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Gene set enrichment analysis of basal and in vitro irradiation differentiates breast cancer patients with late skin radiotherapy toxicity

ABSTRACT: Radiation-induced late effects remain a common cause of morbidity amongst cancer survivors. The purpose of this study was to investigate the molecular basis underlying the radiotherapy-induced late skin toxicity in breast cancer patients who were previously assessed for radiation-induced lymphocyte apoptosis (RILA).

ORGANISM(S): Homo sapiens

PROVIDER: GSE178708 | GEO | 2022/05/10

REPOSITORIES: GEO

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Human mesenchymal stem cells prevent neurological complications of radiotherapy

Project description:Radiotherapy is a highly effective tool for the treatment of brain cancer. However, radiation also causes detrimental effects in the healthy tissue, leading to neurocognitive sequelae that compromise the quality of life of brain cancer survivors. Despite the recognition of this serious complication, no satisfactory solutions exist at present. Here we investigated the effects of intranasal administration of human mesenchymal stem cell (hMSCs) as a neuroprotective strategy for cranial radiation in mice. Our results demonstrated that intranasally delivered hMSCs promote radiation-induced brain injury repair, improving neurological function. The molecular analysis revealed that hMSC administration reduces persistent activation of damage-induced c-AMP response element-binding signaling in the irradiated neurogenic niches. Furthermore, hMSC treatment did not compromise survival of glioma-bearing mice. Our findings encourage the therapeutic use of hMSCs as an effective and non-invasive approach to prevent neurological complications of radiotherapy, improving the quality of life of brain tumor survivors.

2019-06-21 | GSE115735 | GEO

Radiotherapy induces persistent innate immune reprogramming of microglia into a priming state

Project description:More than half of all brain tumour survivors experience debilitating and often progressive cognitive decline after treatment with radiotherapy. Microglia, the tissue-resident macrophages of the brain, have been implicated in this decline. In response to various insults microglia can develop innate immune memory (IMM), which can either enhance (priming) or repress (tolerance) the response to subsequent inflammatory challenges. Here, we investigated whether radiation can affect the IMM of microglia by irradiating the brains of rats and later exposing them to a second inflammatory challenge. Transcriptomic profiling of microglia isolated from irradiated rats showed a stronger immune response to a second inflammatory insult demonstrating that radiation can lead to long-lasting molecular reprogramming of microglia. Transcriptomic analysis of post-mortem non-tumour brain tissue of glioblastoma patients indicates that radiation-induced microglial priming is conserved in humans. Targeting microglial priming after radiotherapy or avoiding further inflammatory insults could decrease progressive radiotherapy-induced cognitive decline.

2024-02-19 | GSE229940 | GEO

Novel Epigenetic Markers for Toxicity after Intraoperative and Conventional Radiotherapy for Breast Cancer

Project description:Ionizing radiation is a common treatment option for cancer but its use is limited by the unpredictable and highly heterogeneous onset of late side effects, especially radiation-induced fibrosis. Clinically applicable biomarkers and effective treatments for radiation fibrosis are currently unavailable. In order to identify novel markers we ran a genome-wide DNA methylation screen in primary dermal fibroblasts obtained from breast cancer patients before intraoperative radiotherapy. Cells from patients developing fibrosis within a three-year follow up were compared to those without fibrosis (12 individuals per group). Illumina Infinium HumanMethylation450 BeadChip Technology was used.

| EGAS00001001279 | EGA

Gene set enrichment analysis of basal and in vitro irradiation differentiates breast cancer patients with late skin radiotherapy toxicity

Project description:Gene set enrichment analysis of basal and in vitro irradiation differentiates breast cancer patients with late skin radiotherapy toxicity

| PRJNA740045 | ENA

Genomic profiling by SNParray of human sarcomas developed in the field of irradiation after radiotherapy

Project description:Genomic signature of the ionizing radiation effect in sarcomas developed in the field of irradiation after radiotherapy

2012-06-08 | E-MEXP-3248 | biostudies-arrayexpress

Transcription profiling by array of human sarcomas developed in the field of irradiation after radiotherapy.

