A study on the radiosensitivity of radiation-induced lung injury at the acute phase based on single-cell transcriptomics
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ABSTRACT:
PROVIDER: PRJNA850641 | ENA |
REPOSITORIES: ENA
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Project description:Radiation-induced lung injury (RILI) is the most common complication associated with chest tumors, such as lung and breast cancers, after radiotherapy; however, the pathogenic mechanisms are unclear.Here, a single-cell transcriptome map was established in a mouse model of acute RILI. In total, 18,500 single-cell transcripts were generated, and 10 major cell types were identified. The heterogeneity and radiosensitivity of each cell type or subtype in the lung tissues during the acute stage were revealed. It was found that immune cells had higher radiosensitivity than stromal cells. Immune cells were highly heterogeneous in terms of radiosensitivity, while some immune cells had the characteristics of radiation resistance. Two groups of radiation-induced Cd8+Mki67+ T cells and Cd4+Cxcr6+ helper T cells were identified. In summary, This study investigated the dynamic changes in the cellular microenvironment during acute lung injury.
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Project description:Twenty-five miRNAs were identified as having differential expression post-irradiation in CL1-0 or CL1-5 cells. Among these miRNAs, miR-449a, which was down-regulated in CL1-0 cells at 24 h after irradiation, was chosen for further investigation. Overexpression of miR-449a in CL1-0 cells effectively increased irradiation-induced DNA damage and apoptosis, altered the cell cycle distribution and eventually led to sensitization of CL1-0 to irradiation. MiR-449a might be a novel radiosensitizer for clinical applications. Two lung adenocarcinoma cell lines (CL1-0 and CL1-5) with different metastatic ability and radiosensitivity were used. In order to understand the regulatory mechanisms of differential radiosensitivity in these isogenic tumor cells, both CL1-0 and CL1-5 were treated with 10 Gy radiation, and were harvested respectively at 0, 1, 4, and 24 h after radiation exposure. The changes in expression of miRNA upon irradiation were examined using Illumina Human microRNA BeadChips.
2012-12-30 | E-GEOD-40602 | biostudies-arrayexpress
Project description:RATIONALE: A step-by-step procedure may help health care practitioners diagnose and treat cancer patients with bowel injury symptoms caused by radiation therapy.
PURPOSE: This randomized clinical trial is studying the care of cancer patients with bowel injury caused by radiation therapy to the pelvis.
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Project description:Our team has constructed a prediction model based on the phase separation level of DNA repair factors (MRNIP、NONO、NOP53) to predict radiation-induced late intestinal injury (RLII) and verified the predictive efficacy of the system in retrospective studies. This clinical study intends to further prospectively verify the accuracy of this prediction model in rectal cancer patients. In this study, we plan to enroll 200 patients diagnosed with locally advanced rectal cancer by pathology and MRI, who undergo neoadjuvant chemoradiotherapy (NCRT) and total mesorectal excision (TME). We will follow up the occurrence and progression of radiation-induced intestinal injury within 1 year after TME. Phase separation level of DNA repair factors will be detected in pathological tissue after TME and applied to the prediction model to predict RLII. Based on the clinical diagnosis of RLII, the area under curve (AUC), accuracy, precision, specificity, and sensitivity of this prediction model in predicting RLII will be evaluated. The main outcome hypothesis is that the AUC of RLII predicted by the prediction model based on the phase separation level of DNA repair factors is more than 0.8.
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Project description:To explore long non-coding RNA (lncRNA) associated with radiosensitivity in colorectal carcinoma cell lines, expression profiles of Lovo, RKO and SW480 cell lines with different levels of radiosensitivity were investigated on ArrayStar platform. A probe-remapping strategy was applied to aquire the accurate probe annotation. By comparing expression profiles of cells with exposure to radiation with those of control sample (cells without exposure), a list of lncRNAs associated with radiation response was compiled. GSEA was then performed to explore their biological functions.
2017-03-03 | GSE95606 | GEO
Project description:Radiation-induced lung injury is a common late side-effect of thoracic radiotherapy. The inflammatory microenvironment plays a key role in this process. Endothelial cells are the goalkeeper of inflammation. Endothelial dysfunction following leukocytes infiltrated is a prominent feature in the pathogenesis of radiation-induced lung injury. Tyrosine phosphatase Shp2 is a key regulator of endothelial functions and inflammation. Here, we established a clinical-mimicking mouse model of radiation-induced lung injury and found that Shp2 activity was elevated in endothelium after injury. Mice with endothelium-specific Shp2 deletion showed relieved collagen deposition along with disrupted radiation-induced Jag1 expression in the endothelium. Furthermore, endothelium-derived Jag1 activated the alternative activation of macrophages in vitro and in vivo by paracrine Notch signaling. Consistently, Notch pathway was significant activated by chest irradiation in the peripheral blood leukocytes of cancer patients. Collectively, this is the first demonstration of radiation-induced lung injury regulation by endothelial Shp2. Shp2 participates in the radiation-induced endothelial dysfunction and subsequently inflammatory microenvironment producing.
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Project description:To test Arabidopsis thaliana radiosensitivity to gamma radiation, 6 days old seedlings were exposed for 48 h to 60-Co source at dose rates 1, 10, 40,100 or 290 mGy/h.
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Project description:Our team has constructed a prediction model based on the expression level of lncRNA (lncRNA-UCID、NEAT1、ciRS-7) to predict the chronicization of radiation-induced acute intestinal injury (RAII) and verified the predictive efficacy of the system in retrospective studies. This clinical study intends to further prospectively verify the accuracy of this prediction model in rectal cancer patients. In this study, we plan to enroll 200 patients diagnosed with locally advanced rectal cancer by pathology and MRI, who undergo neoadjuvant chemoradiotherapy (NCRT) and total mesorectal excision (TME) and develop RAII during NCRT or within 1 month. We will follow up the occurrence and progression of radiation-induced intestinal injury within 1 year after TME. Expression levels of lncRNA will be detected in pathological tissue after TME and applied to the prediction model to predict the chronicization of RAII. Based on the clinical diagnosis of chronic radiation-induced intestinal injury, the area under curve (AUC), accuracy, precision, specificity, and sensitivity of this prediction model in predicting the chronicization of RAII will be evaluated. The main outcome hypothesis is that the AUC of chronicization of RAII predicted by the prediction model based on the expression level of lncRNA is more than 0.8.
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Project description:The development of a biodosimetric assay based on the combined gene expression analysis of ex vivo-irradiated human peripheral blood (PB) and humans treated with total body irradiation has been developed. Gene expression profile signature of human radiation injury into a rapid and high-throughput chemical ligation-dependent probe amplification assay (CLPA) has been shown to discriminate 6 radiation dose levels in human PB. Candidate gene lists were first developed assaying human ex vivo and human TBI samples on the Affymetrix platform.
2014-10-21 | GSE58613 | GEO
Project description:In order to test Norway spruce radiosensitivity to gamma radiation, 6 days old seedlings were exposed for 48 h to 60-Co source at dose rates 1, 10, 40 or 100 mGy/h.
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