK7, CCNA2, CROP, CYR61, SDFR1, and SMAD4 differentially responded to C-ions and X-rays among 4 cell lines. CCNA2 was down-regulated by C-ions more than X-rays at 3 h after irradiation, and C-ions induced G2/M arrest more than X-rays in three cell lines at 30 h. Many of p53 target genes, such as ATF3, BTG2, CDKN1A, GADD45A, SESN1, and TNFRSF6 were up-regulated by C-ions at 3 h. The expressions of p53 target genes were not changed in HMV-I and MeWo. In MeWo, APG3L, RPL26 and PCNA were down-regulated or E2F2 and LIMS3 were up-regulated, and in HMV-I, ATF3, FOS, and CYR61 were up-regulated at 1 h after C-ions. In conclusion, C-ions affected p53-dependent and p53-independent pathways of cell death and cell cycle. Individual mechanism in activating of cell death was observed in each cell line of 6 melanomas. Keywords: Specific gene expression prfiles after carbon ion irradiation
2008-06-01 | GSE6630 | GEO