Project description:Transcriptome signature of the ionizing radiation effect in sarcomas developed in the field of irradiation after radiotherapy

2011-03-31 | E-MEXP-2687 | biostudies-arrayexpress

Cranial Irradiation Impairs Juvenile Social Behavior and Modulates Hippocampal Physiology

Project description:Cranial and craniospinal irradiation are the oldest central nervous system prophylaxis treatments considered for pediatric patients with lymphoblastic leukemia (ALL). However, survivors of childhood ALL that received cranial radiotherapy are at increased risk for deficits in neurocognitive skills. The continuous and dynamic response of normal tissue after irradiation has been identified as one of the causative factors for cognitive changes after cranial radiation therapy. The aim of our study was to investigate the radiation effects on social behavior and neuronal morphology in the hippocampus of adult mice. Twenty-one-day-old male C57BL/6 mice were irradiated with the small-animal radiation research platform (SARRP). Animals were given a single 10-Gy dose of radiation of X-ray cranial radiation. One month following irradiation, animals underwent behavioral testing in the Three-Chamber Sociability paradigm. Radiation affected social discrimination during the third stage eliciting an inability to discriminate between the familiar and stranger mouse, while sham successfully spent more time exploring the novel stranger. Proteomic analysis revealed dysregulation of metabolic and signaling pathways associated with neurocognitive dysfunction such as mitochondrial dysfunction, Rac 1 signaling, and synaptogenesis signaling. We observed significant decreases in mushroom spine density in the Cornu Ammonis 2 of the hippocampus, which is associated sociability processing.

2022-02-15 | PXD017596 | Pride

Proteomic profiles in Acute Respiratory Distress Syndrome differentiates

Project description:Bronchoalveolar Lavage Fluid protein profile was characterized in ARDS subjects. Patients were divided into three groups: 1) Early phase survivors 2) Early phase non-survivors and 3) Late phase survivors. Bronchoalveolar lavage fluid was pooled within each group for sample preparation and mass spectrometry

2016-07-07 | PXD001095 | Pride

Genetic Predictors of Adverse Radiotherapy Effects (Gene-PARE)

Project description:<p>The goal of this study was to identify SNPs and CNPs that are associated with development of normal tissue toxicities resulting from radiotherapy for prostate cancer. The study population includes approximately 1,400 men treated with brachytherapy, external beam radiation therapy, or a combination of the two treatments, and assessed for adverse effects at baseline and following radiotherapy. Three toxicity endpoints were investigated using a two-stage GWAS approach: urinary morbidity, rectal bleeding and erectile dysfunction. The study sample was split into a discovery set (N=367) and a replication set (N=417), and an additional 647 samples, which were not part of this original cohort, were also included as an independent replication set. The replication set was developed via collaboration developed under the framework of the Radiogenomics Consortium (RGC).</p> <p>The long-term goal of this project, and other radiogenomics projects lead by the RGC, is two-fold: 1) Develop an assay capable of predicting which cancer patients are most likely to develop radiation injuries resulting from treatment with a standard RT protocol, and 2) Obtain information to assist with the elucidation of the molecular pathways responsible for radiation-induced normal tissue toxicities. These studies focus on multiple cancer types including prostate, breast, lung, and head and neck cancers.</p>

| phs000772 | dbGaP

Inefficient DNA-DSB repair via the homologous recombination pathway in prostate cancer patients with late radiation toxicity

Project description:Purpose: Severe late normal tissue damage limits radiotherapy treatment regimens. This study aims to validate γ-H2AX foci decay ratios and induced expression levels of DNA double strand break (DSB) repair genes, found in a retrospective study, as possible predictors for late radiation toxicity. Methods and Materials: Prospectively, decay ratios (initial/residual γ-H2AX foci numbers) and genome-wide expression profiles were examined in ex vivo irradiated lymphocytes of 198 prostate cancer patients. All patients were followed ≥2 years after radiotherapy, clinical characteristics were assembled and toxicity was recorded using the Common Terminology Criteria (CTCAE) v4.0. Results: No clinical factors were correlated with late radiation toxicity. Analysis of γ-H2AX foci uncovered a negative correlation between the foci decay ratio and toxicity grade. Significantly smaller decay ratios were found in grade≥3 compared to grade 0 patients (p=0.02), indicating less efficient DNA-DSB repair in radio-sensitive patients. Moreover, utilizing a foci decay ratio threshold determined in our previous retrospective study correctly classified 23 of the 28 grade≥3 patients (sensitivity, 82%) and 9 of the 14 grade 0 patients (specificity, 64%). Grade of toxicity also correlated with a reduced induction of the homologous recombination (HR) repair gene-set. The difference in average fold induction of the HR gene-set was most pronounced between grade 0 and grade≥3 patients (p=0.008). Conclusions: Reduced responsiveness of HR repair genes to irradiation and inefficient DSB repair correlate with an increased risk of late radiation toxicity. Using a decay ratio classifier, we could correctly classify 82% of the patients with grade≥3 toxicity. Additional studies are required to further optimize and validate the foci decay assay and to assess its predictive value for late radiation toxicity in patients prostate cancer

2017-01-30 | GSE85570 | GEO

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